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Q: How to do auto-reloading of jinja 2 data in Flask without refreshing page? I'm trying to load the data into json2 template as soon as there is new data available without refreshing the page but I'm unable to do that, this is what I tried till now main Function @app.route("/") def index1(): return render_template("index.html",gamest=get_games()) endpoint on the server that returns info. @app.route("/sys_info.json") def index(): return get_games() jinja 2 scripts: <script src="https://code.jquery.com/jquery-3.2.1.js"></script> <div id="content">{{ index }}</div> {# this is the original system_info passed in from the root view #} <script> setInterval(function(){ // load the data from your endpoint into the div $("#content").load("/sys_info.json") },1000) </script> <div class="list-group"> {% for game in gamest %} <a class="score-size text-xs-center nounderline list-group-item list-group-item-action" > <div class="row"> <div class="col-xs-4"> {% if game["Batting_team_img"] %} <img class="team-logo" src="/static/{{ game["Batting_team_img"] }}"> {% endif %} {{ game["Batting team"] }} {{ game["runs10"] }} </b> <br> {{ game["wickets10"] }} </div> I can see only change in the value in terminal but I can't see any changes in webpage data remains static, how can I fix this so data are changed dynamically in the website without refreshing page? A: The data is requested but the html is not refreshed by the js script. You have to add the logic for the browser to load the data in the html. For example: setInterval(function() { // load the data from your endpoint into the div $.getJSON("/sys_info.json", function (data) { $.each(data, function (_, element) { $('.list-group').append('<div>' + elment['Batting team'] + '</div>); }); }) },1000) You need the client browser to do the same you do on the server with jijna.

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Q: Remove spaces and underscores from a T List Problem: A T list of object (aTSource) contains a list of field names with extra spaces and underscores preventing matches to a variable without. I have a T list of object from my Model class. This list includes a Field name, value and the field type. I want to go into the field names and remove any spaces and underscores from the name. The purpose of the code is to compare fields from an Excel document and WPF form and return a list of those field names in common. foreach (DataRow dataRow in dataTable.AsEnumerable().ToList()) { T aTSource = new T(); foreach (PropInfo aField in commonFields) { PropertyInfo propertyInfos = aTSource.GetType().GetProperty(aField.Name); var value = (dataRow[afield.Name] == DBNull.Value) ? null : dataRow[afield.Name]; ... propertyInfos.SetValue(aTSource, value, null); list.Add(aTSource); } } Sample values from aTSource: IP_Address null string Product Name null string A: Create two Foreach loops with replacement statements, the first for the list of Excel field names and the second for the WPF form of field names, to ensure that the field names both match. foreach (DataColumn column in dataTable.Columns) { column.ColumnName = column.ColumnName.Replace(" ", ""); column.ColumnName = column.ColumnName.Replace("_", ""); }

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This comparison has been created by Life's Abundance and is meant to illustrate the differences in pricing between pet food it provides under the mark Life’s Abundance® and those provided by other companies. All entries related to pricing in the comparison table have been made on the basis of information available March 2017 and are based on typical suggested retail or list price of each brand, gathered from searching various online retailers March 2017. Life’s Abundance® price is based on Autoship price of an 18 lb. bag. Life's Abundance is in no way associated, sponsored, or affiliated with any of the manufacturers listed. NutriSource Grain Free Chicken & Pea Formula is a registered trademark of KLM Family Brands, Acana Regional Free Run Dry Dog Food is a registered trademark of Champion Pet Foods LP, Blue® Freedom Grain Free Chicken Recipe for Adult Dogs is a registered trademark of The Blue Buffalo Co., Canidae® Grain Free PureElements Formula Dog Food is a registered trademark of Canidae Corporation, Hill’s Ideal Balance® Natural Chicken & Potato Adult Recipe Dry Dog Food is a registered trademark of Hill’s Pet Nutrition, Inc. This comparison has been created by Life's Abundance and is meant to illustrate the differences in pricing between pet food it provides under the mark Life’s Abundance® and those provided by other companies. All entries related to pricing in the comparison table have been made on the basis of information available March 2017 and are based on typical suggested retail or list price of each brand, gathered from searching various online retailers March 2017. Life’s Abundance® price is based on Autoship price of a 6 lb. bag. Life's Abundance is in no way associated, sponsored, or affiliated with any of the manufacturers listed. Earthborn Holistic Primitive Feline Dry Cat Food is a registered trademark of Midwestern Pet Foods, Inc., Blue® Basics Grain Free Turkey & Potato Recipe Dry Food is a registered trademark of The Blue Buffalo Co., Hill's Ideal Balance Adult Grain-Free Natural Chicken & Potato Cat food is a registered trademark of of Hills Pet Nutrition, Inc., NOW Fresh Grain Free Adult Recipe Dry Cat Food is a registered trademark of Petcurean Pet Nutrition LP, Orijen Cat & Kitten Grain-Free Dry Cat Food is a registered trademark of Champion Petfoods. Some consumers feel hesitant about feeding new foods or treats to their dogs, especially if they’re unfamiliar with the seller’s protocols for bringing safe products to the market. We want you to know, with Life’s Abundance, you can feel completely at ease about feeding any of our products because our safety measures are of primary concern. While the majority of our ingredient suppliers and manufacturers are based in the U.S.A., the quality and safety of a product isn’t as simple as knowing its country of origin. For example, our all-natural buffalo chew treats are produced in India, but that’s not the whole story. The factory scores a Grade A on all of their annual inspections, audited by the SGS Group, the world’s leading inspection, verification, testing and certification company, setting the benchmark for quality and integrity. The buffalo chews also are tested to ensure that they’re free from e.coli, salmonella, yeast and mold contamination. In addition, our premium buffalo products undergo an extra level of protection to prevent food-borne illnesses and ensure safety. The chew treats are irradiated according to protocols implemented by U.S. FDA standards. The FDA has evaluated this food processing technique for more than 30 years and has clearly demonstrated its safety. The World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC) and the U.S. Department of Agriculture (USDA) have also endorsed the safety of this food treatment. We are certain that you will find our grass-fed, free-range buffalo chew treats are healthy additions to your dog’s diet. Feeding Instructions: Feed as a reward for good behavior or as a delicious, healthy snack. Felix Henckel Never tried to hard to eat , got our Motki since her dental surgery got a cracked tooth. 70 days ago Heather Madison This treat is another favorite of all my dogs! 112 days ago Robert Caruso These Buffalo Lungs must be pretty tasty. My dog goes crazy over them! 168 days ago Linda g Jennings Sink but the dogs are in love with these. 188 days ago Janice Clements My dogs loves them but I never have enough of them so I always buy more. 189 days ago Jenny Fedei Lip smacking good! When I open the bag, no matter which room of the house they are, in they come running with their tails wagging! They gobble these up like candy, except I know they are getting a protein rich healthy treat. My little guy Rascal, managed to get a hold of the whole bag once and he demolished its entire contents! I thought he might make himself sick from eating the entire bag, however there were no side effects from his binge... only a happy pup! Needless to say I keep the treats out of reach now, but at least I know my dogs are getting healthy, wholesome treats that are completely safe. Happy owner here! 189 days ago Dale Rew This product might be quite odoriferous, but dogs absolutely love it. I think this bag of treats is a great value for the cost because the treats break into small pieces and last a long time. 202 days ago Angela Ivey My dogs love these treats and rush to their bed in anticipation 203 days ago Shanae Stirling These are amazing, our dogs love them! Nice quantity for the price! 212 days ago Rich Leaver I use these as "rewards" for letting me cut nails! It works!! 223 days ago Gary Price My dog would not touch this 223 days ago Robert Gardner Great healthy treat for our Westie. Great altertanive to the unhealthy and dangerious rawhide. 336 days ago Sheri Legat Life's Abundance Buffalo Fillets are by far the favorite treat of all our dogs, and our friends dogs too! If you're having trouble motivating your dog to perform commands, try a little piece, you will be amazed with the results! 356 days ago Aimee Kyriss Dogs love these. I do make them eat them outside. There is no doubt that these are natural. 362 days ago Jillaine Huxol My dogs love this product. Its clean without mess. My puppies train with it for stacking and learning how to learn forward and upward when stacking. 371 days ago Katherine Fandel Maddy and Molly's favorite treats! 419 days ago Judith Weber The lung filets are a big hit in my house. My dogs know when it is time for their lung filet and they will not let me forget. They look forward to the treat and I love giving it to them because their is nothing in it but lung no fillers. Great product! 426 days ago Amelia h Johnson These fillets have made a beggar out of my dog...she just loves them! 448 days ago Alice Sills I think my dogs would kill the buffalo themselves for these treats. 455 days ago Kimberly Gillet Are these right up and begged for more 468 days ago Nikki Timberlake This is a wonderful product. I haven't found a dog yet that doesn't like this. It is easy to break into smaller pieces and makes a great training treat. 474 days ago Megan Smith These are fantastic, and a great value. I use pieces of them in place of liver treats, and whole fillets for a special treat. I can tell my dogs are smiling when they get one of these! 476 days ago Daniel Dendanto These are fantastic. I cut them up and use them as a high-value treat for training new behaviors. They are also a nice reward for getting into the crate. I think they are my dogs' overall favorite product from Life's Abundance. 480 days ago Judi Morrell My dog absolutely LOVES these treats. 487 days ago Joanna Darling Dogs loved these, they can be messy, but so worth it! 488 days ago Arlene Smith My dogs love these. I break them up and sprinkle in their food as a treat. 490 days ago Patricia Leblanc My dogs Cyrus and Cloey go bonkers every time they hear the bag opening. They love these healthy treats. 503 days ago Lori Boyd Great product that the dogs LOVE! 505 days ago Connie Todd My dog loves them way too much. He sees the bag and runs in circles hoping I will give in. 505 days ago Maria Vardal Thumbs up for these treats! Wholesome and my dog loves them! 510 days ago Dale Rew This product is great for all dogs including those with sensitivities. 511 days ago Donna Schlosser Have noticed some stool changes with these so I don't order any longer. 511 days ago Carol Rosecrans My dogs love these treats. They break apart easily, so that I can give the dogs the size treat that is right for them. When I forget to order enough and run out, the dogs get very disappointed until I get more in. 518 days ago Nancy Smallwood My dogs Love the fllets ,, they are digesting them well!! i am very happy with them No odor 518 days ago Kristin Great crunchy treat for my dogs. Might be a bit large for smaller dogs. 518 days ago Mike Shamp A big favorite in our house. 518 days ago Debra Harsh One of our dogs refuses all other treats when he knows we have these buffalo treats in the house. The odor is not very strong and they can be broken into smaller pieces to make them last a little longer. But this is a favorite of all the dogs in our house.

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Udbina Udbina () is a small town and a municipality in historical Krbava, in the Lika region of Croatia. It is administratively a part of the Lika-Senj County. Geography The town is located in the large karst field called Krbava. The field has a small airport, the only one in Lika. History Udbina was one of ilirians territories. In the medieval Kingdom of Croatia, Udbina was known as Civitas Corbaviae (Town of Krbava) and was the seat of a Diocese of Corbavia from 1185, when it was separated from the Archdiocese of Split, until 1460, when the diocese seat moved to the Krbava's former canonical territory of Modruš due to Ottoman military campaigns in the area. The Bishop's Court was built during Bishop Bonifacio in the 14th century. In the Middle Ages, Udbina was a seat () of the historic Krbava County. The name Udbina was mentioned for the first time in 1493, following the Battle of Krbava Field in which the Croats under ban Emerik Derenčin and the Frankopans suffered defeat from the Ottoman Empire. The medieval fortified town, from which only the remains were preserved, was governed in 1509 by Ban Ivan Karlović and between 1527 and 1689 by the Turks as part of the Eyalet of Bosnia.The 1712 census of Lika and Krbava records that 44 Croatian, 6 Bunjevci and 20 Vlach families live in Udbina. Ancient tombstones were discovered near the remains of the Church of St. Mark Graveyard (Named after the folk tradition that martyr saint and several heroes of the Battle of Krbava were buried on the site), which was a shrine with a triangular ending destroyed by the Serbs in 1942. In the vicinity, near Mutilić, there are ruins of the old Church of St. Augustine (quadrangular sanctuary with a bell tower). In the late 19th and early 20th century, Udbina was part of the Lika-Krbava County of the Kingdom of Croatia-Slavonia. According to the 1910 census, the town of Udbina was inhabited by a Croat majority and Serb minority; 1,317 Croats and 621 Serbs. Despite the fact that by 1942 the entire population of Udbina and Podudbina had been inhabited by Croat Catholics, the government of the Kingdom of Yugoslavia erected in Udbina a monument to the King Alexander I which was removed only after the establishment of the Independent State of Croatia (NDH). During World War II, Udbina was part of NDH's territory. Local gendarmerie sergeant Drakulić gave 200 rifles to the local Serbs, which on 12 April 1941 began with an ethnic cleansing of Lika from Gračac to Gospić. In 1942, Serbs burned two Catholic churches, Church of St. Nicholas and Church of St. Mark Graveyard. In December of the same year, the Croatian population was expelled from Udbina. In order to conceal ruins, Serbs after the war built a hotel on the site of the Church of St. Nicholas, and used stone from the Church of St. Mark Graveyard for building a sheep barn. In addition, Serbs also destroyed the Church of St. Augustin in Mutilić and the Catholic cemetery in Korija. During the war, many local Serbs were killed by Ustaše and local Croats by Chetniks and Yugoslav Partisans. The Orthodox Church of St. Nicholas (filial of the Church of the Holy Transfiguration of Mutilić) was also destroyed during World War II. Most Croats fled from Udbina after the massacre on the eve before the St. Lucy's Day. Croats fled through Trovro mountain all the way to Lovinac. After World War II, the new Yugoslav authority took away the houses and lands from the Croats and gave them to Serbs who comprised Udbina's majority, as confirmed by 1961–91 censuses, with smaller numbers of Croats and Muslims. It seems that there was a Franciscan monastery of St. John on the "Udbina hill". Yugoslav authorities erected a monument to the Yugoslav Partisans on the site without doing any archeological research or getting approval from the Institute for the Protection of Cultural Monuments. During the construction of the Partisan monument, remains of medieval edifices and human bones were found on the site. In SFR Yugoslavia, Udbina was part of the Korenica municipality. During the Croatian War of Independence, Udbina was under control of the Republic of Serbian Krajina. During that time, the remaining Croats from Krbava were forced to leave. The only remaining Croatian settlement on Krbava, Podlapač was saved from the Serb mob by the UNPROFOR's Czech battalion. The local airport was used as an airbase for offensive operations against Croatia and Bosnia and Herzegovina, in direct defiance of NATO's Operation Deny Flight. The airstrip was eventually destroyed by a NATO's 39 aircraft-strong strike on 21 November 1994. Udbina was taken on 7 August 1995 by Croatian forces during the Operation Storm. In the 2001 census, 51% of Udbina's population were Croats, mostly from Bosnia. Today, Udbina is a part of the Lika-Senj County. In recent years, Udbina recorded an increase in tourist visits. Settlements The settlements in the municipality are (2011 census): Breštane, population 5 Bunić, population 133 Čojluk, population 11 Debelo Brdo, population 78 Donji Mekinjar, population 31 Frkašić, population 33 Grabušić, population 66 Jagodnje, population 32 Jošan, population 66 Klašnjica, population 3 Komić, population 20 Krbava, population 37 Kurjak, population 28 Mutilić, population 38 Ondić, population 40 Pećane, population 35 Podlapača, population 74 Poljice, population 9 Rebić, population 22 Srednja Gora, population 25 Svračkovo Selo, population 10 Šalamunić, population 38 Tolić, population 9 Udbina, population 960 Vedašić, population 2 Visuć, population 69 Demographics According to the 2011 census, there were 1,875 residents in the municipality, of which 51% were Serbs and 45% were Croats. In 2016 on the instructions of Vlaho Orepić, Minister of Interior in the Cabinet of Tihomir Orešković, Croatian police started intensive patrols and checking out the residence of local population and that resulted in 71 deletions from the residence register. Voices of criticism of police action were raised, including the one of the Deputy Mayor of Udbina Milan Uzelac, claiming that the action is disproportionately and primarily targeted at the Serbs of Croatia and promoted by a president of a local right wing organization close to the ruling Bridge of Independent Lists. Representatives of local Serb population organized a meeting with Serb National Council to discuss the issue. 2011 census was the first post-war census at which Serbs of Croatia, many of whom left the area during the Operation Storm, constituted the majority of local population. Minister Vlaho Orepić in his statements prior to Police activities in Udbina and the rest of the country called out the Serb minority for election manipulation with the fictive residences. Notable locals Rade Šerbedžija (born 1946), actor, born in Bunić Tomislav Sertić (1902–1942), Ustasha General, born in Udbina Petar Smiljanić - leader of a Morlach clan, born in Udbina Jovanka Broz (1924–2013), wife of Yugoslav president Josip Broz Tito, was born in Pećane References External links Category:Populated places in Lika-Senj County Category:Municipalities of Croatia Category:Serb communities in Croatia

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[Effecacy of three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma]. To observe the local control rate, survival time and side effect of three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma. Forty patients with postoperative recurrent rectal carcinoma received three-dimensional conformal radiation therapy, 1.8 - 2.0 Gy/once, 5 times every week and the total dose was 54 - 65 Gy. At the same time, the patients took Tegafur orally 40 mg/m(2) twice per day for consecutive 28 days, and one cycle lasted for 42 days. The chemotherapy was applied for 2 cycles after radiotherapy. The total effective rate (CR + PR) was 70.0%, improvement rate was 90.0%, 1-year survival rate was 70.0%, and 1-year local control rate was 62.5%. There was only a little side effect. Three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma have definite effect, with a high local control rate, and patients well tolerance the treatment without serious side effect. It can apparently improve the life quality of the patients.

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Image copyright Getty Images Islamophobia has become the driving force behind the rise of far-right movements in the UK, according to an anti-racism charity. Hope Not Hate says anti-Muslim prejudice has replaced immigration as the "key driver" of the groups. A report from the charity carries a poll suggesting 35% third of Britons thought Islam was "generally a threat to the British way of life". This compares with 30% who thought it was compatible. The State of Hate report blames the 2017 terror attacks in London and Manchester for a "lasting negative impact" on attitudes towards Muslims. It says while the number of people arrested over terror-related offences in 2018 was down on the previous year, the UK was witnessing a growing threat of far-right terrorism. The report refers to the threat of lone-wolf terrorists and right-wing extremists, who are getting radicalised over the internet. It said the far right has become more extreme, younger and is successfully tapping into the "political rage" felt by many in society. Mansoor Clarke, an Imam at the Baitul Futuh Mosque in south London, says Hope Not Hate's report was "worrying" and shows increasing division in society. "As a white-British Muslim I feel conflicted," he added. "How do you define being British? I would say its being tolerant, truthful, polite... those sort of things." Exploiting Brexit The Hope Not Hate poll conducted in July 2018, found 49% of those who voted Conservative in the 2017 general election thought Islam was generally a threat to the British way of life, compared with 21% who said it was compatible. Among Labour voters, 22% said Islam was generally a threat, and 43% thought it compatible. The report says the Conservatives should do more to challenge the negative view of its voters. It said there was a "very real" left wing anti-Semitism problem among a "small but very vocal group" of people. A larger group is said to be engaged in "conspiratorial anti-Semitism" on social media, although overt anti-Semitism and Holocaust denial is uncommon. The row within the Labour Party over anti-Semitism is also highlighted in the report. Hope Not Hate suggested that the far-right could exploit Brexit, stating: "Divisions within Britain are likely to increase and this will further split communities and boost the far-right's populist anti-politics message".

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I love Little Hunan. The food is always totally fresh- very hot and it tastes wonderful. My husband and I are never disappointed when we go in. They are also very fast. When we get food to-go they have it out in minutes-even though they make it fresh after you order it. I love Little Hunan. The food is always totally fresh- very hot and it tastes wonderful. My husband and I are never disappointed when we go in. They are also very fast. When we get food to-go they have it out in minutes-even though they make it fresh after you order it. We recently found this restaurant and eat it many times a month! The service is great and the food is really good--I recommend cashew chicken or pepper beef. They have lunch specials and you get as much food as the dinner specials--for a dollar less! The prices are really affordable and you get enough food for 2 people to share most platters (unless you go in really hungry). My family does "family style" and we order a few platters and then share them. You also get free fortune cookies at the end of the meal! :) We recently found this restaurant and eat it many times a month! The service is great and the food is really good--I recommend cashew chicken or pepper beef. They have lunch specials and you get as much food as the dinner specials--for a dollar less! The prices are really affordable and you get enough food for 2 people to share most platters (unless you go in really hungry). My family does "family style" and we order a few platters and then share them. You also get free fortune cookies at the end of the meal! :) Was this review helpful to you? Wait, you're the expert. If you've been to or used Little Hunan, leave a review. It's easy, only takes a couple of minutes and you'll help thousands make an informed decision.

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Additional Information Additional Information The wind doesn’t stand a chance with the climaproof® Stretch Wind Jacket on your side. Combining water-resistant protection with near-impenetrable defense against chilling gusts, this lightweight jacket will find a permanent home in your bag.

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1. Field of the Invention The present invention relates to a pre-ignition estimation/control device for an internal combustion engine, which is installed on a vehicle or the like and can prevent pre-ignition. 2. Description of the Related Art Pre-ignition causing combustion noises and fluctuations in output may occur in a high-compression-ratio spark-ignition internal combustion engine. The pre-ignition refers to a phenomenon of an excessively large fluctuation in pressure inside a combustion chamber of an internal combustion engine, which results from combustion. Pre-ignition which occurs before the spark ignition is generally known. In addition to this type of pre-ignition, there are phenomena including pre-ignition in which a mixture (mixed gas of the air and a fuel) in the combustion chamber reaches high temperature by compression and is auto-ignited, and pre-ignition in which a deposit or the like at a tip of a spark plug forms a hot spot and causes ignition. Moreover, there is known a knock in which an end gas at a periphery of the combustion chamber is auto-ignited in the combustion process after the ignition. These phenomena cause noises and vibrations as well as damages in the combustion chamber of the internal combustion engine, and the internal combustion engine may finally become no longer operable. To address this, methods of estimating occurrence of pre-ignition based on environmental conditions and operation conditions, thereby preventing the pre-ignition, have conventionally been proposed. In a conventional method of preventing the pre-ignition, pre-ignition, which occurs at low rotation speed, under a high load, and at high temperature, is determined based on the temperature and operation states of the internal combustion engine, and an effective compression ratio is reduced as the temperature increases, thereby preventing the pre-ignition (refer to Japanese Patent Application Laid-open No. 2005-76466, for example). Moreover, in another conventional method of preventing the pre-ignition, the octane number of a fuel is estimated, and a likelihood of occurrence of the pre-ignition is determined based on the estimated octane number of the fuel, thereby preventing the pre-ignition on startup by decreasing the effective compression ratio on the startup according to the environmental temperature of the internal combustion engine (refer to Japanese Patent Application Laid-open No. 2009-114973, for example). Japanese Patent Application Laid-open No. 2005-76466 describes that the pre-ignition is prevented by decreasing the effective compression ratio according to the increase in the temperature of the internal combustion engine. However, causes of the occurrence of the pre-ignition include fuel properties in addition to the temperature in the internal combustion engine and the increase in temperature caused by the compression in the combustion chamber, and it is known that the pre-ignition occurs more frequently as the octane number of the fuel becomes low. In view of the above, even in a case where the environmental temperature (temperature of an intake air to be introduced into the combustion chamber as an ambient temperature around the internal combustion engine, for example) is low, if the octane number of the fuel is low, pre-ignition possibly occurs. The opposite holds true, and even if the octane number is high, high environmental temperature possibly causes pre-ignition. Japanese Patent Application Laid-open No. 2009-114973 describes that a likelihood of occurrence of the pre-ignition is determined, and the pre-ignition on startup is prevented by setting the effective compression ratio on the startup according to the determination. However, Japanese Patent Application Laid-open No. 2009-114973 describes only the prevention of the pre-ignition that occurs on the startup (prevention of the pre-ignition refers to prevention of such an operation state that possibly causes the pre-ignition), and does not consider pre-ignition which occurs “after the startup”. Moreover, Japanese Patent Application Laid-open No. 2009-114973 does not consider a method of avoiding pre-ignition after the preventive operation of the pre-ignition (avoidance of pre-ignition refers to a change of an operation state to prevent pre-ignition from occurring any more when pre-ignition actually occurs). In addition, though it is assumed that the likelihood of the occurrence of the pre-ignition depends on the intake air temperature, the coolant temperature, and the octane number of the fuel, which are considered independently, the likelihood of the occurrence of the pre-ignition is not considered under a combined condition thereof. There are a plurality of conditions which cause the pre-ignition more frequently, and it is necessary to consider the respective conditions, thereby producing an index of the likelihood of the pre-ignition. The method described in Japanese Patent Application Laid-open No. 2009-114973 describes that the likelihood of the pre-ignition is determined according to the octane number. When a fuel having a high octane number is used, at whatever high intake air temperature and whatever high water temperature the startup may be conducted (hot start at 50° C. of the intake air temperature and 110° C. of the water temperature in a desert, for example), control of reducing the effective compression ratio is not provided. However, even if a fuel having a high octane number (high octane fuel of 95 [RON], for example) is used, it is experimentally known that pre-ignition may occur at high intake air temperature and high water temperature.

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Infrastructure of Iraq Infrastructure of Iraq describes the infrastructure of the country of Iraq. Throughout the history of Iraq, the country's infrastructure, along with its politics and economy, have been affected by armed conflicts; none more serious than the 2003 Invasion and subsequent reconstruction. Transport Iraq has 45,550 km of roads, with 38,400 km, of them paved (1996 est.) Iraq has 4,350 km of crude oil pipelines, and 1,360 km for natural gas. There are about 113 airports. (1999 est.) Major airports include Baghdad International Airport Basra International Airport Mosul International Airport Erbil International Airport Sulaimaniyah International Airport Najaf International Airport There is significant rail transport in Iraq. In November, 2008, an overground service dubbed the Baghdad Metro began service. Energy Baghdad continues to suffer regular power outages. In the hot summer of 2004, electricity was only available intermittently in most areas of the city. According to a member of Paul Bremer's staff, the problems with electricity were exacerbated by a surge in the use of air conditioners which were previously banned by Saddam Hussein. Health During the Gulf War of 1991 aerial bombardment caused severe damage to the electric grid that operated the pumping stations and other facilities for potable water delivery and sewage treatment, causing massive problems with Water supply and sanitation in Iraq. The sanctions imposed by the UN at the conclusion of the Gulf War exacerbated these problems by banning the importation of spare parts for equipment and chemicals, such as chlorine, needed for disinfection. The 2003 invasion of Iraq produced further degradation of Iraq’s water supply, sewerage and electrical supply systems. Treatment plants, pumping stations and generating stations were stripped of their equipment, supplies and electrical wiring by looters. The once-capable cadre of engineers and operating technicians were scattered or left the country. Reconstruction efforts faced a nation with a severely degraded infrastructure. Communications The 2003 Iraq war severely disrupted telecommunications throughout Iraq, including international connections. USAID is overseeing the repair of switching capability and the construction of mobile and satellite communications facilities. Main telephone lines in use: 833,000 (as of 2005) Number of mobile cellular phones: 9,000,000 (as of 2005) Domestic telephone network: Repairs to switches and lines have been made. Cellular service is in place since 2004. Cellular service is still spotty in some locations. It is expected to improve further.USA Today from 2005 about Iraq and its Telecommunications Iraqna, an Orascom Telecom company, led by Shamel CCO is the biggest GSM Cell phone provider in Iraq. International connections: 2 Intelsat satellite earth stations (1 Atlantic Ocean region, 1 Indian Ocean region) 1 Intersputnik satellite earth station (Atlantic Ocean region) 1 Arabsat satellite earth station (inoperative) Coaxial cable and microwave radio relay to Jordan, Kuwait, Syria, and Turkey (the line to Kuwait is probably not operational) Al Iraqiya (or Iraqi Media Network) is Iraq's main public broadcaster. Since the overthrow of Saddam Hussein, Internet in Iraq has become commonplace. Uruklink, originally the sole Iraqi Internet service provider, now faces competition from other ISPs, including broadband satellite internet access services from both Middle East and European VSAT hubs. The premier military telecom service provider in Iraq is Ts 2. See also List of schools in Iraq References Category:Infrastructure in Iraq

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Falmer Stadium: Brighton & Hove Albion Farmer Stadium is the home of Brighton and Hove Albion Football Club, though it’s known as The American Express Community Stadium because of sponsorship reasons. It’s also known as The Amex for simplicity reasons! It’s located near to the village of Falmer, which is where it got its original name from. The Amex replaced the club’s former stadium, the Goldstone Ground, owing to the fact that the club’s former owners sold it to developers. Because the old owners didn’t line-up a replacement ground for Brighton they ended up bouncing around a number of different stadiums whilst they looked for their own home. Originally they ground-shared with Gillingham at Priestfield Stadium before using Withdean Stadium for a time. The location that would eventually be the building area for Falmer Stadium was actually identified as early as 1998. However delays in planning permission meant that Brighton had to wait over a decade until their new stadium was officially opened in 2011. Falmer Stadium Seating Plan & Where to Sit Like most new stadiums, The Amex is constructed in a bowl style. It still has four distinct sections, though, somewhat imaginatively called the North, South, East and West stands. The East Stand has two tiers and The West Stand has three, whilst the North and South Stands are single-tiered. The North Stand - With room for over 2,500 supporters, this stand is the one that houses the club’s most vocal supporters. Unlike with The South Stand behind the opposite goal this are of the ground is not joined up to the other sections by corner seating. The East Stand - Over 5000 supporters can sit in this part of the stadium and it is considered to be the most family friendly area of the ground. If travelling supporters ever get an increased allocation of tickets then this is the part of the ground that they’ll sit in. The South Stand - With a central seating section as well as seating in the corners to connect it to the rest of the stadium, this is a touch larger than The North Stand. It’s also where the travelling fans are normally accommodated. The West Stand - The three tiers of The West Stand allow it to hold over 11,000 supporters, making it the largest section of the stadium. Brighton & Hove Albion Ticket Prices As is the case with most clubs in the country, Brighton & Hove Albion categorise their games depending on the opposition they face. Prices also differ within each category depending on where in the ground you are looking to sit. The ticket also includes free bus and rail travel from within a subsidised zone. Here are the cheapest and most expensive ticket prices for adults and concessions in each category: Category A: £32-£42 / £24-£30 Category B: £30-£40 / £22-£28 Category C: £25-£35 / £20-£28 How To Get Brighton & Hove Albion Tickets Brighton & Hove Albion have an excellent website with easy to understand ticket pricing. That would be your first port of call if you’re hoping to buy tickets to see the club play live. You can also call the club’s ticket office directly to discuss your ticketing options or you can call in at the ticket office at the ground itself. Getting To Falmer Stadium How you would go about getting to The Amex was one of the chief concerns that was taken into account when the stadium was built, so access is surprisingly easy and well thought out. Here are some of the more conventional methods you’ll want to consider! Train - Falmer Railway Station is just 150 metres from the ground, so you’ll be able to walk it in about a minute. It’s on the East Castaway Line and Southern Railways operate services there about four times an hour. Brighton itself is, of course, a little bit out of the way from the rest of the country. A train from London can take anywhere from an hour to an hour and half, whilst a journey from further North will take however long it takes you to get to London plus the time it takes to change trains. Bus - There are two bus stops really close to the ground that you can get to on bus numbers 23, 25 and 84. There are also services that run from the University of Sussex campus as well as match day services put on by the club. Car - The club is conscious of its environmental footprint, so it positively discourages people from driving to the ground. There are Park & Ride options available from both The University of Brighton and Mill Road as well as Brighton Racecourse. If you’re driving from London then you’ll want to get onto the M25 before taking the M23 to the A27. From there you’ll get onto the B2123 and this is the road on which you’ll find the Amex. If you’re travelling from somewhere up North, Manchester for example, then you’ll take the M6 (or M6 toll) to the M40 before getting onto the London Orbital and following the route outlined below. By Air - All of the London airports are within easy distance of Brighton, so if you’re coming from abroad then you’ll want to consider which of those airports is best for you and take it from there. Gatwick, as an example, is just half an hour away from Brighton by train. There is an airport called Shoreham, or Brighton City, but this is typically the reserve of private light aircrafts. Taxi - A taxi from Brighton Train Station to The Amex will set you back something in the region of about £20 and your journey will take about the same amount of minutes to complete. Obviously if you end up travelling at a busier time then you will inevitably end up paying more money! Parking Near Falmer Stadium As well as the excellent park and ride options the club also offers parking at two sites near to the ground. Parking there needs to be pre-booked, so do bear that in mind. You can head to either Sussex University’s Stanmer Park or Bridge Car Park. There is no on-street parking near to the ground and if you attempt to do that you may well end up with a fine or your car being towed away. Located in Woodingdean, about one and a half miles from the stadium, this hotel sits above a restaurant-cum-bar and has a garden, barbecue grills and a picnic area. There’s also free Wi-Fi in the reception area, free parking and a free breakfast included with your stay. More details. Brighton’s Jurys Inn can be found about a mile from the beach and a little over three miles from The Amex. It’s got over 200 rooms, a restaurant and bar, nine meeting rooms and a conference space. There’s also free Wi-Fi and multilingual staff for those of you coming from abroad or who just like to test your GCSE French on an unsuspecting hotelier. More details. Three and a half miles from Brighton & Hove Albion’s home ground and within walking distance of the city’s Sea Life Centre is this charming guest house. With just seven rooms, free wi-fi and free breakfast you know you’ll get a very personal experience if you choose to spend your pre-match night here. More details. Pubs & Bars Near Falmer Stadium Just as the nearby sea front means there are plenty of hotels to choose from in Brighton, so there are also a huge amount of bars and pubs for your consideration. We’ve tried to pick some that are particularly welcoming to sports fans for you here: The Swan Inn Middle Street, Falmer, BN1 9PD (01273 681842) This is the closest pub to the stadium and us such is pretty much the sole consideration of the home supporters, with away supporters encouraged to consider having a drink elsewhere. It shows all of the sport that you might be hoping to watch and it also serves delicious food. You can get a drink there too, obviously. The Evening Star 55/56 Surrey Street, Brighton, BN1 3PB (01273 328 931) This is the home of The Dark Star brewing company, the place where it all began. Because of that it’s fair to say that you’ll be able to pick up a decent real ale or two here! The Post & Telegraph 155-158 North St, Brighton BN1 1EA (01273 827540) This is a JD Wetherspoon pub, so don’t be expecting anything too spectacular. That said you’ll get cheap food, cheap booze and sport on televisions dotted around the place, so it’s not a bad place to head for a pre-match pint or two! Facilities The facilities at The Amex are excellent, with padded seats, excellent views and good legroom on offer for all supporters within the stadium. The concourses behind the scenes are large and welcoming, with numerous stalls offering food and drink options before the match and at half-time. For those that care about such things there are also tremendous acoustics within the ground, meaning that there can be quite an atmosphere during matches that the supporters get ‘up’ for. Prices Programme: 3.50 Pie: 4.10 Cup of tea: 2.10 Hospitality Nominated in four different categories in the 2015 Stadium Events and Hospitality awards, it’s safe to say you’ll get a brilliant experience if you choose to take advantage of one of the hospitality packages available at The Amex. The stadium boasts ten lounges as well as 21 executive boxes, so your options are numerous should you wish to watch the match from a position of comfort and luxury. Lounges typically open about two and a half hours before the game is due to kick off and they close at 11pm. There are different menus available depending on which lounge you have tickets for and what type of hospitality package you have selected. In the East and South lounges you will typically be offered ‘pub’ style food of burgers, ribs, curry or a vegetarian selection. Hospitality at The Amex comes under the name of The 1901 Club, so this is what you’ll be looking for it you want to seek out some more specific information. Private Hire Those ten lounges and 21 executive boxes aren’t only there to cater to supporters hoping to enjoy a nice bite to eat before the game. They’re also the idea place to hold meetings, parties and even weddings for those hoping to hold such an occasion in Brighton. You can hire out the board room if you’re hoping for a professional looking, intimate affair, or you can opt for one of the larger lounges in order to host a dinner dance for up to 500 people. Whatever you opt for you’ll benefit from state-of-the-art equipment such as plasma screens, PA systems and wireless internet access. You can even combine two of the executive boxes for a larger meeting that still feels intimate or as a breakout space from a larger meeting, should that be what you’re looking for. Stadium Tours & Museum Whether or not you’re a fan of The Seagulls, a tour of The American Express Community Stadium is well worth your time if you ever find yourself at a loose end in Brighton. They run on Mondays, Thursdays and Saturdays, even if there’s a 3pm kick off, and the tour lasts for about an hour and three quarters. Whilst on the tour you’ll take the upper part of The West Stand, the trophy room, the hospitality lounges, the press area, both sets of changing rooms and the dug-outs on the side of the pitch. Access to the club’s new museum, located next to Dick’s Bar, is also included in your ticket price. The whole thing costs £13 for adults and £6.50 to people under 16 or over 65. About Brighton & Hove Albion Souvenir postcard of Brighton & Hove Albion Football Club, celebrating their Southern League title and Southern Charity Cup win in the 1909-1910 season -By Upload: Rugby pioneers Original: Ebenezer Pannell of Church Road, Hove, the official photographer to Brighton & Hove Football Club. See Ebenezer Pannell - Brighton & Hove Photographer, which confirms Mr Pannell died in 1934. [Public domain or Public domain], via Wikimedia Commons Brighton & Hove Albion, commonly referred to as simply ‘Brighton’, has been in existence as a football club since 1901. Nicknamed either The Seagulls or The Albion, they were elected to the Football League proper in 1920, having previously taken part in the Southern League. The club enjoyed its most successful spell in the early ‘80s, playing their football in the top-tier of English football and reaching the final of the FA Cup. They lost out on the trophy to Manchester United after a replay, though not before they picked up a number of admirers. Their main rival is, strangely, Crystal Palace, despite the fact that the clubs are more than 40 miles apart from each other. Brighton nearly went into liquidation after a number of years of mismanagement. They were nearly relegated out of the Football League and into the Conference before a boardroom takeover saved them and they ended up returning to the country’s Second Division. They have spent the past fourteen years moving between the second and third tiers of English football. Falmer Stadium History The stadium is one of the newest in the South coast area, opening as it did in 2011. The first game played there was between Tottenham Hotspur and Brighton, with the London club running out 3-2 winners. The first competitive match took place between the home side and Eastbourne Borough in the final of the Sussex Senior Cup. A strange quirk of fate meant that the stadium’s first home game came against Doncaster Rovers - the same team against whom the last match at the club’s previous permanent home had been played. Despite being a young stadium the record attendance has already changed a number of times. The first record was 21,897, set when Liverpool came to play The Seagulls in the League Cup in 2011. The Merseyside club were also the first away team to win a competitive match at The Amex. In 2012 the stadium’s capacity was increased and a new record attendance of 26,684 was set when Brighton saw out a goalless draw against Nottingham Forrest. The current record attendance of 30,278 was set when Arsenal played Brighton in the fourth round of the FA Cup in January of 2015. Future Developments There are no current plans to expand The Amex any further, even if the club gain promotion to the Premier League in the future. There are plans to continue to develop the region around the ground, though, with hopes that it will become something of a gateway between the area near the stadium and the town centre.

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1998 California lieutenant gubernatorial election The 1998 California lieutenant gubernatorial election occurred on November 3, 1998. The primary elections took place on June 2, 1998. State Assemblyman and Speaker of the Assembly Cruz Bustamante, the Democratic nominee, decisively defeated the Republican nominee, State Senator Tim Leslie, to succeed the incumbent Gray Davis, who chose not to seek re-election in favor of running for governor. Primary Results Final results from the Secretary of State of California Democratic Republican Peace and Freedom Others General election results Final results from the Secretary of State of California Results by county Final results from the Secretary of State of California. See also California state elections, 1998 State of California Lieutenant Governor of California List of Lieutenant Governors of California References External links VoteCircle.com Non-partisan resources & vote sharing network for Californians Information on the elections from California's Secretary of State Category:1998 California elections 1998

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Miami Dolphins players who protest on the field during the national anthem could be suspended for up to four games under a team policy issued this week. [New: NFL suspends ban on national anthem protests amid talks with players' union] The "Proper Anthem Conduct" section is just one sentence in a nine-page discipline document provided to The Associated Press by a person familiar with the policy who insisted on anonymity because the document is not public. It classifies anthem protests under a large list of "conduct detrimental to the club," all of which could lead to a paid or unpaid suspension, a fine or both. Miami's anthem policy comes after the NFL decided in May that teams would be fined if players didn't stand during "The Star-Spangled Banner" while on the field. The league left it up to teams on how to punish players. None of the team policies have been made public. [Opinion: NFLPA is going to lose its national anthem lawsuit and hurt the NFL in the process] The NFL rule forbids players from sitting or taking a knee if they are on the field or sidelines during the national anthem, but allows them to stay in the locker room if they wish. The new league rules were challenged this month in a grievance by the players union. The NFL declined to comment. Team officials had no immediate comment. "Players who are on the field during the Anthem performance must stand and show respect for the flag and the Anthem," says the 16th and final bullet point in the list of conduct considered detrimental, below riding motorcycles during the season and disparaging teammates, coaches or officials including NFL Commissioner Roger Goodell. The NFLPA said earlier this month that the NFL policy, which the league imposed without consultation with the players union, is inconsistent with the collective bargaining agreement and infringes on player rights. The filing will be heard by an independent arbitrator, an NFLPA spokesman said. When the league announced the policy, Goodell called it a compromise aimed at putting the focus back on football after a tumultuous year in which television ratings dipped nearly 10 percent. The union said when it filed the grievance that it proposed having its executive committee talk to the NFL instead of litigating. The union said the NFL agreed to those discussions. In 2016, then-49ers quarterback Colin Kaepernick began protesting police brutality, social injustice and racial inequality by kneeling during the national anthem and the demonstration spread to other players and teams. It became one of the most controversial and sensitive issues in sports. Critics led by President Donald Trump called the players unpatriotic and even said NFL owners should fire any player who refused to stand during the anthem. Some players countered that their actions were being misconstrued and that they are seeking social change rather than protesting the anthem itself. Trump's criticism led more than 200 players to protest during one weekend, and some kept it up throughout the season. The NFL started requiring players to be on the field for the anthem in 2009. "We want people to be respectful of the national anthem. We want people to stand," Goodell said at the May meetings, when he dismissed concerns about the lack of union involvement by contending the league met with countless players over the past year. "We've been very sensitive on making sure that we give players choices," the commissioner added, "but we do believe that moment is an important moment and one that we are going to focus on." The league and a coalition of players have been working in tandem to support player initiatives for a variety of social issues. The NFL is committing $90 million over the next seven years to social justice causes in a three-segment plan that involves league players. Kaepernick didn't play at all last season and still hasn't been picked up by another team. He threw 16 touchdown passes and four interceptions in his final season in 2016. Safety Eric Reid, one of Kaepernick's former teammates and another protest leader, is also out of work. Both have filed collusion grievances against the NFL.

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Joined up with the Monmouthshire Regiment, but due to huge losses, soldiers from different depleted regiments found themselves transferred to others to make up the numbers.They were defending a small hill, Kemmel, a strategic viewpoint above marshland, and faced a German offensive which was different to those previously experienced.There were no big guns to start with but a "surprise" lightly armed attack which caught the British unawares. It signalled the start of some fierce battles over the next few months, with hand to hand fighting.​It is likely George was buried by the Germans before being re-buried later after British advances

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Q: Proof of x-intersection of the Mandelbrot Set? I'm trying to prove that the Mandelbrot set intersects the X-axis on the interval [-2,.25]. I understand and have proven that the Mandelbrot set lies in a radius of 2. Mostly, I'm wondering how to prove that .25 is the greatest possible point on the X-axis. I've attempted to develop a proof using this argument: $ z_{n+1}=z_n^2+c $ $\\ 0=z_n^2+c-z_{n+1}$ Upon finding the discriminant, $ \sqrt{1-4c} $, it's clear that the only values for which the equation yields real answers are those with $ c \geq 1/4$. But, given the recursive definition, I'm not sure manipulating the quadratic equation is valid. Thanks! A: It is straightforward for real values of $z_n$: $$ z_{n+1} - z_n = z_n^2 - z_n + c = \left(z_n - \frac12\right)^2 +c -\frac14 \ge c-\frac14, $$ so if $c-\frac14 > 0$ you get by induction that $z_n \ge z_0 + n\left(c-\frac14\right) \to \infty$ for $n \to \infty$. A: Let me write $f=f_c(x)=x^2+c$. The proof that $c\notin M$ for $c>1/4$ was already given by Lukas, although there is an even softer argument: observe (using the quadratic formula) that $f_c(x)=x$ has no solutions for for $c>1/4$, and hence $f_c(x)>x$ for all $x$ (since this is true for large $x$). So, for every $x_0\in \mathbb{R}$, the corresponding sequence $x_n$ is increasing, and hence either has a finite limit or converges to infinity. But if $x_n\to x\in\mathbb{R}$, then we would have $$ f(x) = f(\lim_{n\to \infty} x_n) = \lim_{n\to\infty} f(x_n) = \lim_{n\to\infty} x_{n+1} = x $$ by continuity, and this is a contradiction to $f$ not having any fixed points. For $c\leq 1/4$, there is a fixed point $$ \beta(c) = \frac{1 + \sqrt{4-c}}{2},$$ again found using the quadratic formula. (Actually if $c<1/4$, there are exactly two fixed points, but we only care about the larger one.) Let us change coordinates, for convenience, to the logistic family, given by $$ g_{\lambda}(t) := g(t) := \lambda t (1-t), \qquad \lambda = 2\cdot \beta(c), \qquad t = \frac{1}{2} - \frac{x}{\lambda}.$$ (It is easy to check that this change of coordinate does indeed transform $f$ to the function $g$.) Now $c\in [-2,1/4]$ corresponds to $\lambda\in [1,4]$, and in this case we have $g([0,1])\subset [0,1]$. (Note that $g(0)=0$, $g(1)=0$, and $g$ takes its maximum at $t=1/2$: $g(1/2)=\lambda/4$.) It follows that the critical point $t=1/2$ (which corresponds to $x=0$) has bounded orbit. This implies that $c\in M$. Finally, if $c<-2$, then we see, again considering the function $g_{\lambda}$ and setting $t_0=1/2$, that $t_1 = g(t_0) = \lambda/4 > 1$, $t_2 = g(t_1) < 0$, and $g(t_{n+1}) < t_n$ for all $n\geq 2$. As above, it follows that $t_n\to -\infty$, and $c\notin M$. [If you do not wish to change coordinates, of course you can do the calculations also in the original parameterisation, but it becomes a little awkward.]

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What can I do about pain in my foot, between the base of the toes and the arch of the foot. It occurred 4 days ago but prior to that I hadn't run for a week. The last run I did was 20 miles. Sorry to hear you've developed an issue with your foot, it can be really frustrating especially when you are clearly progressing with your training up to 20 miles. Before you do anything else, I'd suggest you book an appointment with a physio. They will be able to fully assess the problem and suggest the best course of rehabilitation. This will likely be a schedule of stretches and strengthening exercises to perform. It's impossible to assess an injury without a detailed examination by a physio, which is why it’s key you see one as soon as you can. I have recently pulled my groin whilst running, should I continue training or should I take some time of for it to heal. I have tried swimming instead but not sure how this will help me running longer distances. Tick Tick Thanks You have signed up for our newsletter You are already signed up to our newsletter You have previously requested to be completely removed from our mailing list (GDPR SAR request). We are not allowed to re-subscribe you via any of our sites, you can re-subscribe via our newsletter provider (Mailchimp) using their form, by following this link

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So I remember Savannah (I think) mentioning that she had some cool pins made up for LEO gifts one year. I thought that would be fun to do. I'm hoping to get some cute junior police/ranger badges made up. I'm reaching out to a few friends in the promo business to see if I can get a short run of these: Truthfully, all of my experiences were pleasant. It helped that as I flew in I carried zero contraband and did not spend much time at the big sound camps. They're human beings too and I like to think that creating positive experiences for them could carry over into their dealings with other Burners. I think I was the person who mentioned I made pins for LEO's. It was a very cool 2" pin that had a police shield, American flag and the BM logo on it. I kept them in my backpack and would offer them to friendly police along the way, but realized they were concerned that I was digging in my bag for "something" for them. I pinned a few on my hat and offered them from there. If they wanted an extra, they were ok at that point with me getting another one from my backpack. This past year, I went over to a Pershing County Sheriff car after seeing them snap a few photos of some amazing art on the playa. It turns out that they were enjoying the event as much or more so than the participants. I'll bet we talked for 15 minutes and I gave them some great swag to take home. One asked for an extra necklace for his wife! Shambala wrote:I think I was the person who mentioned I made pins for LEO's. It was a very cool 2" pin that had a police shield, American flag and the BM logo on it. I kept them in my backpack and would offer them to friendly police along the way, but realized they were concerned that I was digging in my bag for "something" for them. I pinned a few on my hat and offered them from there. If they wanted an extra, they were ok at that point with me getting another one from my backpack. This past year, I went over to a Pershing County Sheriff car after seeing them snap a few photos of some amazing art on the playa. It turns out that they were enjoying the event as much or more so than the participants. I'll bet we talked for 15 minutes and I gave them some great swag to take home. One asked for an extra necklace for his wife! Yep. It was you! Thanks for the idea. I'm obviously stealing it! And thanks for the heads up about how to gift them without looking suspicious. This is a fantastic idea...I love it that you will be (one of) our goodwill ambassador to the LEO's. You are exactly right that it will help with attitude adjustment. I'm planning on making some pendant necklaces as gifts as well, I think I'll tailor a few to be specific to the LEO's. My interactions have always been positive and the only time I saw any police taking action, it was to provide medical help to a burner who had gone a little too far with their party. I'd love to be able to reward the LEO's who are there to make our burn fun & safe! "It is all very beautiful and magical here - a quality which cannot be described. You have to live it and breath it., let the sun bake it into you" - Ansel Adams I have long been an advocate of a charm offensive with the LEO's. In selecting slogans or words on LEO gifts here is an idea: something that is authentic to the higher aspirations of the LEO culture and the Nevada culture/ and something that reenforces participants desires about what we want LEO's focused on. Here are some ideas: "Protecting the Black Rock Desert", "Keeping Burning Man Participants Safe", "A Force For Good", "We're Here to Help". Sure readers can come up with more. Also a lot of maker spaces have laser engravers which make small runs of lettering inexpensive. Check ahead on what materials they can engrave. some seeing eye wrote:I have long been an advocate of a charm offensive with the LEO's. In selecting slogans or words on LEO gifts here is an idea: something that is authentic to the higher aspirations of the LEO culture and the Nevada culture/ and something that reenforces participants desires about what we want LEO's focused on. Here are some ideas: "Protecting the Black Rock Desert", "Keeping Burning Man Participants Safe", "A Force For Good", "We're Here to Help". Sure readers can come up with more. Also a lot of maker spaces have laser engravers which make small runs of lettering inexpensive. Check ahead on what materials they can engrave. That idea is all kinds of fabulous. *** 2013 Survival Guide ***"I must've lost it when I was twerking at the trash fence." -- BBadger

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Introduction {#s1} ============ Amelogenins are a set of low molecular-weight enamel matrix proteins belonging to a group of extracellular matrix (ECM) proteins whose genes are greatly preserved, with a key role in tooth enamel advance (Deutsch, [@B12]; Moradian-Oldak, [@B30]; Grandin et al., [@B18]). Amelogenin gene is conserved across vertebrate species, mainly in the N- and C-terminal regions. There are two amelogenin genes (AMELX and AMELY) located on the X and Y chromosomes, respectively. The coding sequence of AMELX had 95.1% identity to that of AMELY (Delgado et al., [@B11]). The heterogeneity of amelogenins in terms of molecular size and amino acid composition is an outcome of the extended population of their related mRNAs, produced by alternative splicing and translated into a broad mixture of nascent proteins and peptides, among which the most abundant species are the isoforms I and II differing only at the 19--34 peptide level (Svensson Bonde and Bulow, [@B47]). Amelogenins show a hydrophobic amino terminal fragment and a hydrophilic carboxyl-terminal one, conferring them bipolar properties; moreover, the prevalence of proline, glutamine, leucine, and histidine residues in their aminoacidic composition drives amelogenins to a self-assembling process into large hydrophobic aggregates, which seems to be one of the mechanism engaged in periodontal or tissue regeneration (Khan et al., [@B22]; Yoshimi et al., [@B53]). The solubility varies depending on temperature and pH and it is low at neutral pH. Under these conditions, amelogenin species aggregate into larger arrangements, up to form a sort of platelets resembling a stable extra cellular matrix and this transitory complex supplies adhesion sites for cells to connect themselves (Bonde and Bülow, [@B4]). In literature two main functions of amelogenins are well-documented: their role in dental enamel formation and their involvement in regeneration processes (Grandin et al., [@B18]). Amelogenins are mainly involved in dental enamel formation and tooth repair playing an important role in enamel crystal edification, direction, and maturation during crown formation and, thus, they serve as a regulator of enamel biomineralization, endorsing renewal of the periodontium (Grandin et al., [@B18]). On the contrary, mutations of the human AMELX gene leads to X-linked amelogenesis imperfecta (AI), an inborn disease affecting the tooth development in primary and permanent dentition (Sasaki and Shimokawa, [@B38]). On this basis, amelogenins are currently considered a relevant adjuvants in the treatment of periodontal defects and they are the main components of the enamel matrix derivative Emdogain® (Emdogain, Straumann), a gel preparation protecting tooth and promoting the regeneration of hard and soft tissues in periodontitis (Sculean et al., [@B40]). Besides, based on the pharmacological ability of amelogenins in the successful healing of oral wounds, several studies focused the attention on their potential role in other regeneration processes, such as skin wound healing and angiogenesis (Hoang et al., [@B20]). Indeed, several studies have shown the helpful role of amelogenins on wound healing and tissue regeneration, activating several crucial cell reactions for tissue restoration and healing, such as proliferation, migration, adhesion and differentiation (Vowden et al., [@B49]). A care product Xelma® (Xelma, Mölnlycke Health Care) containing amelogenins has been marketed and used in treatment of chronic wounds (Romanelli et al., [@B35],[@B36]). Furthermore, periodontal ligament cells (PDL) have been treated with amelogenins for monitoring their effects on cell recruitment, proliferation, and differentiation, indicating an amelogenin-mediated proliferation. This role together with enhanced migration of cells points toward a beneficial wound-healing effects observed for PDL cells stimulated by amelogenins *in vitro* (Davenport et al., [@B10]). Moreover, a higher proliferation of gingival and dermal fibroblasts following treatment with amelogenins has also been observed (Weinberg et al., [@B50]). Finally, amelogenins seemed to encourage the angiogenic activity of HUVEC and HMVEC cells stimulating their proliferation and migration also by upregulating mRNA expression of the angiogenic factor *ANG-2* and adhesion molecules *ICAM-1* (Bertl et al., [@B3]). In order to increase the knowledge on these regeneration processes, Fukuda and co-workers developed and published a functional proteomic analysis of the amelogenins biological partners. They identified several cytoskeletal proteins and chaperones of heat shock protein 70 (HSP70) family in SaOS-2 osteoblastic cell lysates, as amelogenins partners. Moreover, the proteomic outlines of amelogenin-partners in the membrane fraction of the cell extracts revealed the endoplasmic reticulum (ER)-associated proteins as its best targets, such as glucose-regulated protein 78 (Fukuda et al., [@B16]). Since no data are available to unravel amelogenin mechanism of action in chronic skin healing restoration at molecular level, we moved to the full characterization of the interactome of AMELX isoform II, here called AMEL-2, in the secretome and lysate of human umbilical vein endothelial cells (*HUVEC*), chosen as an appropriate *in vitro* model, using a functional proteomic strategy. Functional proteomics is a multi-faced strategy useful to characterize proteins interactions and it has gaining increasing interest to define the "targetome" of macromolecules to elucidate their activity through the affinity with their partners, forming transient and/or stable complexes which in turn mediate biological responses (Raida, [@B32]). Our best approach is based on the "in solution pull-down" strategy, in which the macromolecule is used as a bait to fish out its specific partners among a complex mixtures, then identified by tandem MS and bioinformatics (Margarucci et al., [@B27]). Here, we have identified several AMEL-2 potential targets and, among them, we pointed out thrombospondin-1 (TSP-1) as its novel and interesting partner validating the direct binding between the counterparts thought orthogonal biophysical approaches. Materials and methods {#s2} ===================== Cell culture and secretome -------------------------- HUVEC cells were grown in plates using EGM2 with 1% (v/v) growth factors (hFGF, VEGF, R3-IGF-1), hydrocortisone, ascorbic acid, glutamine and heparin, keeping them incubated at 37°C in a 5% CO~2~ atmosphere and collected in the first phase of the cell cycle (G1). The cells were harvested by centrifugation (600 g, 5 min), washed twice with PBS (NaH~2~PO~4~ 50 mM and NaCl 150 mM, pH 7.4) and resuspended in 450 μl of PBS at 0.1% of Igepal together with 50 μl of protease inhibitor cocktail (AESBF (4- (2-Aminophenylbenzenesulfonyl fluoride hydrochloride), aprotinin, bovine hydrogen chloride, E-64 \[N- (trans-epoxy succinyl\] -L-leucine, 4-guanidiobutylamide, EDTA, salt of leupeptine bisulfate) to avoid protein degradation. The resuspended pellet was subjected to homogenization by a manual "Dounce" homogenizator and centrifuged at 10,000 rpm for 5 min at 4°C (Centrifuge 5424-R, Eppendorf). Protein-rich supernatant was extracted and thus separated from insoluble pellets, consisting of membranes and cytoplasmic organelles. The concentration of protein lysate was estimated by Bradford assay and diluted to obtain a concentration of 1 mg/ml (Bradford, [@B7]). The secretome was harvested from the cultured cells and concentrated using an Amicon membrane (Millipore); protein concentration was evaluated by Bradford\'s assay to obtain a final value of 6 mg/ml. Cloning, expression, and purification of recombinant AMEL-2 ----------------------------------------------------------- AMEL-2 was a kind gift of Prof Leif Bülow (Department of Pure and Applied Biochemistry, Lund University, Lund, Sweden) and it was expressed and purified according to the protocol outlined by Svensson Bonde and Bülow ([@B4]). MALDI-TOF analysis ------------------ AMEL-2 sample at a concentration of 12.5 nM (1 μl) was mixed on the spot of the MALDI plate with 1 μl of the saturated CHCA matrix solution (Sigma Aldrich) in 50% ACN, 50% H~2~O, 0.1% TFA and subjected to mass-spectrometric analysis using MALDI-TOF (MALDI micro MX, Waters) to verify its molecular weight. MALDI analysis was conducted in linear mode, with laser values ranging from 250 to 280 arbitrary units. As calibrant, a mixture of lysozyme and albumin from bovine serum was used. Peptide mapping of AMEL-2 ------------------------- One microgram of AMEL-2 were incubated in AMBIC 50 mM with 10 ng of Tryp / Lys-C (1:100) (Promega) in AMBIC (NH~4~HCO~3~) 50 mM at 37° C for 4 h. The peptide mixture obtained by proteolytic digestion was measured by MALDI-TOF (MALDI micro MX, Waters) using saturated CHCA matrix solution (Sigma Aldrich) in 50% ACN, 50% H~2~O, 0.1% TFA. 1 μl of the peptide mixture was mixed with 1 μl of matrix on the spot of the sample holder plate. Mass spectra were acquired in positive linear or reflectron mode. Biotinylation of AMEL-2 functional groups ----------------------------------------- Five micromolar of AMEL-2 and 75 μM (1:15) sulfo-NHS-SS-biotin (Thermo Scientific) were incubated in NaHCO~3~ 50 mM and monitored by MALDI-TOF mass spectrometry as reported before at different time intervals *t* = 0 min; *t* = 5 min; *t* = 15 min. The biotinylation step was followed by quenching with 0.05% acetic acid. The concentration and purification steps of the samples were carried out on centricon (Millipore) with a 5,000 Da cut-off centrifuge (Centrifuge 5424-R, Eppendorf) at 10,000 rpm at 4°C for 15 min. SDS-PAGE at 15% of acrylammide was then run and colored by Comassie Brillant Blue staining. Combination of affinity chromatography and proteomic analysis ------------------------------------------------------------- AMEL-2-biotin adduct (1 or 3 nmol) and the control linker were distinctly incubated with 1 mg of HUVEC cells lysate or secretome, under continuous shaking (1 h, 4°C) and then, 20 μL of streptavidin modified beads (Pierce) were added and left for 1 h at 4°C. The beads were centrifuged (865 g, 1 min,4°C) and rinsed six times with PBS (pH 7.4). The proteins interacting with AMEL were eluted by adding 35 μL of Laemmly buffer for 30 min at 30°C, separated on 12% SDS-PAGE and stained with Coomassie G-250 (Bio-Rad, Hercules, CA). SDS-PAGE gel lanes were divided in several pieces and digested. The procedure has been done twice with opportune controls as the matrix bearing the linker without any protein and the sole EGM2. Each gel piece was rinsed with water and CH~3~CN and exposed to *in situ* breakdown as described by Shevchenko et al. ([@B45]). Concisely, each gel piece was treated with 10 mM 1,4-dithiothreitol (DTT) and then with 54 mM iodoacetamide, rinsed and rehydrated in trypsin solution (12 ng/mL) on ice for 1 h. Following AMBIC treatment (30 μL, 50 mM, pH 7.5), protein breakdown was carried out overnight at 37°C. The solution was gathered and peptides were extracted from the gel pieces using 100% CH~3~CN. The peptide sample was dehydrated and suspended in formic acid (FA, 10%) before MS analysis. The peptide mixture (5 μL) was introduced in a nano-ACQUITY UPLC system (Waters). Peptides were separated on a 1.7 mm BEH C18 column (Waters) at a flow rate of 400 nL/min. Peptide elution was achieved with a linear gradient (solution A: 95% H~2~O, 5% CH~3~CN, 0.1% FA; solution B: 95% CH~3~CN, 5% H~2~O, 0.1% FA); 15--50% B over 55 min). MS and MS/MS data were acquired on a LTQ XL mass spectrometry system (ThermoScientific). The five most intense doubly and triply charged ions were broken. The MS results were treated by MS Converter software to obtain the peak lists for protein identification. Database searches were performed on the Mascot server (<http://www.matrixscience.com/>). The SwissProt database was employed \[settings: trypsin with possible two missed cleavages; carbamidomethyl (C) as fixed modification and oxidation (M) and phosphorylation (ST); peptide tolerance 80 ppm; MS/MS tolerance 0.8 Da\]. STRING analysis --------------- STRING analysis (Search Tool for the Retrieval of Interacting Genes/Proteins, <http://string.embl.de/>) have been carried out using STRING-10 server to predict the protein-protein interaction (Sharma et al., [@B43],[@B44]; Sharma and Bisht, [@B41],[@B42]) of AMEL targets. STRING database employs a mixture of prediction approaches and an combination of experimental data (neighborhood, gene fusion, co-expression, experiments, databases, text mining, co-occurrence). Network was completed at 0.4 confidence level. Validation of the interaction between AMEL-2 and TSP-1 by western blotting and surface plasmon resonance -------------------------------------------------------------------------------------------------------- Proteins eluted from the above-described experiments were separated on 12% SDS-PAGE and moved to a nitrocellulose membrane. The membrane was put for 1 h in a blocking solution made by 25 mM Tris pH 8, 125 mM NaCl, 0.05% Tween-0, 5% non-fat dried milk, primary antibodies raised against TSP-1 (1:500; Novus Biologicals). The recognition of specific epitopes was favorite overnight, at 4°C. Then, membrane was put for 1 h with an anti-rabbit peroxidase-conjugated secondary antibody (1:5,000) (Sigma-Aldrich). TSP-1 was detected by a chemo-luminescence detection system. AMEL-2 was immobilized onto a Biacore 3,000 (GE Healthcare) using a CM5 sensor chip using standard amine coupling procedures. Phosphate--buffered saline (10 mM Na~2~HPO~4~ and 150 mM NaCl, pH 7.4) was the running buffer. The carboxymethyl dextran surface was activated as reported by the GE Healthcare protocol and AMEL-2 was diluted to a final concentration from 50 nM and injected at flow rate of 5 μl/min. After several injections, a RU of 10,000 was measured. The activated carboxymethyl dextran surface was finally blocked with a 7-min injection of 1.0 M ethanolamine-HCl, pH 8.5, at 5 μl/min. TSP-1 solutions(Abnova; from 50 nM to 1 μM) or alternative BSA and lysozime as negative controls, were prepared in running buffer and injected. Since the binding curve went back to baseline in a reasonable time, no regeneration process was mandatory. The experiments were done at a flow rate of 10 μl/min, using a 3 min injection time. The dissociation time was set at 600 s. Rate constants for associations (ka) dissociations (kd) and the dissociation constants (K~D~) were calculated by using results from injections of all concentrations, using the BIAevaluation software and the 1:1 Langmuir binding model. Results {#s3} ======= Our process to disclose AMEL-2 action targets has been planned in the next steps: (a) Production of AMEL-2 biotin-tagged specie, (b) Incubation and recovery of its specific partners and identification of the interactome by mass spectrometry and bioinformatics, c) Corroboration of AMEL-2 interactions by bio-orthogonal *in vitro* assays. Protein expression, purification, and characterization ------------------------------------------------------ A fraction of the expressed AMEL-2 (Figure [1A](#F1){ref-type="fig"} for sequence, UNIPROT code [Q99217](Q99217), see isoform 2) was measured by MALDI-MS giving a MW of around 19,800 Da, compatible with the isoform II. Protein analysis was performed by digestion with trypsin and MALDI analysis, and three protein fragments were measured and recognized as the 1-24 and 25-168 and 25-170 residues (Supplementary Figure [S1](#SM1){ref-type="supplementary-material"}), covering almost the entire sequence of AMEL-2. {#F1} Generation of mono-biotinylated AMEL-2 -------------------------------------- As a first step, AMEL-2 was treated with a N-hydroxysuccinimide activated S--S biotin linker, providing the AMEL-2--biotin derivative reported in Figure [1B](#F1){ref-type="fig"}. The reaction was monitored by MALDI-MS and tuned with different molar ratios of the reagents and incubation time, with the best results with a molar excess of biotin of 20 times over AMEL-2 (AMEL-2:biotin 1:20) and 15 min of incubation at room temperature. A mono-modified AMEL-2 species was recovered together with the unreacted species (Figure [1C](#F1){ref-type="fig"}), following separated from the biotin excess by filtration on a 5 kDa membrane tube, without sample loss (Supplementary Figure [S2](#SM1){ref-type="supplementary-material"}). Affinity chromatography and mass spectrometry --------------------------------------------- Samples of HUVEC protein extracts and the corresponding secretomes were separately incubated with the biotinylated AMEL-2 (1 and 3 nmol, respectively) to endorse the interaction among the protein and its potential target(s) in solution. As control experiments, a sample of the biotin linker modified with ethanolamine was incubated in the same conditions, and a sample of EGM2 culture medium was incubated with the biotinylated AMEL-2. After 1 h, all the parallel experiments were treated with streptavidin-bearing matrix beads to recover, taking advantage of the strong biotin/streptavidin affinity, the biotinylated adducts together with their interactome. Then, the resins were extensively washed to remove the aspecific bound proteins, whereas the tightly bound interactors were released using a Laemmly buffer solution. The eluted protein mixtures were resolved by 12% SDS-PAGE (Figure [2](#F2){ref-type="fig"}), and gel lanes were divided in pieces and exposed to *in situ* digestion using trypsin (Shevchenko et al., [@B45]) The tryptic mixtures were investigated through nano-flow RP-HPLC/MSMS and protein identification was carried out presenting the MSMS peak lists to the Mascot database analysis. A refined list of the AMEL-2 partners was obtained after filtering all the hits in common with the control experiments, removing all the proteins with an incongruous molecular weight, all the proteins with a Mascot score less than 40 and all the proteins identified with less than 10 matched peptide signals (Table [1](#T1){ref-type="table"} and Supplementary Table [S1](#SM1){ref-type="supplementary-material"} for details). {#F2} ###### List of AMEL-2 partners found in both HUVEC cell lysate (upper Table) and HUVEC cell secretome (lower Table). **Accession** **Score** **Mass** **Matches** **Pep(sig)** **Sequences** **Seq(sig)** **emPAI** **Description** --------------- ----------- ---------- ------------- -------------- --------------- -------------- ----------- ---------------------------------------------------------- TBB5_HUMAN 706 50,095 48 29 24 18 6.22 Tubulin beta chain TBB4B_HUMAN 659 50,255 41 27 23 19 6.16 Tubulin beta-4B chain FLNB_HUMAN 357 280,157 49 18 48 18 0.36 Filamin-B TBB6_HUMAN 279 50,281 21 16 15 13 2.72 Tubulin beta-6 chain MYH9_HUMAN 243 227,646 39 14 36 13 0.31 Myosin-9 FAS_HUMAN 188 275,877 31 13 31 13 0.25 Fatty acid synthase ENOA_HUMAN 186 47,481 12 7 11 7 1.00 Alpha-enolase ATPB_HUMAN 145 56,525 14 8 13 8 0.95 ATP synthase subunit beta EF2_HUMAN 134 96,246 22 8 21 8 0.48 Elongationfactor2 RACK1_HUMAN 89 35,511 11 7 9 6 1.21 Guanine nucleotide-binding protein subunit beta-2-like 1 PDIA1_HUMAN 89 57,480 14 4 14 4 0.39 Protein disulfide-isomerase PRDX1_HUMAN 87 22,324 13 6 12 6 0.52 Peroxiredoxin-1 TSP1_HUMAN 46 133,291 7 2 7 2 0.07 Thrombospondin-1 FINC_HUMAN 495 266,052 47 19 46 19 0.40 Fibronectin TSP1_HUMAN 200 133,291 18 10 16 10 0.43 Thrombospondin-1 *For each protein, the following parameters are reported: Mascot score (Score), molecular weight (mass), number of matched peptides (Matches) and unique peptides used in the identification process \[Match(sig)\], number of sequences (Sequences) and the number of significant distinct sequence matches in the protein identification process \[Seq(sig)\] and the relative quantization of each protein (emPAI)*. String analysis --------------- We analyzed AMEL-2 targets, identified by proteomics both in cell lysate (Figure [3A](#F3){ref-type="fig"}) and secretome (Figure [3B](#F3){ref-type="fig"}), using STRING-10 software with an intermediate confidence threshold of 0.4 and build an interactome network to find out the known protein-protein interaction (PPIs) and predict functional associations. First of all, actually no interactions of AMEL-2 are reported with its fished out proteins. It has to notice that Fukuda et al. reported the interaction of amelogenin with similar cytoskeletal proteins so it can be feasible to postulate a direct interaction of AMEL-2 with reported tubulins which are involved in an extended interaction pathway, comprising Filamin B, Myosin 9, ATP synthase and others. On the other side, the interaction between TSP-1 and fibronectin, which are the unique two proteins fished out in cell secretome, is very well-documented in STRING. Both are high-molecular weight adhesive glycoproteins, mainly found in the ECM and secreted by various cells, primarily fibroblasts, and they assembled into an insoluble matrix in a complex cell-mediated process. {#F3} Validation of the interaction between AMEL-2 and its counterpart TSP-1 ---------------------------------------------------------------------- As described in Table [1](#T1){ref-type="table"}, a few proteins were identified as the most appropriate partners of AMEL-2 and, among them, the trombospondin-1 protein (TSP-1), fished out by AMEL-2 both in the cell lysate and, mostly, in the secretome was selected for further investigation. The interaction of AMEL-2 with TSP-1 was then confirmed by immune-blotting analysis both the interactome fished out by AMEL-2 on the lysate and the secretome of the HUVEC cells. As clearly reported in Figure [4A](#F4){ref-type="fig"}, a strong band was evident on the gel lanes corresponding to the experiment with the biotilnylatedAMEL-2, while no signal was detected in the control lanes. Then, surface plasmon resonance was used for corroborating proteomic data and to give evidence of a direct interaction between AMEL-2 and TSP-1, measuring their binding affinity, while bovine serum albumin and lysozime were used as negative controls (Supplementary Figure [S3](#SM1){ref-type="supplementary-material"}) AMEL-2 was immobilized on a CM-5 sensor chip prior to the injection of TSP-1 at different concentrations (from 50 to 5,000 nM, Figure [4](#F4){ref-type="fig"}). Sensorgram analysis gave a dissociation constant (K~D~) of the AMEL-2-TSP-1 complex as 878 (±125) nM, while no binding was observed for BSA and lysozime. {#F4} Discussion {#s4} ========== Matricellular proteins are extracellular biomolecules acting through their multiple connection to different ligands (Hugo et al., [@B21]): this is the key feature of these proteins, elucidating their typical variety of functions. These interactions can take concurrently place having various effects on the receptor/ligand equilibrium having different downstream signals, such as the activation of receptors, the arrangement of macro complexes, inhibition of growth factors, change of protein localization and so on (Resovi et al., [@B33]). In this scenario, a complete mapping of the amelogenin interactome is required to elucidate its functional role. In addition, the identification of new ligands and protein-protein networks might shed light on its mechanism of action and/or point to new roles for amelogenin in physiological and pathological processes. Amelogenin partners were well-characterized in osteoblast activation by coupling affinity chromatography with proteomics in fractionated SaOS-2 osteoblastic cell lysate (Fukuda et al., [@B16]). In the cytoplasm, the amelogenin interacting proteins were mainly cytoskeletal and heat shock proteins as heat shock protein 70 (HSP70) whereas in the membrane fraction were mainly endoplasmic reticulum (ER)-associated proteins, such as glucose-regulated protein 78 (Grp78/Bip). These data were promising for understanding the cellular and molecular bases of amelogenin mechanisms in periodontal tissue regeneration. On the contrary, looking at amelogenin task in chronic skin healing reinstatement, no data were available to unravel its mechanism of action. In this study, the HUVEC cells were used as an opportune model of healing restoration and AMEL-2 partners were disclosed both in the cell lysates and in secretomes through a functional proteomic approach. Several proteins were pulled-down and identified in the cell lysates as potential AMEL-2 targets, mainly cytoskeletal proteins, such as tubulins, myosin and filamin, that were expected on the basis of previous studies (Fukuda et al., [@B16]). These cytoskeletal proteins are strictly connected giving a network of protein-protein interaction (PPI see Figure [3](#F3){ref-type="fig"}) as also suggested by STRING interactome analysis and they could be involved into the wound healing process modulating cell locomotion, crucial for repair of injury and for immune response. Actin polymerization represents a central node for the formation of protrusive structures that drive cell mobility (Ridley et al., [@B34]). Actin dynamics is an orchestrated cascade of biochemical events that involves a number of regulatory signals and several actin-binding proteins (Lambrechts et al., [@B25]). Besides, myosin motor proteins play a pivotal role in cells spreading since actin/myosin stress fibers generate the contractile forces that allow the detachment of the rear of the moving cell and, in turn, cell translocation (Lauffenburger and Horwitz, [@B26]). Specific roles of different myosin isoforms have been reported. In particular, Myosin 9, also called Myosin IIA which targets AMEL-2, is involved in cytoskeleton reorganization, focal contacts formation and lamellipodial retraction negatively affecting cell migration and regulating microtubule dynamics, maintaining a balance between the actomyosin and microtubules. Furthermore, Myosin IIA depletion from human cancer cells resulted in an increased rate of wound closure (Even-Ram et al., [@B14]). Filamins function as scaffold proteins connecting actin filaments to various cell membrane constituents. Both Filamin A and Filamin B are enriched in focal adhesion which mechanically and biochemically links actin bundles to the ECM acting on cell migration (Tosse et al., [@B48]). The interaction of AMEL-2 with protein belonging to the tubulin family may also play a role in wound healing. Although the exact mechanism of tubulin action in this process remains debated, the microtubules dynamics regulates many aspects of cell migration (Ganguly et al., [@B17]; Charafeddine et al., [@B8]). AMEL-2 is postulated to interact also with Protein disulfide-isomerase (PDIA-1) in the present work. PDI is a member of the thioredoxin superfamily mainly localized in endoplasmic reticulum, where it ensures proper disulfide bond formation in newly synthesized proteins and endowed with three catalytic activities including, thiol-disulfide oxi-reductase, disulfide isomerase and redox-dependent chaperone (Ali Khan and Mutus, [@B2]). PDI was also found to localize on the surface of platelets, endothelial cells, and leukocytes and to be released into the extracellular environment by endothelial cells and bound platelets during thrombus formation (Flaumenhaft, [@B15]) Several lines of evidence have raced the idea that PDI is directly involved in thrombus formation by regulating the activation of proteins required in this process. Interestingly, although this interaction was not fully investigated, TSP-1 was identified as a potential PDI substrate (Bowley et al., [@B6]). Moreover, the ability of PDI to catalyze the formation of TSP-1-Thrombin--Antithrombin III complex was shown *in vitro* (Milev and Essex, [@B29]). A fine tuning of Peroxiredoxin 1 activity, strictly connected to extracellular hydrogen peroxide (H~2~O~2~) levels, was suggested to play a role in wound healing process. H~2~O~2~ is normally produced by mammalian cells as result of metabolic processes. In specific conditions, such as wound healing, the amount of produced H~2~O~2~ increases considerably, representing a protection against pathogens, but its toxic accumulation must be prevented by enzymes also belonging to the peroxiredoxin family (Schäfer and Werner, [@B39]). Low levels of H~2~O~2~ are essential for propagation of intracellular signaling triggered by growth factor and required for re-epithelization. Peroxiredoxin 1 resulted inactivated at the margin of healing cutaneous wounds in mice to allow wound repair mediated by H~2~O~2~ (Woo et al., [@B51]). Alpha-enolase (ENO1) is another AMEL-2 interactor, involved in regeneration processes. Indeed, ENO1 is a key glycolytic enzyme that catalyzes the dehydration of 2-phospho-D-glycerate to phosphor-enol-pyruvate. Besides its cytoplasmic localization, ENO1 is exposed on the cell surface where acts as a plasminogen receptor (Miles et al., [@B28]). When translocated to the cell surface, ENO1 contributes to pericellular plasmin generation that in turn plays a crucial part in degradation of fibrin provisional matrix and other ECM components. The ENO1 increased cell-surface expression was suggested to have an important role also in inflammatory cell invasion (Wygrecka et al., [@B52]). Guanine nucleotide-binding protein subunit beta-2-like 1, commonly defined as RACK1, is a WD40 repeat protein that showed a wide variety of cellular interactors involved in determining the physiology of healing wounds. Many other biological partners may be involved in RACK1 dependent regulation of cell migration (Hermanto et al., [@B19]; Cox et al., [@B9]; Songhai et al., [@B46]). Among all potential AMEL-2 targets, we pointed out our attention mainly on TSP-1. This protein was fished out by AMEL-2 both in HUVEC cell lysates and secretomes, as the unique common partner. Moreover, in the HUVEC secretomes fibronectin (FINC) was identified as an AMEL-2 interacting protein. Since fibronectin is a well-known specific target of TSP-1 as also reported by interactome analysis by STRING, we were interested to better analyze this PPI pathway. Indeed, both TSP-1 and FINC are extra-cellular matrix glycoproteins with adhesive domains interacting between each other. On this basis, we first validated our proteomic results by immunoblotting analysis and then we proved the direct interaction between TSP-1 and AMEL-2 by surface plasmon resonance, measuring a dissociation constant of around 800 nM. This data excluded a potential role of fibronectin as connection between AMEL-2 and TSP-1 interaction, instead giving evidence for the first time of TSP-1 as new specific AMEL-2 partner. TSP-1 is a multifunctional extra-cellular matrix glycoprotein produced by several cell types implicated in wound repair, such as keratinocytes, fibroblasts, endothelial cells, and macrophages (Dipietro et al., [@B13]). Thrombospondins (TSPs) are a small group of secreted, modular glycoproteins. TSP-1 is the most considered element of this class, together with TSP-2, and it is found inside and outside the cell as a 450-kDa trimer. TSP-1 is a prototype matricellular protein that can physically interact with a variety of ligands (Sage and Bornstein, [@B37]), and seems to be caught up in the regulation of several processes in the healing of skin wounds (Kyriakides and MacLauchlan, [@B24]). Its mechanism of action has not be yet fully elucidated and controversial data are present in literature: for instance, the ability of TSP-1 to serve as an adhesive substratum was reported in TSP-1 assembly by macrophages facilitating the repair process and providing evidence that TSP-1 production is an important component of optimal wound healing (Dipietro et al., [@B13]). However, in other cases, TSP-1 supports cell attachment but not spreading and is counter adhesive when added to an adhesive protein, such as fibronectin (Sage and Bornstein, [@B37]). Moreover, in endothelial cell, numerous investigations have documented that TSP-1 inhibits endothelial cell chemotaxis, adhesion, attachment, and capillary growth *in vitro* (Murphy-Ullrich and Höök, [@B31]). Finally, wound healing studies in TSP1-null mice specified a tardy repair, characterized by loosely compacted and disorganized granulation tissue (Agah et al., [@B1]). On this basis, the finding of a direct interaction between AMEL-2 and TSP-1 can represent an important result to give a better understanding about the role of AMEL-2 in the complex network of the regeneration process. We can postulate that AMEL-2 interaction with TSP-1 may modulate the recognition between this latter protein and FINC which induces a TSP-1 conformation change related to its stabilization and its incorporation into ECM (Tan and Lawler, [@B23]). This, in turn, may alter the regeneration process and wound healing. This result open the way to following studies to evaluate the potential mechanism of amelogenins in the wound healing process. Author contributions {#s5} ==================== AR, MC, AGC, and MM conceived and designed the experiments; ANC, CC, and GA performed the experiments; ANC, CC, RR, and MM analyzed the data; RR and MM wrote the paper. Conflict of interest statement ------------------------------ The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Prof Leif Bülow (Department of Pure and Applied Biochemistry, Lund University, Lund, Sweden) is kindly acknowledged for providing AMEL-2. Dr. M. Festa and Prof. M.C. Turco (University of Salerno) are kindly acknowledged for providing HUVEC cells. **Funding.** This work was supported by grants from MIUR ITALY PRIN2015 "Top-down and Bottom-up approach in the development of new bioactive chemical entities inspired on natural products scaffolds" (Project N. 2015MSCKCE_003). The financial support by University of Salerno and DAMOR Farmaceutici s.r.l. is also gratefully acknowledged. Supplementary material {#s6} ====================== The Supplementary Material for this article can be found online at: <https://www.frontiersin.org/articles/10.3389/fchem.2017.00074/full#supplementary-material> ###### Click here for additional data file. [^1]: Edited by: John D. Wade, Florey Institute of Neuroscience and Mental Health, Australia [^2]: Reviewed by: Divakar Sharma, Aligarh Muslim University, India; Wentao Chen, University of California, San Francisco, United States [^3]: This article was submitted to Chemical Biology, a section of the journal Frontiers in Chemistry

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Welcome to The Barack Obama Show! Like it or not, TV's most expensive reality program, The Barack Obama Show, is hitting prime time again for its fourth episode Wednesday night, costing the networks a cool $10 million per hour in combined lost advertising revenue. Lucky them. It's costing the rest of us a $1.8 trillion budget deficit this year alone. The Barack Obama Show may be a prime-time mainstay, but like a daytime soap it has a tendency to repeat story lines. We can certainly hope the president will completely surprise us by saying, "I'm going to take a break from proposing any more grand projects for now. What'd everybody think of that guy stealing home in the Red Sox-Yankees game?" It seems more likely, though, that he'll fall into his usual habits of trying to sell an increasingly skeptical public on fantastically grandiose schemes using misdirection, twisted logic, straw men, and a simultaneous blend of reassurance and warning -- a brand of feel-good alarmism -- unique to this presidency. Here's what to listen for in the latest biggest speech ever, and what those words actually mean: Ideology. Partisanship. Rigidity. The Past These are all very bad things, dangerous traps to fall into. Except when we're talking about rigid, unquestioning fealty to a curious, unproven idea from the past -- 1931 -- known as Keynesian economics. Which means betting $787 billion of money we don't have, most of which won't be spent this year, to fight a recession that most economists think will be over in a few months. With respect to this partisan ideology, we must remain completely silent, not bothering to weigh its proposals to competing ones, before it is signed into law. Retaining some provision for flexibility in the stimulus? That would have been too rigid. And measuring the current plan against history, such as the failed Keynesian stimulus in Japan in the 1990s, would amount to getting stuck in the failed notions of the past. False tradeoffs Obama will probably make the point again that anyone who says that more of A means less of B just isn't using his imagination. Why is he so popular? Who doesn't like something for nothing? It's easy to get caught up in the madcap joy of his reasoning. He's like a toddler making his first trip to Toys R Us whose policy is to grab all he can, as fast as he can, and let somebody else pay. Obama keeps saying that only five percent of our neighbors -- the intimidating people we don't know in the mansion on the hill -- will have to pay for anything. And it's a big anything. It includes unlimited free health care with no pesky worries about all the problems that crop up in socialized meds countries, converting the energy grid to operate on rainbows and smiles, and a first-class education guaranteed to set every girl and boy on a path to becoming a powerful lobbyist/cabinet appointee.

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In System F, the type exists a. P can be encoded as forall b. (forall a. P -> b) -> b in the sense that any System F term using an existential can be expressed in terms of this encoding respecting the typing and reduction rules. In "Types and Programming Languages", the following exercise appears: Can we encode universal types in terms of existential types? My intuition says that this isn't possible because in some way the "existential packaging" mechanism simply isn't as powerful as the "type abstraction" mechanism. How do I formally show this? I am not even sure what I need to prove to formally show this result.

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Theory of piezo-phototronics for light-emitting diodes. Devices fabricated by using the inner-crystal piezopotential as a "gate" voltage to tune/control the carrier generation, transport, and recombination processes at the vicinity of a p-n junction are named piezo-phototronics. Here, the theory of the photon emission and carrier transport behavior in piezo-phototronic devices is investigated as a p-n junction light-emitting diode. Numerical calculations are given for predicting the photon emission and current-voltage characteristics of a general piezo-phototronic light-emitting diode.

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The design and development of therapeutic monoclonal antibodies (mAbs), be it for improving the activity of existing therapeutic mAbs or bringing new therapeutics to patients, have advantages over other non‐mAb therapeutic modalities. The improvements can be accomplished by optimizing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of therapeutic antibodies, which can improve efficacy while minimizing adverse events and enhancing patient experience and compliance.[1](#cts12597-bib-0001){ref-type="ref"} Because immunoglobulin G (IgG) is the most commonly used structural format in antibody therapeutics, this review will focus on tailoring both the PK and the PD properties of IgG antibodies to optimize antibody design. Detailed knowledge of antibody structure and function allows PK/PD scientists to guide engineering of antibodies to address PK/PD‐related issues. The PK/PD behavior of therapeutic antibodies is impacted by numerous factors, including antigen‐binding specificity and affinity, molecular size, format, physicochemical properties, folding stability, solubility, effector functions, and the pharmacological activities mediated by the antibody. For example, having an in‐depth understanding of the interaction of the variable and constant (Fc) regions of antibodies with their binding partners has allowed the engineering of antibodies with optimal pharmacological properties, such as enhanced target specificity and effector functions.[2](#cts12597-bib-0002){ref-type="ref"}, [3](#cts12597-bib-0003){ref-type="ref"} Furthermore, understanding how antibody charge and glycosylation impact antibody PK is key to designing antibodies that are more homogeneous and stable and have optimal clearance and desired effector functions for their therapeutic application. The fact that many of those properties are interdependent highlights the inherent challenges in therapeutic antibody design, in which improving one antibody property can sometimes lead to defects in others. In addition to improving inherent qualities, the introduction of new activities through novel scaffolds serves to similarly enhance antibody potency and function by altering aspects of their PK/PD properties. The scope of this review is limited to therapeutic mAbs that are primarily based on an unconjugated whole IgG backbone. Improving PK through antibody design {#cts12597-sec-0002} ==================================== The neonatal Fc receptor {#cts12597-sec-0003} ------------------------ Modifying the clearance of antibodies to achieve increased drug exposure and serum half‐life offers numerous advantages, including reduced dose or less frequent dosing and potentially lower cost.[3](#cts12597-bib-0003){ref-type="ref"} The serum half‐life of human IgG antibodies, which averages 21 days for subclasses 1, 2, and 4, is long and one of the advantages of using IgGs as a therapeutic. Although this review is focused on human IgGs, it should be clarified that murine IgGs, which generally are the initial IgGs used in the early phases of biotherapeutic development (prior to humanization), have different nomenclature and function compared with human IgGs (**Table** [1](#cts12597-tbl-0001){ref-type="table"}). For IgGs (human or murine), the long half‐life is predominantly governed by the interaction with the recycling neonatal Fc receptor (FcRn).[4](#cts12597-bib-0004){ref-type="ref"} FcRn binds to the CH2‐CH3 domain of the IgG with a stoichiometry of two FcRn molecules per IgG antibody. FcRn is a membrane‐associated receptor that is structurally related to major histocompatibility complex class I molecules. FcRn is expressed in the mammary gland, placenta, kidneys, brain, eyes, liver, and skin, as well as by intestinal epithelial cells, endothelial cells, macrophages, monocytes, and dendritic cells. Key functions of FcRn from a PK/PD perspective include recycling of the therapeutic mAbs (long half‐life), IgG transport (distribution in tissues), and antigen presentation of multimeric immune‐complexes (may impact immunogenicity).[5](#cts12597-bib-0005){ref-type="ref"}, [6](#cts12597-bib-0006){ref-type="ref"} Following nonspecific pinocytosis, IgG is internalized into endosomes where it binds FcRn and is protected from lysosomal degradation. Subsequently, the FcRn‐bound IgG is recycled and released extracellularly into systemic circulation resulting in long serum half‐life, whereas IgGs that do not bind to FcRn are degraded by endosomal proteases.[6](#cts12597-bib-0006){ref-type="ref"} The interaction between IgG and FcRn is strictly pH‐dependent, which is critical for IgG recycling and the long half‐life. IgG binds to FcRn at the endosomal acidic pH (6.0--6.5) with nanomolar (nM) affinity, whereas negligible binding occurs at a physiological pH of 7.4. This lack of binding at pH 7.4 results in IgG‐FcRn complex dissociation at the cell surface neutral pH (7.0--7.4) and release of IgG for continuing circulation.[7](#cts12597-bib-0007){ref-type="ref"} ###### **Human IgG subclasses and corresponding "functional" murine subclasses** [a](#cts12597-note-0002){ref-type="fn"} [73](#cts12597-bib-0073){ref-type="ref"}, [114](#cts12597-bib-0114){ref-type="ref"} Human Murine ------- -------- IgG1 IgG2a IgG2 IgG3 IgG3 IgG2b IgG4 IgG1 IgG, immunoglobulin. The human subclasses were numbered based on their abundance. The basis for the murine nomenclature is not clear. John Wiley & Sons, Ltd It is important to note that human IgG binds murine FcRn with higher affinity at acidic pH compared with murine IgG in wild‐type mice, which should be taken into consideration when PK properties of human therapeutic IgGs are evaluated in rodents.[8](#cts12597-bib-0008){ref-type="ref"} Cynomolgus monkeys have been shown to be more reliable surrogates for predicting human clearance of therapeutic human or humanized mAbs that are mediated by FcRn‐mediated proteolysis.[9](#cts12597-bib-0009){ref-type="ref"} The use of humanized FcRn transgenic mice has also been recently evaluated for this purpose.[10](#cts12597-bib-0010){ref-type="ref"}, [11](#cts12597-bib-0011){ref-type="ref"} Modulating the FcRn--IgG interaction through point mutations allows altering the PK profile of therapeutic antibodies by enhancing/reducing their half‐lives. **Table** [2](#cts12597-tbl-0002){ref-type="table"} includes examples of mutations in the CH2/CH3 region of mAb Fc that increase or decrease FcRn binding affinity. The YTE mutant is the only mutant that has been tested clinically so far. Motavizumab‐YTE showed an impressive decrease in clearance (71--86%) and a twofold to fourfold increase in half‐life compared with Motavizumab in healthy volunteers.[12](#cts12597-bib-0012){ref-type="ref"} ###### **Examples of mutations in the CH2/CH3 interdomain region of mAb Fc that increase or decrease FcRn binding affinity** [58](#cts12597-bib-0058){ref-type="ref"}, [115](#cts12597-bib-0115){ref-type="ref"} ---------------------------------------------------------------------------------------------------- Goal AA Mutations ----------------------- -------------------------------------------------- ------------------------- Increase FcRn binding Ala330 Ala330Val Ala378 Ala378Val/Thr Asp312 Asp312Ala Asn315, 361 Asn315Asp and Asn361Asp Asn434 Asn434Ala Gln311 Gln311Ala Glu380,382\ Glu380Ala and Glu382Ala\ Met252 Met252Tyr[a](#cts12597-note-0004){ref-type="fn"} Phe241 Phe241Leu Pro230 Pro230Ser/Thr Pro238\ Pro238Ala\ Ser254 Ser254Thr[a](#cts12597-note-0004){ref-type="fn"} Thr256,307 Thr256Ala and Thr307Ala Val264\ Val264Ala/Glu\ Thr256 Thr256Glu[a](#cts12597-note-0004){ref-type="fn"} Decrease FcRn binding His310, 435 His310Ala and His435Ala Ile253 Ile253Ala Ser254 Ser254Ala Tyr436 Tyr436Ala ---------------------------------------------------------------------------------------------------- AA, amino acid; FcRn, recycling neonatal Fc receptor; mAb, monoclonal antibody. Met(M)252Tyr(Y)/Ser(S)254Thr(T)/Thr(T)256Glu(E) is the triple mutation known as YTE. John Wiley & Sons, Ltd IgG‐FcRn interactions are believed to be restricted to the Fc region; however, a recent report suggested that Fab regions influence FcRn binding due to the conformational flexibility of the Fab arms.[7](#cts12597-bib-0007){ref-type="ref"} This observation was also supported by Schlothauer *et al*.[13](#cts12597-bib-0013){ref-type="ref"} who showed that IgGs with identical Fc regions differed in their dissociation from FcRn, which suggested that the Fab region influenced FcRn binding. It was also shown that the charge distribution in the distal variable fragment (Fv) of IgGs is involved in binding to FcRn, leading to reduced terminal half‐lives.[7](#cts12597-bib-0007){ref-type="ref"} It is still not entirely clear whether the faster clearance of these antibodies is due to FcRn‐mediated effects or due to nonspecific binding to tissues.[14](#cts12597-bib-0014){ref-type="ref"} Another important consideration when modifying the mAb binding to FcRn is that engineering IgGs with excessive binding to FcRn at both pH 6.0 and pH 7.4 (i.e., reduced pH dependence) can exhibit fast clearance.[15](#cts12597-bib-0015){ref-type="ref"} Using a panel of novel Fc variants with high affinity binding at acidic pH and various affinities at pH 7.4, Borrok *et al*.[16](#cts12597-bib-0016){ref-type="ref"} demonstrated an affinity threshold of neutral pH binding that limits efficient IgG recycling. Increasing neutral FcRn affinity binding beyond this threshold reduces half‐lives and offsets the benefits of increased acidic binding. This highlights the inherent limits of FcRn‐mediated half‐life extension and its dependence on pH binding. Other work in the modification of FcRn binding has focused on understanding the impact of FcRn binding on s.c. bioavailability. FcRn is expressed not only by immune cells but also by blood vessel endothelial cells in the skin, and can thus influence s.c. bioavailability by contributing to the rate and extent of presystemic IgG catabolism.[17](#cts12597-bib-0017){ref-type="ref"} Deng *et al*.[18](#cts12597-bib-0018){ref-type="ref"} showed that the s.c. bioavailability of murine IgG2a was affected by mouse FcRn‐binding affinity. Upon examining three antiamyloid β mAbs with different binding affinities to mouse FcRn, the authors found that loss of FcRn binding at either pH 6.0 or pH 7.4 led to loss of the FcRn‐mediated protection from catabolism at the absorption site and subsequently the lowest bioavailability (41.8%) as compared with the wild‐type mAb. On the other hand, using mAbs engineered with the Thr250Gln/Met428Leu Fc mutations that improve their FcRn interactions seems to improve clearance but not s.c. bioavailability in cynomolgus monkeys.[19](#cts12597-bib-0019){ref-type="ref"} These results suggest that other factors may have a stronger influence and also highlight that additional studies are needed to understand the role of FcRn, if any, and its impact on s.c. bioavailability. The role of FcRn in mediating IgG clearance is not fully understood in other types of tissues, such as the brain or the eyes. FcRn seems to play a role in the clearance of amyloid beta‐peptide (Aβ)--specific IgG complexes across the blood brain barrier (BBB).[20](#cts12597-bib-0020){ref-type="ref"} However, FcRn does not seem to contribute significantly to the BBB transcytosis, because intravenously‐administered IgG1 displayed similar brain‐to‐plasma concentration ratios in FcRn‐deficient mice and wild‐type mice.[21](#cts12597-bib-0021){ref-type="ref"} The impact of FcRn on IgG disposition in the ocular space is equally confounding to that of the brain. FcRn has been shown to be expressed by the ciliary epithelium and retinal and choroidal vasculature, which may affect the clearance of IgGs administered into the vitreous of the eye.[22](#cts12597-bib-0022){ref-type="ref"} One role for FcRn has been demonstrated in transporting full‐length IgGs administered into the vitreous across the blood‐retina barrier in rats.[23](#cts12597-bib-0023){ref-type="ref"} Furthermore, others have shown that IgG and IgG‐FcRn null (mAb with Fc mutations that prevent binding to FcRn) show similar kinetics in the rabbit eye after intravitreal injection.[24](#cts12597-bib-0024){ref-type="ref"} pH‐dependent antigen binding {#cts12597-sec-0004} ---------------------------- Fukuzawa and colleagues[25](#cts12597-bib-0025){ref-type="ref"} have developed recycling antibody or antibody with pH‐dependent antigen binding through variable region engineering to improve the PK/PD profile of IgG by increasing the clearance of the antigen but not the antibody. When coupled with sweeping technology (through constant region engineering), which has increased FcRn binding at neutral pH, an enhanced FcRn‐mediated uptake of the antibody--antigen complex into the endosome can be achieved and, thereby, an increase in the number of cycles of antigen binding and lysosomal degradation.[26](#cts12597-bib-0026){ref-type="ref"} Igawa *et al*.[27](#cts12597-bib-0027){ref-type="ref"} generated a sweeping antibody variant of tocilizumab, an antibody against the soluble and membranous interleukin‐6 receptor (IL‐6R). This increased the number of cycles of antigen binding and lysosomal degradation, which, coupled with Fc engineering to increase binding to FcRn, significantly improved both PK and PD in cynomolgus monkeys. Additionally, they showed that the Fc gamma receptor FcγRIIb is a major contributor in the cellular uptake of monomeric immune complexes.[27](#cts12597-bib-0027){ref-type="ref"} Subsequently, the authors expanded the sweeping technology to accelerate the clearance of pH‐dependent anti‐IL‐6R by engineering the Fc to selectively enhance human FcγRIIb (instead of FcRn) binding. In absence of concomitant Fc engineering, similar results were still achieved with recycling technology in a hypercholesterolemia antibody (anti‐PCSK9).[28](#cts12597-bib-0028){ref-type="ref"} ### Isoelectric point and charge {#cts12597-sec-0005} Charged amino acids within the complex IgG structure are not only crucial determinants of protein--protein interactions of IgG necessary for biological activity but also determinants of PK.[29](#cts12597-bib-0029){ref-type="ref"}, [30](#cts12597-bib-0030){ref-type="ref"} On the same lines, the overall charge of the mAb as measured by the isoelectric point (pI) has also been shown to influence both serum clearance and tissue. Furthermore, recent studies have suggested that the electrostatic interaction of antibodies is influenced by both the overall net charge and the distribution of the charges on the surface.[31](#cts12597-bib-0031){ref-type="ref"}, [32](#cts12597-bib-0032){ref-type="ref"}, [33](#cts12597-bib-0033){ref-type="ref"} Anionization (reducing pI) partially abrogates the interaction with cell surfaces and extracellular matrices, reducing nonspecific tissue uptake and increasing serum half‐life. In the study by Igawa *et al* [30](#cts12597-bib-0030){ref-type="ref"} the authors demonstrated that lowering the pI by engineering the variable region could reduce the elimination of IgG antibodies. In another report, it seemed that antibodies with lower pI values exhibited slower systemic clearance and higher s.c. bioavailability in both humans and minipigs compared with antibodies with higher pI values (\> 9).[32](#cts12597-bib-0032){ref-type="ref"} However, this study was limited by the number of antibodies studied. On the other hand, Khawli *et al*.[34](#cts12597-bib-0034){ref-type="ref"} isolated the acidic (pI: 8.7--8.9), basic (pI: 9.16), and main (pI: 9) components of a humanized IgG1 mAb and observed no differences in serum PK in rats, suggesting that the pI differences among the fractions were not sufficient to induce measurable changes in PK. Conversely, IgGs with increased pI (cationization) display increased plasma clearance, volume of distribution, and tissue uptake, most likely due to enhanced binding to negatively charged cell surface molecules (heparin sulfate proteoglycans and phospholipids) and pinocytic uptake.[35](#cts12597-bib-0035){ref-type="ref"} Cationization by converting surface carboxyl groups to positively charged groups, such as primary amines, has been used to improve uptake of IgG in target tissues (such as crossing the BBB).[36](#cts12597-bib-0036){ref-type="ref"}, [37](#cts12597-bib-0037){ref-type="ref"} However, the advantages of cationization must be interpreted with caution due to additional consequences of IgG retention in nontarget tissues. For example, a study of antihepatitis C virus E2‐glycoprotein antibody variants showed very fast clearance for a variant with a pI of 8.61 compared with a variant with a pI of 6.10. Although both variants had comparable FcRn binding, the high pI variant was catabolized in the liver and spleen, suggesting that antibody charge can influence antibody catabolism independently of FcRn‐mediated recycling.[29](#cts12597-bib-0029){ref-type="ref"} As noted previously, reducing or increasing the pI can have notable impact on mAb PKs. However, improved PK properties have also been demonstrated through charge modifications (with no demonstrable impact on overall pI) being applied to charge patches (clustering of charged amino acid residues) through either substitutions of charged amino acids or direct chemical modification of amino acid side chains with positive, negative, or neutral chemical groups.[35](#cts12597-bib-0035){ref-type="ref"} Datta‐Mannan *et al*.[38](#cts12597-bib-0038){ref-type="ref"} studied two humanized mAbs with unexpectedly rapid clearance in mice and attributed their fast clearance to solvent‐exposed positive‐charge patches on the complementarity‐determining region (CDR). Rationally balancing the CDR charge without affecting pI yielded significant improvement in peripheral exposure and reduced tissue catabolism. Bumbaca Yadav *et al*.[31](#cts12597-bib-0031){ref-type="ref"} studied the impact of charge on the PK as well as s.c. bioavailability of two mAbs targeting lymphotoxin alpha (anti‐LT‐α) and human epidermal growth factor receptor 2 (anti‐HER2). The authors engineered the Fv region to have either high or low Fv charge as compared with the parent antibody, with only a minimal change (\< 1 pI unit) in pI measured for the whole antibodies. PK studies in cynomolgus monkeys demonstrated that high Fv charge mutants displayed faster clearance, whereas low Fv charge mutants displayed either no change (anti‐HER2) or decreased (anti‐LT‐α) clearance. The impact on s.c. bioavailability was also striking, with increased bioavailability observed for the low Fv charge mutant of anti‐HER2 and decreased bioavailability observed for the high Fv charge mutant of anti‐LT‐α. Similar PK profiles were observed in rats and mice.[31](#cts12597-bib-0031){ref-type="ref"} Because the charge of variable region has impact on the PK properties, attempts have been made to use surface charge to predict antibody clearance. Sharma *et al*.[39](#cts12597-bib-0039){ref-type="ref"} used the net charge of the Fv domain at pH 5.5 as a criteria to identify antibodies with fast clearance in cynomolgus monkeys (i.e., \> 10 mL/day/kg). While achieving \~70% accuracy of prediction, this approach did not incorporate other critical factors that affect antibody PK/PD (e.g., structure, charge distribution). Alternative approaches, such as developing a quantitative structure‐activity relationship model using mutational charge distributions from a single IgG framework, might offer better predictions. ### Affinity {#cts12597-sec-0006} High‐affinity antibodies (*K* ~d~ \< 1 nM) are desirable not only for their assumed enhanced potency and efficacy but also for reducing the dose and the frequency of administration.[40](#cts12597-bib-0040){ref-type="ref"}, [41](#cts12597-bib-0041){ref-type="ref"}, [42](#cts12597-bib-0042){ref-type="ref"} The delicate balance that exists among conformational stability, solubility, and high affinity highlights the challenge of rationally designing antibodies with engineering strategies that allow the prediction and control of this balance. The desired affinity for an antibody depends on several factors, including antigen density and turnover, mechanism of action (for example, agonistic or antagonistic antibody), dose, drug concentrations that can be achieved at the site of action, and the desired pharmacological effect. For example, Putnam *et al*.[43](#cts12597-bib-0043){ref-type="ref"} studied high‐affinity anti‐IgE antibody‐1 (HAE1), a high‐affinity version of the US Food and Drug Administration--approved anti‐IgE mAb omalizumab with the same IgG1 framework but different CDRs. A change of nine CDR residues reduced *k* ~off~ of HAE1 to IgE by \~22‐fold and enhanced the binding affinity to IgE by \~23‐fold. In a subsequent PK/PD study in cynomolgus monkeys, HAE1 had a similar PK profile to that previously generated with omalizumab but required lower concentrations to suppress free serum IgG levels, suggesting that the higher affinity of HAE1 may translate into greater *in vivo* potency.[44](#cts12597-bib-0044){ref-type="ref"} PK/PD modeling can be used to determine the optimal affinity range provided when information about the antigen kinetics, dose range, and human PK is available.[45](#cts12597-bib-0045){ref-type="ref"}, [46](#cts12597-bib-0046){ref-type="ref"} The avidity of the antibody to its receptor can also be leveraged to improve potency.[47](#cts12597-bib-0047){ref-type="ref"}, [48](#cts12597-bib-0048){ref-type="ref"} Enhancing the affinity of an antibody for its target must be balanced with potential increases in nonspecific binding to various tissues, which may counterbalance expected improvements in PK/PD.[49](#cts12597-bib-0049){ref-type="ref"} Wu *et al*.[49](#cts12597-bib-0049){ref-type="ref"} applied a directed evolution approach to improve both the association rate (*k* ~on~) and dissociation rate (*k* ~off~) of palivizumab to the RSV F protein and found that raising the affinity by increasing *k* ~on~ improved virus neutralization for the IgG form of the mAb. However, a subsequent evaluation of several of these affinity‐optimized variants found that *k* ~on~‐driven mutations generated nonspecific binding to various tissues that led to poor serum PK and lung bioavailability. Reverting three of the affinity‐matured amino acids to the original sequences greatly reduced nonspecific binding and resulted in motavizumab, which binds to the RSV F protein 70‐fold better than palivizumab. Although this review is primarily focused on IgG1 therapeutic antibodies, it is an important side note under the aspects of affinity to mention a potential concern for IgG4 antibodies. For IgG4 therapeutic mAbs, a reduction in affinity can sometimes be attributed to Fab arm exchange, which is the random exchange of a half‐molecule (heavy chain "HC" and attached light chain "LC") with that of another IgG4 half‐molecule that effectively creates monovalent bispecific antibodies. Fab arm exchange with plasma IgG4 can reduce therapeutic IgG4 affinity and efficacy because the loss of bivalency renders the resultant mAb incapable of effectively crosslinking the target antigen or undergoing multivalent target binding. Fab arm exchange is attributed to weak CH3‐CH3 interactions and to relatively labile inter‐HC disulfide bonds of the hinge region, which can undergo shuffling under reducing conditions in blood or at cell surfaces.[50](#cts12597-bib-0050){ref-type="ref"}, [51](#cts12597-bib-0051){ref-type="ref"} Labrijn *et al*.[52](#cts12597-bib-0052){ref-type="ref"} observed that natalizumab, an IgG4 mAb against the α4 subunit of α4β1 (VLA‐4) and α4β7 integrins, undergoes Fab arm exchange with endogenous IgG4 in humans, whereas gemtuzumab, an IgG4 mAb against CD33, which contains a core‐hinge mutation, does not. The Ser228Pro mutation (IgG4S228P) stabilizes the disulfides in the core‐hinge of IgG4 molecules and blocks Fab arm exchange. Stubenrauch *et al*.[53](#cts12597-bib-0053){ref-type="ref"} investigated whether the IgG4S228P mutation would be sufficient to stabilize the core hinge region of an IgG4 mAb and prevent Fab arm exchange. Although the mutation did not completely prevent Fab arm exchange *in vitro* under reducing conditions, the process was markedly attenuated *in vivo* in cynomolgus monkeys where serum was virtually free of the Fab‐swapped IgG4. ### Glycosylation {#cts12597-sec-0007} Most therapeutic mAbs are N‐glycosylated at the residue Asn297 in the heavy chain of the CH2 domain with the (Asn)‐X‐Ser/Thr (where X is any residue except a Pro) consensus sequence. Additional glycosylation can also exist in the variable region, such as the antiepidermal growth factor receptor mAb, cetuximab.[51](#cts12597-bib-0051){ref-type="ref"}, [54](#cts12597-bib-0054){ref-type="ref"}, [55](#cts12597-bib-0055){ref-type="ref"} The N‐linked glycans are composed of a conserved biantennary complex structure of N‐acetylglucosamine residues (GlcNAc) and mannose (Man) residues in the core and extending terminal‐sugar residues (e.g., Man, GlcNAc, galactose (Gal), core fucose, and sialic acid) added depending on the host glycosylation machinery.[54](#cts12597-bib-0054){ref-type="ref"}, [55](#cts12597-bib-0055){ref-type="ref"}, [56](#cts12597-bib-0056){ref-type="ref"} The impact of glycosylation is not limited to the PK of therapeutic mAbs but extends to effector functions and PD, which will be discussed in the next section. The prevailing assumption is that the FcRn‐binding site located at the CH2--CH3 domain and variations in Fc glycosylation, specifically IgG1, may also not likely impact FcRn‐mediated clearance pathways of therapeutic antibodies. The position of Fc glycans on the interior surface of the Fc domain makes them inaccessible to glycan receptors that may participate in FcRn‐mediated mAb clearance, such as asialoglycoprotein and Man receptors.[55](#cts12597-bib-0055){ref-type="ref"} Several studies documented a change from an "open" to a "closed" IgG conformation upon removal of glycans and have shown that it impacts binding of FcγRs but not FcRn.[57](#cts12597-bib-0057){ref-type="ref"}, [58](#cts12597-bib-0058){ref-type="ref"} Thus, no measurable or meaningful changes in PK properties are observed with most of the Fc‐glycan variants (except high mannose variants) of mAbs. Leabman *et al*.[59](#cts12597-bib-0059){ref-type="ref"} also showed that aglycosylated and afucosylated mAbs are eliminated with a similar rate compared with to glycosylated or fucose‐containing mAbs, respectively. Although recombinant mAbs produced in murine hybridoma cells can be up to 50% sialylated in sharp contrast to the typical 10% sialylation for human IgG, the degree of sialylation does not seem to impact PK based on a limited number of studies.[56](#cts12597-bib-0056){ref-type="ref"}, [60](#cts12597-bib-0060){ref-type="ref"} Glycan variants, such as desialylated and agalactosylated mAbs, respectively, produced in cell lines deficient in attachment of sialic acid (Lec 2) and Gal (Lec 8) were comparable to wild‐type mAbs with respect to *in vivo* half‐life.[61](#cts12597-bib-0061){ref-type="ref"} So far, the only glycan that negatively impacts PK is high terminal Man content by increasing the clearance and the reducing half‐life (**Table** [3](#cts12597-tbl-0003){ref-type="table"}). Wright *et al*.[62](#cts12597-bib-0062){ref-type="ref"} showed that M5 IgG (produced by the glycosylation‐mutant cell line Lec1, and consisting of 100% M5 glycan variants) demonstrated faster clearance in mice and tended to distribute to the liver. Similarly, Yu *et al*.[63](#cts12597-bib-0063){ref-type="ref"} have shown that high‐Man mAbs (such as \> 99% M5, or \> 99% M8/9) displayed threefold faster clearance and about twofold shorter half‐lives than the IgG containing the complex glycans in mice. They also showed that higher Man variants, such M7/8/9, are converted to M5 by mannosidase. ###### **Selected studies on the impact of high‐mannose glycoforms on mAb PK** Impact on PK mAb Mannose composition References ------------------------------------------ ----------------------------------------------------------------------- ------------------------------------------ ------------------------------------------ Increased clearance Dansyl‐specific (chimeric IgG1) Produced by Lec1 CHO cells: 100% M5 [68](#cts12597-bib-0068){ref-type="ref"} CD20‐specific (chimeric IgG1) Produced by Lec1 CHO cells: 100% M5 [69](#cts12597-bib-0069){ref-type="ref"} Engineered with kifunensine: 100% M8--M9 WT‐mAb (IgG1) Produced by *Pichia pastoris*: fungal‐type high mannose glycosylation [62](#cts12597-bib-0062){ref-type="ref"} mAb1‐mAb4 (human IgG1 or 2) 5--17% M5 (excluding M6--M9 to M5 *in vivo* conversion) [73](#cts12597-bib-0073){ref-type="ref"} No effect on clearance Omalizumab (humanized IgG1) 5--7% M5 [70](#cts12597-bib-0070){ref-type="ref"} mAb1 (human IgG1) Enriched for high mannose: 52% M5--M8 [71](#cts12597-bib-0071){ref-type="ref"} IL1R‐specific (human IgG2) M6--M9 (% composition not specified) [72](#cts12597-bib-0072){ref-type="ref"} CHO, Chinese hamster ovary; IgG, immunoglobulin G; IL‐1R, interleukin 1 receptor; mAb, monoclonal antibody; PK, pharmacokinetics; WT; wild type. John Wiley & Sons, Ltd In humans, Chen *et al*.[64](#cts12597-bib-0064){ref-type="ref"} showed that the serum levels of several high‐Man mAbs (M6‐M9) decreased faster than other glycoforms due to their conversion to M5 by mannosidases rather than their clearance and concluded that antibody clearance in humans is not significantly affected by the Fc glycan structure. On the other hand, in a follow‐up study[65](#cts12597-bib-0065){ref-type="ref"} the authors from the same group used a highly sensitive analytical method (peptide mapping using high‐resolution mass spectrometry) to follow changes to the glycan PK profile of four therapeutic mAbs over time and found that M5 cleared faster than other non‐Man glycan variants. A twofold difference in the half‐life between the variants was also reported. There are few studies in mice and rats that have reported no impact on PK of the high‐Man variants.[66](#cts12597-bib-0066){ref-type="ref"}, [67](#cts12597-bib-0067){ref-type="ref"}, [68](#cts12597-bib-0068){ref-type="ref"} Harris[66](#cts12597-bib-0066){ref-type="ref"} showed that omalizumab (5--7% M5) has a similar PK profile to the other glycoforms in mice. Millward *et al*.[68](#cts12597-bib-0068){ref-type="ref"} showed that a preparation of a mAb enriched for high mannose glycoforms (52% M5--M8) showed similar clearance rates in mice to those of the parent mAb (3% M5--M7). One of the reasons for the discrepancy between different PK studies is the reduced amount of high‐Man variants present compared with the previous studies.[61](#cts12597-bib-0061){ref-type="ref"}, [63](#cts12597-bib-0063){ref-type="ref"} Overall, the published data sugget that high‐Man glycoforms are cleared more rapidly than other glycoforms, and emphasize the importance of controlling the levels of Man variants, and having it as a critical quality attribute for PKs. Structural Variants to Improve Tissue‐Specific Delivery {#cts12597-sec-0008} ======================================================= As previously noted, the focus of this review is on mAbs; however, an important exception is noted with tissue uptake with bispecifics. Recently, antibodies have been designed to improve delivery to the site of action. For example, bispecific antibodies that bound transferrin receptor and beta‐secretase, with no binding to FcγRs or complement proteins, were used to improve delivery of the antibody to the brain. The binding affinity to transferrin receptor was optimized to obtain favorable brain PK/PD profiles.[45](#cts12597-bib-0045){ref-type="ref"} A more recent advancement in the tissue‐specific delivery of antibodies has been development of Probody Therapeutics that are designed to be activated only in the disease tissue microenvironment by taking advantage of the upregulation of protease activity in the disease tissues.[69](#cts12597-bib-0069){ref-type="ref"} Improving Pharmacodynamics Through Antibody Design {#cts12597-sec-0009} ================================================== The primary goals of all previously discussed factors that influence PK design was to enhance the overall activity and clinical efficacy of therapeutic mAbs. As noted, this could be through enhanced affinity and/or a tailored half‐life. Engineering mAbs to improve their PDs and ultimately their therapeutic potential also involves modifying the variable region for enhancing antigen‐binding activity and modifying the Fc‐mediated effector function to further increase clinical potential. Modifying effector functions {#cts12597-sec-0010} ---------------------------- The Fc portion of mAbs contains binding sites for FcRs and complement proteins, through which mAbs (upon forming immune complexes) can initiate immune effector functions that enhance the killing and removal of mAb‐bound target cells. These functions bridge the adaptive humoral immune response to innate cellular defense mechanisms, which include antibody‐dependent cell‐mediated cytotoxicity (ADCC), complement‐dependent cytotoxicity (CDC), and antibody‐dependent cell‐mediated phagocytosis (ADCP).[51](#cts12597-bib-0051){ref-type="ref"}, [70](#cts12597-bib-0070){ref-type="ref"} Another Fc‐mediated function is the clustering effect crucial to the activity of agonistic mAbs (such as anti‐CD40), in which the Fc‐FcR interaction leads to higher order clustering of the antibody and, thus, of the target receptor bound by the variable domain, triggering downstream signaling.[71](#cts12597-bib-0071){ref-type="ref"} However, not much progress has been made in the translation of agonistic mAbs into effective therapies for patients. FcRs are divided into type I FcRs (generally known as FcγRs) and type II FcRs (which include CD23 and CD209) and are classified based on their binding to IgG. Type I FcRs bind the Fc in the open conformation near the hinge proximal region and with a 1:1 stoichiometry; type II FcRs bind IgG in the closed conformation in the CH2‐CH3 domain with stoichiometry of two receptors per antibody. Although the engagement of type II FcRs leads to suppression of antibody‐mediated and T cell‐mediated inflammation, the engagement of type I FcRs results in ADCC and ADCP.[72](#cts12597-bib-0072){ref-type="ref"} Recently, additional FcRs have been identified, including Fc receptor‐like molecules and TRIM21. Their role is not well understood. On the other hand, binding of IgG to the type I FcRs (FcγRs) has been extensively leveraged for designing mAbs with modified effector functions and is discussed briefly here. FcγRs are further subdivided into activating and inhibitory receptors depending on their intracellular motif (**Table** [4](#cts12597-tbl-0004){ref-type="table"}). B cells, innate immune cells, including myeloid cells (dendritic cells, monocytes, macrophages, neutrophils, basophils, and eosinophils), and natural killer (NK) cells differentially express these receptors.[72](#cts12597-bib-0072){ref-type="ref"}, [73](#cts12597-bib-0073){ref-type="ref"} T cells do not express FcγRs,[74](#cts12597-bib-0074){ref-type="ref"} although there is a recent report of FcγRIIb expression on memory CD8 T cells.[75](#cts12597-bib-0075){ref-type="ref"} The outcome of the IgG‐FcγR interaction is governed by several factors, such as the Fc isotype and structure, the cellular and preferential expression patterns of FcγRs, allelic variation of FcγRs, ratio of the activating vs. inhibitory receptor engagement, and species differences. Many of these factors have been studied in mice but not in humans. It is also suggested that macrophages largely drive ADCP activity via FcγRII and FcγRIII, whereas ADCC is driven by NK cells via FcγRIII only. The binding affinities of the various Fc isotypes to IgG are governed by the N‐linked glycosylation pattern at Asn297 as well as the amino acid structure, both of which determine which of the two dominant conformational states the Fc domain may adopt. Consequently, glycoengineering (modifying glycosylation patterns) and protein engineering (modifying the amino acid sequence using display libraries and/or structure‐guided design) have been adopted to either enhance or reduce/abrogate Fc effector function depending on the desired therapeutic activity of the mAb. Because the screening for Fc activity of IgG mAbs is performed *in vitro* (such as ADCC, ADCP, and CDC assays) as well as *in vivo* (such as antitumor efficacy in murine models or toxicology studies in nonhuman primates), the species differences in expression of FcγRs and in affinities should be taken into account, because they can complicate the contribution of Fc activity, and the clinical translation of preclinical activity.[76](#cts12597-bib-0076){ref-type="ref"}, [77](#cts12597-bib-0077){ref-type="ref"}, [78](#cts12597-bib-0078){ref-type="ref"} ###### **Human IgG subclasses and binding affinity to human FcγRs** [a](#cts12597-note-0007){ref-type="fn"} ~b~ Fc receptors IgG1 IgG2 IgG3 IgG4 -------------- ---------------- ------------ ------------ ------ ------ Activating FcγRI High No binding High High FcγRIIa~H131~ Medium‐low Low Low Low FcγRIIa~R131~ Medium‐low Very low Low Low FcγRIIIa~V158~ Medium‐low Very low High Low FcγRIIIa~F158~ Low No binding High Low Inhibitory FcγRIIb Low No binding Low Low IgG, immunoglobulin. The murine FcγRs that functionally correspond to the human FcγRI (hCD64), FcγRIIa (hCD32a), FcγRIII (hCD16), and FcγRIIb are FcγRI, FcγRIII, FcγRIV, and FcγRIIB, respectively. bC1q binding: IgG3 \> IgG1 \> IgG2. IgG4 does not bind C1q. John Wiley & Sons, Ltd ### Enhancing Fc effector functions. {#cts12597-sec-0011} Enhanced Fc‐mediated effector functions are highly desirable when the removal of the mAb‐targeted cell is crucial to clinical efficacy, such as tumor cells or virally infected cells. Specifically in oncology, several mAbs with potent effector functions (ADCC, ADCP, and/or CDC) are clinically approved, including rituximab, obinutuzumab, trastuzumab, and cetuximab. More recently, several next‐generation antitumor mAbs optimized for Fc‐mediated effector function have progressed into clinical development.[72](#cts12597-bib-0072){ref-type="ref"} To induce immune cell activation, mAbs must first overcome the activation threshold dictated by the presence of both activating and inhibitory FcγRs. This is achieved by enhancing the relative engagement of the activating (most importantly FcγRIIIA) vs. inhibitory FcγRs (increasing the A‐I ratio) through glycoengineering and protein engineering.[72](#cts12597-bib-0072){ref-type="ref"} #### Glycoengineering {#cts12597-sec-0012} The glycosylation pattern of mAbs at Asn297 regulates the conformational state of the Fc domain and subsequent binding to Fc receptors.[57](#cts12597-bib-0057){ref-type="ref"} These N‐glycans are crucial for the structural integrity of the FcγR‐binding site, and their removal has been shown to abrogate FcγR affinity and complement binding/effector functions.[79](#cts12597-bib-0079){ref-type="ref"}, [80](#cts12597-bib-0080){ref-type="ref"} Reducing fucose and sialyl groups and increasing bisecting GlcNAc, Gal, and Man have proven to enhance Fc‐mediated ADCC and/or CDC.[81](#cts12597-bib-0081){ref-type="ref"} Afucosylation has by far been the most effective glycoengineering approach to enhancing Fc effector function of mAbs. Shinkawa *et al* [82](#cts12597-bib-0082){ref-type="ref"} showed that the absence of fucose, rather than the presence of bisecting GlcNAc or Gal, is necessary for maximal enhancement of ADCC activity. Furthermore, afucosylation does not affect binding to FcγRI, C1q, or FcRn.[82](#cts12597-bib-0082){ref-type="ref"}, [83](#cts12597-bib-0083){ref-type="ref"} Importantly, afucosylation enhances ADCC activity regardless of FcγRIIIA polymorphism.[84](#cts12597-bib-0084){ref-type="ref"}, [85](#cts12597-bib-0085){ref-type="ref"} Several glycoengineered afucosylated mAbs have demonstrated clinic success, the first of which is mogamulizumab, a humanized mAb targeting C‐C chemokine receptor type 4 approved for patients with relapse or refractory C‐C chemokine receptor type 4‐positive T cell leukemia or lymphoma.[86](#cts12597-bib-0086){ref-type="ref"} Another example is obinutuzumab, an afucosylated anti‐CD20 mAb that contains a bisecting GlcNAc. Obinutuzumab was approved in 2013 for the treatment of patients with previously untreated chronic lymphocytic leukemia. Compared with rituximab, obinutuzumab displays 50‐fold higher affinity to human FcγRIII, 10--100‐fold increase in ADCC against CD20‐expressing lymphoma cell lines, and superiority in clinical trials for patients with chronic lymphocytic leukemia.[87](#cts12597-bib-0087){ref-type="ref"}, [88](#cts12597-bib-0088){ref-type="ref"} A third example is benralizumab, a humanized afucosylated anti‐IL‐5Rα that mediates ADCC depletion of IL‐5Rα‐expressing eosinophils implicated in asthma exacerbations. Reed *et al*.[89](#cts12597-bib-0089){ref-type="ref"} showed that a single intravenous dose of benralizumab (MEDI‐563) led to a robust depletion of eosinophils in mild asthmatics that was sustained for 8--12 weeks. High mannose content (Man5/8/9) has been associated with affinity for FcγRIIIA and enhanced ADCC activity, but this may rather be due to afucosylation, because high‐mannose glycans do not have core fucosylation similar to bisecting GlcNAc‐variants.[63](#cts12597-bib-0063){ref-type="ref"}, [90](#cts12597-bib-0090){ref-type="ref"} #### Protein engineering {#cts12597-sec-0013} Another approach to enhance Fc effector functions is through introduction of Fc domain point mutations. This approach is not limited to FcγRIII and allows manipulating the interactions of the Fc domain with multiple activating FcγRs. A series of Fc variants of therapeutic mAbs (rituximab, cetuximab, trastuzumab, and the anti‐CD52, alemtuzumab) were engineered and showed increased FcγRIIIA affinity, reduced FcγRIIB affinity, and enhanced ADCC activity for the double mutant Ser239Asp/Ile332Glu and the triple mutant Ser239Asp/Ile332Glu/Ala330Leu.[91](#cts12597-bib-0091){ref-type="ref"} Several preclinical studies demonstrated the enhanced *in vivo* activity of Fc protein‐engineered mAbs against cancer and viruses,[92](#cts12597-bib-0092){ref-type="ref"}, [93](#cts12597-bib-0093){ref-type="ref"} and a number of these mAbs have entered clinical development, such as anti‐CD19 Xmab5574 for leukemia, anti‐CD30 Xmab2513 for lymphoma, and anti‐HER2 margetuximab for breast cancer.[72](#cts12597-bib-0072){ref-type="ref"} Fc protein engineering can also enhance ADCP activity using the Gly236Ala mutation, which selectively enhances affinity for FcγRIIA. The enhancement was further improved through combining the Gly236Ala mutation (the macrophage‐mediated ADCP and NK cell‐mediated ADCC) as well as the ADCC‐enhancing Ser239Asp/Ile332Glu double mutation.[94](#cts12597-bib-0094){ref-type="ref"} Mutations located in the upper hinge region can selectively enhance CDC activity by enhancing binding to C1q, such as the tryptophan substitutions.[95](#cts12597-bib-0095){ref-type="ref"} Other point mutations, such as Lys326Trp and Glu333Ala, in the CH2 domain have been shown to enhance CDC.[96](#cts12597-bib-0096){ref-type="ref"} Double mutants, such as Lys326Trp/Glu333Ala, Lys326Ala/Glu333Ala, and Lys326Met/Glu333Ser, as well as triple mutants, such as Ser267Glu/His268Phe/Ser324Thr, have displayed further increases in CDC as compared with those observed with individual mutations.[96](#cts12597-bib-0096){ref-type="ref"}, [97](#cts12597-bib-0097){ref-type="ref"} Reducing/silencing Fc effector functions. {#cts12597-sec-0014} ----------------------------------------- Although enhancing Fc effector functions can enhance therapeutic efficacy and/or reduce the dose or dosing frequency, it may also lead to Fc‐mediated activation of immune cells and more frequent or severe adverse events in patients. Moreover, Fc effector functions can be undesirable for the required efficacy of some therapeutic mAbs, such as benign blocking, where the interaction with the antigen is sufficient and ADCC/ADCP‐mediated depletion is unwarranted as with effector T cells.[98](#cts12597-bib-0098){ref-type="ref"}, [99](#cts12597-bib-0099){ref-type="ref"} To minimize or eliminate Fc effector functions, glycoengineering and protein engineering approaches have been used. ### Glycoengineering {#cts12597-sec-0015} Common approaches to reduce Fc‐mediated cell killing include using fucosylated mAbs and/or low‐bisecting GlcNAc content. Another approach is to increase the affinity of the Fc domain to inhibitory type II FcRs using sialylation, which induces a closed conformation of Fc.[72](#cts12597-bib-0072){ref-type="ref"} This property is also exploited with intravenous IgG (IVIG), which is used for the treatment of autoimmune and inflammatory diseases. IVIG preparations contain 10% Fc‐sialylated IgG, to which the anti‐inflammatory properties of IVIG are attributed.[100](#cts12597-bib-0100){ref-type="ref"} Binding of IVIG to DC‐SIGN induces the expression of inhibitory FcγRIIB on inflammatory cells, which attenuates inflammation.[101](#cts12597-bib-0101){ref-type="ref"} To recapitulate the anti‐inflammatory effect of IVIG, the glycoengineered addition of 2,6 sialylation to IgG1 or increasing the sialylation levels demonstrates lower affinity for FcγRIIIA and reduced ADCC potency.[102](#cts12597-bib-0102){ref-type="ref"}, [103](#cts12597-bib-0103){ref-type="ref"} ### Protein engineering {#cts12597-sec-0016} In addition to glycoengineering, efforts to reduce Fc effector functions include introducing point mutations and/or using the IgG2 and IgG4 isotypes that have poor effector functions. The effect of reducing Fc effector functions and its impact on the PD profile has been explored with anti‐IgE antibodies (HAE1 and HAE2). Using a single‐point mutation (Asp265Ala) in the Fc region, which reduces HAE2‐IgE complex binding to FcγRI, II, and III by \~85‐fold as compared with HAE1, the authors observed reduced IgE‐HAE2 complex clearance and increased total IgE serum concentrations in cynomolgus monkeys, suggesting the importance of effector functions in elimination of anti‐IgE--IgE complexes.[44](#cts12597-bib-0044){ref-type="ref"} Besides silencing IgG1 activity, switching to a different subclass (e.g., IgG4) is also commonly used for therapeutic mAbs whose Fc effector functions are undesirable, such as natalizumab and the anti‐PD‐L1 mAb, BMS‐936559. Both mAbs are designed to inhibit leukocyte interactions implicated in disease pathology without eliminating the leukocytes through Fc‐mediated depletion. It is important to note that effector functions are not completely attenuated with the IgG4 subclass. Another isotype‐based approach is the use of hybrid IgG2‐IgG4 Fc domains in mAbs. Examples include eculizumab, which targets the complement component C5. To avoid proinflammatory responses induced by complement activation or Fc‐expressing inflammatory cells, components of both human IgG2 and IgG4 constant regions were included, because IgG2 does not bind Fc receptors as well as IgG1, and IgG4 does not activate the complement cascade.[104](#cts12597-bib-0104){ref-type="ref"} Other examples include r18D11, which blocks CD14 and is used to attenuate inflammatory responses. The human IgG2/IgG4 hybrid C region was used to remove undesired Fc‐mediated functions, such as platelet activation and IL‐8 release.[105](#cts12597-bib-0105){ref-type="ref"} Combining point mutations with IgG2/ IgG4 subclasses has also been examined. One example is IgG2 with four‐point mutations (His268Gln/Val309Leu/Ala330Ser/Pro331Ser) derived from IgG4.[106](#cts12597-bib-0106){ref-type="ref"} It is worth noting that most of these approaches do not completely abrogate Fc effector function. For example, Arce Vargas *et al*.[77](#cts12597-bib-0077){ref-type="ref"} showed that both human IgG1 and IgG2 anti‐CTLA‐4 mAbs showed similar regulatory T‐cell depletion in mice. Complete silencing has been demonstrated by some groups.[107](#cts12597-bib-0107){ref-type="ref"}, [108](#cts12597-bib-0108){ref-type="ref"} Vafa *et al*.[108](#cts12597-bib-0108){ref-type="ref"} utilized a combination of an IgG2 backbone and seven‐point mutations (Val234Ala/Gly237Ala/Pro238Ser/His268Ala/Val309Leu/Ala330Ser/Pro331Ser) to induce structural perturbations of the Fc and completely "mute" it by eliminating affinity for FcγR and C1q. Importantly, the affinity to FcRn was not affected, and a circulating half‐life similar to that of IgG1 and IgG2 was observed in cynomolgus monkeys. Modifying activity. {#cts12597-sec-0017} ------------------- The biological activity of mAbs is a mainstay of the PD profile and is chiefly determined by the variable region through which the mAb interacts with its target. In addition to improving the PD profile of mAbs through engineering the Fc‐mediated effector functions, enhancing the biological activity of mAbs can be achieved by improving the design of the variable region through affinity maturation and through modulating glycosylation. Affinity maturation. {#cts12597-sec-0018} -------------------- Enhanced affinity can translate into better potency, enhanced biological activity, and lower doses. For example, Ahmed *et al*.[109](#cts12597-bib-0109){ref-type="ref"} matured the affinity of an anti‐B7‐H3 mAb (8H9) that is used for radioimmunotherapy of B7‐H3‐positive tumors using sequential random mutagenesis. The authors achieved twofold to ninefold enhancement in affinity, which translated into higher tumor uptake in mouse xenografts and improved ADCC activity. However, this may not always be true, as observed in several studies. For example, Rudnick *et al*.[110](#cts12597-bib-0110){ref-type="ref"} studied six different anti‐HER2 IgG variants that differ in single‐point mutations in the CDR region affecting their affinity. The authors observed that higher affinity did not always translate into enhanced tumor targeting but rather promoted mAb internalization and degradation, leading to limited tumor penetration. Interestingly, the different affinity variants showed differences in spatial distribution within the tumor. Their studies also emphasized that tumor antigen expression levels, antigen recycling rates, antibody‐antigen dissociation rate, together with the affinity impacted antibody uptake and distribution, and, therefore, activity. In another interesting study by the same group, Tang *et al*.[111](#cts12597-bib-0111){ref-type="ref"} showed that the affinity to the tumor antigen HER2 impacted the extent and efficiency of ADCC. Additional data are necessary to fully understand the role of affinity in tumor uptake, distribution, and activity. Furthermore, these studies highlight the challenge in translating *in vitro* studies of biological affinity into *in vivo* targeting and ultimately, clinical efficacy. Conclusions {#cts12597-sec-0019} =========== Optimization of the PK/PD properties of therapeutic mAbs is an ongoing effort not only for novel mAbs still in the pipeline but also for approved mAbs. In this review, we have discussed the PK and PD properties of antibodies, pinpointed challenges, and highlighted approaches undertaken to overcome these challenges. Notwithstanding the interdependence of these properties, other issues instrumental to improving mAb design include the need for better understanding of the structural variants of mAbs and how heterogeneity ultimately affects mAb design and function. In addition, better understanding of the role of FcRn in IgG bioavailability, tissue uptake, and of the impact of non‐FcRn binding regions on FcRn binding can provide potential for enhancing PK properties through FcRn‐dependent antibody engineering. Another important issue is the mechanistic understanding of the impact of mAb affinity to the different FcγRs, and the role of FcγR‐expressing immune cells in mediating the therapeutic efficacy of mAbs, particularly those being designed for cancer therapy. Lastly, novel mAb formats, such as sweeping antibodies, YTE mutants, afucosylated mAbs, and bispecifics, such as T‐cell engagers, have expanded the repertoire of design tools and supplied new opportunities for designing mAbs with optimal clearance, extended serum half‐life, enhanced Fc functions, and pharmacological activity. New efforts in developing a quantitative structure‐activity relationship model[112](#cts12597-bib-0112){ref-type="ref"}, [113](#cts12597-bib-0113){ref-type="ref"} for predicting human clearance for antibodies as routinely done with small molecule drugs may overcome the slow progress in mAb optimization and revolutionize the field of PK/PD design of antibody therapeutics. Nonetheless, additional robust technologies and tools (both experimental and *in silico*) are still critically needed to understand structural determinants of the mAb that impact its PK/PD properties and use these determinants to predict the PK/PD properties and guide antibody optimization. Funding {#cts12597-sec-0020} ======= No funding was received for this work. Conflict of Interest {#cts12597-sec-0021} ==================== Both authors are employees of Genentech, a member of the Roche Group, and hold financial interest in Hoffman‐La Roche.

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London EV drivers rewarded with car parking discount Plug-in vehicle drivers in the capital are set to be rewarded by a new parking tariff scheme at a central London car park which discounts parking for low-emission cars. The central London branch offers universal charging points to accommodate the rising number of electric vehicles (EVs) The Clipstone Street branch of car park operator CitiPark will perform vehicle emissions checks using advanced software. Vehicles emitting less than or equal to 75g/kg of CO2 will qualify for a new tariff, which will cost up to 20% less compared to the standard charge. CitiPark managing director Ben Ziff said: “We believe that the infrastructures supporting the automotive industry and governmental green agendas should also be adopting the same forward thinking approach. We are investing a great deal into our London car parks at the moment, not just aesthetically but operationally too”. CitiPark recently partnered with Tesla to offer customers the use of Tesla plug-in across their car park portfolio, including three points at Clipstone Street. The central London branch also offers a further three universal charging points to accommodate the rising number of electric vehicles (EVs). Air of caution The emissions-based tariff supports the same principles as the recently announced £10 T-Charge, which alongside the Congestion Charge, could cost the most polluting vehicles in London around £21.50 daily. The T-Charge is the latest weapon in Sadiq Khan’s arsenal to combat air pollution. London plans to introduce the world’s first Ultra Low Emission Zone as early as 2019, and Mayor has committed to double spending on air quality to £875m over the next five years. Air pollution is a major health concern in London, as well as numerous UK cities, with more than 9,000 Londoners dying prematurely due to long-term exposure to high levels of pollutants. A rise in car club members in London, however, is reducing the number of diesel vehicles on the roads, leading to less air pollution and a reduction in vehicle carbon emissions. The Government's recent proposals to clean up the UK's toxic levels of air pollution have been received with widespread condemnation for being both "toothless" and "woefully adequate". The overdue air quality plan, released earlier this month, failed to commit to a targeted diesel scrappage scheme, and provided no formal strategy to end illegal pollution in the foreseeable future.

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New Lakers stars give Time Warner Cable reason to cheer The Lakers' addition of Steve Nash may make life easier for Time Warner… (Brian van der Brug / Los Angeles…) Lakers fans aren't the only ones cheering the recent additions of Steve Nash and Dwight Howard to the team's starting lineup. Time Warner Cable is also probably sending Lakers brass a big thank-you note. In October, Time Warner Cable will launch both English-language and Spanish-language sports channels in Los Angeles, and a strong Lakers team is key to the company's success. The addition of two superstars to the team will give the cable company a little more juice in negotiations for distribution with satellite broadcasters DirecTV and Dish as well as AT&T's Uverse and other pay-TV providers in the region. So far, the only distributor Time Warner Cable has persuaded to carry its two channels is itself. Though Time Warner Cable has about 2 million subscribers in Southern California, it needs the other distributors, particularly DirecTV, to be a success. Time Warner Cable is asking distributors to pay almost $4.00 per-month, per-subscriber to carry the two channels. That's more than any other regional sports network in the country, according to industry consulting from SNL Kagan. With over 1 million subscribers in this area, DirecTV is crucial. But the satellite broadcaster has been playing hardball with programmers as of late. It got into a very public battle with Viacom, parent of Nickelodeon and Comedy Central, over a new deal and even stopped carrying its channels until the two finally reached an agreement. Although the launch of Time Warner Cable's sports networks is only about six weeks away, talks with DirecTV and other distributors are not likely to heat up until mid-to-late September. If DirecTV ends up not reaching a deal with Time Warner Cable, sports fans won't be totally out of luck. DirecTV just signed an agreement to carry beIn Sport, an Al Jazeera-owned sports channel that specializes in soccer.

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Q: density shadow around the data with ggplot2 (R) I am trying to have 2 "shadows" on the background of the below plot. These shadows should represent the density of the orange and blue points separately. Does it make sense? Here is the ggplot to improve: Here is the code and the data (matrix df) I used to create this plot: PC1 PC2 aa A_akallopisos 0.043272525 0.0151023307 2 A_akindynos -0.020707141 -0.0158198405 1 A_allardi -0.020277664 -0.0221016281 2 A_barberi -0.023165596 0.0389906701 2 A_bicinctus -0.025354572 -0.0059122384 2 A_chrysogaster 0.012608835 -0.0339330213 2 A_chrysopterus -0.022402365 -0.0092476009 1 A_clarkii -0.014474658 -0.0127024469 1 A_ephippium -0.016859412 0.0320034231 2 A_frenatus -0.024190876 0.0238499714 2 A_latezonatus -0.010718845 -0.0289904165 1 A_latifasciatus -0.005645811 -0.0183202248 2 A_mccullochi -0.031664307 -0.0096059126 2 A_melanopus -0.026915545 0.0308399009 2 A_nigripes 0.023420045 0.0293801537 2 A_ocellaris 0.052042539 0.0126144250 2 A_omanensis -0.020387101 0.0010944998 2 A_pacificus 0.042406273 -0.0260308092 2 A_percula 0.034591721 0.0071153133 2 A_perideraion 0.052830132 0.0064495142 2 A_polymnus 0.030902254 -0.0005091421 2 A_rubrocinctus -0.033318659 0.0474995722 2 A_sandaracinos 0.055839755 0.0093724082 2 A_sebae 0.021767793 -0.0218640814 2 A_tricinctus -0.016230301 -0.0018526482 1 P_biaculeatus -0.014466403 0.0024864574 2 ggplot(data=df,aes(x=PC1, y=PC2, color=factor(aa), label=rownames(df))) + ggtitle(paste('Site n° ',Sites_names[j],sep='')) +geom_smooth(se=F, method='lm')+ geom_point() + scale_color_manual(name='mutation', values = c("darkorange2","cornflowerblue"), labels = c("A","S")) + geom_text(hjust=0.5, vjust=-1 ,size=3) + xlim(-0.05,0.07) A: Here are some possible approaches using stat_density2d() with geom="polygon" and mapping or setting alpha transparency for the density fill regions. If you are willing to experiment with some the parameters, I think you can get some very useful plots. Specifically, you may want to adjust the following: n controls the smoothness of the density polygon. h is the bandwidth of the density estimation. bins controls the number of density levels. df = read.table(header=TRUE, text= " PC1 PC2 aa A_akallopisos 0.043272525 0.0151023307 2 A_akindynos -0.020707141 -0.0158198405 1 A_allardi -0.020277664 -0.0221016281 2 A_barberi -0.023165596 0.0389906701 2 A_bicinctus -0.025354572 -0.0059122384 2 A_chrysogaster 0.012608835 -0.0339330213 2 A_chrysopterus -0.022402365 -0.0092476009 1 A_clarkii -0.014474658 -0.0127024469 1 A_ephippium -0.016859412 0.0320034231 2 A_frenatus -0.024190876 0.0238499714 2 A_latezonatus -0.010718845 -0.0289904165 1 A_latifasciatus -0.005645811 -0.0183202248 2 A_mccullochi -0.031664307 -0.0096059126 2 A_melanopus -0.026915545 0.0308399009 2 A_nigripes 0.023420045 0.0293801537 2 A_ocellaris 0.052042539 0.0126144250 2 A_omanensis -0.020387101 0.0010944998 2 A_pacificus 0.042406273 -0.0260308092 2 A_percula 0.034591721 0.0071153133 2 A_perideraion 0.052830132 0.0064495142 2 A_polymnus 0.030902254 -0.0005091421 2 A_rubrocinctus -0.033318659 0.0474995722 2 A_sandaracinos 0.055839755 0.0093724082 2 A_sebae 0.021767793 -0.0218640814 2 A_tricinctus -0.016230301 -0.0018526482 1 P_biaculeatus -0.014466403 0.0024864574 2") library(ggplot2) p1 = ggplot(data=df, aes(x=PC1, y=PC2, color=factor(aa), label=rownames(df))) + ggtitle(paste('Site n° ',sep='')) + stat_density2d(aes(fill=factor(aa), alpha = ..level..), geom="polygon", color=NA, n=200, h=0.03, bins=4) + geom_smooth(se=F, method='lm') + geom_point() + scale_color_manual(name='mutation', values = c("darkorange2","cornflowerblue"), labels = c("A","S")) + scale_fill_manual( name='mutation', values = c("darkorange2","cornflowerblue"), labels = c("A","S")) + geom_text(hjust=0.5, vjust=-1 ,size=3, color="black") + scale_x_continuous(expand=c(0.3, 0)) + # Zooms out so that density polygons scale_y_continuous(expand=c(0.3, 0)) + # don't reach edges of plot. coord_cartesian(xlim=c(-0.05, 0.07), ylim=c(-0.04, 0.05)) # Zooms back in for the final plot. p2 = ggplot(data=df, aes(x=PC1, y=PC2, color=factor(aa), label=rownames(df))) + ggtitle(paste('Site n° ',sep='')) + stat_density2d(aes(fill=factor(aa)), alpha=0.2, geom="polygon", color=NA, n=200, h=0.045, bins=2) + geom_smooth(se=F, method='lm', size=1) + geom_point(size=2) + scale_color_manual(name='mutation', values = c("darkorange2","cornflowerblue"), labels = c("A","S")) + scale_fill_manual( name='mutation', values = c("darkorange2","cornflowerblue"), labels = c("A","S")) + geom_text(hjust=0.5, vjust=-1 ,size=3) + scale_x_continuous(expand=c(0.3, 0)) + # Zooms out so that density polygons scale_y_continuous(expand=c(0.3, 0)) + # don't reach edges of plot. coord_cartesian(xlim=c(-0.05, 0.07), ylim=c(-0.04, 0.05)) # Zooms back in for the final plot. library(gridExtra) ggsave("plots.png", plot=arrangeGrob(p1, p2, ncol=1), width=8, height=11, dpi=120)

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The effects of spatial and temporal factors on the perception of stroboscopic rotation simulations. In the present two experiments subjects viewed discontinuous, i.e. stroboscopic, simulations of a transparent sphere partially filled with randomly positioned luminous dots and rotating about the y axis in depth. Over a range of stimulus conditions, such simulations elicited coherent sensations of continuous rotation and internal volume of the sphere. By manipulating both spatial and temporal variables in the simulations, it was attempted to define the boundary conditions for which corresponding elements of a simulation are perceptually paired from frame to frame to yield coherent sensations of rotation and depth. The results indicated that the process that matches or pairs corresponding elements in a three-dimensional simulation cannot be identified with the process that matches corresponding elements in similar two-dimensional displays. Furthermore, temporal factors influenced the perception of these simulations more than did spatial factors, and rotation-judgment accuracy and perceived depth were different functions of temporal frequency. Over a range of temporal frequencies, such three-dimensional simulations are apparently processes in a manner similar to that in which objects undergoing real motion are processed.

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Q: Get image dimensions after resizing I have encountered a problem that other people had in this website before but none of the solutions helped me slightly. I have a method that updates an image inside a div (read: user uploads a new image) where the image is resized to fit the set proportions (max-height and max-width are 45x45). I have to resize the div that holds the image to 2* it's dimensions such as the example below: Original image is 180x180. It is resized to 45x45. Div has to be 90x90. Code is as follows: function uploadThumbnail(id, xCoord, yCoord) { var oFReader = new FileReader(); oFReader.readAsDataURL(document.getElementById("thumbnailLoader"+id).files[0]); oFReader.onload = function(oFREvent) { var mapThumbnail = updateMapThumbnail(oFREvent.target.result, id); var mapContainer = document.getElementById("thumbnail"+id); var informationContainer = document.getElementById("container"+id); console.log(mapThumbnail.width); mapContainer.removeChild(document.getElementById("mapThumbnail"+id)); informationContainer.removeChild(document.getElementById("infoThumbnail"+id)); informationContainer.insertBefore(updateInfoThumbnail(oFREvent.target.result, id), informationContainer.firstChild); mapContainer.appendChild(mapThumbnail); }; }; function updateMapThumbnail(result, id){ var newThumbnail = document.createElement("img"); newThumbnail.src = result; newThumbnail.style.maxWidth = "45px"; newThumbnail.style.maxHeight = "45px"; newThumbnail.id = "mapThumbnail" + id; return newThumbnail; } As you can see I added a console.log method there for test purposes. The problem I am facing is that generating mapThumbnail with set max dimensions (45x45) still has the height and width attributes set with the original image size. I tried reading image.height/width and image.style.height/width as well as naturalHeight/width and clientHeight/width. None of these solutions return the height and width after resizing. Thanks for your time. Also, please refrain from offering solutions that require JavaScript libraries. Edit: forgot to mention that the image placed inside the div is re-sized to the dimensions that I do want it to be. It's just the attributes that seem to be wrong. A: There are four different and undependant widths on an image: 1) img.naturalWidth is the width in px the original image file has. It doesn't change when you set the other widths to some value. This value is rendered when the others are not defined. 2) img.width is an attribute of img. You find it inside the html img tag and can set it with img.setAttribute('width', 'value'). It doesn't change when the others are set to some value. This value is rendered when 3) is not defined and 4) is >= img.width or not defined. 3) img.style.width is a css-property of the images style. You can set it in your css or into the style-attribute in the img tag with img.style.width = 'value';. It doesn't change when the others are set to some value. This value is rendered when it is <= 4) or 4) is not defined. 4) img.style.max-width is another css-property of images style. You can set it in your css or into the style-attribute in the img tag with img.style.maxWidth = 'value';. It doesn't change when the others are set to some value. This is rendered when 2) or 3) are not defined or have values > 4). So you have to decide by yourself which value you want to receive or set. Its the same with height, there are also four heights. EDIT According to your comment: Inside your function updateMapThumbnail you create a new img. A newly created img has no .width unless you define it with newThumbnail.setAttribute('width', 'value). Same with img.style.width: unless you set it explicitely somewhere it's simply not there.

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Recently CCP Games reignited its virtual reality (VR) esports ambitions by updating Sparc with new content. It’s a field more developers are experimenting with due to esports seemingly evergrowing popularity, and now Phaser Lock Interactive is getting in on the action, with its real-time strategy (RTS) title Final Assault taking part in the World Cyber Games (WCG) 2019 in Xi’an, China this week. Final Assault is the only VR title to have been chosen for the event which starts tomorrow and ends on Sunday, 21st July. It’ll join the ranks of some big names in the esports field, such as Dota 2, Starcraft 2, Hearthstone, Warcraft 3, Crossfire and Clash Royale, included as part of the WCG’s “New Horizons” division. Over the course of 2019 the WCG has been running preliminary matches with players from around the world including North America, the Netherlands, Poland, Australia, South Korea, and China. 12 players won the opportunity to be flown to Xi’an, with the six winners now competing for a chance to be crowned the first-ever VR Champion of the World Cyber Games. To celebrate Final Assault taking part in the WCG, Phaser Lock Interactive will be running a free to play weekend from 18th-21st July on Steam. In addition, Final Assault will also be discounted by 35% starting tomorrow, ending on 26th July as part of the World Cyber Games promotion. After a short Early Access period beginning in March this year, Phaser Lock Interactive fully launched Final Assault in May. With a WWII setting, the videogame is a tabletop style battle between Allied and Axis forces, supporting both single-player and multiplayer modes. Players have six divisions to choose from, each with its own unique units, mixing tactics up between, infantry, heavy vehicles, aerial attacks and more. VRFocus reviewed Final Assault for launch, giving it a decent four-star rating whilst saying: “Much, in the same way, VRFocus enjoyed Brass Tactics, Final Assault is another superb example of why table-top gaming works in VR.” Final Assault supports cross-play between Oculus Rift/Rift S, HTC Vive, Valve Index, and Windows Mixed Reality headsets. For further updates from Phaser Lock Interactive, keep reading VRFocus.

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Field of the Invention. This invention relates to yarns of bicomponent filaments suitable for use in arc protection, wherein each filament has a distinct region of aramid polymer having discrete carbon particles homogeneously dispersed therein and a distinct region of modacrylic polymer being free of discrete carbon particles. Description of Related Art. U.S. Pat. No. 4,803,453 to Hull discloses melt-spun filaments having antistatic properties comprising a continuous, nonconductive sheath of a synthetic thermoplastic fiber-forming polymer surrounding an electrically conductive polymeric core comprised of electrically conductive carbon black dispersed in a thermoplastic synthetic polymer. U.S. Pat. No. 4,309,476 to Nakamura et al. discloses a core-in-sheath type aromatic polyamide fiber having satisfactory dyeing properties made from a single aromatic polyamide material. When the core-in-sheath fiber is dyed with acid dyes, only the sheath portion is colored. U.S. Pat. No. 4,398,995 to Sasaki et al. discloses the use of the fiber of Nakamura in a paper. U.S. Pat. No. 3,038,239 to Moulds discloses improved composite filaments that have crimp reversibility. The filaments have at least two hydrophobic polymers in eccentric relationship, wherein one of the hydrophobic polymers further contains mixed therewith a minor amount of polymer having a high water absorption rate. U.S. Pat. Nos. 7,065,950 and 7,348,059 to Zhu et al. disclose a yarn, fabric, and garment for use in arc and flame protection that contains modacrylic, p-aramid, and m-aramid fibers. While these fiber blends have been found to be very useful in arc protection, any improvement in arc protection is welcomed as it can potentially save lives.

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Glutamate may be the primary excitatory neurotransmitter in the central nervous Glutamate may be the primary excitatory neurotransmitter in the central nervous program (CNS) and it is a major participant in complex mind features. CNS disorders, including schizophrenia, dependency, main depressive disorder and stress, Fragile X Symptoms, Parkinsons disease, Alzheimers disease and discomfort. [129]. Since glutamatergic innervation from the ventral tegmental region plays a crucial part in burst firing of dopaminergic neurons, the power of mGluR7 to modulate these excitatory Streptozotocin inputs could be indicative of the antipsychotic potential of mGluR7 agonism. Nevertheless, AMN082 didn’t impact basal or cocaine-induced upsurge in dopamine amounts in the nucleus accumbens, although it reduced GABA and improved glutamate amounts [130,131]. The result of AMN082 on glutamate amounts was further been shown to be partially mediated through reduced amount of GABA amounts. Good lack of modulation of dopamine amounts by mGluR7 activation, AMN082 didn’t impact basal or cocaine-induced locomotor hyperactivity in rats [131]. Nevertheless, AMN082 was discovered to stop cocaine-induced reduction in GABA amounts in the ventral pallidum. In conclusion, mGluR7 agonism will not appear to affect dopaminergic neurotransmission in the nucleus accumbens, but can modulate the ventral striatopallidal pathway in condition of extreme dopaminergic firmness in the nucleus accumbens, which might be relevant to the treating positive symptoms. Many studies also have recommended that mGluR7 may control cognitive function. For example, spatial and operating memory continues to Streptozotocin be looked into in mGluR7 knockout mice [132]. Inside a Morris drinking water maze job, mGluR7 knockout mice display a significant hold off in acquiring the positioning from the concealed platform, aswell as with recall through the probe trial. In an operating memory version from the Morris drinking water maze, mGluR7 knockout mice had been impaired and regularly slower to resolve the matching-to-position job, possibly because of Mef2c impairment in short-term storage. In the consecutive extinction studies, mGluR7 knockout mice had been also delayed to look at a fresh search strategy. Used jointly, these data claim that mGluR7 knockout mice possess impaired reference storage acquisition and spatial functioning storage, and a dysfunctional glutamatergic signalling especially in the hippocampus and prefrontal cortex where mGluR7 are portrayed continues to be hypothesized to trigger these deficits. Shows in complex functioning memory tasks such as for example 8-arm radial maze job had been also impaired in mGluR7 knockout mice [133]. Oddly enough, the functioning storage deficit was connected with an elevated hippocampal theta power while executing the task, that was recommended to reflect too little modulation of regional inhibition, subsequently leading to reduced neuronal firing threshold and changed spike timing [134]. On the mobile level, mGluR7 knockout mice had been reported to demonstrate deficits in short-term, however, not long-term potentiation in the hippocampus [135], results in agreement using the hypothesis that short-term potentiation represents the mobile substrate for short-term storage and crucial for functioning memory performances. Used together, these results reveal that mGluR7 positive modulation may stand for a new healing strategy potentially good for the treating positive aswell as cognitive symptoms. Furthermore, since mGluR7s may also be highly portrayed in the amygdala and also have been implicated in anxiousness (see Streptozotocin Major Melancholy Disorder and Anxiousness), a potential influence on adverse symptoms may also be achieved. Nevertheless, because the lines of proof rely on the usage of knockout mice and an individual pharmacological device, additional research using various other selective positive or adverse modulators of mGluR7.

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Sometimes ATP World Tour professionals commit nice gestures and no one notices. Other times, they receive a touching thank-you letter that lets them know just how much they're appreciated. During his second-round match at the 2016 Australian Open, Jo-Wilfried Tsonga stopped play and helped a tearful ball girl who had just been hit in the face by a ball. The Frenchman walked over to the girl, who was standing behind him, wrapped her arm around his and walked her off the court so she could receive help. The gesture was lauded by journalists and on social media, and Tsonga was praised as a gentleman. “It's just normal. She was really in trouble and the eyes were a bit [teary]. It was just normal to help her to go out of the stadium. I hope she's going well now,” Tsonga said last year after the match, according to the Sydney Morning Herald. On Sunday, Tsonga shared the “Merci” note the ball girl, whose name is Giuliana, had sent to him. “Dear Mr Jo-Wilfried Tsonga, I wanted to take the opportunity to say thank you for helping me out on court during your round 2 match of the Australian Open 2016,” the letter begins. “I'm not sure if you remember me but I was the ballgirl you escorted off court. I would also like to take the opportunity to apologise for the times when you asked for the ball but I did not service it to you or acknowledge you.” Giuliana continued, explaining why she might have been off her game that day. “I had picked up a virus which I was unaware of and it caused me to become dizzy and lightheaded. This also affected my vision and hearing,” she wrote. “I apologise for not being able to perform my duties as a ballkid to the high standards that are expected. “Thank you so much for the kindness that you showed me. I really appreciate that you were able to see that I needed some help and were kind enough to escort me off court.” Giuliana concluded the note with a good-luck message to Tsonga, who plays Stan Wawrinka in the Australian Open quarter-finals on Tuesday. “Congratulations on making it to the next round. I wish you all the best for your upcoming games and I hope you are able to make it to the very end of the Australian Open! “Thank-you again, from “Giuliana AO Ballkid no. 180.”

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Article content A national grocery chain says it’s no longer a sponsor of a series of “wellness” expositions where a man convicted in the death of his toddler is scheduled to be a featured speaker. Sobeys had been sponsoring the Health and Wellness Expos of Canada, which lists David Stephan as a speaker at events this month and next in Saskatoon, Winnipeg, Calgary and Edmonton. We apologize, but this video has failed to load. tap here to see other videos from our team. Try refreshing your browser, or Sobeys pulls support from expo where Alberta father convicted in 19-month-old son's death is keynote speaker Back to video But in an emailed statement on Sunday, a spokeswoman said the company couldn’t support the organizers’ decision to host Stephan as a speaker. In 2016, Stephan and his wife were both found guilty of failing to provide the necessaries of life in their son Ezekiel’s 2012 death from bacterial meningitis. Their trial in Lethbridge, Alta., heard they treated the 19-month-old boy with garlic, onion and horseradish rather than taking him to a doctor. The Stephans eventually called 911 but the little boy died in hospital. Stephan was sentenced to four months in prison, and his case is scheduled to be heard by the Supreme Court in May. Some people took to Twitter to call on Sobeys to pull its support of the expo, given Stephan’s involvement.

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Year of conflict in South Sudan has stolen future of a generation of children – UNICEF UNMISS/Ilya Medvedev Children in South Sudan. 12 December 2014 The scale of the crisis facing children in South Sudan is “staggering” according to the United Nations Children’s Fund (UNICEF), which warned today that the future of an entire generation of the country’s children was being “stolen” by the year-long conflict. Since violence erupted in December 2013, almost 750,000 children have been internally displaced, with 320,000 more living as refugees. UNICEF says that approximately 400,000 children were missing school, 12,000 reported as being used by armed forces and groups, and children were subject to violence, malnutrition and disease. “Monday [15 December] will mark the first anniversary of the return to conflict in South Sudan. The world’s newest country, which began with so much promise three years ago still faces only a fragile peace,” UNICEF spokesperson Sarah Crowe told reporters today in Geneva, and one year after the conflict began, children are still under daily threat. Echoing that concern from on the ground, Jonathan Veitch, UNICEF Representative in South Sudan, said: “The future of South Sudan’s children – and of the country itself – is being grossly undermined by the ongoing fighting…we will continue our enormous relief operation targeting hundreds of thousands of children, but what they need more than anything, is peace.” As the end of the rainy season improves access on South Sudan’s dirt roads, UNICEF is pre-positioning life-saving supplies at key locations, strengthening its emergency response in Jonglei, Unity and Upper Nile – the three contested states where needs are most acute. “We must seize the opportunity the dry season affords us,” said Mr. Veitch. “Any humanitarian gains we make, however, are extremely precarious. Should the fighting intensify, as many fear, this will trigger yet more large-scale displacements, and deepen the vulnerability of already exhausted communities and their children.” That created the urgent need to bring peace and stability to the country by early 2015. While South Sudan avoided falling into famine this year, continued conflict is likely to cause a much more devastating food crisis. Despite avoiding famine, malnutrition rates among children in South Sudan have doubled during the conflict. To meet the challenge, UNICEF has scaled up its nutrition programme, bringing additional partners in to help with the expanding caseload. So far, more than 80,000 severely acutely malnourished children have been admitted to therapeutic care. UNICEF and the UN World Food Programme (WFP) Rapid Response Missions have also been reaching remote communities by air, delivering a range of critical services, including screening and treatment of children for malnutrition as well as safe water and sanitation, immunizations and registration of separated children so they can be reunited with their families. To counter the interruption of the education of vast numbers of children, a campaign called “Back to Learning” is working to rehabilitate 225 damaged classrooms and provide the estimated 400,000 children forced out of school with access to education. To fund its emergency response in 2015, UNICEF will need approximately $166 million. News Tracker: Past Stories on This Issue Never in recent memory have so many children been subjected to such unspeakable brutality, the United Nations Children’s Fund (UNICEF) said today, as 2014 has been “devastating” for some 15 million children caught up in violent conflicts around the world.

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The invention relates to a packaging container made of plastic film, in particular, a bag, pouch, or the like that can be closed at its upper end, comprising a carrying handle arranged within the contour of the container. In a known packaging container of the aforementioned kind, a corner area is separated from the interior by a heat seal seam in which corner area a grip opening is cut out. Such a configuration reduces the filling space of the packaging container and limits the possibilities for arranging the carrying handle to the corner areas in order for the carrying handle not to impair filling and emptying of the packaging container. In bags that are open at the upper end and comprised of multi-layer material, it is known to provide handle loops that project past the upper edge of the container and are secured with their attachment ends between layers of the container wall in the upper edge area. Such a configuration of the carrying handles impairs handling of the bag because of the projecting handle loops. Such handles are moreover limited to bag or pouch configurations that do not have closure means at the upper edge. In the case of valve bags, it is known to provide a carrying handle on the bag bottom that comprises a bottom patch supporting a strap handle. Such a carrying handle configuration is not suitable for containers that are closable at their upper edge after filling and are provided, for example, at their upper edge with an edge closure device for reclosing the bag. The invention is concerned with the problem of providing a packaging container of the aforementioned kind with a carrying handle that can be easily attached, enables carrying of the bag in an orientation similar to a stand-up position, and that leaves open the upper edge area of the container for closing and reclosing devices.

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A blog written in the dead of night and delivered to you in a brown paper bag. It’s a cornucopia of tidbits, rants, and observations for the discerning eye. Good luck with all that. Now, for something completely different! They say that politics makes for strange bedfellows. Well, it doesn’t get much stranger than this. BAM racing has solicitied the Barack Obama campaign to sponsor one of their cars. This would make for a strange combination indeed. Nascar and its fans are a bastion of right-wing conservative Republicans that lean to the left only on the racing track. It seems his money would be better spent elsewhere. BAM team spokesman Rhett Vandiver told The Associated Press on Friday that the team has made a sponsorship proposal to the Democratic presidential hopeful’s campaign, and has made similar proposals to the campaign of Republican John McCain and at least one third-party candidate. It appears they are bound and determined to have some sort of political sponsorship no matter where it comes from. Sports Illustrated first reported the proposal on its Web site, saying Obama’s campaign is in talks with BAM, a part-time operation that hasn’t raced in recent weeks, to sponsor its No. 49 car in the Aug. 3 race at Pocono. “I don’t know how far along the discussions are,” Vandiver told AP. Asked about the talks, Obama campaign spokeswoman Jen Psaki said, “We get a lot of good ideas every day, but there are no such agreements in place at this time.” But BAM’s choice of drivers and car brands might turn out to be a little too sticky politically for the Obama camp. The car, a Toyota, the only foreign automaker racing in NASCAR, would be driven by veteran Ken Schrader. According to the Federal Election Commission’s Web site, Schrader gave $1,000 to the campaign of North Carolina Republican congressman Robin Hayes in June 2004, and a total of $2,500 in 2003 and 2004 to the failed Virginia congressional campaign of Republican Kevin Triplett, a former NASCAR official. Also according to the FEC, Mrs. Ann Schrader of Concord, N.C. and Ken Schrader Racing donated a total of $2,000 to President Bush’s campaign in May 2004. None of this makes any sense for Obama. It just seems stupid. It all looks like BAM racing is desperate to find sponsorship anywhere and is clutching for straws. A “vote for Obama” car zipping around the oval driven by Republicans, maintained by Republicans and built by Republicans is just wrong on so many levels. It just seems a little like the beginning of the apocalypse or at least a sign of it anyway. LUNCHBOX SAVES MANS LIFE Don’t go anywhere without your lunchbox. Carlos Juarez says his lunchbox saved his life. That’s quite a claim. He was waiting for his ride to work early Tuesday in his driveway when two attempted robbers accosted him, demanding money. Right in your own driveway, is nothing sacred? Carlos replied he had no money and the would-be thieves opened fire, hitting him twice in the side. Juarez said he reflexively held up his lunch cooler over his chest to shield himself from the bullets and the cooler was hit twice. It’s not everyone that can say their lunchbox took a bullet for them, let alone two. “He thinks the cooler saved his life,” Carlos Paz, a friend who translated for Juarez, told The Associated Press. “If he doesn’t have the cooler, the shots come maybe in the heart.” Juarez still has one of the bullets that was in the cooler. I might keep a souvenir too. A lunch container of rice and meat has a bullet hole, as does a package of gum also in the cooler. After Juarez was shot, he climbed the stairs of the apartment building with the cooler still in his hand. “Carlos, I got shot,” he told his friend. Paz said at first he didn’t believe it, but then saw blood on his friend’s side and called police. Blood would give you a clue. Juarez, who was treated at a hospital and released, says doctors have been unable to remove two bullets from his side because of swelling. He also had a cut on his forehead that he suffered when one of the men hit him with what he thinks was a bat as Juarez reached for the cooler. Juarez, who came to the United States from Ecuador about five years ago, works for a concrete flooring company. No arrests had been made Wednesday. $55,000 FOUND IN JAIL BATHROOM Somebody lose something? Possibly a lot of money? Well check lost and found, it appears they have it. A correctional officer at the intake facility at the St. Louis County Justice Center in Clayton, Missouri, last week found $55,000 stuffed behind a toilet paper dispenser. The bundle of money was in $100 and $50 bills, said Clayton Police Chief Thomas Byrne. Officials interviewed inmates about the money, but none admitted knowing anything about the stashed cash. I bet they didn’t. Cash like that inside of prison sounds like a pyoff for something to me. That’s one deal that won’t go down.The money was placed in a special bank account until the owner can be determined, Byrne said. Or arrested, I bet. CITY POTTY TRAINING RESIDENTS Imagine, as a grown adult, your city trying to teach you how to properly use the restroom. That is exactly what one city in South Taiwan has started to do. To reduce over 340 tons of waste generated daily, Tainen launched it’s new potty training program which is geared towards teaching its 764,000 residents to flush their toilet paper instead of throwing it in trash cans. Yuck. “An old habit is to throw toilet paper in the trash can beside the toilet, which causes a major stink that’s bad for public sanitation.” Ya think? When “Japanese and Western visitors come to Taiwan, they find this Taiwan toilet habit to be quite poor.” I’d say that’s an understatement. This habit developed because of pipe backup and clogging problems, however the current system can handle the load without backing up. In addition to solving the issue of trash buildup and smell concerns, flushing the toilet paper will actually save the city $600 million a year in trash treatment costs. WESTERN SPAGHETTI This is a creative little piece that I just found clever and fun.Check it out. In an exclusive interview with Bill Clinton in People Magazine, he’s asked would Chelsea ever consider a career in politics? This leaves some interesting prospects for the future. A Clinton dynasty? Well it’s got to be better than the one the Bush’s have handed us. Clinton had an interesting answer. “Before Iowa, I would have said, ‘No way. She is too allergic to anything we do.’ But she is really good at it. It all changed after Iowa. She realized her mother lost Iowa 100 percent because of younger voters. She was upset, bawled, went to her employer and said, ‘Look, you got to let me go or give me an indefinite leave of absence. I’m not letting my mother go down like this.'” It appears that Chelsea has some of her mother’s tenacity and getting her mother’s back gets her big time points. Chelsea has been a continuing presence in Hillary’s campaign and has been dealing with some tough questions on some tough issues. In the People interview, Clinton called his daughter’s “emergence” the “second best thing” of the campaign, after his wife’s resiliency. The former President also made a comment about a press bias against Hillary. “I think most of the press people are in Obama’s demographic. They need a feeling more than they perceive they need a President. There have been times when I thought I was literally lost in a fun house.” I’m not so sure he’s correct there, but he does go on to say about Obama, “I don’t know him very well. But, I do think it’s better to have made a lot of decisions before you get to be President.” This People interview is definately worth a read and it hits newstands today. Could Chelsea get a taste for politics? Could we be seeing the continuation of the Clinton influence on American politics for the future? It sounds awfully Kennedy to me. NEW CAR DEAL – GUN OR GAS? At a new car dealership in Butler, Missouri they are offering a bang-up special deal. You can put $250 to either get a new handgun or gas with any purchase through the end of the month. General Manager, Walter Moore of Max Motors says most people are opting for the handgun. He recommends the semi-automatic model because it holds more rounds. That doesn’t surprise me, with the handgun you can get your gas for free. Moore says, “Down here, we all believe in God, guts and guns.” Well, this IS the state that gave us Frank and Jesse James. GERMAN GOVERNMENT OFFICIALS LOCKED UP BY ACCIDENT A group of German officials were locked away in a jail previously run by the East German Stasi, the former secret police. Thinking all visitors had left, staff closed up the memorial museum that was the Stasi’s main jail, and shut the high-ranking representatives from Germany‘s 16 states inside. I bet that brought on some unintentional enlightenment. “It was a misunderstanding,” said Siegfried Reiprich, deputy director of the complex in eastern Berlin, on Wednesday. I’m sure he was hoping that he wouldn’t be fired over the mixup. Realizing they were trapped, the group called the federal Chancellery late on Tuesday and urgently requested to be let out. About half an hour later the officials were freed from the complex where political opponents of the East German regime were once interrogated by their captors. I wish some of our politicians would “accidentally” get locked away. Then just don’t answer the phone. Anybody up for a trip to Alcatraz? BRITISH MAN HAS BARE BUTT POSTERED AROUND TOWN Pasha Cummings of Seaford, England is the latest victim of the fury of a woman scorned. According to his recently exited wife, Carol, he had been cheating on her and she decided to get even. She had 200 posters of him printed and then posted all over town on lampposts, bus stops, and walls that shows him and his bare butt posing at a barbeque. I have to admit, that would be something that should come under a blight law. Beneath the ‘glamour shot’, the posters read: ‘Pasha Cummings: lying, cheating, two-timing arse! Sandra Beckworth is no better.’ Sandra is apparently the “other” woman. Carol exited the country for Cyprus immediately upon distribution of the controversial poster. People have come up with the most creative ways to slander each other lately. Youtube, Ebay, now this. They’re certainly being creative. What ever happened to keeping your dirty laundry behind closed doors. MAN CLAIMS SEX WITH 1000 CARS Never buy a used car from this man, “used” being the operative word here. Edward Smith has a sexual attraction for mechanical vehicles. I guess they wouldn’t complain if you’re not very good. Smith, 57, says he first had sex with a car at the age of 15 and has banged out the fenders of more than 1000. He claims he has never been attracted to women or men and cars are just his preference. OK, something went seriously wrong here. I’ve heard of having a passion for your cars but, this is a bit over the top. They even have a name for this: mechaphilia. He is now part of a global community of more than 500 “car lovers” brought together through the Internet. Smith, who now lives with his current “girlfriend,” a white Volkswagen Beetle named Vanilla, said he has no desire to change his ways. Of course not, all his desire is aimed at this poor VW’s fender. “I’m not sick,” he said, “And I don’t want to hurt anyone.” That, may be a matter of opinion. If the car doesn’t start, does that mean no? Does he consider Herbie the Love Bug porn? This guy would be a riot at a NASCAR rally. Once again, the two dueling democratic candidates split primaries and came out fighting. Barack Obama has moved within 100 delegates of officially taking the nomination, but Clinton had another very lopsided victory in Kentucky. Like she has been right along, Hillary vows to stay in the race to the bitter end. She’s not giving up and wants the country to know it. Clinton won at least 47 delegates in the two states and Obama won at least 32, according to an analysis of election returns by The Associated Press. So far Clinton has actually gained more delegates than Obama and trimmed his lead. All the Kentucky delegates were awarded, but there were still 24 to be allocated in Oregon, and Obama was in line for many of them. As the primary season comes to an end, it is beginning to appear that neither candidate will actually have a decisive amount for the convention. Though many, including Obama are claiming he has the nomination sewed up, there still could be some surprises. Somehow I keep feeling, his overconfidence is going to come back and bite him. There are some very strong calls for Clinton to stay in, particulary from the Women’s voter base. They’re taking out ads encouraging Clinton and trying to raise more money and support. This one certainly is not going to be over until the former First Lady sings. Or her husband plays sax. CHILD ARRESTED FOR DRUNK DRIVING This story is just wrong on so many levels. An Arkansas pre-teen faces a drunken driving charge after he and a friend drank his parents’ beer and crashed his stepfather’s pickup truck. Sheriff Jimmy Dorney said the 12-year-old boy and his 10-year-old friend drove off in the truck May 4 to find a girl they met at a rodeo. Ok, drunk adolescents chasing an adolescent girl. This is seriously backwoods south cliche. The boys made it about 10 miles before the 12-year-old lost control of the truck. Dorney said the truck hit and jumped over a guardrail, sending it careening 50 feet down a steep hill into a forest. Clark James, who lives down the road from the crash site, said he answered the boys’ banging at his front door with shotgun in hand about 2:30 a.m. “I opened the door and the first thing the boy said to me was, ‘I’m drunk and I had a wreck,'” James said. “I looked at him and I thought ‘You’re kind of young to be out drinking. And you sure shouldn’t be driving.'” Well that’s a no brainer. No one was paying attention to these kids? Was there a NASCAR race somewhere? NEW YORK RESTAURANT TOPS BURGER IN GOLD A good burger is one of my favorite things, but this is a bit over the top-pings. A Manhattan restaurant is offering a hamburger that costs $175 and is topped with gold. And I complain about a $6.00 burger. It’s made of Kobe beef. It comes with black truffles, foie gras and Gruyere cheese in addition to gold flakes. What, no mayo? This shows you how gourmet I am, I’ve never heard of any of this crap other than gold, and I’m not about to eat that. Wall Street Burger Shoppe co-owner Heather Tierney thinks of it as “a work of art.” Tierney says the item attracts Wall Street types who down a few beers and then fork over $175 to show off to their friends. you’d think if they can afford that much for their burger, they’d have something to drink a little more stylish than a brew. 75 YEAR OLD ATTEMPTS MOUNT EVEREST 75-year-old Yuichiro Miura of Japan is trying to be the oldest man to ever reach the summit of Mount Everest. This is one guy who doesn’t believe in growing old gracefully. He is accompanied by his son, Gota. Yuichiro is a professional skier who in 1970 became the first person to ski down Mount Everest using a parachute as a brake. Miura was into extreme sports before it was popular. He was diagnosed a few years ago with a heart arrhythmia. He says his greatest challenge is how his heart will hold up. Well, if he doesn’t make it. I have no doubt that he going to give it his best shot. No rocking chairs for him! URINAL VIDEO GAME FOR TWO The Belgians have come up with a solution for what to do when you are using the urinal in the public bathroom. It’s the urinal video game for two. Two beer fans out there have created a video game called “Place to Pee,” in which players race down ski slopes and kill aliens while whizzing. Apparently how you aim is how you play the game. Sensors inside the urinal keeps your game tally. The game is the creation of software developer Werner Dupont and electrical engineer Bart Geraets, who had consumed considerable beer when the idea dawned on them. There’s a revelation. They probably figured out the specs on a beer coaster. Now you don’t have to experience that uncomfortable silence when standing next to someone in the bathroom. Play with them instead. See how well you can score. Ladies, you don’t have to feel left out. They’ve invented a special cup attachment just for you. I'm an Author, Journalist, Columnist, Photographer, Editor and Publisher and have been writing for about 30 years. For several years I published my own magazine about Michigan's Upper Peninsula. I live in Sault Sainte Marie, Michigan. Currently I've been blogging around the internet - MAKE SURE YOU CHECK OUT MY OTHER HUMOR BLOG "What Were They Thinking?" AT: http://mikelclassen.wordpress.comTo learn more about the writer behind the blog, go his website at www.mikelclassen.com Sign the guestbook while you're there.

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vide k? False Suppose -4*w + 3*w = -2. Suppose -4*a = -5*g + 5, -w*a + a - 5*g + 5 = 0. Is (1430/(-30))/(a + (-2)/6) a multiple of 11? True Let p = 32550 + 2774. Is 114 a factor of p? False Suppose 4*g + 2*t = -24, 10*g - 3*t - 32 = 15*g. Let f(o) = -41*o + 32. Is f(g) a multiple of 33? False Suppose -10*s = -30672 - 21108. Does 59 divide s? False Let g(p) = -3*p**3 - 12*p**2 + 31*p + 111. Does 132 divide g(-28)? False Let x = 7186 - 1336. Does 130 divide x? True Suppose 0 = -2*p - 10*d + 2810, -5*p + 5441 = 3*d - 1716. Is 41 a factor of p? True Let w(s) = s**3 + 2*s**2 - s - 35. Let v be w(0). Let x = v + 37. Does 6 divide (x/(-4))/(2*4/(-480))? True Suppose 41*i + 145157 - 1207350 = 69407. Is i a multiple of 50? True Let p be (-11)/(143/258) - 2/13. Let g be (-1)/((-2)/p)*(-132)/3. Suppose 2*q = -4*k + g, -2*q = q + 4*k - 656. Is 36 a factor of q? True Let q = -106 - -96. Let k be (-1)/3*q/(40/36). Suppose k*m - 271 = -3*b + 4*b, 175 = 2*m + 5*b. Is m a multiple of 45? True Let v(j) = -j**3 + 21*j**2 - 6*j + 32. Let p be v(20). Let k = 336 - p. Is k a multiple of 3? True Let i(l) = 14 + 1373*l + 2*l**2 - 701*l - 698*l. Does 7 divide i(13)? True Suppose -155*g = -127*g - 17332. Is g a multiple of 2? False Let z = -183 - -182. Does 8 divide 4 + z - (-875)/7? True Let i(n) = 5*n**2 + 4*n + 9. Let r(x) = x**3 - 4*x**2 - 4*x - 9. Let k(v) = -5*i(v) - 6*r(v). Is k(-3) a multiple of 23? False Let u be (-1 - 2)*7/3. Let n(h) = h**3 + 7*h**2 - 2*h - 10. Let d be n(u). Suppose 4*j - 2*k = 404, 0 = d*j - 3*k - 285 - 117. Is j a multiple of 26? False Suppose 5*x + 0*x = 165. Let v(i) = 2*i**3 - 65*i**2 - 15*i - 54. Is 36 a factor of v(x)? True Is -4 + 18 - (-57628)/4 a multiple of 19? True Is (1660/14)/((-216)/(-9072)) a multiple of 30? True Let b = 30 + -29. Let k be (1/b)/(-1 - -2). Is k*-4*(-26)/4 a multiple of 8? False Let g be (-91)/(-21)*3/2*-2. Let m be (g/(-5) - 1) + (-16)/(-40). Suppose 5*t + 43 = r, t + 86 = 2*r - m*t. Is r a multiple of 43? True Let x(o) = -243*o - 5. Let q be x(-1). Suppose 4*s + 122 = -26*z + 28*z, -q = -4*z + 2*s. Does 5 divide z? False Let m(v) = -9*v**3 + 3*v**2 + 6*v + 2. Let p(h) = 3 - 4*h - 8*h**3 + 5*h + 2*h**2 - 1 + 4*h. Let y(o) = -4*m(o) + 5*p(o). Is y(-2) a multiple of 18? False Let b = 447 - 422. Is 19 a factor of -1*b*((-10 - -3) + 6)? False Let p = -445 - -1617. Suppose 12*u = 5156 - p. Does 12 divide (1 + (-6)/4)/((-2)/u)? False Let w(z) = z**2 + 9*z - 73. Let m be w(-15). Suppose -m*y = -21*y + 860. Let l = y - -145. Is l a multiple of 36? True Let h(n) = -n**3 + 14*n**2 + 2. Let c be h(14). Suppose -c*y = 6, 0 = -2*g + y + 350 + 17. Does 14 divide g? True Suppose -2*c + 2*f = f - 140, 4*c - 5*f = 268. Suppose -39*r + 40*r - c = 0. Suppose r = -23*k + 25*k. Does 18 divide k? True Suppose 8*s - 5160 = -2*m, -16*m + 3*s = -15*m - 2622. Is 4 a factor of m? True Suppose 11*j - 8*j - 4*b - 5 = 0, j = 3*b. Suppose c = -h + 546, -j*h - 11 = 1. Is 11 a factor of c? True Suppose -6*w = -6 - 6. Suppose -2*v + 363 = -4*r + 85, -w*v - 3*r + 264 = 0. Suppose 8*h = 7*h + v. Does 27 divide h? True Let v be 288/1 + 0/(24 + -13). Let o = -273 + v. Does 5 divide o? True Let d(u) = 68*u**3 - 3*u**2 + 6*u - 112. Does 74 divide d(6)? True Let l be 7 - 8*5/10. Suppose -5*s = 5, 0*s + 3 = -3*p - l*s. Suppose 2*t - 7*t + 100 = p. Is t a multiple of 4? True Let n = -31 + 35. Suppose -4*w + 769 = -n*x - 487, 0 = w + 5*x - 302. Is w a multiple of 39? True Let h(a) be the second derivative of 15*a**4/8 - a**3 - 11*a**2 - 19*a. Let t(m) be the first derivative of h(m). Is 29 a factor of t(4)? True Let o(w) = -w**3 - 5*w + 40*w + 21*w**2 - 38 - 10*w. Is o(22) a multiple of 7? True Suppose 5*b - 7788 = 2752 - 2195. Is 106 a factor of b? False Let d(j) = 162*j + 736. Let i(k) = -53*k - 245. Let v(s) = 2*d(s) + 7*i(s). Does 13 divide v(-6)? True Suppose 5*p = c + 66599, -p + 4*c + 13315 = -c. Suppose -13*g = 2*g + p. Does 51 divide (-4)/(-2)*g/(-16)? False Suppose -258*d + 254*d + l = -137376, 0 = 4*d + 2*l - 137352. Is 34 a factor of d? False Let d(l) = -32*l**3 - 2*l**2 - l - 13. Let m be d(3). Does 45 divide 152/190*(2 - m)? True Let w(t) = -4*t**3 + 17*t**2 - 6*t - 12. Let o be w(-14). Suppose -o + 5371 = -39*g. Does 53 divide g? False Let z be (-3 + 5)/2 + 18. Suppose 49*k - 245 = 14*k. Let v = z - k. Is v a multiple of 2? True Let a = 196 - 14. Suppose -6*q = -538 - a. Is q a multiple of 8? True Suppose -5*j + 2*j = -0*j. Suppose -4*w + 5*w + 2 = j. Does 29 divide (w/4)/((-5)/1450)? True Suppose 21*x - 3443 = 16213. Does 29 divide x? False Let c = 105 - 107. Let x(h) = -39*h**3 + 4*h**2 - h - 8. Let t be x(c). Is 15 a factor of 2 + t*4/8? False Let u = 13697 - 7187. Is 105 a factor of u? True Let x = -5268 + 10437. Is 8 a factor of x? False Suppose 0 = -3*x - x. Let z = -23023 - -23101. Suppose -5*c + 86 = -3*c - 3*s, -2*c - s + z = x. Does 18 divide c? False Let n(l) = 5*l**2 - 7*l**2 + 16 - 6*l + 20*l. Let a be n(8). Suppose a = 5*c - 20, -3*p + 62 + 64 = -3*c. Is p a multiple of 9? False Let h(m) = -m**3 - 89*m**2 - 44*m + 325. Does 22 divide h(-90)? False Suppose 4*h + 9 = 5*p, 5*p = -5*h - 0*h. Let v(b) = -179*b + 363. Let n(l) = -89*l + 167. Let r(f) = 13*n(f) - 6*v(f). Does 19 divide r(h)? True Let l = -22085 + 35022. Does 17 divide l? True Let t(y) = -5*y**3 - 5*y**2 + 9*y - 5. Let i be t(-5). Suppose 29*z - i = 19*z. Is z a multiple of 6? False Does 244 divide 3/(-2) + ((-7476)/(-72))/((-11)/(-957))? False Suppose 342238 - 922494 = -121*a + 1704466. Does 134 divide a? False Let l(g) = -16*g**2 - 5*g. Let k be l(4). Let t = k - -284. Is 8 a factor of t? True Suppose 3 = 3*t, -t = -4*i + 2 - 15. Let u(a) = 28*a**2 - 5*a - 8. Does 36 divide u(i)? False Suppose 3*d - 7*d = 5*c - 40, -5*d - c + 50 = 0. Let q(v) = v**2 + 2*v - 30. Let n be q(d). Suppose -n = -7*p + 4*p. Is 9 a factor of p? False Suppose -54*t + 56*t = -8, -4*p + 49780 = -t. Does 183 divide p? True Suppose 1990*q - 3*l = 1995*q - 272011, 5*l = -15. Does 14 divide q? True Let m(l) = l**3 + 26*l**2 - 72 + 6 + 7 - 10*l. Is m(-26) a multiple of 21? False Suppose 4*c - 617 = 5*y, 3*c - 3*y - 460 = -2*y. Suppose 155*v = c*v + 520. Is 16 a factor of v? False Let h(g) = 6*g**2 + 14*g. Let c be h(-9). Let p = -38 + c. Is p a multiple of 23? True Let x = 1083 - 1621. Let n = 1150 + x. Does 10 divide n/63 - 4/(-14)? True Suppose 0 = 59*x - 72*x + 60827. Suppose -20*l + x = -7821. Is l a multiple of 34? False Suppose 0 = 7*r + 1 - 15. Suppose -4*m - 864 = -r*w, -2*m - 156 = -2*w + 708. Is w a multiple of 16? True Let k(x) = x**3 + 10*x**2 - 13*x - 12. Let d be k(-11). Let l be d*((-72)/20 + 4). Suppose r = l*h - 274, -h + 6*r = 3*r - 74. Is 15 a factor of h? False Let b(j) = 22*j**2 - 6*j + 6. Let t(u) = 3*u**3 - 2*u + 3. Let q be t(1). Does 47 divide b(q)? False Suppose w - 6510 = -147*u + 143*u, -2*u = 5*w - 32388. Does 53 divide w? False Let t(n) = -n - 9. Let m be t(5). Let y(w) = 2*w**2 + 28*w + 32. Is 2 a factor of y(m)? True Suppose 149*c = -12*c - 14*c + 7901600. Is c a multiple of 83? True Let d be (0/(-5 - 7))/1. Let h(z) = -z**2 - 6*z - 2. Let k be h(-5). Does 7 divide 1 + (k + -3 - d) + 99? False Let h = -115 - -372. Suppose 5*s - 1375 = 3*v, s + 0*v + 3*v - h = 0. Is 16 a factor of s? True Let r = 184 - 184. Suppose -p - 1440 = -4*p + 3*d, 5*p - 2*d - 2400 = r. Is p a multiple of 20? True Let d = 133028 + -71832. Does 19 divide d? False Is 44 a factor of 2/(-1) - (-1739 + 15/5)? False Let v(y) = -y**3 - 10*y**2 - y - 7. Let o be v(-10). Let s be -4*1/(-18) + 1202/18. Suppose h = -u + 5*h + s, -o*h = -3*u + 192. Is u a multiple of 9? True Let m be ((-8)/6 + 1)/((-3)/18). Suppose 0 = -m*r + c + 264, 2*c - 394 = -3*r + 3*c. Is r a multiple of 10? True Let b(c) = 21*c - 36. Let r be -1 - -5 - 1*-2. Is 47 a factor of b(r)? False Let b be ((-738)/(-45))/(1/5). Suppose -a + 103 = -b. Does 26 divide (-2)/((-4)/(-6)) + a? True Let t = -3403 + 15595. Is t a multiple of 32? True Let w(h) = -108*h - 8. Let d be w(-7). Suppose a - g = d, -5*a + 3*g = -0*g - 3732. Is 10 a factor of a/14 - 1/7? False Let y(n) = n**3 - 4*n**2 + 4*n - 6. Let k be y(6). Suppose -k = 7*b - 5*b. Let a = -5 - b. Is 5 a factor of a? True Let d(a) = a**3 + 12*a**2 + 17*a - 5. Let t be d(-9). Suppose

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Role of tumor-infiltrating lymphocytes in patients with solid tumors: Can a drop dig a stone? In recent years, multiple strategies for eliciting anti-tumor immunity have been developed in different clinical studies. Currently, immunotherapy was clinically validated as effective treatment option for many tumors such as melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Some surface receptors of immune cells, called immune checkpoint receptors, may inhibit activity of proinflammatory lymphocytes, following binding with specific ligands. Cancer cells exploit these mechanisms to inactivate tumor-infiltrating lymphocytes (TILs) to escape from immunosurveillance. Among the different tumor-infiltrating immune cell populations, including leucocytes, macrophages, dendritic cells and mast cells, TILs are considered a selected population of T-cells with a higher specific immunological reactivity against tumor cells than the non-infiltrating lymphocytes. In this review we will discuss the promising role of TILs as biomarkers reflecting the immune response to the tumor, describing their potential ability to predict the prognosis and clinical outcome of immunotherapy in some solid tumors.

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The effects of genistein on testicular cells, TM3, TM4, and GC‐1 spg, were studied in vitro. First, each cell line was cultured with pre‐determined concentrations of genistein for a maximum of 72 h to assess the effects of genistein on in vitro growth of the test cells. A second series of experiments were performed to determine the degree of genistein‐induced apoptosis in these cells, using Apop‐TagR kit reagents, to detect apoptotic cells in situ by specific end labeling, and detection of DNA fragments produced by the apoptotic process. The results obtained indicate that: i) genistein inhibits the growth and proliferation of testicular cells; ii) growth inhibition and proliferation is dose‐ and exposure‐time dependent; iii) there is significant difference in sensitivity of the different testicular cells to genistein; iv) genistein induces apoptosis in testicular cells in a concentration‐dependent manner. Genistein‐induced apoptosis identifies genistein as a potential diagnostic and therapeutic tool in testicular pathophysiological research.

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116 Ill. App.3d 80 (1983) 451 N.E.2d 612 HERBERT HAYEN et al., Plaintiffs-Appellees, v. THE COUNTY OF OGLE, Defendant-Appellant (Aurand Construction et al., Intervenors-Appellants). No. 82-313. Illinois Appellate Court — Second District. Opinion filed July 6, 1983. *81 Dennis Schumacher, State's Attorney, of Oregon, for appellant County of Ogle. Gerard C. Smetana, of Arvey, Hodes, Costello & Burman, of Chicago, for other appellants. Joseph W. Phebus and Janet A. Flaccus, both of Phebus, Tummelson, Bryan & Knox, of Urbana, for appellees. Judgment affirmed. PRESIDING JUSTICE SEIDENFELD delivered the opinion of the court: This appeal challenges the constitutionality of "An Act regulating wages of * * * workers employed in any public works * * *" (Prevailing Wage Act) insofar as it is construed to define "general prevailing rate of wages" as wages paid to employees working on public works only. Ill. Rev. Stat. 1981, ch. 48, par. 39s-1 et seq. The county board of Ogle County passed a resolution ascertaining the prevailing wages to be paid on public works projects in the county by first inquiring into wage rates paid on both public and private construction projects for similar trades. Using this information, the county board passed a resolution which averaged the rate set for each of the construction crafts to arrive at the prevailing wage for each craft. The plaintiffs, who are representative of certain trade unions in the county, objected to this method, claiming that the statute limits the inquiry to wages paid on public works projects. They further claim error in the mathematical computation. Following a hearing, the county board adhered to its resolution. Plaintiffs sought administrative review in the circuit court. Various parties doing business in Ogle County were permitted to intervene as of right. The circuit court, finding no issue of fact, reversed the county board's determination based on the law and directed the county to reascertain the prevailing rate of wages by limiting its inquiry to wages paid on public works. The county and intervenors appeal, contending that the statute, so construed, is unconstitutional as a violation of due process and equal protection standards. We consider first the contention of the plaintiffs that the county lacks standing to challenge the constitutionality of the Prevailing *82 Wage Act because a municipal entity is not a "person" entitled to fifth and fourteenth amendment protections of due process and equal protection under the Federal Constitution and under similar provisions in the State Constitution. (See Village of Riverwoods v. Department of Transportation (1979), 77 Ill.2d 130, 136; Franciscan Hospital v. Town of Canoe Creek (1979), 79 Ill. App.3d 490, 496-97.) This argument was not advanced by petitioners in the trial court and they are therefore precluded from raising it on appeal. (Demchuk v. Duplancich (1982), 92 Ill.2d 1, 11; Kravis v. Smith Marine, Inc. (1975), 60 Ill.2d 141, 147.) We will therefore consider the constitutional arguments without reviewing the issue of the standing of the county and the intervenors to raise them. The statute provides, as pertinent: "Sec. 1. It is the policy of the State of Illinois that a wage of no less than the general prevailing hourly rate as paid for work of a similar character in the locality in which the work is performed, shall be paid to all laborers, workers and mechanics employed by or on behalf of any and all public bodies engaged in public works, exclusive of maintenance work." Ill. Rev. Stat. 1981, ch. 48, par. 39s-1. "Sec. 2. This Act applies to the wages of laborers, mechanics and other workers employed in any public works, as hereinafter defined, by any public body and to anyone under contracts for public works. As used in this Act, unless the context indicates otherwise: `Public works' means all fixed works constructed for public use by any public body, other than work done directly by any public utility company, whether or not done under public supervision or direction, or paid for wholly or in part out of public funds. * * * The terms `general prevailing rate of hourly wages,' `general prevailing rate of wages' or `prevailing rate of wages' when used in this Act mean the hourly cash wages plus fringe benefits for health and welfare, insurance, vacations and pensions paid generally, in the locality in which the work is being performed, to employees engaged in work of a similar character on public works." Ill. Rev. Stat. 1981, ch. 48, par. 39s-2. "Sec. 3. Not less than the general prevailing rate of hourly wages for work of a similar character on public works in the locality in which the work is performed, and not less than the general prevailing rate of hourly wages for legal holiday and *83 overtime work, shall be paid to all laborers, workers and mechanics employed by or on behalf of any public body engaged in the construction of public works, exclusive or maintenance work. * * *" Ill. Rev. Stat. 1981, ch. 48, par. 39s-3. "Sec. 4. The public body awarding any contract for public work or otherwise undertaking any public works, shall ascertain the general prevailing rate of hourly wages in the locality in which the work is to be performed, for each craft or type of worker or mechanic needed to execute the contract * * *." (Ill. Rev. Stat. 1981, ch. 48, par. 39-4.) The county and the intervenors contend that the act as construed by the circuit court unconstitutionally deprives the taxpayers of Ogle County of property by forcing them to pay, they claim, substantially higher wages to workers on public projects than is paid on private projects, without a rational relation to the purpose of the act. They also contend that the statutory construction substantially interferes with the right of contractors to contract with their employees and materially increases the costs of construction. • 1 This court has previously decided that the phrase "on public works," which was added to section 2 of the act in 1961, has the effect of limiting the inquiry in ascertaining the prevailing wage rate to only those wages paid on public projects. (Anderson v. County of Jo Daviess (1980), 81 Ill. App.3d 354, 358.) The appellants appear to be arguing that we should reassess our holding in Anderson, apparently for the reason that, they argue, Anderson does not deal with the declaration of policy found in section 1 of the act which was not changed following the amendment to section 2 in 1961. They argue that the purpose of the act since its enactment, as stated in section 1, has been to effectuate a policy that workers on public contracts receive not less than wages paid for similar work throughout the locality, not merely wages paid on public works. Thus, the statute as we have construed it can never achieve the legislative purpose of equalizing public and private wages and therefore does not bear a rational relation to the legislative purpose. We find these arguments unpersuasive for several reasons. First, the policy declaration is essentially neutral. Section 1 does not state that it is State policy to equalize public works and private construction wages. Rather, it declares the policy to be "that a wage of no less than the general prevailing hourly rate * * * in the locality * * * shall be paid" to all laborers on public works projects. (Emphasis added.) The underlined phrase is defined in section 2 as wages and benefits paid generally in the relevant locality to "employees engaged *84 in work of a similar character on public works." There is thus inherent harmony rather than conflict between sections 1 and 2. We recognized in Anderson that the legislature intended the act as amended to provide for the equalization of wages paid for similar jobs within only the public works sector. Anderson v. County of Jo Daviess (1980), 81 Ill. App.3d 354, 358. • 2, 3 Further, "a declaration of policy, like a preamble, `is no part of the Act.'" (Brown v. Kirk (1976), 64 Ill.2d 144, 152.) The provision of the act as amended unambiguously indicates that only public works wages are to be equalized. It is an improper mode of construction of statutes to create ambiguity by reference to a policy section of the statute. (Brown v. Kirk (1976), 64 Ill.2d 144, 152-53.) The real issue is whether the statute serves any legitimate State objective. A law does not violate due process as long as it bears a rational relation to a proper legislative purpose and is neither arbitrary nor discriminatory. (Kidd v. Industrial Com. (1981), 85 Ill.2d 534, 538; Thornton v. Mono Manufacturing Co. (1981), 99 Ill. App.3d 722, 725. See also Williamson v. Lee Optical (1955), 348 U.S. 483, 488, 99 L.Ed. 563, 572, 75 S.Ct. 461, 464.) The court applying the rational basis test is not charged with isolating the legislature's actual "purpose" in passing a statute and then determining whether the statutory means are rationally related to the actual goal of the legislature. Rather, it is settled that there is a "rational basis" if the legislature could have concluded that the law is reasonably related to any legitimate State objective. The court is not restricted to examining the rational connection between the statute and the goal that the legislature had in mind when it passed the law; if there is a plausible reason for the legislative action it is "`constitutionally irrelevant whether this reasoning in fact underlay the legislative decision.'" (United States R.R. Retirement Board v. Fritz (1980), 449 U.S. 166, 179, 66 L.Ed.2d 368, 378, 101 S.Ct. 453, 461.) Thus the test is whether there exists a rational relation between the statute and "a" proper legislative purpose. (Kidd v. Industrial Com. (1981), 85 Ill.2d 534, 538; United States R.R. Retirement Board v. Fritz (1980), 449 U.S. 166, 175-78, 66 L.Ed.2d 368, 376-78, 101 S.Ct. 453, 459-61; Thornton v. Mono Manufacturing Co. (1981), 99 Ill. App.3d 722, 725.) This is consistent with the view that a law does not violate substantive due process if it is not arbitrary or discriminatory. United States R.R. Retirement Board v. Fritz (1980), 449 U.S. 166, 173 n. 8, 66 L.Ed.2d 368, 375 n. 8, 101 S.Ct. 453, 458 n. 8. • 4 The same reasoning applies if the statute is subjected to a constitutional equal protection analysis. The argument that the act violates *85 equal protection is essentially based on the assertion that it may require contractors to pay higher wages on public works projects than they might pay on private works projects. This difference is no ground for invalidating the statute and is adequately supported by the State's interests in controlling the conditions under which public works projects are performed, so as to "give some assurance that the work will be completed without * * * delay by workmen of average skill." (Bradley v. Casey (1953), 415 Ill. 576, 586; Atkin v. State of Kansas (1903), 191 U.S. 207, 48 L.Ed. 148, 24 S.Ct. 124.) The act, which in essence sets a minimum wage for public works projects, is not arbitrary and thus violates neither due process nor equal protection. • 5 We also find no merit in the other constitutional arguments raised by the county and intervenors. The act does not violate the privileges and immunities clause of the fourteenth amendment; the economic interests involved here are not within the rights of national citizenship protected by that clause. (Murphy v. Mt. Carmel High School (7th Cir.1976), 543 F.2d 1189, 1192-93; Slaughter-House Cases (1873), 83 U.S. 36, 74-75, 21 L.Ed. 394, 408.) Finally, the argument that the statute unconstitutionally delegates the power to fix wages on public works projects to private parties was rejected by this court in Anderson v. County of Jo Daviess (1980), 81 Ill. App.3d 354, and we see no reason to disturb our holding there. • 6 A further question has been raised as to whether the county is required to take into consideration the number of hours worked at each rate before determining the prevailing general hourly rate. The act does not require the county to use any specific formula in calculating the generally prevailing wage. Rather, the county must simply ascertain the "generally current" or "most frequent" wage for each particular craft in public construction projects in the area. (Bradley v. Casey (1953), 415 Ill. 576, 583.) The county's determination will not be upset unless it is not supported by evidence. (See Fox River Valley Carpenters v. Board of Education (1978), 57 Ill. App.3d 345, 347-48; Union School District v. Commissioner of Labor (1961), 103 N.H. 512, 517, 176 A.2d 332, 336.) In Anderson, this court approved use of questionnaires and the division of total pay by total hours worked within the trade. The focus, however, should be on what is "most frequent" or "generally current." (Bradley v. Casey (1953), 415 Ill. 576, 583.) We find no error in the method used by the county to ascertain the generally prevailing wage. The judgment of the circuit court of Ogle County is affirmed. *86 Affirmed. REINHARD, J., concurs. JUSTICE HOPF, dissenting: I respectfully dissent. I agree with the majority that a statute does not violate due process as long as it bears a rational relationship to a proper legislative purpose and is neither arbitrary nor discriminatory. However, I do not believe a legitimate purpose exists to the Prevailing Wage Act as amended; nor do I believe that the limiting phrase "on public works" bears a reasonable relationship to the actual and original policy behind the act. The original Illinois Prevailing Wage Act was one of many prevailing wage acts throughout the country which was enacted during the Depression to combat the economic and social conditions of the times. (See Leader & Janero, Implied Private Right of Action Under the Davis-Bacon Act: Closing Some Loopholes in Administrative Enforcement, 29 DePaul L. Rev. 793 (1980) (hereinafter Leader); see also Annot., 18 A.L.R.3d 944 (1968).) During that period, widespread unemployment increased the competition among contractors for government employment at a time when the government was required to award its contracts to the lowest bidder. (See Leader, at 795; Ill. Rev. Stat. 1929, ch. 24, par. 129.) In order to capture this limited market, some contractors were employing migrant workers and paying them wages far below the rate paid locally. Local workmen and contractors were unable to compete with this migrant labor force. (Leader, at 795-96; see also Annot., 18 A.L.R.3d 944 (1968).) The prevailing wage acts were attempts by the various State and Federal legislatures to resurrect the depressed labor market by prohibiting wage differentials from becoming a major competitive advantage in bidding on government construction projects. (Leader, at 795-96; Annot., 18 A.L.R.3d 944 (1968).) Thus, the acts required taxpayers to pay increased wages to public works employees so that public wages would equal those paid generally in the community. In Bradley v. Casey (1953), 415 Ill. 576, 585-86, 114 N.E.2d 681, the court found that under the Illinois act the increased burden on the taxpayer and contractor was reasonable "when balanced against the advantage to the state of having the work performed under conditions which give some assurance that the work will be completed without interruptions or delay by workmen of average skill." The legislature's redefinition in 1961 of "prevailing wages" so as to limit it to wages paid only to public works employees had the corresponding *87 effect of incorporating by reference the new definition into the policy provision of the Act. (Ill. Rev. Stat. 1961, ch. 48, pars. 39s-1, 39s-2.) Thus, when the statute is construed as a whole (see Jahn v. City of Woodstock (1981), 99 Ill. App.3d 206, 425 N.E.2d 490), the current policy of the Act as amended provides for the equalization of wages paid for similar jobs within only the public works sector itself. The result is a separate rate of pay for public workers which is unresponsive to the market generally and is allegedly 20% to 30% higher than the wages paid in the private sector. The reasoning to give some assurance that the work would be completed without delay by workmen of average skill may have been an appropriate justification when the Act was interpreted to bring public workers up to standards in the private industry. However, where the legislation as amended and applied provides for wages roughly 30% over private industry in the same locality, can we say that this result is necessary to assure that the work will be completed diligently by workers of average skill? In other words, there is a rationale in paying like wages in a given locality, but does the same reasoning apply so that public employees be paid over and above workers in a given locality? I think not. I am cognizant of the principle of statutory interpretation that a law does not violate due process as long a it bears a rational relation to a proper legislative purpose and is neither arbitrary nor discriminatory. (Kidd v. Industrial Com. (1981), 85 Ill.2d 534, 538, 426 N.E.2d 822; Thornton v. Mono Manufacturing Co. (1981), 99 Ill. App.3d 722, 425 N.E.2d 522.) However, I find no legitimate legislative purpose in creating a self-perpetuating financial arrangement. I am mindful of the caveat that the courts should not substitute their judgment for that of the legislature. (Kidd v. Industrial Com. (1981), 85 Ill.2d 534, 538, 426 N.E.2d 822; Illinois Gamefowl Breeders Association v. Block (1979), 75 Ill.2d 443, 454, 389 N.E.2d 529.) However, just because the legislature has legislated does not mean that analysis must end. Otherwise no statute could ever be found to be arbitrary. (See United States R.R. Retirement Board v. Fritz (1980), 449 U.S. 166, 187, 66 L.Ed.2d 368, 383, 101 S.Ct. 453, 465 (Brennan, J., dissenting).) I have difficulty determining what the purpose of the amendment to section 2 is, other than to lock in one class of worker to a higher wage scheme to the detriment of the taxpayer and those working in the private sector. Would it not be possible that a worker on a public project could receive many times what his counterpart in the private sector is receiving? If we say that the original intent of the act was to guarantee to the public the services of workers of average capability, this new amendment should guarantee the *88 cream of the crop. I therefore conclude that the original purpose of the act remains intact and that the limiting phrase "on public works" bears an unreasonable relationship to that purpose. (Ill. Rev. Stat. 1981, ch. 48, pars. 39s-1, 39s-2; cf. Anderson v. County of Jo Daviess (1980), 81 Ill. App.3d 354, 401 N.E.2d 265, where we found no unconstitutional delegation of authority in the phrase "on public works.") The purpose of equalizing wages in the public and private sectors of the economy can never be achieved if in ascertaining the general prevailing wage public bodies may only inquire into wages paid on public works projects. I would therefore hold that section 2 of the Prevailing Wage Act, insofar as it purports to limit such an inquiry to only public works wages and results in payment of wages up to 30% higher than those in the private sector, is unconstitutional as both a denial of due process and equal protection.

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However, coverage for this population is only one step; delivering care to individuals once they leave the prison system is a larger challenge, and a new report from The Commonwealth Fund shows that states are undertaking innovative approaches to making sure that individuals are not just insured, but also connected with comprehensive care upon release. Prior to the Affordable Care Act, many adults leaving jail or prison were ineligible for Medicaid because coverage was not available to most adults without children. However, by mid 2018, 33 states and the District of Columbia had expanded Medicaid eligibility to include all adults with incomes below 138% of the federal poverty level, which has made Medicaid available to more individuals upon their release. Formerly incarcerated individuals have a pressing need for healthcare; The Commonwealth Fund estimates that 80% of this population has a long-term health need, such as a substance use disorder, a chronic medical condition, or a psychiatric condition. Those who have been incarcerated also have rates of active tuberculosis, hepatitis C, and HIV that are many times that of the general population. However, upon release, many people’s most pressing concerns relate to finding housing and social supports, and seeking healthcare coverage may take a backseat to addressing these urgent needs. One way to make sure that individuals have access to care as soon as they are released is to suspend—rather than terminate—Medicaid coverage when a person enters prison or jail. Federal law carries an exclusion that bans incarcerated people from receiving Medicaid, but states are finding that 80% to 90% of people are eligible for Medicaid upon release, so pausing coverage allows for coverage to resume immediately when a person is released. In cases in which individuals are not already covered by Medicaid, they can be enrolled at any time prior to release, including at intake or as part of the release-planning process. Once individuals are enrolled in Medicaid, data exchange systems may be part of the equation of delivering post-release care; in New York City, the correctional health service notifies health homes when individuals are released so that they can conduct outreach—such as home visits—to begin care planning. In other states, such as Florida, through “in-reach” program, clinicians may be sent into a jail or prison to meet with an individual to plan for postrelease care. Medicaid plans and health homes can also play a role in addressing formerly incarcerated people’s need for housing; New York’s Brooklyn Health Home, for example, uses community-based care mangers who work with clients to find housing and address other pressing social and economic issues that can impact health outcomes. Another important feature of addressing social determinants of health can involve support specialists; the Transitions Clinic Network, for one, which operates in multiple states, employs community health workers with a history of incarceration to identify patients who would be well served by the clinic. These workers identify patients through outreach to emergency departments (ED), faith-based organizations, homeless encampments, and other locations, and also help individuals adhere to the conditions of their release. In a 2-year study, the clinic’s clients had 50% fewer ED visits during their first program year compared with individuals who were part of a control group. “Medicaid expansion has provided states with a powerful tool to address the health care needs of justice-involved individuals,” write the report’s authors, but added, “The challenge going forward is to solidify coverage upon discharge, maintain it, and connect people leaving the prison system with the comprehensive health care, social supports, and care management they need.” The authors say that promising programs, like the use of in-reach and support specialists, could potentially become requirements for Medicaid managed care plans or provided as part of health homes.

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Loving this color! How do they make it look so perfect?! I tried gel nails for the first time the other week and boy does that stuff stand up to the life of a mama! A friend of mine had her own machine that her mom bought her- it worked great and costs less than $30 on Amazon. I am super tempted to invest. Isn't this just beautiful?! It looks like a lot of time but I bet it would be worth it- but I tend to like these 'tedious' baking adventures. THIS Moment If you follow me on Instagram you've seen this. This was a moment from my first day back at home with Gabriel after teaching for 6 days. He was in GREAT hands but boy did I miss being the one taking care of him. I've heard of the Love & Logic books and thought they sounded good, but we're not quite there yet (although probably will be much sooner than we think!). We'll be sure to check them out when the time comes. Hope you see some good results! Your group sounds great - looking forward to hearing more about it and what you learn from it! I'm trying to figure all of this out too. I've learned that the general term for this way of thinking is 'gentle positive discipline'. I've found that learning from multiple sources that differ slightly but are aiming toward the same goal is best because then I can decide what works best for us. So far, I love L&L, Janet Lansbury, this webinar: http://m.youtube.com/watch?v=sX0MQ5ZXVio&desktop_uri=%2Fwatch%3Fv%3DsX0MQ5ZXVio, and gentle positive discipline is what we learn at our co-op preschool also. I just always figured that children were doomed to be wild, naughty and misbehaved little people, and I dreaded the thought! I feel so much more joy in parenting now that I realize what a joy and privilege it is to disciple our children and watch them figure out the world. Still pretty confused at it all though. :) I'm a L&L fan! Wish I had been able to go to his conference. I'm sending this post on to a friend from Coram Deo who is just starting the book. Also wish we lived closer so we could do the book group with you!! I have heard of L&L, but since the twins are only 13 mo, we're not quite there yet. I have heard both positive and negative about it. The consensus seems to be that it's awesome, as long as you use it correctly. That when you give them choices about misbehaving, that the choices make sense and aren't belittling or talking down to the child. Does that make sense? I have also heard from several other moms that this is good for empathy building. I will definitely keep it in mind for when the kiddos get older! Gabriel is 14 months. :) His strategies start as young as birth and develop as the child gets older. For example rather than saying 'no thank you' (which I don't know about you but that started at the same time we needed to do a little baby proofing) he suggests singing, 'uh-oh!' That then turns into a little song as they get older and understand more. Parenting is a hot topic so yes, there is never going to be one approach that everyone agrees on- nor will there be the perfect approach for everyone. You got to search out which will work best with your personality and your family! I thought you might be. :) It seems to be the thing with schools in this area. When did you first learn about it? Some day soon (ish)! You really aren't that far away but when thinking of baby and naps and the works that 40 minute drive seems to triple in length! Any days work for you next week?! I would love to "pop" down! You are awesome- thanks for all the info and resources! Every time you mention your co-op preschool I wish I lived in your area! We don't have (as far as I can find) anything like that here for under 2... I'm looking forward to giving it all a go! I LOVE singing uh-oh instead of politely saying, "no thank you." That is the main change we have had since the conference. It just seems so much more effective. If you've started saying "no thank you" then you are there. :) He has little tactics that start very young. We're already seeing the effect and Gabriel is one of those kids that always gets us asked, "is he always that calm? Is he always this mellow? Does he always play this nice?" To which we answer, yes- he has his moments but yes. :) A couple of years ago I starting hearing about L&L at the school, and then I bought this book here a few months ago. I have a few good friend who I really admire as parents who follow these philosophies and that has been inspiring as well!

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Cetiedil, a drug that inhibits acetylcholine release in Torpedo electric organ. The effects of cetiedil, a vasodilatator substance with reported anticholinergic properties, were examined on cholinergic presynaptic functions at the nerve electroplaque junction of Torpedo marmorata using either synaptosomes or slices of intact tissue. Cetiedil abolished the calcium-dependent release of acetylcholine (ACh) triggered by depolarization or by addition of A23187 ionophore, a finding localizing the site of action downstream from the calcium entry step. In addition, a direct effect on the release process itself was indicated by the observation that cetiedil blocks the release of ACh mediated by a recently isolated presynaptic membrane protein, the mediatophore, reconstituted into ACh-containing proteoliposomes. In all three preparations, ACh release was inhibited by cetiedil with a Ki of 5-8 microM. Under the conditions used in these release experiments, the synthesis of ACh and its compartmentation within the nerve terminals were not modified. However, the drug was able to reduce high-affinity choline uptake and vesicular ACh incorporation when it was given together with the radioactive precursor, a result showing that cetiedil has a broad inhibitory action on cholinergic uptake processes.

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This invention relates in general to hydraulic braking systems for vehicles and in particular to vehicular anti-lock braking systems not having a pump. Anti-lock braking systems for vehicles are well known. A typical system utilizes a hydraulic control unit (HCU) incorporating several solenoid valves for control of brake fluid pressure to the wheel brakes and/or brake channels. For example, in a system utilizing an isolation valve and a dump valve for each wheel, a total of eight solenoid valves are housed in the HCU. Such a system also includes a pump housed in the HCU for dumping fluid through the dump valves and an electric motor for operating the pump. It is desirable to reduce the cost of an anti-lock braking system by reducing the number of components required by the system, and in particular the number of components housed in the HCU. Furthermore, a reduction in the number of components housed in the HCU may result in a weight reduction of the HCU. Also, it is desirable to reduce noise emanating from the HCU during an anti-lock mode. A large source of noise is the pump and its electric motor. If the pump and motor are eliminated from an anti-lock braking system, a significant reduction in noise may be obtained.

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EnamoreRuby camisole Enamore has fashioned this camisole from pure organic cotton, making it less harmful to the environment and more suitable for sensitive skin types. With a large keyhole detail at the bust, it is embellished with a pointelle heart design and satin ribbons. Product code: ENA-RC08LR 100% Organic Cotton Returns Items returned in their original condition can be exchanged or refunded, provided that it's within 20 days of you receiving your order. We cannot accept anything that is not in it's original packaging, that has been worn or marked, that has been washed or has had any labels detached. Some items are excluded from our returns policy for hygiene reasons and are therefore described as non-returnable on the product page. These conditions do not affect your statutory rights.

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Q: Where to stop a service during device rotation When my activity starts, I start a service that fetches data then sends it back to the activity so it can update the UI. If a config change occurs: If I already have the fetched data, I save it in the onSaveInstanceState method. If I haven't received the fetched data, I want to cancel the running service and relaunch it using the new activity. So my onSaveInstanceState currently looks like this: @Override public void onSaveInstanceState (Bundle outState) { if (data != null) { outState.putSerializable(DATA_IN_BUNDLE, data); } // Stop any data fetching that may be going on. stopService(new Intent(this, FetchService.class)); } However, I've noticed that this method is called during the normal starting of the activity, which I didn't know happened, so when it's run the service is always cancelled. So my questions are: Is this documented somewhere? Couldn't find anywhere that said onSaveInstanceState is called during activity start. What would a better place to stop the service be? onConfigurationChanged? Thanks! A: You have a few choices: Don't allow Android to kill and restart your Activity. Manage the config changes yourself. Usually this is pretty simple to do and prevents you from having to deal with stopping and restarting background stuff. Pass the ServiceConnection (or whatever you are using as a communication channel to the Service) from the old Activity instance to the new Activity instance by using onRetainNonConfigurationInstance() and getLastNonConfigurationInstance() Use a service-bus architecture, so that one Activity can start something and another Activity can register for the callback. Send the response from the Service to the Activity using a broadcast Intent, which can be seen by the new Activity after a config change.

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Ultrasonographic evaluation of renal transplantation. Ultrasonography of the renal transplant is still a key screening examination for transplant dysfunction. The addition of Doppler technology has permitted screening for hemodynamic alterations. Ambitious researchers predicted that these hemodynamic profiles would permit the differentiation of rejection from other complicating factors; however, recent research and clinical experience has shown this to be ineffective. Imaging identification of a dilated collecting system identifies the patient population that should undergo a Whitaker procedure. Identification of large or increasing fluid collections helps focus attention to possible hemorrhage or urine leak. Similarly, the ultrasonographic identification of a lymphocele as the cause of leg edema or hydronephrosis rapidly focuses surgical treatment. Doppler evaluation of hemodynamics must be performed on all renal transplant recipients. Although the role of the resistive index in predicting rejection has been minimized lately, numerous vascular complications, if untreated, would result in loss of the kidney. Doppler sonography identifies those patients who would benefit most from renal arteriography. The evaluation of renal morphology on the basis of ultrasonography alone has little role in predicting the cause of transplant dysfunction. We continue to evaluate renal size and to correlate it with the clinical presentation as well as resistive index to defer patients from biopsy if a more obvious cause of dysfunction is identified.

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Monday, November 7, 2016 My Every Day Winter Makeup Routine Good morning and happy Monday beauties! Can we talk about how cold this weekend was? Even though winter has not yet started, it certainly feels like we are right in the middle of it. With dropping temperatures and icy winds, it's hard to want to leave the house at all, especially in the morning when it's dark out and all you want is 5 more minutes in bed. I love winter, I really do but getting up in the morning…not so much. This is why, the night before I will lay out my clothes and sort out my hair, keeping my morning routine as simple as possible as all I have to do is my make-up. In the morning, when I'm still half-asleep I do not want to overthink or overdo my makeup, I want products with a long-lasting finish, great coverage and a natural look. Ever since fall started I switched round my products and here are my go to winter makeup goodies I can bet on every day. BASE A good primer is a must and whilst my first budget choice is Maybelline Baby Skin Pore Eraser, I've been using this Collection Primed & Ready Pore Minimiser (£4.99) and I really like it. Apart from being inexpensive, it keeps my foundation in place and my skin matte. It manages to cover up my pores rather well too and for a product this cheap, I was expecting much, making it a great bargain buy. For the main base product, I cannot go wrong with L'Oreal Paris Infallible Matte Foundation (£10.99) which I reviewed here. In short, this gives me great coverage and matches my skin tone perfectly. Whilst it doesn't keep my skin matte for 24 hours as it claims to do, lasting power is amazing at around 8-9 hours and even after a rough gym session, this stuff is still on thanks to its waterproof and steam proof properties. To cover my pesky dark circles I need something hardcore and my go-to has always been the UD Naked Skin Concealer but given that is not a cheap option for every day, the Collection Lasting Perfection Concealer (£4.19) is a great alternative. This is highly raved in the blogging world and rightfully so! It highlights the darker tones of my skin and conceals my dark circles extremely well, the consistency is just right and, the wand makes application super easy; a must have in your make-up bag! To seal all of this in, my trusty Vichy Dermablend Setting Powder* (£15) does the job exceptionally well. When applied over the foundation, it reinforces the hold of the base without looking too unnatural or cakey and being translucent, it doesn't change the colour of the foundation which is always a plus. This contains SPF30 so I honestly cannot think of a better option all year round (review here). CONTOUR & HIGHLIGHT One cannot simply leave the house without a good amount of bronzer, blusher and highlighter. My bronzer of choice has to be Benefit Hoola Bronzing Powder (£23.50) as it is matte and not at all orange looking. Despite me being very pale, this matches my skin tone perfectly and gives me an all-around sunkissed glow. For blusher, I've been obsessed with Sephora Colorful Face Powder shade 28 ($14) ever since I got it back in August. It is pigmented, but not too intense looking. I loved wearing it when I was tanned but it goes with my ghostly complexion rather well too. To give my face that blinding glow we all love, my firm choice is always Mac Soft & Gentle Mineralize Skinfinish Highlighter (£24). It is so intense looking; I leave the house feeling like a million bucks whenever I am wearing it. EYES I keep the eyes simple, so no eyeshade nor eyeliner involved to avoid any mistakes and poking my eye out so early in the morning. My brows aren't the same if I'm not wearing the Anastasia Beverly Hills Dip Brow Pomade (£15) since last year and honestly I do not see myself moving away from this product anytime soon, that's how good this stuff is! I use it in Medium Brown and it is my brows' best friend! Maybelline Brow Drama Sculpting Mascara (£4.99) is the perfect finishing touch as it holds my brows in place all day long and it is super easy to use. To define my eyes and give back their natural shape which was taken away with layers upon layers of foundation and concealer, I blend some of my bronzer into my crease et voilá! Finish it off with a generous amount of Maybelline Lash Sensational Luscious Mascara (£7.99) to really open up the eyes and look a lot more awake. I reviewed this mascara here if you fancy a read but in short, this is a great mascara for its price tag. I do like its original version better but lately, this has been my go-to which speaks for itself. LIPS I swear this isn't a Maybelline-sponsored post but it sure seems like one huh?! Maybelline Nude 725 Tantalizing Taupe Lipstick (£6.99) is one of my favourite nude shades ever, and I've mentioned this shade a few times here on the blog. I love everything about it; it is a gorgeous nude with pink tones that suits my skin tone extremely well and doesn't wash me out like other nudes do. Its lasting power isn't so great (roughly 3 hours) but its formula is moisturising (aka winter perfect) and extremely easy to apply. I love pretty much all of these products especially the L'Oreal Infallible Pro Matte, Collection concealer and Lash Sensational mascara. Great post, I really want to try the Collection primer and the Maybelline lipstick in Tantalising Taupe looks very me haha. Thanks for sharing xxx agreed! this weekend was so unbelievably cold, it felt like christmas morning everyday! I totally agree with Maybelline as an amazing drugstore, love their lash sensation mascara and oh my goodness that Maybelline Nude 725 Tantalizing Taupe Lipstick is beautiful! You can never have too many nudes in my opinion! I love wearing hoola this time of the year as it makes me look like I've just got a bit more colour and healthiness to my skin! xx I totally agree with you. dear Pam, I love winter, that is my favorite season - well, autumn, winter :) But getting up in the morning is oooooohhhh :) I loved your products, and I need to try this L'Oreal Infallible foundation, since you said it is so good. Also, I want to try the MAC highlighter, since my favorite highlighter broke some months ago and since then I am trying to find a good one to no avail. Hope you have a nice week!DenisesPlanet.com Ohh getting out of bed on winter mornings can be a kind of torture haha, and it's definitely my least favroite part of winter too, although it's a beautiful season.Your selection of makeup for these colder months is a really good one! I'm also a L'Oreal Infallible Pro-matte fan ;) Your Vichy setting powder sounds awesome and I've never tried it! Plus, the SPF30 is always a great thing. Oh, and I always love the lipsticks you wear whenever I see a selfie of yours on IG!!xx I really need to get the hoola bronzer! I love it and everytime at the benefit boutique I'm thinking of getting it :D I always love your beautiful makeup pam :) you always look so beautiful <3http://www.youtube.com/c/MissLovelyAttitudehttp://lovelyattitude.com For the first time I used this last year, when I did my makeover from Lina, she used only few drops and this was so awesome. I loved my outlook. The way my makeup came out and last for long time. She is very good , I so love her. She also trains best make up lesson by Lina Cameron in my town!

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Introduction {#s1} ============ Self-report questionnaires are a dominant assessment methodology in the social sciences. They are used to estimate important information about a participant\'s personality, attitudes, values, and beliefs. However, self-report questionnaires are prone to various biases that challenge the utility of this methodology including the validity of the data. These biases include cultural artifacts (e.g., measurement artifacts and differences in response sets due to differences in communication styles between cultures; Van de Vijver and Leung, [@B90]; Fischer, [@B24]), active deception (e.g., Ziegler et al., [@B98]), and personal biases in response styles such as extreme responding, midpoint responding, and acquiescent (i.e., a tendency to agree with items and hence only using the upper half of the response option scale) and disacquiescent responding (i.e., a tendency to generally disagree with items and hence only use the bottom half of the response option scale; Van Vaerenbergh and Thomas, [@B92]). Cross-cultural biases occur because participants compare themselves to the standards and values of their cultural group, also known as their reference group (Peng et al., [@B70]; Heine et al., [@B33]). The difference in item responses between the two groups is called *Differential Item Functioning* (DIF; Holland and Wainer, [@B36]; Osterlind and Everson, [@B68]). There are several reasons why an item, used in a cross-cultural context, can show DIF (Ellis et al., [@B22]). An item can display DIF because of (1) mistakes in the item\'s translation, (2) because participants ascribe unique meanings to the item because of their culture, or (3) participants have different cultural knowledge (Johnson et al., [@B43]). The anchoring vignette technique is a method that can detect DIF and adjust for some of these cross-cultural biases that lead to item DIF (King et al., [@B49]; King and Wand, [@B48]; Hopkins and King, [@B37]). Understanding the impact of DIF is important for the development of new assessment tools and especially for their application. The anchoring vignettes provided in this study are a useful and easily applicable technique that can be applied to existing personality measures in cross-cultural research, which will help combat DIF. To sufficiently support our hypotheses, the introduction is organized as follows. First, we provide an overview of traditional techniques for detecting DIF, followed by a summary of Anchoring Vignettes (*AV*s) and why they are superior over traditional methods. Second, we summarize how *AV*s have been applied both generally and specifically in personality research, specifically in regards to the Big Five Personality factor model. Finally, we demonstrate the utility of *AV*s for combating DIF in the assessment of the Big Five Personality factors, based on data from two countries: Rwanda and the Philippines. The following passage describes several traditional techniques that are applied to detect DIF. Huang et al. ([@B40]) used the five-factor personality model in two cultural contexts, the Philippines and America, and compared two DIF-statistics to examine measurement equivalence at the item level: (1) Item Response Theory (IRT) and (2) Mantel-Haenszel method (e.g., Ellis et al., [@B22]; Huang et al., [@B40]). DIF can be detected by classic IRT statistics, such as item discrimination and item difficulty (e.g., Camilli and Shepard, [@B13]), or by the area between two cultures\' item characteristic curves (Thissen et al., [@B86]). IRT item parameters are often assumed to be invariant over groups of participants. However, this is often not true (Rupp and Zumbo, [@B79]). Instead, parameter invariance can be assessed to identify items that lack measurement equivalence, which means the item assesses the central construct differently for each group. However, it is argued that demonstrating factor congruence across cultures does not guarantee measurement equivalence (Bijnen et al., [@B8]; Huang et al., [@B40]). The Mantel-Haenszel, a chi-square statistic comparing the actual and expected frequencies, can be used to detect DIF (Holland and Thayer, [@B35]). This method has a lot of advantages including its simplicity and easy implementation. However, it does not detect *non-uniform-*DIF, which is an interaction between trait level and group membership so that mean differences in trait level between cultures would not be detected (Rogers and Swaminathan, [@B76]). Most historical DIF-statistics focused on binary scored items. Ordinal scaled items, such as Likert-scale items, require a different treatment, such as a logistic regression. Zumbo ([@B100]) estimated a logistic regression to test DIF for ordinal scored items using the responses as a dependent variable with a grouping variable, total scale score, and an interaction of the group and the total scale score as independent variables (e.g., Crane et al., [@B18]). DIF can be also detected using multiple-group confirmatory factor analysis through establishing measurement invariance (Thissen et al., [@B86]; Stark et al., [@B82]; Teresi, [@B85]). Configural invariance, the first step in testing measurement invariance, models the same factor structure across groups (Vandenberg and Lance, [@B93]; Stark et al., [@B82]). In the case where a sample does not demonstrate configural invariance across countries, it can be assumed that single items, or even the whole test, is affected by DIF (Teresi, [@B85]). Likewise, DIF can be detected by comparing item factor loadings (e.g., Eysenck et al., [@B23]). The use of *AVs* (Thissen et al., [@B87]) is perhaps the most promising approach that can be applied to detect DIF and the method offers the possibility to correct for it. The idea is to relate self-report answers with external benchmarks that measure the same concept but are more likely to be free of biases and therefore free of some DIF forms. Anchors specifically have been proposed as a useful tool to adjust the answers of different individuals to one underlying standard scale (King et al., [@B49]). Anchors normally include descriptions (within vignettes) of one hypothetical person who, based on the theoretical description of the trait of interest, is described in a way to illustrate a certain trait level (Chevalier and Fielding, [@B16]). Each participant then evaluates the behavior of this person on the same scale they used to answer the self-report questions. Because the anchors provide an external benchmark, *AV*s have a number of advantages over traditional DIF-detection procedures (Mõttus et al., [@B59]). Primarily, while traditional DIF-statistics (described above) essentially plot single item scores against latent trait scores, with both types of scores derived from the same data, with *AV*s, there is independence between the scores (Mõttus et al., [@B59]). The following passage provides a short and general overview over the application of *AV*s in different research areas. *AV*s are not widely employed, though there are a few isolated instances of their use. They have been used in work related research (e.g., Kristensen and Johansson, [@B51]), in research on life satisfaction (e.g., Kapteyn et al., [@B47]) and quality of life (e.g., Crane et al., [@B17]), in personality research (e.g, Mõttus et al., [@B59]), and in an educational context (e.g., student-reported teachers\' classroom management; OECD, [@B64]; Vonkova et al., [@B94]). These applications mostly indicate that the use of *AV*s was beneficial and resulted in a more valid measure that offered cleaner comparisons between groups. Research on life satisfaction (Angelini et al., [@B4]), for example, found that Danes and Italians report different levels of life satisfaction. But after adjusting self-report answers with *AV*s, these differences disappeared. Likewise, *AV*s helped improve measurement invariance in the Programme for International Student Assessment *(PISA)* (He and Van de Vijver, [@B31]), and *AV*s were effectively used to identify and correct for DIF in a self-report physical health scale (Knott et al., [@B50]). Personality research, which is conducted in several countries, can especially benefit from the application of *AV*s. A long history of psychological research has shown that the Big Five Factor model of Personality represents the set of constructs that are most strongly differentiated, non-overlapping, and predictive across domains (Roberts et al., [@B75]). Although they were first discovered in the English language, replication studies in other languages yielded the same five factors (see e.g., McCrae and Terracciano, [@B56]; Schmitt et al., [@B80]). But already Allport and Odbert ([@B2]) noticed that culture and time period can influence responses. There are especially large differences in answering personality items when comparing Western and non-Western cultures (e.g., Mpofu and Nyanungo, [@B61]; Byrne and Campbell, [@B12]). DIF in personality items is known to appear because of inadequate translation, research, or development, sampling biases, and different response styles (e.g., Grimm and Church, [@B26]; Van de Vijver and Leung, [@B91]; Schmitt et al., [@B80]). *AV*s have been shown to increase the reliability of scales assessing Conscientiousness and Openness in a representative study of 12th grade students in Brazil (*N* = 8,582) (Primi et al., [@B71]). The study applied a set of three vignettes for Conscientiousness and Openness. Interestingly, they showed that the Openness vignettes were more frequently misordered relative to the Conscientiousness vignettes. In a study using *AVs* to compare facet-level measures of Conscientiousness across 21 countries, it was determined that, contrary to expectations, self-reported Conscientiousness was minimally affected by cultural differences (Mõttus et al., [@B59]). Hence, the researchers concluded that it is not necessary to address comparability problems using *AVs* in personality. However, the sample size for each country was relatively small and some of the vignettes were abstract and most likely had differences in meaning due to the numerous translations. Hence, it is possible that the participants applied different standards in answering the *AVs* and the self-report personality questionnaires and hence violated the assumption of Response Consistency (discussed in detail below). Likewise, Primi et al. ([@B71]) as well as Mõttus et al. ([@B59]) do not report whether or not they tested any measurement assumptions (i.e., Response Consistency and Vignette Equivalence, which are described in detail below), which must be fulfilled in order to use *AV*s. He et al. ([@B32]) compared different methods and procedures to improve the comparability between cultures including a vignette set with two levels of conscientiousness (*N* = 3,560 university students in 16 countries). They reported that the vignette sets showed a lack of invariance (arguably due to the characteristics of the vignettes) and hence were not free of DIF. However, they also found that the vignette technique was the only method which resulted in higher internal consistencies. Likewise, the use of *AV*s for the assessment of self-reported teamwork led to increased test information and item discrimination, and higher factor loadings and better model fit in a confirmatory factor analysis (Ham and Roberts, [@B30]). In our study, we evaluated the use of *AVs* in the assessment of personality in two countries: Rwanda and the Philippines. We selected these countries for several reasons. First, Rwanda is one the few African countries where the Big Five have not been replicated (Roberts et al., [@B75]). Thus, the comparison of responses from a country where DIF in the Big Five has already been shown, specifically the Philippines, with another country where the Big Five factor structure have not been replicated, and has a different cultural and historical experience, is informative. Identifying a different structure to the Big Five Factor model for Rwanda would challenge the previously proclaimed generalizability of the Big Five Factor model. Reviewing cross cultural personality research where *AV*-adjustment was not applied suggests a mean trait-level difference between the Philippines and Rwanda. Researchers who administered the BFI in 56 nations using 28 languages found significant differences in Openness to Experience in the geographical regions of South East Asia compared to other world regions (Schmitt et al., [@B80]). Likewise, a comparison of the United States and the Philippines on the Big Five found significant mean differences between the groups. However, in that study, almost 40% of the items administered in the Philippines showed DIF, despite surveying both groups in English (Huang et al., [@B40]). There is also evidence suggesting a cultural difference in the approach toward a self-report questionnaire and the use of the response options. For example, Rwandans tend to place an extremely high value on authorities and people in a high status position, which can affect responding on self-report questionnaires (Staub et al., [@B83]). Likewise, citizens of several African countries (i.e., Benin, South Africa, Senegal, and Burkina Faso) and Southeast Asia (e.g., the Philippines) showed the highest rates of extreme responding to self-reported personality (Mõttus et al., [@B59]). In contrast, Germany shows the lowest rates of extreme responding, and most European nations and the United States are characterized by medium extreme responses. Thus, this suggests that individuals from the Philippines and African countries are characterized by a difference in understanding and interpretation of self-report questionnaire items, namely those assessing personality, which could explain the aforementioned mean trait-level differences. As such, it is important to test the extent to which there is DIF between the Philippines and Rwanda and whether this can be addressed through the use of *AV*s. As our study is the first to apply vignette sets (with three levels) on the BFI-44, comparison to previously published results with other countries is not possible. The Big Five are linked to several important aspects of our life. Life satisfaction, a component of subjective well-being, is correlated to the Big Five, but the correlations are somewhat inconsistent between countries. In a representative Dutch sample, life satisfaction had small to medium positive correlations with all Big Five factors (Müller, [@B62]). However, in an Iranian sample, researchers found small negative correlations of life satisfaction with Conscientiousness, Openness, and Extraversion (*r* = −0.24 to −0.28) and non-significant correlations with Neuroticism and Agreeableness (Hosseinkhanzadeh and Taher, [@B39]). In a Nigerian sample, correlations of life satisfaction with Neuroticism were negative but positive with the other Big Five factors (Onyishi et al., [@B66]). The Big Five are also linked to work behavior. In a USA sample, all Big Five dimensions had small to medium negative correlations with counterproductive work behavior (Mount et al., [@B60]). The extent to which this relation differs between cultures is unclear. Overall, we hypothesize that using the *AV* technique will improve the psychometric characteristics and the cross-cultural comparability of self-reported personality. Here are our specific hypotheses: *Hypothesis 1*: Using *AVs* to adjust self-report responses will improve the BFI-44 reliability, measured with omega ω (an indicator of factor saturation; McDonald, [@B58]), for each of the Big Five Personality factors, with estimates ranging from good to excellent. This hypothesis will be tested by comparing the overlap of the 95% confidence intervals of the omegas.*Hypothesis 2: AV*-adjusted scores fitted in a graded response model will show an increase in discriminant power, relative to the original scores, resulting in a wider range of thresholds and larger discrimination parameters. Furthermore, the increase in overall test information for the *AV*-adjusted scores will be indicated by a broader range of θ-levels and small standard errors.*Hypothesis 3:* In a confirmatory factor analysis, models of the Big Five based on *AV*-adjusted scores will show acceptable fit to the data (CFI ≥ 0.90 and RMSEA ≤ 0.08) and a correlational structure such that Neuroticism is weakly negatively correlated with all of the other dimensions, and the other dimensions are weakly positively correlated with each other, supporting the theoretical structure of the Big Five model. We expect this result to hold for both samples.*Hypothesis 4:* Test-criterion relationships of life satisfaction and counterproductive work behavior with the *AV*-adjusted Big Five factor scores will be significantly stronger for the *AV*-adjusted scores. Methods {#s2} ======= Procedure and sample -------------------- The studies were conducted in Rwanda (Sample 1) and in the Philippines (Sample 2). Participants were recruited through the educational institute Akilah Institute for Woman of Akazi College in Africa, which is partially supported by the Educational Development Center (*EDC*) in Washington D.C. This study was carried out in accordance with the recommendations of the institutional review board *(IRB*; *IRB* Registration: IRB00000865) of the *EDC* Human Protections department. In addition, all participants provided written informed consent in accordance with the Declaration of Helsinki. In the Philippines, the parents of the participants were also informed of the study and the possible involvement of their child with a letter. The newly-developed *AV*s were tested in psychology labs before the study was conducted. All items and translations were reviewed several times by all institutes involved. The studies were conducted by local interviewers who were employed and trained for data collection by the *EDC*. Each participant completed the questions in the same order, which were presented on a tablet provided by the *EDC*. Due to technical problems and power supply issues in both countries, some participants completed paper-pencil versions of the test material. The paper-pencil versions were entered into an electronic database by the local staff. Participation in these studies was voluntary and participants could withdraw from the study at any moment. The samples are summarized in Table [1](#T1){ref-type="table"}. The samples are based on adolescents and young adults who were either finishing school and/or applying for jobs. Several articles support this application of the Big Five in young adult and adolescent samples (see for example, Bratko and Marušić, [@B10]; Digman, [@B20]; Ehrler et al., [@B21]; Rothbart et al., [@B78]). This sampling procedure resulted in a relatively homogeneous sample regarding age and education, which were biases what we wanted to avoid. The participants completed the study during their college course time; therefore, they did not receive any financial compensation. ###### Descriptions of the Rwanda and Philippines samples. ***N*** **Age** **Sex** ---------------------- --------- ------------------------ ------------------------- Sample 1: Rwanda 423 *M* = 21.79 *SD* = 2.7 Female: *N* = 356 (84%) Range: 15--33 Male: *N* = 67 (16%) Sample 2:Philippines 143 *M* = 15.5 *SD* = 0.83 Female: *N* = 99 (69%) Range: 14--19 Male: *N* = 44 (31%) *The Rwanda sample includes two different schools in different regions of Rwanda. The Philippines sample includes one school*. Measures -------- All measures were translated from English into either Kinyarwanda or Filipino. The translation was supervised by the *EDC* using backward and forward translation checks. The participants completed demographic questions first where they were asked to provide information about themselves, their family, and their home situation. These questions were also tailored for each country; for example, Filipinos were asked if they have a computer at home and Rwandans were asked if they have access to running water. Therefore, the demographics differed between both samples. As the studies were part of a larger project, additional measures were also included including 10 Situational Judgment Tests for Conscientiousness and the Conscientiousness Facet-Tool (MacCann et al., [@B54]). Because of the focus of the article, these measures are not discussed further. ### Anchoring vignettes The *AVs* included 15 hypothetical descriptions; three hypothetical descriptions for each personality dimension of males or females who embodied a certain level of the corresponding personality dimension. The *AVs* were developed by scientists from the Professional Examination Service in New York. Table [2](#T2){ref-type="table"} shows *AVs* for the Big Five, which show different levels of Conscientiousness, Agreeableness, Neuroticism, Openness, and Extraversion. In the first *AV* for conscientiousness, Sophia represents someone with a low level of Conscientiousness. In the second, Jacob shows a medium level of Conscientiousness, and in the third, Emma displays a high level of Conscientiousness. Participants were asked to rate the extent to which they agreed with the statement that Sophia, Jacob, and Emma are Conscientious. In this case, the suggested ratings for following the correct order would be "disagree strongly" or "disagree a little" for Sophia\'s statement, "neither agree nor disagree" for Jacob\'s statement, and "agree a little" or "agree strongly" for Emma\'s statement. Therefore, the person in Vignette 1 is rated as having lower Conscientiousness relative to the person in Vignette 2. Also, the person in Vignette 3 is rated as having the highest conscientiousness and is therefore higher than on conscientiousness the persons in described in Vignette 2 and 1. ###### *AV*s for Conscientiousness (C), Agreeableness (A), Neuroticism (N), Openness (O), and Extraversion (E). **How much do you agree with this statement?** **Disagree strongly** **Disagree a little** **Neither agree nor disagree** **Agree a little** **Agree strongly** ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------- ----------------------- -------------------------------- -------------------- -------------------- C1. Sophia tends to be somewhat careless. Other workers also comment that she is lazy. Sophia often also appears disorganized. Based on this information, to what extent do you agree with the statement "Sophia is conscientious/hard-working"? O O O O O C2. Jacob is a reliable worker and does all work with great efficiency, but he is easily distracted. Based on this information, to what extent do you agree with the statement "Jacob is conscientious/hard-working"? O O O O O C3. Emma always does a thorough job. She perseveres until all tasks are finished. Emma also makes plans and follows through with them. Based on this information, to what extent do you agree with the statement "Emma is conscientious/hard-working"? O O O O O A1. Jean tends to disagree with others, and as a result often starts quarrels. Indeed, many people consider Jean quite rude. Based on this information, to what extent do you agree with the statement "Jean is an agreeable person"? O O O O O A2. Even though Nicole is helpful and unselfish with others, some people find her cold and unfriendly. This does not matter so much, as she has a forgiving nature. Based on this information, to what extent do you agree with the statement "Nicole is an agreeable person"? O O O O O A3. Claude is considerate and kind to almost everyone. He is very trusting, and finds it easy to cooperate with others. Based on this information, to what extent do you agree with the statement "Claude is an agreeable person"? O O O O O N1. Carine frequently appears quite depressed to other people. She gets nervous easily. Based on this information, to what extent do you agree with the statement "Carine is emotionally stable"? O O O O O N2. Although in tense situations Paul remains calm, he can be quite moody. And he tends to worry quite a lot. Based on this information, to what extent do you agree with the statement "Paul is emotionally stable"? O O O O O N3. Aline always appears relaxed and to handle stress well. Indeed, she never comes across as upset. Aline remains calm in all situations. Based on this information, to what extent do you agree with the statement "Aline is emotionally stable"? O O O O O O1. Emmanuel has few artistic interests, and is not especially sophisticated either in music or literature. This has led some people to observe that Emmanuel does not appear especially curious about anything. Based on this information, to what extent do you agree with the statement "Emmanuel is open-minded"? O O O O O O2. Emma has an active imagination. This has led some people to calling her a deep thinker. Even so Emma prefers work that is routine. Based on this information, to what extent do you agree with the statement "Emma is open-minded"? O O O O O O3. Jean Bosco is original and always coming up with new ideas. This has led some people to calling him inventive. But beyond this, Jean Bosco values artistic, aesthetic experiences. Based on this information, to what extent do you agree with the statement "Jean Bosco is open-minded"? O O O O O E1. Claudine is very reserved. She tends to be quiet no matter what the circumstance. Indeed, people find her shy and inhibited. Based on this information, to what extent do you agree with the statement "Claudine is extraverted"? O O O O O E2. Emile is often talkative and generates a lot of enthusiasm in others. But on his day, Emile can be rather shy and inhibited. Based on this information, to what extent do you agree with the statement "Emile is extraverted"? O O O O O E3. Rosette has an assertive personality, and as a result appears outgoing and sociable. Indeed, people are always commenting on how full of energy Rosette is. Based on this information, to what extent do you agree with the statement "Rosette is extraverted"? O O O O O ### The big five inventory (BFI-44) The BFI-44 (John et al., [@B42]; Benet-Martínez and John, [@B5]) uses 44 items to measure the Big Five Personality factors: Extraversion (e.g., "*I am someone who is talkative")*, Agreeableness (e.g., "*I am someone who is helpful and unselfish with others")*, Conscientiousness (e.g., "*I am someone who does a thorough job")*, Neuroticism (e.g., "*I am someone who is depressed, blue")*, and Openness (e.g., "*I am someone who is original, comes up with new ideas")*. The items are answered on a five-point Likert-scale with the poles "disagree strongly" and "agree strongly". John and Srivastava ([@B41]) established the validity and factor structure of this measurement. The reliabilities before and after the *AV*-adjustment are presented in the results section. ### Satisfaction with life scale This scale measures global life satisfaction with five items (e.g., "*I am satisfied with my life"*). It is known for good internal reliability and validity (Diener et al., [@B19]). The reliability of the scale for the whole study was acceptable (ω = 0.76). ### Counterproductive behavior This construct was measured with an adaption of the Interpersonal and Organizational Deviance items (Bennett and Robinson, [@B6]) for a school and work context (e.g., "*How often have you publicly embarrassed someone at school or work"*). Respondents answered the items on a seven-point Likert-scale ranging from "never" to "daily." The original instrument shows an acceptable fit in a confirmatory factor analysis and a two-factor structure. Our shorter adapted form has acceptable reliability (ω = 0.79). Statistical analysis -------------------- ### Data cleaning To appropriately test the hypotheses and address cross-cultural comparability, we took several steps in terms of data cleaning and scoring prior to calculating the models. For data cleaning in both studies, we applied the following *a priori* standards to decrease noise in the data. Noise in the data can be due to inattentive participants or participants that are not willing to or fail to follow instructions (cf. Oppenheimer et al., [@B67]; Maniaci and Rogge, [@B53]). Noise can lead to low variance or indicate inappropriate response patterns in the data (e.g., participants always selecting the same response option), and it can lead to consistent order violations of the *AVs* due to the inattentive reading of instructions. Therefore, we removed participants with: more than 10% missing entries in the datalow variance (\<0.5) in answering the self-report questionnaires and *AVs*inappropriate response patterns in the *AVs*consistent order violations in the *AVs* 18.7% of the original *N* = 520 participants in Sample 1 (Rwanda) and 28.5% of the original *N* = 200 participants in Sample 2 (Philippines) were removed in accordance to these criteria. Most participants were removed because of omissions in the data, which mostly originated from the paper-pencil versions. Analyzing the anchoring vignettes --------------------------------- In our study, we used a set of three vignettes varying in intensity to adjust self-report responses using a non-parametric approach. Specifically, responses to the self-report questionnaires were compared against the responses to the vignettes (see Table [2](#T2){ref-type="table"} for all examples relating a single self-report answer to a set of three vignettes). In this process, the responses of the original 5-point Likert-scales spread across a new 7-point Likert-scale. These adjusted answers are hypothetically free of some DIF forms and can thus be analyzed and interpreted like any other Likert-scale (King et al., [@B49]; Wand, [@B95]). Table [3](#T3){ref-type="table"} shows the *AV*-adjusted scores if the participant rates the vignettes in the defined order. Of course, participants show individual differences in their ratings of these vignettes. For example, it is possible for participants to evaluate two vignettes equally if they decide that two hypothetical persons display the same intensity of a trait. Hence, they do not distinguish between two or even three vignettes (e.g., Vignette 1 = Vignette 2 \< Vignette 3), which is referred to as tying one or more vignette pairs. Alternatively, participants can rate the vignettes as having a different intensity than originally defined, such as rating Vignette 2 as lower than Vignette 1 (Vignette 2 \< Vignette 1 \< Vignette 3) when the correct order is Vignette 1 \< Vignette 2 \< Vignette 3. ###### Rules for recoding self-report responses with three *AVs*. **Relative order ratings** **Adjusted score** ------------------------------------------------ -------------------- Self \< Vignette 1 \< Vignette 2 \< Vignette 3 1 Self = Vignette 1 \< Vignette 2 \< Vignette 3 2 Vignette 1 \< Self \< Vignette 2 \< Vignette 3 3 Vignette 1 \< Self = Vignette 2 \< Vignette 3 4 Vignette 1 \< Vignette 2 \< Self \< Vignette 3 5 Vignette 1 \< Vignette 2 \< Self = Vignette 3 6 Vignette 1 \< Vignette 2 \< Vignette 3 \< Self 7 "*Self" represents a single self-report answer about one\'s own personal traits. Vignettes 1, 2, and 3 are the corresponding vignette set measuring the same trait, with the trait level highest in Vignette 3, followed by Vignette 2, with the trait level lowest in Vignette 1*. These ties and order violations add complexity to analyses resulting in fragmentary information (Hopkins and King, [@B37]). If the participant orders the vignettes in the correct order, the non-parametric adjustment through *AV*s eventuate in a single value (see Table [2](#T2){ref-type="table"}). Ties and order violations instead result in an interval solution and therefore in a set of values (King et al., [@B49]). In our example, the interval can range from one to seven. The non-parametric approach has only a limited range of options for dealing with ties and order violations in *AV*s (Paccagnella, [@B69]). Previous research has shown that choosing the lower bound of these intervals as an *AV*-adjusted answer leads to improved reliabilities (Kyllonen and Bertling, [@B52]). It is important that the assumptions of vignette equivalence and response consistency are met before evaluating *AV*-adjusted scores (King et al., [@B49]). *Vignette equivalence* means that every participant perceives the *AV*s in the same way and therefore with the same ranking (Grol-Prokopczyk et al., [@B28]), which should generally occur. This assumption would be violated if a large proportion of participants systematically interpret the vignettes in another way. Violation of this assumption leads to problems in non-parametric adjustments and incomparable thresholds in the parametric approach. In previous literature, this assumption was either assumed prima facie (Grol-Prokopczyk et al., [@B28]) or considered to be met by simply looking at the consistencies when rank-ordering the vignettes (King et al., [@B49]; Kristensen and Johansson, [@B51]; Rice et al., [@B74]). However, this assumption can be assessed by analyzing the amount of order violations within the *AV*s rank-order, with 10% or more indicating a significant amount of order violations. Generally, order violations are treated as measurement error. However, patterns in order violations can also have a diagnostic impact, providing information about the sample, the translation, or the quality of the vignette. For example, the World Health Organization (WHO) self-care vignettes show an order violation of 35.71% compared to an average 10% order violation for the other WHO vignettes. Systematic order violations can be also due to isolated "bad vignettes" (Grol-Prokopczyk et al., [@B28]). Only if there are patterns in order violations is it problematic to analyze *AV*s based on the non-parametric approach (described later). The assumption of *response consistency* tests the extent to which participants use the same thresholds for answering the self-report items and the *AV*s. Response consistency is violated if participants apply alternative standards to the self-report items and to the *AVs* or use varying standards in answering the *AV*s. Violations of this assumption lead to problems in adjusting self-report responses with the non-parametric approach (Grol-Prokopczyk et al., [@B28]). There are options to test response consistency, such as comparing the thresholds of the *AV*s and the self-report items collected in different waves (Kapteyn et al., [@B45]) or comparing thresholds of objective measures and self-report measures with responses to the *AV*s (Gupta et al., [@B29]; Soest et al., [@B81]; Hirve et al., [@B34]). However, these options are often not available. Instead, another possibility is simply examining the IRT parameters, specifically the overlap of the threshold confidence intervals in a graded response model (i.e., a mathematical model for ordered polytomous categories) for the *AVs*. Mostly, this assumption is not examined but is instead assessed indirectly through interpreting the plausibility of the study results (King et al., [@B49]; Grol-Prokopczyk, [@B27]). In our study, *AVs* were analyzed with the *anchors* package in R Studio version 3.3.2 (Wand et al., [@B96]). Using this package, we assessed entropy (King and Wand, [@B48]), which is an indicator of the informativeness of a given *AV* set. These statistics showed that all vignette sets, including the three vignettes in their defined order, were mostly informative. Next, we applied the non-parametric approach and calculated the *AV*-adjusted scores. Table [S1](#SM1){ref-type="supplementary-material"} in Supplemental Material shows an example of R-Code syntax used for the analysis of the *AV*s. Based on recommendations in the literature, we treated order violations as ties and chose the lower bound of the intervals (Kyllonen and Bertling, [@B52]). Figures [1](#F1){ref-type="fig"}, [2](#F2){ref-type="fig"} show the means for the BFI-44 items for the original 5-point Likert-scale before the *AV*-adjustment and the means of the 7-point Likert-scale after the *AV*-adjustment, separated by country. {#F1} {ref-type="fig"}.](fpsyg-09-00325-g0002){#F2} Computational approach ---------------------- We assessed DIF through a multiple-group confirmatory factor analysis, establishing configural measurement invariance on the Big Five factor model between both samples. Then, several indices and programs were used to evaluate support for our hypotheses. The first hypothesis was tested by applying McDonald\'s ω (McDonald, [@B58]), an estimate of general factor saturation that is considered a better indicator of reliability than Cronbach\'s α (Zinbarg et al., [@B99]), and the confidence intervals of ω were interpreted to evaluate whether reliability significantly improved after AV-adjustment. For testing Hypothesis 2, we used a graded response model for the original and the *AV*-adjusted scores. The graded response model belongs to the polytomous item response theory models and can be applied for ordinal manifest variables. Reise and Waller ([@B72]) showed that two-parameter logistic *IRT* models can be used for multidimensional data, which describes Personality questionnaire data. The graded response model was fitted with the multidimensional item response theory (full-information item factor analysis) *MIRT* package in R Studio version 3.3.2 (Chalmers, [@B14]). DIF and Hypothesis 3 were assessed based on a confirmatory factor analysis with the BFI items as manifest indicators of their respective Big Five Personality factor, which were allowed to correlate. Previous studies have reported problems in modeling personality self-report questionnaires in a confirmatory factor analysis (Marsh et al., [@B55]). For example, the NEO-PI-R is known for encountering problems such as model misfit, negative item loadings, and high error correlations (e.g., Borkenau and Ostendorf, [@B9]; McCrae et al., [@B57]). A common technique for improving model fit in such a situation involves deleting items that are not loading high enough onto the corresponding factor (Aluja et al., [@B3]; Tully et al., [@B88]). Based on this procedure, items that were completely misfitting the model through small or even negative loadings were deleted from the original measure. In this study, this procedure resulted in a 36-item version of the BFI. To ensure comparability, all models are based on a 36-item solution. In the evaluation of Hypothesis 3, we modeled the 36-item solution of the BFI-44 for the unadjusted self-report scores \[Model \#1 (Rwanda) and \#3 (Philippines)\] and for the *AV*-adjusted scores \[Model \#2 (Rwanda) and \#4 (Philippines)\]. We then compared improvement in fit for each country (Model \#1 vs. Model \#2 and Model \#3 vs. Model \#4). A final model (Model \#5), which includes all participants and is based on the *AV*-adjusted scores, was estimated to evaluate whether the *AV*-adjusted scores provide stronger support for the Five Factor structure (i.e., orthogonal factorially-pure scales). As all models are based on the same factor structure based on the same 36 items, models can be compared by looking at improvement in the fit indices. In a confirmatory factor analysis, several indices can be used to describe the fit between the theoretical model and the actual model. We used the criteria that a Comparative-Fit-Index (CFI) (Bentler, [@B7]) greater than or equal to 0.90 and a Root Mean Square Error of Approximation (RMSEA) (Steiger, [@B84]) less than or equal to 0.08 indicates acceptable fit (Steiger, [@B84]). The confirmatory factor analyses were conducted with the either Mplus 7 (Muthén and Muthén, [@B63]) or the *lavaan* package in R Studio version 3.3.2 (Rosseel, [@B77]). Basic statistics are based on the *psych* package (Revelle, [@B73]) and the violin plots in Figure [3](#F3){ref-type="fig"} are based on the package *vioplot* (Adler, [@B1]). {#F3} Results {#s3} ======= Evaluating DIF -------------- First, we tested the extent to which the original scores were affected by DIF. To this end, we conducted a multiple-group confirmatory factor analysis, with the above described fit standards for fit indices. In the first model, with all 44 items, imposing configural measurement invariance led to poor model fit (*CFI* = 0.60, *RMSEA* = 0.06). This indicates that the underlying five-factor model is not comparable between samples, and different constructs are represented. Likewise, there were large differences between the factor loadings, which ranged from −0.55 to 0.78. Based on these results, we conclude that configural invariance between both studies on the full scale is not met and hence different constructs are assessed. To compare improvement in fit from the original scores to the *AV*-adjusted scores, we conducted a second multiple-group confirmatory factor analysis based on the original self-report scores, but with the 36-item solution (Baseline Model: *CFI* = 0.67, *RMSEA* = 0.07). The poor model fit supports our initial conclusion that the original self-report items are affected by DIF and need an *AV*-adjustment to achieve cross-cultural comparability. Vignette equivalence and response consistency --------------------------------------------- Next, before interpreting the AV-adjusted scores, we checked vignette equivalence and response consistency assumptions. The percentage of vignettes with the correct order ranged from 26 to 66% (Rwanda) and 37 to 72% (Philippines; see Table [4](#T4){ref-type="table"} for the percentage of all possible orders for each domain). In our study, the chance of randomly violating the correct order is 74% while the chance of randomly correctly ordering the *AV*s is 8%. Violations of 10% or lower can be treated as measurement error, however systematic violations (e.g., participants using answer pattern resulting in order violations) have to be excluded. Conscientiousness, Agreeableness, and Extraversion for both samples, as well as Openness for the Philippines sample, had order violations of 10% or less, indicating no problematic vignettes. However, violations for Neuroticism (Rwanda: 15%; Philippines: 18%) and Openness for the Rwanda sample (23%) were higher. For the latter, Openness displayed a higher amount of ties (51%) than correct orders (26%), in addition to the large percentage of order violations. Given there was only a partial violation of the vignette equivalence assumption, we felt comfortable continuing in the analyses. Possible reasons for these violations, as well as examples of other research where the same violations were found, is discussed in the Discussion section. ###### Percentage of correctly ordered vignettes, vignette ties, and order violations for each Big Five Personality factor, and the percentage of random chance ordering. **Correct order (1 \< 2 \< 3) random chance of correct order = 8%** **Ties (e.g., 1 = 2 \< 3) random chance of ties = 18%** **Order violations (e.g., 2 \< 1 \< 3) random chance of order violation = 74%** ----------------------- --------------------------------------------------------------------- --------------------------------------------------------- --------------------------------------------------------------------------------- **CONSCIENTIOUSNESS** Rwanda 66% 30% 4% Philippines 72% 18% 10% **AGREEABLENESS** Rwanda 61% 33% 6% Philippines 52% 43% 5% **NEUROTICISM** Rwanda 42% 43% 15% Philippines 37% 45% 18% **OPENNESS** Rwanda 26% 51% 23% Philippines 49% 41% 10% **EXTRAVERSION** Rwanda 47% 44% 8% Philippines 56% 34% 10% Response consistency was evaluated through an examination of whether or not respondents used the same thresholds while answering the *AVs* and the self-report questionnaire. We fitted a graded response model for the *AVs* and the self-report questions and compared the four thresholds of the *AVs* against the corresponding self-reports. The confidence intervals of most thresholds overlapped. Therefore, we consider the Response Consistency requirement met. Hypothesis testing ------------------ Next, we applied the non-parametric approach (King et al., [@B49]) on the data to produce *AV*-adjusted scores. These *AV*-adjusted scores are what was compared with the original self-report answers. 1. *Hypothesis 1:* Reliability before and after AV-adjustment We compared McDonald\'s ω (McDonald, [@B58]), a measure of reliability, for the original and *AV*-adjusted scores (see Table [5](#T5){ref-type="table"}). For the original scores, omega indicated poor reliability (ω = 0.32 −0.66) for all dimensions except conscientiousness (ω = 0.74). Following the *AV*-adjustment, the omegas increased for every dimension in both samples to acceptable or good (ω = 0.80 −0.92). Looking at the 95% confidence interval, we see that the intervals of the omega estimates for original and the *AV*-adjusted scores do not overlap. In sum, the analysis shows that the *AV*-adjusted scales show better reliability than the original self-report scales, supporting hypothesis 1. ###### Scale reliability, indicated by McDonald\'s omega, and 95% Confidence Intervals for the original and *AV*-adjusted Big Five Personality factors. **Rwanda** **Philippines** ------------------- --------------------- --------------------- --------------------- --------------------- Conscientiousness 0.74 \[0.69 −0.78\] 0.92 \[0.90 −0.93\] 0.76 \[0.64 −0.83\] 0.89 \[0.84 −0.92\] Agreeableness 0.32 \[0.21 −0.42\] 0.87 \[0.83 −0.90\] 0.63 \[0.45 −0.80\] 0.89 \[0.85 −0.92\] Neuroticism 0.66 \[0.60 −0.72\] 0.80 \[0.76 −0.83\] 0.63 \[0.50 −0.70\] 0.82 \[0.77 −0.87\] Openness 0.66 \[0.61 −0.71\] 0.91 \[0.89 −0.92\] 0.57 \[0.46 −0.66\] 0.88 \[0.84 −0.91\] Extraversion 0.51 \[0.39 −0.59\] 0.81 \[0.77 −0.84\] 0.62 \[0.48 −0.71\] 0.82 \[0.77 −0.88\] *McDonald\'s omega and 95% confidence interval of omega for a model with five correlated factors. Original, original (5-point) self-report Likert-scale (before the AV-adjustment); AV-adjusted, 7-point Likert-scale (DIF-free, after the AV-adjustment)*. 1. *Hypothesis 2:* Item functioning before and after AV-adjustment Next, we investigated the item and category function of the original and the *AV*-adjusted scores. Here, we assume that the DIF-free scores increase the discriminant power, as compared to the original self-report scores, because they are comparable between countries and more relevant to the measured trait in both studies. The violin plot in Figure [3](#F3){ref-type="fig"} shows that, for both studies, the discrimination parameters mostly increase as a result of the *AV*-adjustment. The discriminant power also increases as the range of the threshold widens. The original self-report scores are based on a 5-point Likert-scale while the *AV*-adjusted scores use a 7-point Likert-scale. This results in a different number of thresholds: b~1~ to b~4~ (original 5-point Likert-scale) and b~1~ to b~6~ (7-point Likert-scale for the *AV*-adjusted answers). As b~1~ to b~6~ span a wider range of values, this indicates that the *AV*-adjusted scores differentiate higher levels of proficiency compared to the original self-report scores. In particular, for the original self-report scores, the last threshold was more effective in differentiation relative to the last category (b~4~). As we compared four to six thresholds, we examined correlations between the thresholds of the original and the *AV*-adjusted scores. This comparison shows that most thresholds are highly correlated with one another (*r*s = 0.47 to 0.94). Only the last threshold of the *AV*-adjusted scores (b~6~) shows negative correlations with the thresholds of the original self-report scores. Next, we evaluated the overall test information (i.e., the degree of certainty of the proficiency estimates) for the original and *AV*-adjusted scores. The test information curve includes θ-levels from −6 to 6. For the original self-report scores, the test is mostly informative for θ \< 0. Above zero, however, the standard error increases greatly and the test information decreases. For the *AV*-adjusted scores, the test is less informative for θ \< 0, but it is still informative for θ \> 0, particularly between 2 and 4. Overall, we conclude that hypothesis 2 was supported. 1. *Hypothesis 3:* Big five factor structure before and after AV-adjustment Next, we tested our hypothesis that the *AV*-adjusted scores will have improved model fit and a better loading pattern in a confirmatory factor analysis, relative to the original scores, thus showing better support for the Big Five factor structure. Table [6](#T6){ref-type="table"} shows the results of the confirmatory factor analysis, based on the 36-item version of the BFI. As expected, the models based on the original self-report scores \[Model \#1 (Rwanda) and \#3(Philippines)\] have poor fit to the data, yielding a non-positive definite covariance matrix, with item loadings weak in magnitude, not significant, or even negative. These models are not clearly identified but are displayed here for purposes of comparison. In sum, Model \#1 and \#3 do not support the Big Five factor structure. ###### Confirmatory Factor Analysis model fit estimates based on the original and *AV*-adjusted scores. **\#** **Model type** **CFI** **RMSEA** **χ^2^** -------- ------------------------------------------------ --------- ----------- --------------------- 1 Rwanda: Original^+^ 0.68 0.06 χ~2~(584) = 1,479 2 Rwanda: *AV*-adjusted 0.90 0.06 χ^2^~(584)~ = 1,423 3 Philippines: Original^+^ 0.56 0.08 χ^2^~(584)~ = 1,165 4 Philippines: *AV*-adjusted 0.80 0.08 χ^2^~(584)~ = 1,034 5 Rwanda and Philippines Combined: *AV*-adjusted 0.90 0.05 χ^2^~(584)~ = 1,640 *All models are with the 36-item version. + These models have a non-positive definite covariance matrix, indicating they are not clearly identified; they are displayed her merely for comparison purposes*. The models including the *AV*-adjusted scores (Model \#2, \#4, and \#5) show high item loadings and better model fit then Models \#1 and \#3. However, while Model \#2 (Rwanda) and \#5 (Rwanda and Philippines combined) show acceptable fit, the fit of Model \#4 (Philippines) is not acceptable. For Model \#5, the model fit improved over the original Baseline Model reported above, which was based on the original scores (*CFI* = 0.67, *RMSEA* = 0.07). Therefore, we assume that the studies are now comparable. In Model \#5, Neuroticism is negatively correlated with every other dimension (*r* = −0.17 to −0.31) and all other dimensions are weakly and positively correlated with one another (*r* = 0.13 to 0.31). Thus, the correlations of the *AV*-adjusted scores are much more in line with previous findings than the correlations for the original self-report scores. In sum, the confirmatory factor analysis shows that the *AV*-adjusted scores better support the original factor structure of the Big Five, supporting hypothesis 3. 1. *Hypothesis 4:* Test-criterion relationships Finally, we evaluated test-criterion relations with external outcome variables: satisfaction with life and counterproductive behavior (either at school or at work). The outcome variables were correlated with the Big Five Personality factors before and after the *AV*-adjustment (see Table [7](#T7){ref-type="table"}). The correlations of counterproductive behavior with Conscientiousness, Agreeableness and Neuroticism, decreased significantly after the *AV*-adjustment. However, for life satisfaction, with two exceptions, correlations were not significantly different after the *AV*-adjustment. The two exceptions are for the Rwanda sample where life satisfaction is negatively correlated to Openness and Conscientiousness after AV-adjustment, but unrelated before the adjustment. Overall, hypothesis 4, which stated correlations with satisfaction with life and counterproductive behavior should be stronger after *AV*-adjustment, was not supported. ###### Correlations (Spearman rho) of the Big Five Personality factors, based on the original and *AV*-adjusted scores, with two outcome variables. **Life satisfaction** **Counterproductive behavior** ------------------------------------- ------------------------------------------------ ------------------------------------------------------------------------------------- **CONSCIENTIOUSNESS** Rwanda: Original/*AV*-adjusted *−0.01/−0.12*[^\*^](#TN2){ref-type="table-fn"} −0.25[^\*\*^](#TN1){ref-type="table-fn"}/−0.19[^\*\*^](#TN1){ref-type="table-fn"} Philippines: Original/*AV*-adjusted 0.07/0.05 *−0.51[^\*\*^](#TN1){ref-type="table-fn"}/−0.30*[^\*\*^](#TN1){ref-type="table-fn"} **AGREEABLENESS** Rwanda: Original/*AV*-adjusted −0.03/−0.04 *0.22[^\*\*^](#TN1){ref-type="table-fn"}/−0.13*[^\*\*^](#TN1){ref-type="table-fn"} Philippines: Original/*AV*-adjusted 0.04/−0.02 *−0.50[^\*\*^](#TN1){ref-type="table-fn"}/−0.19*[^\*^](#TN2){ref-type="table-fn"} **NEUROTICISM** Rwanda: Original/*AV*-adjusted −0.01/−0.01 0.11[^\*^](#TN2){ref-type="table-fn"}/0.07 Philippines: Original/*AV*-adjusted 0.08/0.07 *0.24*[^\*^](#TN2){ref-type="table-fn"}*/0.12* **OPENNESS** Rwanda: Original/*AV*-adjusted *−0.04/−0.14*[^\*^](#TN2){ref-type="table-fn"} −0.10[^\*^](#TN2){ref-type="table-fn"}/−0.12[^\*^](#TN2){ref-type="table-fn"} Philippines: Original/*AV*-adjusted 0.07/−0.14 −0.05/0.05 **EXTRAVERSION** Rwanda: Original/*AV*-adjusted 0.03/−0.05 0.01/0.01 Philippines: Original/*AV*-adjusted 0.15/0.13 −0.02/0.03 *p \< 0.01*; *p \< 0.05*. *Correlations presented in italics mean there is a significant difference in relations with that personality factor depending on whether the original or AV-adjusted scoring was used*. Discussion {#s4} ========== Overall, the results suggest that the *AV* methodology is an appropriate tool for cross-cultural research, although the change in test-criterion relationships warrants further investigation. Summary and interpretation of the results ----------------------------------------- We demonstrated that not even the weakest degree of measurement invariance, configural invariance, was present across both countries. Hence, we show that the BFI-44 test and its items are affected by cross-cultural DIF. Because we performed several backward and forward translation checks, we presume our items showed no evidence of any translation problems, and that the observed DIF most likely occurred because participants from different countries displayed different probabilities of item endorsement. Thus, we utilized *AVs* to correct for DIF. Before interpreting the AV-adjusted scores, we showed that the *AV*s mostly met the two basic assumptions of vignette equivalence and response consistency. On average, 89% of the participants ordered all vignettes correctly or rated them as ties. Thus, we can assume there was generally vignette equivalence, with most participants perceiving the vignettes in the same way and in the defined order. However, Neuroticism and Openness showed a non-negligible amount of order violations. A possible reason for the order violation on the Neuroticism *AVs* is that they were presented on a reversed scale. In previous studies, the use of a reversed scale also created confusion for participants (He et al., [@B32]). The order violations within Openness are probably due to the conceptualization of the Openness factor and the corresponding *AV*-set. Primi et al. ([@B71]) discovered similar results and suggested that this is because Openness is different from the other domains and is not as easy to rate as it mostly includes not observable behaviors compared to the other domains, such as Conscientiousness, which has observable behaviors. Likewise, given response consistency is traditionally difficult to confirm or disconfirm, we proposed a novel statistical solution and tested it with the present data set. We showed that the confidence intervals of most thresholds overlapped, implying that participants applied the same thresholds in answering *AVs* and the original self-report questions. Thus, we could conclude that the response consistency assumption was met. We examined how the *AV*s influenced other psychometric characteristics by testing a series of hypotheses. In evaluation of the first hypothesis, we examined scale reliability, estimated through omega, for each of the Big Five factors before and after *AV*-adjustment. We found support for this hypothesis such that there was a higher internal consistency for the *AV*-adjusted scores indicating better measurement properties. Hypothesis 2 was also confirmed: the discrimination parameters based on the AV-adjusted scores were larger, while the thresholds spanned a wider range. In sum, the *AV*-adjustment increased the overall test information, adding power and precision to the test. This finding again suggests that the *AVs* are very beneficial from a psychometric perspective. To test Hypothesis 3, we assumed that the *AV*-adjusted scores provided clearer support for the Big Five Factor structure of personality, compared to the original scores, which were DIF-affected items and failed to show measurement invariance. Overall, we found the *AV*-adjusted scores better predict the estimated level of the latent factor, including more reliable and factorially-pure scales aligned with the Big Five Factor structure. They are therefore more in line with previous findings (mostly based on exploratory factor analysis) regarding the Big Five factor structure (notably obtained with samples that are more homogenous culturally than the two chosen for the present investigation). It has to be noted that Model \#4, based on the *AV*-adjusted scores for the Filipino sample, did not have acceptable fit. However, with personality data, a confirmatory factor analysis is not always desirable due to specific characteristics of the data (e.g., model complexity; Hopwood and Donnellan, [@B38]; Fischer, [@B25]). In general, the confirmation of the third hypothesis is also in line with the findings of the graded response model (Hypothesis 2). In conclusion, all psychometric characteristics are improved following the *AV*-adjustment: *AV*-adjusted items that are DIF-free appear to improve comparability across countries. For the final hypothesis (Hypothesis 4), we evaluated test-criterion relationships by examining correlations between the original and *AV*-adjusted scores with two external outcome measures. In our results, Conscientiousness, Agreeableness, and Openness, based on both the original scores and the *AV*-adjusted scores, correlated negatively with counterproductive work behavior, as expected. Likewise, Neuroticism had a slightly positive correlation and Extraversion was unrelated before the *AV*-adjustment. However, the magnitude of these correlations was significantly lower when using the *AV*-adjusted scores. Both studies showed weak non-significant correlations of the Big Five with satisfaction with life. Looking at these correlations, we see that relations of satisfaction with life with Openness and Conscientiousness are significantly different depending on whether *AV*-adjustment is used or not. Agreeableness, Neuroticism, and Extraversion showed no significant variation before and after the *AV*-adjustment. Especially unexpected is the negative correlation of satisfaction with life with Conscientiousness after the *AV*-adjustment. However, these results are in line with previous findings in Iranian samples (Hosseinkhanzadeh and Taher, [@B39]). Notably, the unexpected drop in correlation magnitude of the Big Five with both outcome variables is consistent with the findings of Ham and Roberts ([@B30]) who found a similar reduction in correlation with outcome values after applying the *AV* methodology. One possible explanation for a fairly systematic reduction in these correlations is as follows. *AVs* were only applied on the personality items and not on the outcome measures *per se*; that is, DIF was only corrected for in personality. Thus, this method triggered a decrease in the covariance as the comparison is made between DIF-free items and items that are still DIF-affected. A further explanation is that the individual\'s ranking of personality substantially moved after the *AV*-adjustment, since the correlation between the original self-report dimensions and the *AV*-adjusted dimensions were around *r* = 0.38 to 0.64. Moreover, the stability of the fairly small correlations is somewhat questionable. Some correlations drop to a non-significant level if countries are examined separately. Thus, adjusting both the predictor and outcome variables is worth considering. Limitations ----------- *AVs* are a strong theoretical and practical tool for accommodating DIF. However, this tool faces some general limitations worth mentioning. First, Buckley ([@B11]) demonstrates that context effects can bias the vignette response, as do the order of the vignettes relative to the self-report. We did not test for order effects in the current study (*AV*s came before the BFI-44) largely because of concerns by the local administration of having multiple forms. Nevertheless, this concern is worthy of consideration. Jürges and Winter ([@B44]) showed the importance of vignette equivalence by highlighting that vignette ratings are somewhat sensitive to the sex and age of the hypothetical person described in the vignette. Likewise, participants may apply different thresholds for male and female hypothetical scenarios affecting response consistency (Kapteyn et al., [@B46]). Randomization can be used as a technique to neutralize violations of response consistency (Chan et al., [@B15]). In our study, we randomized the sex of the possible descriptions, as well as the names, which could also show some relation to age groups. However, we were unable to randomize the order of the AVs, which would have allowed us to address contextual effects. Our study was limited in the number of countries assessed, the regions surveyed, and the sample size within each country. In particular, this limitation prevented us from using the parametric approach (King et al., [@B49]) to analyze the *AVs*; hence, we applied the non-parametric approach for both samples. The non-parametric approach shows limitations when dealing with order violations: inconsistencies are grouped and the non-parametric solution can only deal with scalar values, resulting in a loss of information (Paccagnella, [@B69]). Hence, all non-systematic order violations in our study were treated as ties, leading to a loss of information. Most studies experience some degree of order violation. He et al. ([@B32]) reported order violations ranging from 3 to 13% for facets of Conscientiousness, with the exception of the facet industriousness, which had an order violation of 30%. They concluded that all *AV*-sets worked well, even though presenting vignettes with two levels, instead of vignettes with three levels, expect the *AV*-set for the Conscientiousness facet of industriousness, which was hence excluded from the analysis (He et al., [@B32]). In our study, at least two Big Five factors showed more than 10% order violations. It has been argued that it is not problematic for later interpretation when vignettes are ordered incorrectly because a participant experienced the *AV*s differently based on their circumstances (Wand, [@B95]). Any kind of disagreement on the actual vignette order should be explored as a possible design problem and as an indication of a poor vignette. Hence, the quality of our Openness vignettes, where order violations ranged from 10% (Philippines) to 23% (Rwanda), can be improved and a revision of this vignette set, as well as the neuroticism vignettes (15% order violation in Rwanda and 18% on the Philippines), should be pursued in future studies. The representativeness of the results for both countries may be restricted to the specific regions of the countries where the data was collected and may be slightly more representative of females, as both samples include a high percentage of women. Future considerations --------------------- Based on these considerations, future studies should include larger samples, more countries, and more regions within countries, as this will allow the researcher to use the parametric approach. Those results could then be compared to results using a non-parametric approach. Using *AV*-adjustment in countries where the Big Five Factor structure is replicated and well-established would allow for an interpretation of mean-shifts in trait scores after the *AV*-adjustment. Also, it is important to note that the Big Five Factor structure was replicated quite well in Rwanda after the *AV*-adjustment. However, this result should be replicated in future research. Future studies should also further explore test-criterion relationships after *AV*-adjustment, particularly with a wider range of criterion variables, given our work in this area was limited. Our findings are especially relevant for researchers interested in alternative or competing methods to measure personality. Our study provides insights concerning the robustness and the universality of the Big Five Personality factors. Influential articles describe the Big Five as a psychometrically sound measure that can be applied in different countries and cultures (e.g., McCrae and Terracciano, [@B56]; Schmitt et al., [@B80]). Self-report measures of the Big Five, which have their origin in a lexical approach, are based on principal component analysis with a varimax rotation, meaning the five factors are kept orthogonal (e.g., Tupes and Christal, [@B89]). However, if the fit of the model is assessed with confirmatory factor analysis or item response theory, this structure often has a poor fit to the data and insufficient psychometric properties (Olaru et al., [@B65]). The confirmatory models based on the original self-report scores in our study supports these concerns. The *AV*-adjustments leading to DIF-free scores show a promising solution toward a psychometrically sound measurement with interpretable, reliable, and factorially-pure scales. AV-adjustment is especially relevant today given personality research is facing a debate on the comparability of results based Likert-scale response options, ranging from issues with cross-cultural comparison (He et al., [@B32]) to comparability between genders (Weisberg et al., [@B97]). The application of an external benchmark, like the *AVs*, for all Big Five dimensions is not only of interest for correcting cross-cultural bias, but rather for any kind of bias between different groups (e.g., men and women). The *AV*s provided in Table [2](#T2){ref-type="table"} can be applied not only in a research context (e.g., global workforce, developmental and educational research and policymakers), but also in occupational context. For example, large international companies that base their application and selection process on assessed cognitive and non-cognitive skills can apply vignettes in order to minimize cross-cultural bias in the assessment of non-cognitive skills. Conclusion {#s5} ========== This study is one of the first to use *AV* methodology to adjust all Big Five dimensions in more than one country (cf. Primi et al., [@B71]). In order to use *AVs*, we tested and showed that we met the basic measurement assumptions. The literature regarding the utility of *AV*-adjustment for the assessment of personality is mixed, with researchers finding either the method is not necessary or very beneficial. We showed that personality self-reports in Rwanda and the Philippines are affected by DIF and improved with an *AV*-adjustment. Even though the trait-level means for the original and *AV*-adjusted scores were not drastically different, several psychometric characteristics were improved when *AV*-adjusted scores were used. In the end, the DIF-free scores led to more reliable, powerful, and precise scales that are in line with the Big Five Factor structure. However, test-criterion relations were somewhat reduced after the *AV*-adjustment---a finding discussed above. This finding notwithstanding, we argue that the *AV*-adjustment makes personality across countries more comparable and offers a possible solution to cross-cultural comparison problems. In sum, this study and its results act as an important step toward explaining and handling cross-cultural comparability problems. Overall, *AVs* provide a useful external benchmark for adjusting self-report scores when measuring personality. Future studies should consider implementing similar adjustments to the assessment of other psychological constructs. Author contributions {#s6} ==================== SW contributed to the conception of the study, the data analysis, and the interpretation of data for the work. SW drafted the article and finalized the version for publication. RR contributed to the conception and design of the study, and the acquisition and interpretation of the data. RR also edited the final manuscript. SW and RR agreed to be held accountable for all aspects of the work and ensure that questions related to the accuracy or integrity of any part of the work will be appropriately investigated and resolved. Conflict of interest statement ------------------------------ The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The data for this paper was made available by a project implemented by the Education Development Center, Professional Examination Services, and the Akilah Institute for Women that was funded through the Workforce Connections grant, led by FHI360, from the United States Agency for International Development (USAID). Funding for the publication costs of this paper was provided by Ulm University. We thank Sally Olderbak for English edits and helpful feedback on previous versions of this article. **Funding.** The financial support for this study is based on the Workforce Connections award (Grant Number: AID-OAA-LA-13-00008) given to FHI360 through United States Agency for International Development (USAID). Financial support did not influence what is written in the submitted work. The Educational Development Center Washington (EDC) owns the copyrights of the final anchoring vignette questionnaire. Supplementary material {#s7} ====================== The Supplementary Material for this article can be found online at: <https://www.frontiersin.org/articles/10.3389/fpsyg.2018.00325/full#supplementary-material> ###### Click here for additional data file. [^1]: Edited by: Martin S. Hagger, Curtin University, Australia [^2]: Reviewed by: Derwin King Chung Chan, University of Hong Kong, Hong Kong; Yu Yang, ShanghaiTech University, China; Katrin Rentzsch, University of Bamberg, Germany [^3]: This article was submitted to Personality and Social Psychology, a section of the journal Frontiers in Psychology

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854 F.2d 1318Unpublished Disposition NOTICE: Fourth Circuit I.O.P. 36.6 states that citation of unpublished dispositions is disfavored except for establishing res judicata, estoppel, or the law of the case and requires service of copies of cited unpublished dispositions of the Fourth Circuit.Don C. WILSON, Petitioner-Appellant,v.David A. GARRAGHTY, Respondent-Appellee. No. 87-6618. United States Court of Appeals, Fourth Circuit. Submitted Feb. 26, 1988.Decided July 29, 1988. Don C. Wilson, appellant pro se. Thomas Drummond Bagwell, Assistant Attorney General, for appellee. Before DONALD RUSSELL, ERVIN, and CHAPMAN, Circuit Judges. PER CURIAM: 1 Don C. Wilson, a Virginia prisoner, appeals the district court's denial of his petition for habeas corpus relief pursuant to 28 U.S.C. Sec. 2254. In his petition, he asserted that his convictions for rape and burglary were obtained in violation of his constitutional rights. We deny a certificate of probable cause and dismiss the appeal. 2 The district court dismissed the following three claims on the merits: (1) ineffective assistance of counsel on direct appeal due to Wilson's appellate attorney's failure to contest the sufficiency of the evidence; (2) denial of due process due to the Virginia Supreme Court's alleged arbitrary application of its procedural bar rules; and (3) denial of due process due to a grand jury selection which did not comply with state law. We affirm the dismissal of these claims on the reasoning of the district court. Wilson v. Garraghty, C/A No. 86-1020-AM (E.D.Va. Aug. 13, 1987). 3 Wilson also raised six additional claims: (1) ineffective assistance of counsel at trial and during his sentencing hearing; (2) denial of due process due to the admission of unreliable identification testimony; (3) denial of due process due to the prosecution's failure to produce allegedly exculpatory results of a comparison of samples from Wilson and the victims; (4) denial of constitutional rights because the jury was instructed to consider the death penalty as punishment for the rapes; (5) denial of fourth amendment rights due to an allegedly illegal arrest; and (6) denial of a fair trial and compulsory process due to the trial court's failure to call his alleged accomplice, Andrew Brewer, to testify at trial. 4 The district court dismissed these claims on the ground that Wilson had not shown cause and prejudice for failing to raise these claims in his first state habeas corpus petition, as was required by Virginia law.1 See Wainwright v. Sykes, 433 U.S. 72 (1977); Murch v. Mottram, 409 U.S. 41 (1972); cf. Whitley v. Bair, 802 F.2d 1487, 1500 (4th Cir.1986) (failure to appeal adverse decision of state habeas court constitutes a bar to further federal review of a claim), cert. denied, 55 U.S.L.W. 3661 (U.S. Mar. 30, 1987) (No. 86-6309). 5 Based on our review of the record, we conclude that Wilson was not prejudiced by any of the alleged constitutional errors raised in these claims. We therefore deny a certificate of probable cause and dismiss the appeal. We dispense with oral argument because the facts and legal arguments are adequately presented in the materials before the Court and oral argument would not significantly aid the decisional process. DISMISSED 1 Both Va.Code Ann. Sec. 8.01-596(b)(2), which was in effect at the time Wilson filed his petition, and its successor, Va.Code Ann. Sec. 8.01-654(b)(2), contain the following provision, "No writ shall be granted on the basis of any allegation the facts of which petitioner had knowledge at the time of filing of any previous petition."

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Weber, RosaShort and Long-term Integration: Assessing the Impact of Immigrant Social ContactsAbstract: Previous studies come to contradictory conclusions regarding the relationship between immigrants’ social contacts and their labor market integration. This paper tackles this impasse by exploring the short and long-term effects of social contacts on immigrant labor market outcomes using data collected in the Swedish Level-of-Living survey in 2010. Results from Cox and OLS regressions show that social contacts provide meaningful resources in the initial transition period, but loose importance over time in the host country. The findings moreover reveal substantial heterogeneity by reason for migration. Social contacts provide family related migrants and labor migrants with significant resources in their job search, while social contacts are not able to facilitate labor market entry among refugees. Regarding longer-term integration, earnings differences by social contacts are small. However, compared to other migrants, labor migrants continue to experience an advantage in the labor market. The implications of these findings are that distinguishing between short and long-term integration contributes to our understanding of the association between immigrants’ social contacts and their labor market integration. Moreover, information provided by social contacts assists family related migrants and labor migrants in their job search.social contacts;immigrant integration;international migration;‘Stockholm Reports in Demography’;Sociologiska institutionen;Department of Sociology;SUDA;Stockholm University Demography Unit;Stockholms universitets demografiska avdelning2018-10-05

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Q: .ajax Temporarily halting the return to .ajax from a PHP script $.ajax({ url: 'buildquery.php', data: {action: 'test'}, type: 'post', success: function(output) { alert(output); } }); <?php echo "Hello World!"; die(); ?> In this particular case I would like the PHP script to halt so I can see the output in my browser window and not return into the .ajax function. This would be for debugging purposes so I can output some data so my user can see the output while the application is under construction. Can this be done? Alternatives? I though about using the submit function of the form but this is going to cause some code changes between debug and release builds. Thanks for any commentary! A: I would suggest just writing it to a file in the php script. Or use firebug. Or chrome developer tools. (Click network and select XHR)

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The Last Jedi trailer reaction and analysis. So, yesterday at Star Wars celebration, Rian Johnson gave us our first look at The Last Jedi. This movie has been hidden away in secrecy, and many of the main actors have said that it would be so much better if there were no trailers for this movie. But, obviously, Disney wants this movie to break all kinds of box office records, so there is going to be a couple trailers. This is a trailer with a lot of hidden factors, and takes a few viewing’s to fully get to grips with what is going on. I have a couple of theories and Easter Eggs that I have noticed and that I want to share with you guys, as well as my overall thoughts. On first viewing of the trailer, I admit to being a bit underwhelmed. I was watching the live stream from celebration, and was so damn excited for it. I was also one of the first people on the Earth to watch the trailer, so my initial reaction couldn’t be swayed by endless opinions on Twitter and YouTube. I think I was expecting too much. I was glad that this trailer didn’t spoil anything like the Spider-Man Homecoming trailer, and I was excited by all the cool looking shots e.g. the ships that fart red stuff. My way of explaining it is as so: My excitement for this movie was already through the roof. I should’ve realised that a trailer won’t have a huge effect on my excitement level, because it can’t possibly get any higher. I was expecting something as awesome as the recent Thor trailer, which is a movie I was excited for, but the trailer put my excitement through the roof. This is a level that I had already reached with The Last Jedi, meaning that anything I did see would only let me down a tinch. That was only my first viewing experience. Each time that I watch this trailer, I begin to realise just how awesome it actually is. I love it now, and to my surprise, I have done something that I thought was impossible, and my excitement for this movie has gotten to a whole new level. I am going to break down a few parts of the trailer that I feel needs to be discussed. We open with darkness, in what looks like space, we then see stars. This immediately puts us in the world of Star Wars, and also foreshadows of how the darkness will play a part in the movie. We then see Rey’s hand, as she pants. Some think that this is after some hard-core Jedi training with Luke, but I think that Rey is just after coming out of talking to some force ghosts, and was having another similar to the vision she had in The Force Awakens, and also similar to the one that Luke had of Vader in Empire. Perhaps Yoda or Obi-Wan was showing her something, or she was tempted by the dark side. We then see some cool shots of the island off of my home country of Ireland, with Luke narrating, saying “breathe, just breathe” and then “now reach out, what do you see”. Nothing too exciting here, this really just confirms that Luke does decide to train Rey, or Luke guiding Rey through a vision or something. We then cut to a shot of Leia and she had a big map hologram in front of her. Perhaps she has now lost Rey, and needs to try and find both Rey and Luke. It also is really just confirming the presence of Leia and Carrie Fischer in the movie. Rey then is heard saying “Light, darkness, the balance.” This could be Rey answering Luke’s question of what did you see. When Rey says darkness, the music’s tone changed and we get a glimpse of Kylo Ren’s smashed helmet, which is well edited and very interesting. We also get a shot of some big tree with some books, and then a shot of one of those books with the Jedi symbol. This is probably just Rey reading up on some books as part of her training. Then we cut to my favourite shot of the entire trailer. Rey is training with a lightsabre, as Luke watches on. If you look closely at the structure behind Rey, just on top of it, there is Yoda looking creature sitting there. Is it Yoda? Let me know what you think about this shot. Then we get a great shot of some ships farting out red stuff. If you look closely, you will see AT-AT’s in the foreground, approaching slowly. This really shows the silky style that Rian Johnson will bring to this movie, and he clearly is going to bring this movie in a very different yet slightly familiar direction. We then see Finn, and he isn’t doing much. The lack of Finn in this trailer has me a bit worried that we won’t see much of him in this movie. I hope that I am wrong though, as Finn is such a great and different character. We then see Poe running towards an X-wing. This just kind of is there to show that there will be action and conflict in the movie, and that Oscar Issac is back as Poe, as well as BB-8 might I add. It looks as if BB-8 won’t be on the main adventure in this movie, like R2 always was or like K2 was in Rogue One. We then see the Millennium Falcon. This is just showing us that the legacy of Han Solo will be continued in this movie. Surprised we didn’t see and Chewie in the trailer though. Then we get a shot of Rey running with a sabre, until it cuts to Kylo Ren looking pretty dark, and his eyes are filled with redness and rage. This is probably foreshadowing the ultimate fight between these two, perhaps with Luke on Rey’s side. We then see a different angle of the vision that Rey had in The Force Awakens, this time showing us that Kylo Ren is the one that killed all of the in training Jedi, and torched the Jedi temple, leaving Luke and R2 in dismay. There is also a cool shot of a space battle, indicating that we will probably get a cool space battle. Our first real line of dialogue to come from Luke is “It’s time for the Jedi to end” This ties in well with the movie’s title, and the initial theme of the movie. Luke clearly doesn’t want to train any more Jedi, and feels that he isn’t capable after letting his nephew Kylo turn to the dark-side. A really cool line that I think will happen towards the start of the movie. The trailer then cuts to the title, again with some ominous and dark music playing, showing the presence of darkness in this movie. There a few familiar voices very faintly dotted in the trailer that you probably didn’t even notice. I will give you the times that these happen and listen closely.

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# **Table of Contents** 1. Cover 2. Title 3. Copyright 4. About This Book 5. Introduction 1. I.1. Logistics, information systems and software 6. 1 Operational Research Using a Spreadsheet 1. 1.1. Foreword 2. 1.2. Dynamic programming 3. 1.3. Scheduling 4. 1.4. Maximal flows 5. 1.5. Transport model 6. 1.6. Linear programming 7. 2 Dashboards, Spreadsheets and Pivot Tables 1. 2.1. Spreadsheets: a versatile tool 2. 2.2. Example database 3. 2.3. Multiple databases 4. 2.4. Limits and constraints with calculated fields 5. 2.5. Conclusion 8. 3 Scheduling and Planning Using a Project Manager 1. 3.1. Reminders and information 2. 3.2. Example: designing and building a machine-tool 3. 3.3. Project monitoring 4. 3.4. Conclusion 9. 4 Road Traffic Simulation 1. 4.1. Before we start 2. 4.2. Ring road 3. 4.3. RoadTrafficSimulator 4. 4.4. Intersection simulator 5. 4.5. Green Light District (GLD) 6. 4.6. AnyLogic 7. 4.7. Conclusion 10. Conclusion 11. Appendices 1. Appendix 1: Installing the Solver 1. A1.1. Introduction 2. A.1.2. Microsoft Excel 1997, 2002 and 2003 for Windows 3. A1.3. Microsoft Excel 2007–2010 for Windows 4. A1.4. Microsoft Excel 2013 for Windows 5. A1.5. Microsoft Excel for Mac 2008-2011 2. Appendix 2: Installing the Java Development Kit 1. A2.1. Why Java? 2. A2.2. Downloading 3. A2.3. Testing the presence of the JDK compiler 4. A2.4. Creating the environment variable 12. Glossary 13. Bibliography 14. Index 15. End User License Agreement ## List of Tables 1. 1 Operational Research Using a Spreadsheet 1. Table 1.1. The double entry matrix from Exercise 2 2. Table 1.2. Tasks, starts, durations and ends for the sonorization exercise 3. Table 1.3. The precedence table for the installation of an air-conditioning system 4. Table 1.4. Summary of palletized product batch flow 5. Table 1.5. Transport costs between factories and customers 2. 3 Scheduling and Planning Using a Project Manager 1. Table 3.1. Tasks and predecessors 2. Table 3.2. Resources 3. Table 3.3. Allocation 3. 4 Road Traffic Simulation 1. Table 4.1. Properties of the blocks for the two new organigrams ## List of Illustrations 1. Introduction 1. Figure I.1. Knapsack with Microsoft Excel 2. Figure I.2. A critical path calculation matrix 3. Figure I.3. Gantt chart with Microsoft Excel 4. Figure I.4. An example of a spreadsheet for maximal flows 5. Figure I.5. Calculating transport costs using the Microsoft Excel solver 6. Figure I.6. An example of linear programming, spreadsheet and solver 7. Figure I.7. A pivot table mixing numbered and graphic data 8. Figure I.8. A design and manufacturing plan for a machine-tool within Microsoft Project 9. Figure I.9. A simple road network with its intersection and traffic lights 2. 1 Operational Research Using a Spreadsheet 1. Figure 1.1. The table to be created in the spreadsheet 2. Figure 1.2. The VBA code window in VBE attached to Module 1 of the project 3. Figure 1.3. An accounting spreadsheet containing two (Delete and Calculate) procedure buttons (macros) 4. Figure 1.4. The example of paragraph 4.2.3.3 calculated. The results can be seen in the bottom table 5. Figure 1.5. The table to be created in the spreadsheet 6. Figure 1.6. The section on the right with the calculation formulae to be inputted 7. Figure 1.7. The cells located below the CPM matrix with their formulae 8. Figure 1.8. Calculating the critical field and display showing the duration 9. Figure 1.9. Spreadsheet with all cells filled in the matrix. Note the values of I (earliest start) and j (latest end) as well as the length of the project and the critical path that passes through nodes: 1, 2, 4, 7 and 8 10. Figure 1.10. The matrix corresponding to the task table with each of its columns 11. Figure 1.11. Microsoft Excel: insert a 2D STACKED BAR CHART 12. Figure 1.12. The resized graph, positioned under the matrix 13. Figure 1.13. The contextual menu (right click) to format the axis 14. Figure 1.14. The window for configuring the axis in Microsoft Excel 2013, including the checkbox: values in reverse order (in axis options) 15. Figure 1.15. Configuring axes (10 and 5) and labels (high) 16. Figure 1.16. The fields "length" and "end" selected in the window displaying the data source 17. Figure 1.17. The menu and the pop-up tool bar, obtained by right-clicking on the "Start" bar. Note the tools OUTLINE and FILL above the menu 18. Figure 1.18. The finished Gantt chart and its associated table in a Microsoft Excel 2013 spreadsheet 19. Figure 1.19. The table to be created in Microsoft Excel (here the critical tasks are in gray and in bold) 20. Figure 1.20. The MPM chart corresponding to the project: installation of an air conditioning system 21. Figure 1.21. The table recalculated for workdays 22. Figure 1.22. The "Start" and "End" columns in STANDARD format 23. Figure 1.23. AXIS OPTIONS, LABELS and NUMBER 24. Figure 1.24. AXIS OPTIONS, ALIGNMENT -45° 25. Figure 1.25. The finished table and chart corresponding to the Gantt chart for the project 26. Figure 1.26. The spreadsheet to be created in Microsoft Excel 27. Figure 1.27. The spreadsheet with its two buttons ("Create tables" and "Solve") 28. Figure 1.28. The data from Exercise 1 in Chapter 6 entered into the spreadsheet 29. Figure 1.29. The solution from exercise 1 with the set of results displayed 30. Figure 1.30. The table to be created in a Microsoft Excel spreadsheet 31. Figure 1.31. The second table positioned below the first 32. Figure 1.32. Configuring the solver 33. Figure 1.33. The results calculated by the solver 34. Figure 1.34. The two tables for calculating costs 35. Figure 1.35. Configuration of the solver 36. Figure 1.36. The results obtained from using the solver 37. Figure 1.37. The table that will host our future linear programs 38. Figure 1.38. The data from the example, entered into our table 39. Figure 1.39. The different parameters entered in the solver dialogue window 40. Figure 1.40. Calculated results and the SOLVER RESULTS window 3. 2 Dashboards, Spreadsheets and Pivot Tables 1. Figure 2.1. Example database 2. Figure 2.2. The dashboard to create 3. Figure 2.3. The departure chart 4. Figure 2.4. Inserting a calculated field: Net total x 0.32 5. Figure 2.5. The pivot table with the margin calculation 6. Figure 2.6. The conditional formatting tool including its options 7. Figure 2.7. Size configuration in the pivot table options 8. Figure 2.8. The pivot table to be obtained 9. Figure 2.9. The initial table for the second example 10. Figure 2.10. The pivot table showing the total monthly bonus 11. Figure 2.11. The pivot table to be used as a base 12. Figure 2.12. Creating a conditional calculated field 13. Figure 2.13. The initial pivot table, before modification 14. Figure 2.14. Selecting the field for the slicer 15. Figure 2.15. The pivot table and the filter interface for selecting a slicer 16. Figure 2.16. Selecting the date filters 17. Figure 2.17. The pivot table showing only 2015 data 18. Figure 2.18. The filter for selecting the six least effective vendors 19. Figure 2.19. The pivot table showing the six least effective vendors 20. Figure 2.20. Configuring the calculated field for the 2016 target 21. Figure 2.21. The two columns created by adding the "2016 Target" field 22. Figure 2.22. The pivot table with the column "Net Total" for 2015 and the targets for vendors for 2016 23. Figure 2.23. The quantities sold by each of the agencies in 2015 24. Figure 2.24. The pivot table to be obtained, including columns for 2016 for Bordeaux, Caen and Nice 25. Figure 2.25. Creating the column that will contain the calculated item "Nice 2016". Note the formula for calculating the 50% increase and the "CEILING" function 26. Figure 2.26. The pop-up menu for agencies, showing options for sorting, among others 27. Figure 2.27. An example of the range of cells for the "Sales" table 28. Figure 2.28. An example of the range of cells for the "Products" table 29. Figure 2.29. Creating a table 30. Figure 2.30. The two tables: "Sales" (on the left) and "Products" (on the right) 31. Figure 2.31. The dialog box for creating a relationship 32. Figure 2.32. The new relationship 33. Figure 2.33. The pivot table to be created 34. Figure 2.34. Creating the pivot table using multiple tables 35. Figure 2.35. The fields area of the pivot table showing the two active tables: "Products" and "Sales" 36. Figure 2.36. The renamed headers: "Qty sold", "Designation" and "Agency" 37. Figure 2.37. The table to be obtained 38. Figure 2.38. The resulting table from our operations. The values obtained are inconsistent 39. Figure 2.39. The modified formula for calculating the "Net Total" 4. 3 Scheduling and Planning Using a Project Manager 1. Figure 3.1. Creating the "Factory schedule" calendar 2. Figure 3.2. The exceptions in the factory calendar 3. Figure 3.3. The project calendar options 4. Figure 3.4. Project information 5. Figure 3.5. The main recap tasks and traditional tasks entered into Microsoft Project 6. Figure 3.6. The table featuring the filled "Task" and "Antecedents" columns 7. Figure 3.7. A detailed look at some tasks from the "MecaTools" project 8. Figure 3.8. The MPM network (or task network) corresponding to the "MecaTools" project 9. Figure 3.9. The table, to the left of the Gantt chart, to which the two columns: "Free slack" and "Total slack" have been added 10. Figure 3.10. The Gantt chart showing free and total slack. Below is shown the window for configuring style bars 11. Figure 3.11. Creating resource calendars using a copy of the "Factory schedule" calendar 12. Figure 3.12. The resources table 13. Figure 3.13. The table with the "Resource names" and "Resource initials" columns 14. Figure 3.14. The new slack calculated and the Gantt chart showing resource initials 15. Figure 3.15. The team planner. We can see the periods of over-allocation for the "Computer engineer", "Fitter 1" and "Fitter 3" resources 16. Figure 3.16. The resource use table featuring the number of hours for each resource 17. Figure 3.17. A more detailed display showing the resource use table 18. Figure 3.18. The over-allocations in tasks no. 10, 13 and 21 have disappeared 19. Figure 3.19. Rescheduling task no. 16 for the next available date 20. Figure 3.20. There are no remaining over-allocated tasks 21. Figure 3.21. The detailed timeline for the "MecaTools" project 22. Figure 3.22. The window for creating the WBS code structure 23. Figure 3.23. The task table and its WBS number column 24. Figure 3.24. Table displaying work time for each of the tasks 25. Figure 3.25. Table showing the work time for each of the resources 26. Figure 3.26. A pivot table generated by the "Visual reports" tool in Microsoft Project 2013 27. Figure 3.27. The Microsoft Excel spreadsheet, created in Microsoft Project, that allowed us to generate the chart in Figure 3.26 28. Figure 3.28. The burndown and scheduling tools available in the ribbon under the TASK tab 29. Figure 3.29. The tools for managing the status date under the PROJECT tab 30. Figure 3.30. Here we can see the burndown (bold horizontal line in the middle of the task bars) 31. Figure 3.31. The functions of the different shapes of cursor that appear when hovering over a bar representing a task in a Gantt chart 5. 4 Road Traffic Simulation 1. Figure 4.1. The website of Martin Treiber's simulator "Ring road" 2. Figure 4.2. The parameters for simulation no. 1 3. Figure 4.3. The application RoadTrafficSimulator in use with its control interface at the top right 4. Figure 4.4. Two intersections with the indicators (green triangles) representing the traffic lights. For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 5. Figure 4.5. The 7 intersections created for our model 6. Figure 4.6. Our network once the different intersections have been connected 7. Figure 4.7. Blockage and congestion of traffic lanes around an intersection (traffic jam) 8. Figure 4.8. The Intersection simulator program window 9. Figure 4.9. The parameter table 10. Figure 4.10. The TRAFFIC LIGHT system for the bottom lane (Down) 11. Figure 4.11. The TRAFFIC LIGHT system and LEFT SIGN for the bottom lane (Down) 12. Figure 4.12. The ADDITIONAL ARROW, shown to the right of the TRAFFIC LIGHT system 13. Figure 4.13. The histogram showing average waiting times 14. Figure 4.14. Here we can see the number of vehicles waiting on the right-hand side for each direction. In this example, 3 at the bottom, 99 on the right, 41 at the top and 8 on the left 15. Figure 4.15. An example of a TXT file extracted from an exported ZIP file, containing the results of the simulation 16. Figure 4.16. The command for launching the compilation in Apple OSX (at the top) and in Microsoft Windows (at the bottom) 17. Figure 4.17. Result after compilation in Apple OSX (at the top) and in Microsoft Windows (at the bottom) 18. Figure 4.18. The Green Light District editor 19. Figure 4.19. The editor launch file, in Microsoft Windows using the command prompt (at the top) and in Apple OSX using Terminal (at the bottom) 20. Figure 4.20. The "GLDSim" simulator in Green Light District 21. Figure 4.21. The command for launching the simulator, in Microsoft Word using the command prompt (at the top) and in Apple OSX using Terminal (at the bottom) 22. Figure 4.22. The GLD editor toolbar 23. Figure 4.23. The GLD simulator toolbar 24. Figure 4.24. The road network for our example, featuring 4 intersections, F1 to F4. For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 25. Figure 4.25. The four "Traffic lights" type intersections in GLDEdit 26. Figure 4.26. The five "Edge node" type intersections" added to four "Traffic lights" blocks 27. Figure 4.27. Each intersection block 28. Figure 4.28. The model showing road junctions (in pink). The junctions show the traffic lights set up by default 29. Figure 4.29. The GENERAL CONFIGURATION window displayed when confirming your model 30. Figure 4.30. An example of a potential error during confirmation 31. Figure 4.31. Saving a model (in Microsoft Windows), here "MyModel.infra" in the Office folder 32. Figure 4.32. The model centered in the "GLDSim" window and enlarged by 150% 33. Figure 4.33. The different types of vehicle in the model during the simulation 34. Figure 4.34. Display showing the properties of a junction lane, in this case "Drivelane 24" 35. Figure 4.35. Display showing the properties of a node at an intersection, in this case "Junction 8" 36. Figure 4.36. Two graphs: average waiting time for vehicles at the intersection as a function of the time elapsed (on the left) and the number of vehicles having crossed the intersection as a function of the time elapsed (on the right) 37. Figure 4.37. Display showing the properties of an "Edge node", in this case "Edgenode 0" 38. Figure 4.38. The graphs available from the "Edge node" 39. Figure 4.39. The properties panel for the node "Edgenode 0" in our model after modification at the end of roughly 15,000 cycles 40. Figure 4.40. The three statistical graphs for the node EDGENODE 0 in our model after roughly 15,000 simulation cycles 41. Figure 4.41. The categories of options available for managing traffic lights from the OPTIONS menu 42. Figure 4.42. Section 5b of the GLD documentation relating to traffic light options 43. Figure 4.43. The average waiting times at intersections in our model with a random management method (RANDOM – on the left) and using a method with the most cars (MOST CARS – on the right) 44. Figure 4.44. My example model showing the lanes deleted between nodes 7, 9 and 5 45. Figure 4.45. The dialog box for the properties of the junction and its DELETE DRIVELANE button. Here, the lane "Drivelane 25" in the junction "Road 6" has been selected. We can see the corresponding interactive link, underlined and in blue. For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 46. Figure 4.46. The dialog box for lane properties, here "Drivelane 25", and its DELETE THIS DRIVELANE button 47. Figure 4.47. The plan for our model showing the bus lanes (in green). For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 48. Figure 4.48. The model featuring orange lanes restricted to buses. For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 49. Figure 4.49. A section of the model with nodes 5 and 6 surrounded by their direction indicators 50. Figure 4.50. The properties box with the modified direction indicators, TURN RIGHT, ticked, TURN LEFT, unticked, for the lane "Drivelane 12" of junction "Road 9" 51. Figure 4.51. The direction indicators in "GLDEdit" 52. Figure 4.52. Here we can note the green buses on the orange lanes, starting at node 4 and turning right at node 5. For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 53. Figure 4.53. The statistics window in SUMMARY mode (on the left) and TABLE mode (on the right) 54. Figure 4.54. A ".dat" file (top) and the data in Microsoft Excel (bottom) 55. Figure 4.55. The AnyLogic downloads page 56. Figure 4.56. Aerial image from our example (Source: Google Maps) 57. Figure 4.57. The SNIPPING TOOL dialog box in Microsoft Windows 7 58. Figure 4.58. The AnyLogic welcome screen 59. Figure 4.59. The PALETTE tab and its PRESENTATION tools 60. Figure 4.60. Selecting the captured image to be used as your background. Note the area defined by the marker xy 61. Figure 4.61. The image positioned where the marker is in the MAIN window. We can see the scale indicator at the top 62. Figure 4.62. The properties of the road (ROAD) including its name (in this case, "Avenue Boucicaut") and the number of lanes (in this case, 1 and 1) 63. Figure 4.63. The route (one lane to the right and one to the left) in our model and its direction (in this instance, from left to right) 64. Figure 4.64. The two roads and the point where the routes cross (green dot). For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 65. Figure 4.65. The first road, divided into two sections, on both sides of the intersection 66. Figure 4.66. The three properties windows for my three road segments: "Avenue_Boucicaut_NORTH", "Avenue_Boucicaut_SOUTH" and "Rue Rhin_Danube" 67. Figure 4.67. The traffic plan for our example. For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 68. Figure 4.68. The 3 blocks taken from the ROAD TRAFFIC LIBRARY, moved to the MAIN window and connected 69. Figure 4.69. The properties of the CAR SOURCE block, now named "Veh_NORTH" 70. Figure 4.70. The properties of the CARMOVETO block, now named "carMoveTo_SOUTH" 71. Figure 4.71. The simulator window featuring its RUN button below the name of the model, in this case "Chalon Boucicaut" 72. Figure 4.72. The main functions of the simulator toolbar 73. Figure 4.73. Window showing the model during simulation. In this instance, we can see six vehicles (blue, green, cyan, green, green and red) traveling from north to south on road no.1 section 1 and 2. For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 74. Figure 4.74. The organigram featuring three new blocks 75. Figure 4.75. The model in simulation mode featuring four vehicles (green, blue, cyan, green) traveling south, three (green, blue, magenta) traveling east and one (red) arriving from the north. For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 76. Figure 4.76. The three-vehicle management organigrams within our model 77. Figure 4.77. Arriving from different sources, the vehicles will travel in random directions depending on the probabilities entered when the properties were configured. For a color version of this figure, see www.iste.co.uk/reveillac/modeling2.zip 78. Figure 4.78. The CAR TYPE block and the NEW AGENT dialog box with CAR selected 79. Figure 4.79. The new tab CAR next to the MAIN tab, containing the vehicle and its scale indicator 80. Figure 4.80. The NEW CAR field (on the bottom) containing the value CAR, in the properties for the "Veh_NORD" source 81. Figure 4.81. The simulator toolbar and the NAVIGATE TO VIEW AREA icon, as well as the [WINDOWS3D] option (on the right) 6. Appendix 1: Installing the Solver 1. Figure A1.1. The ADD-INS option in the TOOLS menu 2. Figure A1.2. The list of add-ins with the "Solver Add-In" to be ticked 3. Figure A1.3. The option for opening the SOLVER from the TOOLS menu 4. Figure A1.4. Top left – the Office button in Excel 2007 5. Figure A1.5. The Excel add-ins featuring the drop-down list MANAGE (bottom right) and the GO button 6. Figure A1.6. The dialog box displaying the available add-ins 7. Figure A1.7. The dialog box showing the list of available add-ins for Microsoft Excel 2013. At the bottom, we can see the "Manage" field along with its drop-down menu and GO button 8. Figure A1.8. The "Add-Ins" dialog box 9. Figure A1.9. The ribbon in the DATA menu including the solver icon on the right 10. Figure A1.10. The dialog box for installing the solver add-in 11. Figure A1.11. The TOOLS menu and the option SOLVER... (last option on the list) 7. Appendix 2: Installing the Java Development Kit 1. Figure A2.1. The sub-folder "Utilities", located in the "Applications" folder in OSX. Note the application "Terminal" 2. Figure A2.2. The field "Search programs and files" (on the left) and inputting "cmd" in the same field (on the right) 3. Figure A2.3. The "Run" option from "All programs" and the RUN dialog box featuring the field OPEN containing "cmd" 4. Figure A2.4. The "command prompt" option in the "Accessories" folder in Microsoft Windows XP 5. Figure A2.5. The command list for use with "javac" from the Microsoft Windows command menu (on the left) and from the OSX Terminal (on the right) 6. Figure A2.6. From the properties of the work post we can see all of the windows for accessing the environment variable "Path" (Microsoft Windows 7) ## Guide 1. Cover 2. Table of Contents 3. Begin Reading ## Pages 1. C1 2. iii 3. iv 4. v 5. ix 6. x 7. xi 8. xii 9. xiii 10. xv 11. xvi 12. xvii 13. xviii 14. xix 15. xx 16. xxi 17. xxii 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174. 175. 176. 177. 178. 179. 180. 181. 182. 183. 184. 185. 186. 187. 188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 208. 209. 210. 211. 212. 213. 214. G1 215. G2 216. G3 217. G4 218. G5 219. G6 220. G7 221. G8 _Series Editor Jean-Paul Bourrières_ # Modeling and Simulation of Logistics Flows 2 ## _Dashboards, Traffic Planning and Management_ Jean-Michel Réveillac First published 2017 in Great Britain and the United States by ISTE Ltd and John Wiley & Sons, Inc. Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms and licenses issued by the CLA. Enquiries concerning reproduction outside these terms should be sent to the publishers at the undermentioned address: ISTE Ltd 27-37 St George's Road London SW19 4EU UK www.iste.co.uk John Wiley & Sons, Inc. 111 River Street Hoboken, NJ 07030 USA www.wiley.com © ISTE Ltd 2017 The rights of Jean-Michel Réveillac to be identified as the author of this work have been asserted by him in accordance with the Copyright, Designs and Patents Act 1988. Library of Congress Control Number: 2016959837 British Library Cataloguing-in-Publication Data A CIP record for this book is available from the British Library ISBN 978-1-78630-107-9 # About This Book There are already several works about logistics, operational research, decision support, the theory of graphs, dynamic programming, etc., but few of them gather all of these domains together by proposing an overall vision that focuses less on pure and hard mathematical aspects, without totally ignoring them, while offering numerous practical exercises. This book is one of three volumes. This first volume tackles theoretical aspects with corrected exercises for each chapter, finishing with a presentation of the principal software systems dedicated to operational research (OR) and logistical simulation. The second and third volumes are dedicated to practice and specialized applications of software programs. Most of the studies proposed here are able to be completed using a simple calculator, a sheet of paper and a pen or even with the help of a spreadsheet on Microsoft Excel, Apache OpenCalc, Apple Numbers, etc. The presented techniques and their uses are multiple, yet I am sure that a student, a software programmer, a developer, a technician, an engineer, an IT specialist, a decision-maker and you, the reader, will find practical applications that were unexpected in your professional or even personal life. ##### Intended public This work is designed for all those who encounter logistical problems linked to flux management, decision support, optimization of journeys or rounds, research for an aim when confronted with multiple constraints, creation of dashboards, relevant simulations, etc. The works presented require a minimum level of mathematical knowledge, and a post A level student in science or economics will not encounter major difficulties. I tried to maintain simplicity and go straight toward the objective in the theoretical approach without going into great demonstrations, which to me do not seem necessary. In terms of the practical exercises, on a laptop, tackled in Volumes 2 and 3, a good knowledge of the exploitation system (track, records and lists, files, names, extensions, sheet, movement, etc.) will prove essential. Since a few works use a spreadsheet, it is thus necessary to master the basic functionalities of this type of software program. It will also be convenient to know the primary use of pivot table data manipulation tools. If we know about _visual basic application_ (VBA) language or its equivalent, we can easily understand, improve, enrich and create new solutions to certain problems. Lastly, if we understand the basic systems for managing data and relational algebra, then we will be at ease in every domain explored. ##### Organization and contents of the book This work is composed of three volumes: * – Volume 1: Theory and fundamentals; * – Volume 2: Dashboards, traffic planning and management; * – Volume 3: Discrete and continuous flows in 2D/3D. Volume 1 presents an introduction followed by 10 chapters and a conclusion: * – approach for logistics; * – an overall view of operational research; * – basics of the theory of graphs; * – calculation of optimal routes; * – dynamic programming; * – planning and scheduling with PERT and MPM; * – calculation of waves in a network; * – hiding trees and tours; * – linear programming; * – modelization of route traffic; * – diverse software programs for RO and simulation of logistical flux. Here, we will find the fundamental concepts needed in order to understand the second volume. Numerous examples accompany the theory and each chapter ends with a series of exercises with their solutions. The conclusion, as indicated by the name, tries to establish a picture of the current state of theoretical logistics and its future development. Appendices 1 and bring a few other elements. We will find them in the following order: * – table of the law of the normal reduced center; * – a presentation and a mini-manual dedicated to the calculation software program GeoGebra. Volume 2 starts with an introduction completed with four chapters that put into practice the software tools in cases of practical application in order to finish with a conclusion: * – the different tools used in this volume; * – operational research with a spreadsheet; * – dashboards with a spreadsheet; * – scheduling and planning with a project manager; * – simulation of route traffic. The conclusion presents new functionalities that should appear on spreadsheets and project management systems as well as the evolutions and points of similarity between traffic simulators and new infrastructures that emerge in traffic networks. Appendix 1 is dedicated to the installation of a solving tool in Microsoft Excel. Appendix 2 is consecrated to the installation of Java development kit. Volume 3 starts with an introduction followed by four chapters dedicated to the modelization and simulation of flux in a 2D or 3D environment. Each case is different and taken from situations encountered in reality. A conclusion concludes this Volume 3: * – different software programs used in this third volume; * – simulation of discreet computerized flows; * – simulation of mixed flows; * – 3D flows and evacuation simulation; * – 3D flows for transporting and storing. The conclusion conveys the future evolutions of software programs and their integration into society. At the end of each volume, we will find a bibliography and a list of Internet links. A glossary is also available that will elaborate on certain acronyms and some very specific terminology surrounding logistics and operational research. ##### Conventions This book uses the following typographic conventions: * – _italics_ : used exclusively for important terms used for the first time in the text, one can generally be found in the glossary at the end of the work mathematical terms, comments, equations, expressions or variables present in the theoretical and practical chapters among examples and exercises; * – _(italics)_ : these are the terms in English or in foreign languages; * – UPPER CASE: these are reserved for names of windows, icons, buttons, files or lists, menus or submenus. This can also be elements, options or commands present in the window of a program; * – `courier`: this font is used for VBA code lines. These lines can end with the symbol ↵, which implies a return to the obligatory line when inputting. Any comments are signaled by the presence of a keyword: COMMENT. They will complete the explications already provided. Theorems are signaled by the keyword: THEOREM. The figures and tables have captions to further their understanding. ##### Vocabulary and definition Like for all techniques, logistical optimization tools have their own vocabulary. Words, acronyms, abbreviations and specific names that are not always familiar; this is the role of the Glossary found at the end of the book. ##### Acknowledgments It is my particular duty to thank the team at ISTE, and my editor Chantal Ménascé who had confidence in me, Jacqueline Gélinier from the company 1point2, distributor of ExtendSim and PathFinder software programs, Clair Augsburger of FlexSim France, not forgetting my dear friend, Pascal Mauny, director of IUT of Chalon-en-Saône and lecturer at the University of Bourgogne, for the time and attention granted to me for writing the preface. Finally, I would like to thank my wife, Vanna, who has supported me throughout writing this book. Jean-Michel RÉVEILLAC November 2016 # Introduction ## I.1. Logistics, information systems and software The last chapter of Volume 1 of this series ended by looking at the software used for solving the different logistical problems that industrial, commercial and administrative structures face on a daily basis [REV 17a]. Since its inception, logistics has been omnipresent and has undergone significant development. Globalization, the explosion of the internet and the constant push to look to do everything better, quicker, more effectively and for less money, have greatly contributed to its expansion. Although we are still only in the early stages, can we say that logistics has reached full maturity? Nothing could be less certain. The Internet of Things, still in its infancy, should profoundly change the normal rules relating to product management in the years to come. The steps being taken by our cities towards becoming intelligent cities or " _smart cities"_ will soon cause upheaval in our daily lives and our work habits, in public transport, in business and even in our own homes. The centralization of many different kinds of data and the increase in central file storage has only just begun. We are currently living in a world of information systems and databases and that will continue to be the case in the future. However, aside from the impact this has on ourselves as individuals, our environment and the objects we use will be implicated in this massive warehouse of data that is currently being put together. In 1997, the concept of " _big data"_ first appeared. For many researchers this is one of the challenges that the information industry will have to deal with between 2020 and 2030: how to properly manage and analyze this enormous accumulation of content. The optimization and the simulation of logistical flows plays an important role in this phenomenon. Data is collected and is then used to build models and structures in order to optimize constraints present in the field. A variety of different types of software are used and can be divided into two categories: the specifics that deal with particular areas, such as _flow simulations_ (extendSim, FlexSim, Arena, Witness), management and project _planning_ (Microsoft project, Sciforma PS, GanttProject, MicroPlanner), calculating and _optimizing routes_ (Gazoleen, Portatour, Mapotempo, Geoconcept, TourSolver), the management of _warehousing_1 (Speed, Reflex WMS, Mecalux Easy WMS) and general applications, such as spreadsheets (Microsoft Excel, Apple Numbers, OpenOffice Calc) or calculation managers (Mathematica, Mapple, Xcas, GeoGebra). In Volumes 2 and 3 of this series, I wanted to introduce you to the optimization and the simulation of logistical flows across some of these types of software. The ones that I chose and focused on are those that I use in my everyday work, not just in my role as an IT engineering consultant but also when teaching students. The majority of the cases dealt with here come from practical cases that have been bowdlerized several times in order to avoid overloading how they are presented and to thus facilitate access for a novice who can then look into it further should they wish. In this second volume, we will work successively with Microsoft Excel, the project manager Microsoft Project and the road traffic simulators, Ring road, RoadTrafficSimulator, Intersection simulator, Green Light District (GLD) and AnyLogic2. The studies carried out using spreadsheets will employ a number of the operational research techniques described in Volume 1 [REV 17a]. In turn, we will look at: * – Dynamic programming using the so-called Knapsack Problem (KP) problem solving method. This exercise will use a solution employing Visual Basic Application (VBA) with which you will develop two detailed and commentated procedures. **Figure I.1.** _Knapsack with Microsoft Excel_ * – _Scheduling_ : where you will design a critical path resolution matrix based on simple calculation formulae, the majority of which will integrate conditional instructions. **Figure I.2.** _A critical path calculation matrix_ * – The planning of tasks will enable you to discover how a histogram can be used in order to generate a _Gantt chart_ , either connected or unconnected to a calendar. **Figure I.3.** _Gantt chart with Microsoft Excel_ * – The management of _maximal flows_ will lead you to implement, in the same way as dynamic programming, two detailed and annotated procedures in Visual Basic, connected to a spreadsheet. * – The _transport models_ will be based on a tool found in Microsoft Excel, known as Solver. You will learn how to use it by inputting the different elements required for its use: objective, variables and constraints across the two examples. **Figure I.4.** _An example of a spreadsheet for maximal flows_ **Figure I.5.** _Calculating transport costs using the Microsoft Excel solver_ * – _Linear programming_ also requires the use of the solver in order to process the _simplex_. In this exercise you will learn how to create a spreadsheet that will formalize the inequations of the constraints of a PL problem as well as the economic function, followed by configurating the solver in order to find the optimal solution. **Figure I.6.** _An example of linear programming, spreadsheet and solver_ Secondly, the spreadsheet will also make it possible to create _dashboards_ implementing complex _pivot tables_ that will work with one or a number of databases. **Figure I.7.** _A pivot table mixing numbered and graphic data_ Within project management, we will set up a design and manufacturing plan for a machine-tool by integrating the different tasks, the resources, the costs, the creation of dashboards, reports and monitoring. We will see in detail the Gantt chart type displays and the Méthode des potentiels Métra (MPM) network, plus the Work Breakdown Structure (WBS) codification, margin calculation and the management of the over-use of resources. All of these different studies will employ the principles developed in Chapter 5 of the first volume of this series, which dealt specifically with scheduling. **Figure I.8.** _A design and manufacturing plan for a machine-tool within Microsoft Project_ Chapter 4 will focus on a particular field that is highly complex, _road traffic management_. We will examine several problems linked to the circulation of vehicles in a range of situations and contexts, at different levels, while using various programs. Several examples will be given for each of the five applications being studied: * – a traffic jam simulator; * – an editor-simulator of traffic flow in a model incorporating junctions and traffic lights; * – an optimization simulator for an intersection managed by traffic lights; * – an editor-simulator for multi-lane road networks, integrating several kinds of vehicles, with the management of traffic lights; * – a multi-method general simulator featuring a library dedicated to road traffic management. **Figure I.9.** _A simple road network with its intersection and traffic lights_ For each of these, we will develop _scenarios_ with various different constraints in order to get an overview of the functionalities and potentials available for processing and analyzing traffic flows in circulation conditions depending on the structure of the network, the topography of the terrain, the _concentration_ of vehicles, the type of vehicle, the signals, the number of traffic routes, the behavior of drivers and so on. 1 Software for the management of warehousing is often referred to using the acronym Warehouse Management System (WMS). 2 Although Anylogic is a general flow simulation program, the example that I will present in this volume will focus on the modeling of road traffic. # 1 Operational Research Using a Spreadsheet ## 1.1. Foreword In this chapter, I will present various possible ways of using Microsoft Excel for solving classical problems linked to operational research. The version that I use is part of the Microsoft Office 2013 Suite. Most of the exercises shown can easily be adapted for other spreadsheets provided they have similar functions. ## 1.2. Dynamic programming Here, we will examine a problem we first encountered in section 4.2.3 of the first volume of this series, the famous knapsack problem (KP). I will present a solution here based on a spreadsheet linked to two procedures written in Visual Basic Application (VBA). To begin with, we must first create the table in Figure 1.1 in a spreadsheet. Once the input has been carried out, place the following formulae in the indicated cells: * – `E1: =COUNTA(B4:K4)`, calculates the number of objects available; * – `B24: =TOTAL(B23:T23)`, calculates the total value of the objects; * – now save your table; * – switch to VBE, create a module for your project (DEVELOPER tab, VISUAL BASIC icon, right click on the project file, INSERT then MODULE); * – open the module that has just been created, normally MODULE 1 and input the following lines of code: **Figure 1.1.** _The table to be created in the spreadsheet_ Sub Clear()↵     'Clears the contents of the initial table↵     rep = MsgBox("Do you wish to clear the tables' contents to begin a new calculation", vbYesNo, "Clear")↵     If rep = vbYes Then↵         Range("B1").ClearContents↵         Range("B3:K5").ClearContents↵         Range("A8:U17").ClearContents↵         Range("B20:K23").ClearContents↵     End If↵ End Sub↵ ↵ Sub Knapsack()↵     rep = MsgBox("Have you entered the capacity and values in the table above to begin a new calculation ?", vbYesNo, "Calcul")↵     If rep = vbNo Then Exit Sub↵     'Declaration of variables and tables↵     Dim i, j, m1, m2 As Integer↵     'Table of weights↵     Dim p() As Integer↵     'Table of values↵     Dim v() As Integer↵     Dim c As Integer↵     'Allocation of the capacity to the variable c↵     c = Cells(1, 2)↵     Dim n As Integer↵ 'Allocation of the number of objects to the variable n↵     n = Cells(1, 5)↵     ReDim p(n)↵     ReDim v(n)↵     'Objects matrix↵     Dim table() As Integer↵     ReDim table(n, c)↵ ↵     'Reading object weight↵     For i = 1 To n↵         p(i) = Cells(4, i + 1)↵     Next↵ ↵     'Reading object weight↵     For j = 1 To n↵        v(j) = Cells(5, j + 1)↵     Next↵ ↵     Initializing the table, setting its content to 0↵     For j = 0 To c↵         table(0, j) = 0↵     Next↵ ↵   'Constructing and filling the matrix↵     For i = 1 To n↵         For j = 0 To c↵             If j >= p(i) Then↵                 m1 = table(i - 1, j)↵                 m2 = table(i - 1, j - p(i)) + v(i)↵                 If m1 > m2 Then table(i, j) = m1 Else table(i, j) = m2↵             Else↵                 table(i, j) = table(i - 1, j)↵             End If↵             Cells(7 + i, j + 1) = table(i, j)↵         Next↵     Next↵ ↵    'Reading objects↵     Dim ob(8) As String↵     For u = 1 To n↵         ob(u) = Cells(3, u + 1)↵     Next↵ ↵    'Further reallocation of variables↵     i = n↵     j = c↵ ↵     'Determining maximal weight↵     Dim k, m As Integer↵     m = 2↵     For k = c To 0 Step -1↵         If table(i, j) = table(i, j - 1) Then j = j - 1↵     Next↵     Cells(20, 2) = j↵ ↵     'Obtaining the list of objects in the table of results↵     While i > 0 And j > 0↵         If table(i, j) <> table(i - 1, j) Then↵             j = j - p(i)↵             Cells(22, m) = ob(i)↵             Cells(23, m) = v(i)↵             Cells(21, m) = i↵             i = i - 1↵             m = m + 1↵         Else↵             i = i - 1↵         End If↵     Wend↵ End Sub↵ **Figure 1.2.** _The VBA code window in VBE attached to Module 1 of the project_ To launch these two procedures, `Clear()` and `Knapsack()`, create two buttons by inserting two forms to which you will assign each of the two macros (right click on form then ASSIGN MACRO...). Your spreadsheet should look like the one in Figure 1.3. **Figure 1.3.** _An accounting spreadsheet containing two (Delete and Calculate) procedure buttons (macros)_ In order to use the KP calculation, all you need to do is click on the CLEAR button to erase any calculation that has already been carried out and to delete the calculated contents. Secondly, you should input the data in the upper table (`B1` and `B3` to `K5`). For the final stage, click on the CALCULATE button to launch the calculation and to show the results. COMMENT 1.1.– In the spreadsheet that we have just created, you can manage up to 10 objects. Nothing will stop you from increasing this number by making the necessary modifications to the tables and the relevant VBA procedures. **Figure 1.4.** _The example of paragraph 4.2.3.3 calculated. The results can be seen in the bottom table_ ## 1.3. Scheduling In this section, I will describe two possible ways of using the Excel spreadsheet: * – as a method for calculating the critical path and the duration of the project based on a calculation using a matrix (double entry table); * – for creating a simple Gantt chart using a precedence table. ### 1.3.1. _Critical path calculation matrix_ Using a Microsoft Excel spreadsheet containing a matrix constructed around several calculation formulae, we will be able to determine the critical path and the duration of a project (see section 5.8 of Volume 1 [REV 17a]). The table shown is limited to a PERT chart with at most 10 points. It can easily be adapted to a larger number of lines and columns by applying the same logic in order to create the missing calculation formulae. In order to present and explain how this spreadsheet functions, we will re-use Exercise 2 from section 5.14.2 of Volume 1 REV 17a], whose matrix is shown in [Table 1.1. **Table 1.1.** _The double entry matrix from Exercise 2_ Let's now create an accounting spreadsheet like the one in Figure 1.5. We can see that the matrix created is designed for 10 points. The grayed-out areas will contain calculation formulae as well as the columns from the beginning for the earliest start and latest end dates _i_ and _j_. **Figure 1.5.** _The table to be created in the spreadsheet_ Let's begin with the section on the right, in Figure 1.6. Here, you can see the formulae to be inputted (only cells L3 and P6 are shown – the others follow the same pattern). **Figure 1.6.** _The section on the right with the calculation formulae to be inputted_ We will comment on these formulae that fit with the calculation technique described in section 5.8.3 of Volume 1. All they do is automate the approach: * – `M3: =L2+C2`, adds the earliest start date for the first task to the first value encountered; * – `L3: =IF(COUNTA(D2:D3)=0, L2, M3)`, checks for the absence of a value in `D2` and `D3`, if the value is absent, it displays the previous earliest start date, which is `L2`, otherwise nothing is displayed; * – `M4: =IF(D3<>"", L3+D3, "")`, checks for the presence of a value in `D3` and in this case effects the sum `L3+D3`, otherwise nothing is displayed; * – `N4: =IF(D2<>"", L2+D2, "")`, identical to the previous test for cell `D2`. The other group of grey cells, from M5 to `U11`, behaves in the same way, by taking account of each of the values present or absent in the column in question; * – `L4: =IF(MAX(M4:S4)=0, L3, MAX(M4, S4))`, checks the maximal value calculated in the column (the result of the calculations placed in cells `M4` to `S4`). If it is equal to 0, no values will have been calculated, we can therefore assume that all the points have been reached, in which case the last value calculated from the beginning to the end should be copied, which is `L3`, otherwise the maximum is displayed. The same goes for the other formulae placed from `L5` to `L11` with the corresponding cells. Let's now look at the lower part, cells K12 to B21. As was the case with the previous example, only a few formulae are shown. The others follow the same pattern: * – `K12: =L11`, returns to the last value in the column of earliest start dates; * – `C13: =IF(D3<>"", D12-D3, "")`, checks if the cell located below the diagonal is empty and if it is not, calculates the difference with the corresponding cell, which is `D12-D3`, otherwise nothing is displayed. This calculation is identical for all the other cells in the grey zone if the cell references are changed to obtain the appropriate result (see Figure 1.7); * – `C12: =IF(MIN(C13:C21)=0, D12, MIN(C13:C21))`, checks the minimal value calculated in the column (the result of the calculations in cells `C13` to `C20`). If it is equal to 0, no values will have been calculated, we can therefore assume that the vertex has not been reached, in which case the last value calculated for the latest end date is copied, which is cell `D12`, otherwise the minimum is displayed. The same goes for the other formulae located in `D12` to `J12` with the corresponding cells; * – `B12: =MIN(B13:B21)`, calculates the minimal value from zone `B13` to `B21`, to display the latest end date of the first vertex in the graph. **Figure 1.7.** _The cells located below the CPM matrix with their formulae_ We will now concern ourselves with find the critical path through the graph node numbers. The length of the project is associated with the last value for the earliest beginning, `L11`: * – `F23: =IF(B12=L2, B1, "")`, tests if cell `B12` is equal to cell `B2` and displays the node number located in `B1`. This formula is not compulsory, it can simply be replaced by `=L2`, since the first node is always in the critical path, except in specific cases; * – `G23: =IF(MAX(M3)<>0, IF(C12=L3, C1, ""), "")`, we find two interlinked tests. The first verifies that M3 is different to 0, if this was not the case, this would mean that the current node does not belong to the critical path and nothing would be displayed. If `M3` is different to 0 then we check that `C12` is equal to its corresponding cell, `L3`, on the diagonal in the matrix and the node number `C1` is displayed, otherwise nothing is displayed; * – `H23: =IF(MAX(M4:N4)<>0, IF(D12=L4;D1, ""), "")`, identical to the above, but with a zone of `M4` to `N4` to test the maximum; * – the same principle is then applied for the cells from `I23` to `O23` with the corresponding cell references. **Figure 1.8.** _Calculating the critical field and display showing the duration_ See Figure 1.9 for the results obtained after inputting the figures from the table referred to earlier. **Figure 1.9.** _Spreadsheet with all cells filled in the matrix. Note the values of I (earliest start) and j (latest end) as well as the length of the project and the critical path that passes through nodes: 1, 2, 4, 7 and 8_ ### 1.3.2. _Classic Gantt chart_ In order to create this chart, we will use the public address system exercise dealt with in section 5.5 of Volume 1. In the precedence table (Table 1.2) only the columns for task and duration (in minutes) have been retained with the addition of two new columns, start and end. **Table 1.2.** _Tasks, starts, durations and ends for the sonorization exercise_ Task | Start | Duration | End ---|---|---|--- A | 0 | 120 | 120 B | 120 | 20 | 145 C | 120 | 15 | 140 D | 120 | 20 | 140 E | 140 | 10 | 155 F | 140 | 15 | 155 G | 155 | 25 | 180 H | 140 | 20 | 180 I | 180 | 15 | 195 This table is inserted into a Microsoft Excel spreadsheet and we then add a variance column that will calculate the difference between "End" and "Start" (in the cell `E2: =D2-B2`) in order to obtain the matrix in Figure 1.10. **Figure 1.10.** _The matrix corresponding to the task table with each of its columns_ Next, select the table, then carry out the following group of operations: * – INSERT tab, CHARTS toolbar, select INSERT A BAR CHART, select STACKED BARS in 2D BAR (Figure 1.11); **Figure 1.11.** _Microsoft Excel: insert a 2D STACKED BAR CHART_ * – finally, move the graph and resize it (Figure 1.12); **Figure 1.12.** _The resized graph, positioned under the matrix_ * – click on the y-axis; * – right-click, select FORMAT AXIS (Figure 1.13); **Figure 1.13.** _The contextual menu (right click) to format the axis_ * – in the FORMAT AXIS window, select CATEGORIES IN REVERSE ORDER (Figure 1.14); **Figure 1.14.** _The window for configuring the axis in Microsoft Excel 2013, including the checkbox: values in reverse order (in axis options)_ * – click on the x axis to select it; * – in the FORMAT AXIS window, open drop-down LABELS and select HIGH in LABEL POSITION; * – enter 10 and 5 respectively in AXIS OPTIONS as MAJOR and MINOR UNITS (Figure 1.15); **Figure 1.15.** _Configuring axes (10 and 5) and labels (high)_ * – right click on the middle of the graph and click on SELECT DATA; * – a window for selecting a data source will open. Tick "Duration" and "End Date" (you can also remove these using the DELETE button) then validate by clicking the OK button (Figure 1.16); **Figure 1.16.** _The fields "length" and "end" selected in the window displaying the data source_ * – click on the legend and delete it (press DEL or backspace on Mac); * – right click on the "Start" bar on the graph, specify NO OUTLINE and NO FILL by clicking on the corresponding icons (OUTLINE and FILL) in the pop-up tool bar (Figure 1.17); **Figure 1.17.** _The menu and the pop-up tool bar, obtained by right-clicking on the "Start" bar. Note the tools OUTLINE and FILL above the menu_ * – double-click on the title to change it and type "Outdoor public address system"; * – to finish, save your work (Figure 1.18). **Figure 1.18.** _The finished Gantt chart and its associated table in a Microsoft Excel 2013 spreadsheet_ ### 1.3.3. _Gantt chart with a calendar_ In cases where dates have to be managed according to a calendar that can show workdays and holidays, we must consider excluding the latter from the project timeline. Table 1.3 gives an example involving these conditions. Installing an air conditioning system (simplified agenda) (see Table 1.3). **Table 1.3.** _The precedence table for the installation of an air-conditioning system_ Task | Appointment | Duration (days) | Previous ---|---|---|--- A | Needs analysis (electrical equipment, piping, fittings, coolant gas and various other components) | 1 | – C | Order and delivery of electrical equipment | 5 | A D | Order and delivery of the group exchanger and diffusers | 8 | A E | Order and delivery of coolant gas | 4 | A F | Assembly, installation and laying of the group exchanger | 2 | D G | Installation and laying of diffusers | 4 | D H | Laying and connecting pipes | 2 | B, F, G I | Electrical connection | 1 | C, F, G J | Filling the installation, pressurization and clean-up | 1 | E, H K | Switching on, testing installation and tuning | 1 | H, I, J L | Tidying up the work site | 1 | K For this second exercise, we will consider the project start date as being Monday March 2nd 2015. We will begin by entering a table in Microsoft Excel similar to the one shown in Figure 1.19. The dates for the start and the end have been calculated in a standard way using a PERT or MPM type method (the MPM chart is shown in Figure 1.20). **Figure 1.19.** _The table to be created in Microsoft Excel (here the critical tasks are in gray and in bold)_ **Figure 1.20.** _The MPM chart corresponding to the project: installation of an air conditioning system_ In the cell `D4` (End), we have the formula `=B4+C4`, that we will fill downward as far as `D15`. In the cell `E4` (Variance), we have the formula `=D4-B4`, that we will fill downward as far as `E15`. It should be noted that the end dates do not take into account a week where only the days from Monday to Friday will be workdays. To compensate for this we can replace the formula, located in `D4`, by `=SERIES.WORK.DAY(B4;C4)`. This gives the table shown in Figure 1.21. **Figure 1.21.** _The table recalculated for workdays_ In order to properly display the graph, it will be necessary to change the format of the dates in the columns "Start" and "End" by replacing the date format with the standard format: * – select cells `B4` to `B15`, then, while holding down CTRL, cells `D4` to `D15`; * – right click, FORMAT CELLS..., NUMBER tab, GENERAL category. This gives the number of days since 1st January 1900 in each of the cells. **Figure 1.22.** _The "Start" and "End" columns in STANDARD format_ Next, select the table, then carry out the following operations: * – INSERT tab, CHARTS toolbar, scroll down to BAR, select STACKED BAR in 2D BAR; * – move the chart and resize it; * – click on the y-axis; * – right click, select Excel US syntax; * – in the FORMAT AXIS window, tick CATEGORIES IN REVERSE ORDER; * – click on the x-axis to select it; * – in the FORMAT AXIS window, click on the icon in the shape of a bar chart; * – enter 42065 (the value of the cell B4, for 03/02/2015, the start date for the project) in AXIS OPTIONS as MINIMUM; * – next, enter 7 and 1 respectively as MAJOR and MINOR UNITS; * – pull down LABELS and select HIGH in LABEL POSITION; * – pull down NUMBER, select DATE in CATEGORY then *3/14/2001 in TYPE; **Figure 1.23.** _AXIS OPTIONS, LABELS and NUMBER_ * – in the FORMAT AXIS window, click on cross-shaped icon (to the left of the bar chart); * – pull down ALIGNMENT and enter -45° in the field CUSTOM ANGLE in order to pivot the dates on the x-axis; **Figure 1.24.** _AXIS OPTIONS, ALIGNMENT -45°_ * – right click on the bottom of the chart and click on SELECT DATA; * – a 'Data Sources' window will open. Tick "Duration" and "End" (you can also remove these using the DELETE button) then validate by clicking the OK button; * – click on the legend and delete it (hold down DEL or back space on a Mac); * – right click on the "Start" bar on the chart, specify NO OUTLINE and NO FILL by clicking on the corresponding icons (OUTLINE AND FILL) in the pop-up tool bar; * – right click on a date on the x axis, ADD A MINOR GRIDLINE; * – double click on the title to change it and type "Installing an air conditioning system"; * – next, repeat a date format for the "Start" and "End" columns; * – to finish, save your work; * – you can change the colors of the chart by putting, for example, critical tasks in a different color. **Figure 1.25.** _The finished table and chart corresponding to the Gantt chart for the project_ The exercises for creating a Gantt chart that have previously been examined can be adapted for larger projects. The table will be larger but the principles and the practical tasks remain the same. ## 1.4. Maximal flows In order to calculate the maximal flow available in a network between the source and the sink, we will use the Excel solver alongside two VBA procedures and a spreadsheet. In the solution shown here, the number of edges is limited to 25 and the number of vertices is limited to 20. Begin by creating the spreadsheet in Figure 1.26. **Figure 1.26.** _The spreadsheet to be created in Microsoft Excel_ Next, enter the following calculations: * – `G2: =IF(F2="", "", SUMIF(From, F2, Flow)-SUMIF(To, F2, Flow))`, if the cell in the column "Nodes" is empty then nothing is displayed; if not the difference is calculated: the total of the flows equal to F2 in the column "From" – the total of the flows equal to F2 in the column "To". This will determine the net flow; * – "From" and "To" are cell ranges that will be named later using a VBA procedure; * – `Copy G2 downward` as far as cell `G21`; * – `C27: =COUNTA(A2:A26)`, counts the number of edges; * – `G22: =COUNTA(F2:F21)`, counts the number of vertices; * – `C28: =G2`, displays the maximal flow; * – then save your table; * – switch to VBE, create a module for your project (DEVELOPER tab, VISUAL BASIC icon, right click on the project file, INSERT then MODULE); * – open the module that has just been created, ordinarily MODULE 1 and input the following lines of code: Sub Create_tables()↵ Dim CountArc, CountNodes As String↵     'Clear tables↵     'If click on No then clear otherwise quit↵     If MsgBox("Do you wish to clear the table content?", vbYesNo, "Clear") = vbYes Then↵     'Clears the cell content↵         Range("A2:D26, F2:F21, H3:H21").Select↵         Selection.ClearContents↵         'Deletes the cell background color↵         Range("A2:D26, F2:G21, H3:H21").Select↵         Selection.Interior.ColorIndex = 0↵         Range("C28").Select↵         'Relaunch automatic sheet recalculation↵         Application.Calculation = xlCalculationAutomatic↵     Else↵         Exit Sub↵     End If↵    'Name and color allocation↵     CountArc = InputBox("How many edges does your graph have?", "Number of edges")↵     'If click on Cancel then quit↵     If CountArc = "" Then Exit Sub↵     Range(Cells(2, 1), Cells(1 + CountArc, 1)).Name = "From"↵     Range(Cells(2, 1), Cells(1 + CountArc, 3)).Interior.ColorIndex = 40↵     Range(Cells(2, 2), Cells(1 + CountArc, 2)).Name = "To"↵     Range(Cells(2, 2), Cells(1 + CountArc, 3)).Interior.ColorIndex = 44↵     Range(Cells(2, 3), Cells(1 + CountArc, 3)).Name = "Flow"↵     Range(Cells(2, 3), Cells(1 + CountArc, 3)).Interior.ColorIndex = 36↵     Range(Cells(2, 4), Cells(1 + CountArc, 4)).Name = "Capacity"↵     Range(Cells(2, 4), Cells(1 + CountArc, 4)).Interior.ColorIndex = 27↵     CountNode = InputBox("How many vertices does your graph have?", "Number of nodes")↵     'If click on Cancel then quit↵     If CountNode = "" Then Exit Sub↵     Range(Cells(2, 6), Cells(1 + CountNode, 6)).Name = "Node"↵     Range(Cells(2, 6), Cells(1 + CountNode, 6)).Interior.ColorIndex = 17↵     Range(Cells(3, 7), Cells(CountNode, 7)).Name = "NetFlow"↵     Range(Cells(2, 7), Cells(1 + CountNode, 7)).Interior.ColorIndex = 37↵     Range(Cells(3, 8), Cells(CountNode, 8)).Name = "SupplyDemand"↵     Range(Cells(3, 8), Cells(CountNode, 8)).Interior.ColorIndex = 8↵     MsgBox ("You can now enter your" & CountArc & " arcs with their capacity in the FROM and TO column. Then enter the list of your " & CountNode & "nodes in NODES column.")↵     Range(Cells(3, 8), Cells(CountNode, 8)) = 0↵ End Sub↵ ↵ 'Launch the solver to find the solution↵ Sub Resolve()↵     'Reset solver to zero↵     SolverReset↵     'Defining solver parameters↵     SolverOk SetCell:="$C$28", MaxMinVal:=1, ValueOf:=0, ByChange:="$C$2:$C$19", _↵         Engine:=2, EngineDesc:="Simplex LP"↵     SolverDelete CellRef:="$C$2:$C$19", Relation:=1, FormulaText:="Capacity"↵     SolverOk SetCell:="$C$28", MaxMinVal:=1, ValueOf:=0, ByChange:="$C$2:$C$19", _↵         Engine:=2, EngineDesc:="Simplex LP"↵     SolverAdd CellRef:="$C$2:$C$19", Relation:=1, FormulaText:="Capacity"↵     SolverOk SetCell:="$C$28", MaxMinVal:=1, ValueOf:=0, ByChange:="$C$2:$C$19", _↵         Engine:=2, EngineDesc:="Simplex LP"↵     SolverDelete CellRef:="$G$3:$G$10", Relation:=2, FormulaText:="SupplyDemand"↵     SolverOk SetCell:="$C$28", MaxMinVal:=1, ValueOf:=0, ByChange:="$C$2:$C$19", _↵         Engine:=2, EngineDesc:="Simplex LP"↵     SolverAdd CellRef:="$G$3:$G$10", Relation:=2, FormulaText:="SupplyDemand"↵     SolverOk SetCell:="$C$28", MaxMinVal:=1, ValueOf:=0, ByChange:="$C$2:$C$19", _↵         Engine:=2, EngineDesc:="Simplex LP"↵     SolverOk SetCell:="$C$28", MaxMinVal:=1, ValueOf:=0, ByChange:="$C$2:$C$19", _↵         Engine:=2, EngineDesc:="Simplex LP"↵     'Launch automatic calculation of results by the solver↵     SolverSolve (True)↵ End Sub↵ In order to launch these two procedures, `Create_tables()` and `Resolve()`, create two buttons by inserting two forms to which you will assign each of the two macros (right click on form then ASSIGN a MACRO). Your spreadsheet should look like the one in Figure 1.27. **Figure 1.27.** _The spreadsheet with its two buttons ("Create tables" and "Solve")_ In order to use the calculation of maximal flows, all you need to do is click on the CREATE TABLES button to destroy any calculation that has already been carried out and delete the calculated contents. Two dialogue boxes will be displayed one after the other asking you how many edges you want followed by the number of vertices in your graph. Enter the data in the table on the left by mentioning, for each arc, the peak of departure in the column "From" and its vertice (node) of arrival in the column "To" followed by its capacity in the column "Capacity". Now add the flows. I would advise entering the minimal value of the capacity for all of the flows. Next, input all the vertices in the table on the right, in the "Vertices" column, beginning with the source (ordinarily S) and ending with the sink (ordinarily T). The order for the other vertices is irrelevant. It should be noted that the entry fields have been colored in order to make it easier to input data. Lastly, click on the SOLVE button to begin the calculation of the solution by the solver and to display the results. In Figure 1.28, I re-use the data from Exercise 1 in Chapter 6 (Volume 1, section 6.5.1), and you can see all edges and their capacities (18), all the vertices (10) and the starting flow, which is 2000. **Figure 1.28.** _The data from Exercise 1 in Chapter 6 entered into the spreadsheet_ Figure 1.29 shows the result of the calculation launched by clicking on the SOLVE button. **Figure 1.29.** _The solution from exercise 1 with the set of results displayed_ ## 1.5. Transport model There are a variety of logistical problems in transport: often, you need to standardize distances, the costs and the constraints for supplying customers. Below, you will find two classic examples that will be solved using the Microsoft Excel solver. Using this as a basis, it will be easy to use each of these solutions to adapt them to your own problems. ### 1.5.1. _Customer delivery_ A railway company has to transport two batches of palletized products from two departure stations (GD1 and GD2) to three destination stations (GA1, GA2 and GA3) spread out across France. The goods will pass through intermediary marshalling yards (GT1, GT2, GT3, GT4 and GT5). The number of pallets available in the outgoing stations and the storage capacities of the end stations are known, as are the transport capacities of the inter-station railway lines. Table 1.4 groups together the shared information for each station. **Table 1.4.** _Summary of palletized product batch flow_ If we examine the problem in greater detail, we notice that there is a problem involving maximal flow with constraints being exceeded. We will tackle this problem by using a simple double-entry table as well as the solver. First, create and fill a spreadsheet, the table shown in Figure 1.30. **Figure 1.30.** _The table to be created in a Microsoft Excel spreadsheet_ All of the data from the statement is shown here. For this purpose, the table has an S column and a T column, which represent the source and the sink, thus formalizing the number of pallets available at the departure station (DS1: 105 and DS: 75) and the storage capacity of the end stations (ES1: 45, ES2: 45 and ES3: 60). Below the first table, add a second like the one shown in Figure 1.31. **Figure 1.31.** _The second table positioned below the first_ It will be filled as indicated below: * – line 33 will contain the total of each of the columns; * – in cell `C33`, enter : `=TOTAL(C21:C32)`; * – next, copy this formula down to cell `L33`; * – column N will contain the total of each of the lines; * – in Cell `N22`, enter : `=TOTAL(B22:M22)`; * – next, reproduce this below until `N31`; * – in cell `N3`, enter the total of the wells to maximize : `=TOTAL(B31:M31)`; * – launch the solver, DATA tab, SOLVER tool in the tool ribbon. If it is not visible, consult Appendix 1 of this volume to begin its installation; * – configure the solver as shown in Figure 1.32; * – SET OBJECTIVE : `$N$3`; * – BY CHANGING VARIABLE CELLS : `$B$21:$M$32`; * – SUBJECT TO THE CONSTRAINTS : `$B$21:$M$32<=$B$6:$M$17`; * – SUBJECT TO THE CONSTRAINTS : `$C$33:$L$33=$N$22:$N$31`; * – Tick the box MAKE UNCONSTRAINTED VARIABLES NON-NEGATIVE * – SELECT A SOLVING METHOD : Simplex PL; **Figure 1.32.** _Configuring the solver_ * – Next, click on the bottom SOLVE. In a few moments, the solver will display the result window; * – You will then be able to SAVE SOLVER SOLUTION or RESET INITIAL VALUES (to start again) by ticking the appropriate box and clicking on the OK button. This will give you the values from Figure 1.33 in the second table that will specify the number of pallets to be transported between each of the points, taking all restrictions into account. **Figure 1.33.** _The results calculated by the solver_ You can see that the total number of pallets arriving at the destination does not exceed 150 (45+45+60), ensuring that the storage capacity of the arrival stations is not exceeded. ### 1.5.2. _Minimum-cost transport_ In this type of problem, the aim is to transport goods at a minimal cost while taking into account restrictions such as customer demand and warehouse storage capacity. Let's consider three factories (U1, U2 and U3) located in France who wish to deliver to their clients (C1 to C5) spread out across Europe. The transport costs (per ton: 1,000 kg) are specified in Table 1.5. **Table 1.5.** _Transport costs between factories and customers_ Factory stock | C1 | C2 | C3 | C4 | C5 ---|---|---|---|---|--- U1 | $300.00 | $2,400.00 | $300.00 | $1,500.00 | $1,200.00 U2 | $1,500.00 | $1,500.00 | $900.00 | $1,800.00 | $2,100.00 U3 | $600.00 | $900.00 | $1,500.00 | $2,700.00 | $2,400.00 In terms of stock, each factory has a volume of available product estimated at being 7,200 kg for U1, 4,800 kg for U2 and 7,800 kg for U3. The five clients want the following quantities: C1, 3,600 kg; C2, 3,900 kg; C3, 4,350 kg; C4, 3,750 kg and C5, 4,200 kg. It is now necessary to define what mass of product each of the three factories must send to each of the five customers in order to meet demand, taking into account the stock available and minimizing transport costs. First, create the two tables in Figure 1.34 in a Microsoft Excel spreadsheet. **Figure 1.34.** _The two tables for calculating costs_ Next, apply the following operations: * – in cell `B12`, enter the calculation : `=TOTAL(B9:B11)`; * – copy this formula to the right as far as `F12`; * – in G9, enter : `=TOTAL(B9:F9)`; * – next, copy this total downwards as far as `G11`; * – in cell `B14`, we will define the calculation objective for the solver. This is the total that we must minimize; * – enter: `=SUMPRODUCT(B3:F5;B9:F11)`; * – open the solver, DATA tab, SOLVER tool in the ribbon. If it is not visible, consult Appendix 1 for the installation procedure; * – enter the parameters as shown in Figure 1.35; * – SET OBJECTIVE: `$B$14`; * – BY CHANGING VARIABLE CELLS: `$B$9:$F$11`; * – SUBJECT TO THE CONSTRAINTS: `$B$12:$F$12=$B$6 : $F$6`; * – SUBJECT TO THE CONSTRAINTS: `$G$9:$G$11=$G$3 : $G$5`; * – Tick MAKE UNCONSTRAINED VARIABLES NON-NEGATIVE; * – SELECT A SOLVING METHOD: Simplex PL; **Figure 1.35.** _Configuration of the solver_ * – next, click on the SOLVE button and wait a few seconds; * – a window will open. You will then have the option to SAVE THE SOLVER SOLUTION or RESET TO ORIGINAL VALUES (to start again) by ticking the appropriate box and clicking on the OK button. The lower table displays the quantities to be dispatched to each of the factories of each of the customers. We can see that the restrictions relating to customer orders and to factory stocks have been taken into account. **Figure 1.36.** _The results obtained from using the solver_ ## 1.6. Linear programming I will now show you how to use the Microsoft Excel solver to solve classical linear programming problems that would be solved on paper using a simplex. We will create a spreadsheet capable of holding six constraints relating to six variables, by responding to maximization and minimization requests. It will be very easy to increase the amount of data to manage by applying the same calculation formulae on a larger table. ### 1.6.1. _Creating a calculation table_ Build and fill the table in Figure 1.37 in a spreadsheet, then carry out the following: **Figure 1.37.** _The table that will host our future linear programs_ * – In cell H5, enter the formula: `=TOTALPRODUCT (B5:G5;$B$2:$G$2)`. This formula carries out the total of the products between the cells in line 5 (constraint n°1) and line 2 (bi); * – Next, copy this formula downward as far as `H10`; * – In cell B14, enter the formula : `=TOTALPRODUCT(B12:G12;B2:G2)`. This formula calculates the total of the products between the cells in line 12 ( _z_ ) and line 2 (bi); * – Save your spreadsheet. ### 1.6.2. _Entering data_ To fill in our table, we will re-use the example from Chapter 8 (Volume 1, section 8.3.2), which has three constraints and the following profit, _z:_ Enter this data in your spreadsheet in order to obtain the table in Figure 1.38. **Figure 1.38.** _The data from the example, entered into our table_ COMMENT 1.2.– The indicators of inequality (<=) located in column I in our table are only given as an illustrative example – they are not relevant in the calculation. ### 1.6.3. _Using the solver_ Open the solver, DATA tab, SOLVER tool in the ribbon. If it is not visible, consult Appendix 1 for the installation procedure. Complete the different fields for the solver: * – SET OBJECTIVE : `$B$14`; * – Click on the option MAX (for this example we are dealing with an example of maximization); * – BY CHANGING VARIABLE CELLS: `$B$2:$G$2`; * – SUBJECT TO THE CONSTRAINTS : `$B$2:$G$2>=0; $H$10<=$I$10; $H$5<=$J$5 ; $H$6<=$J$6; $H$7<=$J$7 ; $H$8<=$J$8 ; $H$9<=$J$9;` COMMENT 1.3.– The constraints are not all necessary in our example, but the solver has been configured by default in order to solve a problem involving six inequalities. * – Tick the box : MAKE UNCONSTRAINED VARIABLES NON-NEGATIVE; * – SELECT A SOLVING METHOD: Simplex PL; **Figure 1.39.** _The different parameters entered in the solver dialogue window_ * – click on the SOLVE button; * – after a few moments the results will be displayed in the table and the SOLVER RESULTS window will be displayed. **Figure 1.40.** _Calculated results and the SOLVER RESULTS window_ The results found in Chapter 8 (Volume 1, section 8.3.7) are confirmed: _z_ = _15000; x1=0; x2=0 and x3 = 2500_. # 2 Dashboards, Spreadsheets and Pivot Tables ## 2.1. Spreadsheets: a versatile tool Since their creation, in the early 1970s, spreadsheets have become an essential tool in business and even outside of the professional sphere. Today, how many people manage their bank accounts using one? In this chapter, I will introduce you to the possibilities available with any proper spreadsheet using pivot tables that can provide quality decision aid dashboards. The following examples do not hinge on basic functionalities but on advanced usage, with functions that are often not particularly well known, but which are highly effective in terms of processing data and saving precious time for decision-makers. I will therefore make the assumption that the reader has the requisite experience for creating simple pivot tables. In the previous chapter of this volume, I made extensive use of spreadsheets (Microsoft Excel) but here I would like to focus more specifically on the handling of data from a Database Management System (DBMS) or a spreadsheet that itself constitutes a database for creating sophisticated dashboards or contingency tables1. In order to carry out these studies, I made the decision to use the spreadsheet Microsoft Excel 2013, but the examples given can easily be adapted to other versions or other spreadsheets featuring the pivot table concept such as, among others, the OpenOffice "DataPilot" or the FreeOffice "Pivot Tables". ## 2.2. Example database Before beginning our practical examples, we will need to create or import a sufficiently representative database in order for our various experiments to be consistent. I would suggest creating a database with several columns grouped in a single table, created using a DBMS then imported into Microsoft Excel or entered directly into a spreadsheet. The headings for our database will be: * – Date: the date of the sale including day, month, year – format: dd/mm/yy; * – Designation: product labeling, "Product A" to "Product F" – format: text; * – Net UP: Unit price before product tax – format: _($* #,##0.00_); * – Qty: quantity in terms of number of units – format: whole number, 0; * – Vendor: vendor name – format: text; * – Agency: location of the sales agency – format: text; * – Cat client: client category, INDV (individual), PRO (professional) – format: text; * – Client type: N (new), EX (existing) – format: text; * – Client area of residence: C (city), Di (District), D (Departement), C (County), S (State), OS (Outside state) – format: text; * – Net total: quantity x unit price BT – format: ($* #,##0.00_). Figure 2.1 shows an outline of the spreadsheet containing the database. In order to obtain enough combinations to allow us to draw meaningful conclusions, I would advise creating a table or a chart containing at least a hundred rows (tuples or records). **Figure 2.1.** _Example database_ ### 2.2.1. _Calculated field and formatting_ To begin with, we want to create a table that will synthesize the net margin that each vendor has provided for each product depending on the client category. This margin is estimated as being 32% of the net price of the sale regardless of the product. Furthermore, it would be preferable, for ease of interpretation, to be able to quickly visualize the size of the margin in chart form. Figure 2.2. shows the result to be obtained. **Figure 2.2.** _The dashboard to create_ We will create a simple table that can then be customized: * – create a pivot table including "Vendor" for the rows and "Designation" for the columns; * – in options, de-select Autofit column widths on update; * – re-name the headers in order to obtain a consistent table; * – re-size the columns so that the products are of equal width; * – put all cells in currency format (Category: Accounting, Symbol: $, Decimal places: 2). **Figure 2.3.** _The departure chart_ In order to display the necessary margins, we will need to insert a calculated field in our pivot table: * – select a pivot table cell, at the intersection of a vendor and a product; * – open the ANALYZE window, then choose the icon FIELDS ELEMENTS AND SETS in the ribbon; * – select CALCULATED FIELD to open the INSERT A CALCULATED FIELD dialog box; * – in the NAME field, enter "Net margin"; * – in the FORMULA field, delete the value 0 and keep the = symbol; * – in the list of fields, double click on the field "Net total", and it should appear alongside the = symbol; * – enter "*0.32" (in order to calculate the 32% margin) (Figure 2.4). **Figure 2.4.** _Inserting a calculated field: Net total x 0.32_ * – click on the ADD button, then OK; * – change the name "Net margin totals" (upper left of the table) to "Net margins"; * – your table should be filled with this new calculation. **Figure 2.5.** _The pivot table with the margin calculation_ All that is left to do is integrate a histogram representing the value of each of the margins and that of their totals: * – select the margins contained in the "Product A" column; * – open the HOME tab; * – select the CONDITIONAL FORMATTING icon, then the DATA BARS option; * – select a font and a color. The column will be filled with bars of a length proportional to the respective values; * – repeat this step for each of the other products and the "Grand Total"; * – open the HOME tab; **Figure 2.6.** _The conditional formatting tool including its options_ * – select the FORMAT AS TABLE icon; * – choose formatting. COMMENT 2.1.– During operations with pivot tables, the column width automatically adapts to the content and this can be a nuisance. To disable this option, simply select the ANALYZE tab, click on the OPTIONS icon in the PIVOTTABLE OPTIONS section of the ribbon, then de-select AUTOFIT...UPDATE in the LAYOUT AND FORMAT tab. **Figure 2.7.** _Size configuration in the pivot table options_ ### 2.2.2. _Calendar sections, rankings and averages_ In this second example, we would like to use a table grouping together agencies and products to show the net averages for quarterly sales for each establishment depending on the client category and the area of residence. A graph should highlight the best results: the agencies will be listed in alphabetical order while the quarters will be divided by year in ascending order. Figure 2.8 shows the expected results. **Figure 2.8.** _The pivot table to be obtained_ As before, we will start by creating the base table, which will include the following elements: * – FILTERS: "Cat. client" and "Client zone"; * – COLUMNS: "Designation"; * – ROWS: "Agency" and "Date"; * – Σ VALUES: "Net total amount". **Figure 2.9.** _The initial table for the second example_ We will now make the necessary modifications in order to carry out the task: * – move the cursor over one of the totals, then right-click to select VALUE FIELD SETTINGS; * – a dialog box will open. In the CUSTOM NAME field enter "Average net sales"; * – in the drop-down list, select AVERAGE; * – click on the NUMBER FORMAT button. A dialog box will open – select ACCOUNTING in the CATEGORY list, then click on the OK button; * – click again on the OK button to confirm your selections and to close the window. All values in the table should be re-calculated; * – at the top left of the table, replace "Average of Net total" with "AVERAGE NET SALES"; * – select one of the "day" dates, right-click and select GROUP. In the drop-down list, select QUARTERS and YEARS, then click on the OK button; * – select all of the cells under "Grand total" except the one on the last line; * – open HOME tab, click on the CONDITIONAL FORMATTING icon in the STYLE section, select DATA BARS and choose a model; * – for greater clarity, you can also adjust formatting by clicking on the FORMAT AS TABLE icon in the STYLE section of the ribbon and choose a model here. ### 2.2.3. _Conditional calculated fields_ The aim is to calculate the total bonus for each of our vendors depending on the quarter and the month for a given year. The total bonus is a percentage based on the monthly net total of sales made in a month. It follows this rule: * – net total greater than or equal to $1,600.00: Bonus = 1.6%; * – net total greater than or equal to $2,500.00: Bonus = 2.2% The final table should look like the one in Figure 2.10. **Figure 2.10.** _The pivot table showing the total monthly bonus_ To begin with, we will create a table containing all of the necessary elements available: * – create a pivot table with "Vendor" and "Date" in ROWS; * – enter "Net total" in Σ VALUES; * – right-click on one of the dates in the table and select GROUP; * – select "Month" and "Years" from the drop-down list and click on OK. For each vendor, the column should contain a list of months for each year; * – re-name the column "Net total amount" to "Total net sales", then change this to currency format; **Figure 2.11.** _The pivot table to be used as a base_ * – create a calculated field (starting with a pivot table cell, ANALYZE tab, icon FIELDS, ITEMS AND SETS) called "Bonus" and apply the following conditional formula: `=IF('Net Total'>=2500, 2.2%*'Net Total', IF('Net Total'>=1600, 1.6%*'Net Total', 0))` **Figure 2.12.** _Creating a conditional calculated field_ * – switch to the field "Bonus" under Σ VALUES; * – rename the column "Net bonus"; * – note that the sub-totals for each vendor are incorrect – the pivot table tool is not capable of making the calculation, and we will therefore delete them; * – switch to one of the cells of the pivot table, open the DESIGN tab, click on the SUB-TOTALS icon in the ribbon and tick DO NOT SHOW SUB-TOTALS; * – follow the same instructions for the grand totals at the bottom of the table. In the ANALYZE tab, click on the OPTIONS icon under PIVOT TABLE OPTIONS in the ribbon. A dialog box will open – in the TOTALS AND FILTERS tab, untick SHOW GRAND TOTALS FOR COLUMNS; * – click on the OK button to confirm. ### 2.2.4. _Slicers, filtering and calculated fields_ We have just seen a few examples of the use of calculated fields. We will now link this to the filter, the calculated field and the slicer. In the database that I use, each of the vendors made a turnover of between $4,725.00 and $11,520.00 for products A to F. I want my pivot table to show me the target figure that the six least effective vendors should meet for 2016, knowing that it should be 12% higher than 2015. To begin with, we will use the very simple pivot table from Figure 2.13. **Figure 2.13.** _The initial pivot table, before modification_ The following operations will delete the column from 2014, display the six least effective vendors from 2015 and add a column that will calculate their targets for 2016: * – select one of the cells in the pivot table; * – in the ANALYZE tab, click on the INSERT SLICER icon in the ribbon; * – a dialog box will open – tick "Date", then click on the OK button (Figure 2.14); * – a filter interface will open – double-click on 2015 (Figure 2.15). **Figure 2.14.** _Selecting the field for the slicer_ **Figure 2.15.** _The pivot table and the filter interface for selecting a slicer_ COMMENT 2.2.– The filter interface for slicing is still available and you can modify your options at any time by clicking on one of the relevant filtering buttons. If you do not want to use the filter, which you should keep, it is possible to delete 2014 from the pivot table by using the slicer management option. This involves taking the following steps (replacing the steps from before): * – select the 2014 cell in the pivot table; * – right-click and select FILTER, then DATE FILTERS (Figure 2.16); **Figure 2.16.** _Selecting the date filters_ * – a dialog box will open – select IS AFTER in the drop-down menu, then enter 01/01/2015 in the adjacent field; * – click on the OK button. Your pivot table will now only contain data from 2015 (Figure 2.17). **Figure 2.17.** _The pivot table showing only 2015 data_ We will now remove all but the six least effective vendors and create our calculated item, the target figure for 2016: * – select one of the vendors; * – right-click and select FILTER, then TOP 10; * – a dialog box will open – configure, using the different drop-down menus: BOTTOM; 6; ITEMS; BY "Net Total" (Figure 2.18); **Figure 2.18.** _The filter for selecting the six least effective vendors_ * – your pivot table should now only contain the six least effective vendors (Figure 2.19); **Figure 2.19.** _The pivot table showing the six least effective vendors_ * – in the ANALYZE tab, click on the FIELDS, ITEMS AND SETS icon in the ribbon and select CALCULATED FIELD; * – in the NAME field, enter "2016 Target"; * – in the FORMULA field, delete the value 0, then double-click on "Net Total" in the drop-down menu and enter "*1.12" to calculate the 12% increase required in order to meet the target (Figure 2.20); **Figure 2.20.** _Configuring the calculated field for the 2016 target_ * – two new columns will appear in your pivot table, "Sum of 2016 target" and "Total Sum of 2016 Target" (Figure 2.21); **Figure 2.21.** _The two columns created by adding the "2016 Target" field_ * – rename the first "Target for 2016"; * – select the ANALYZE tab, click on the OPTIONS icon under PIVOT TABLE OPTIONS in the ribbon, then in the dialog box, under TOTALS AND FILTERS, untick SHOW GRAND TOTALS FOR ROWS; * – click on the OK button to confirm. The table that you should obtain should be similar to the one in Figure 2.22. **Figure 2.22.** _The pivot table with the column "Net Total" for 2015 and the targets for vendors for 2016_ ### 2.2.5. _Calculated items_ We have previously seen a number of examples of the use of calculated fields, but there is another possibility that limits the range of the target, and this involves calculated items. In this instance, the calculation only applies to some of the items available in one of the ribbons on the database, not all of them. Looking at a recap pivot table for 2015 that compares products with agencies, we notice that "Nice", "Bordeaux" and "Caen" made fewer sales than the other agencies, all products combined (Figure 2.23). **Figure 2.23.** _The quantities sold by each of the agencies in 2015_ In order to rectify this imbalance, we predict an increase in the number of sales: * – 50% more for the agency in Nice; * – 40% more for the agencies in Bordeaux and Caen. In order for the vendors in each of these agencies to have a clearer idea of what quantities they will need to sell in 2016, we will create the pivot table in Figure 2.24, using the previous recap pivot table (Figure 2.23). **Figure 2.24.** _The pivot table to be obtained, including columns for 2016 for Bordeaux, Caen and Nice_ * – In the pivot table, open the pop-up menu in the cell containing "Agency" by clicking on the filter icon and keep only the agencies in Nice, Caen and Bordeaux checked; * – click on one of the agency names to select it; * – in the ANALYZE tab, click on the FIELDS, ITEMS AND SETS icon in the ribbon and select CALCULATED ITEM; * – in the NAME field, enter "Nice 2016"; * – switch to the FORMULA field, delete the 0 value, enter "CEILING" (behind the equal sign, click on "Agency" in the drop-down menu, then double-click on "Nice" in the drop-down list of items, then add "*1.5,1)" to calculate the 50% increase. COMMENT 2.3.– CEILING is present in order to round the product up to the nearest whole number. The figure 1 behind the comma gives the rounded-up value. **Figure 2.25.** _Creating the column that will contain the calculated item "Nice 2016". Note the formula for calculating the 50% increase and the "CEILING" function_ * – click on the OK button to confirm the creation of your new column; * – repeat the two previous operations with the agencies for Bordeaux and Caen, entering a coefficient of 1.4 corresponding to 40%; * – select the ANALYZE tab, click on the OPTIONS icon under PIVOT TABLE OPTIONS in the ribbon. A dialog box will open – under TOTALS AND FILTERS, untick SHOW GRAND TOTALS FOR ROWS; * – click on the OK button to confirm; * – open the pop-up menu for the cell containing "Agency" by clicking on the filter icon, then click on the option SORT A TO Z. The aim here will be to place the columns in order for each of the cities. **Figure 2.26.** _The pop-up menu for agencies, showing options for sorting, among others_ ## 2.3. Multiple databases A recurring question in the use of pivot tables concerns the possibility of extracting data from several tables simultaneously. In a Microsoft Excel spreadsheet, by definition there can only be one single database defined on a range of cells containing a header line that describes each of the fields (ribbons) in the database. This is the type of database that we have used in the previous examples in this chapter. There is, however, a very useful solution, which is little known despite the fact that a very powerful version has been developed in Microsoft Excel 2013. This is the table manager (for tables or data tables). A range of cells can be transformed into a data table. I will not go into detail here on all of the possibilities that this method offers, but should you wish to know more, please consult the bibliography at the end of the volume and the Internet links. COMMENT 2.4. _–_ * – Some of the following examples are only possible in the 2013 version of Microsoft Excel. To use them in the 2010 version, you will need to download an add-in called "PowerPivot", available to download on the Microsoft website. * – For other versions of Excel or other spreadsheets, you should be aware that not all of the features mentioned will be available. To give you an example of the use of pivot tables linked to tables, we will need to modify our initial database (see section 1.2). It should be clarified that table management is in fact an extrapolation of the technique used in _Relationship Database Management Systems (RDBMS)_ where tables2 are linked to each other by _relationships_ (links) with specific characteristics ( _cardinalities)_ , as found in Microsoft Access, Oracle, IBM DB2, Sybase etc. (see the Bibliography at the end of the volume). ### 2.3.1. _New tables for the database_ Our database will have two tables, "Sales" and "Products". The first will be a modification of the table we have been using up to this point. "Sales" table: * – Date: date of sale including the day, month and year – format: dd/mm/yy; * – Reference: FF NNN (family, n°) – format: whole number, 00 000; * – Agency: location of the sales agency – format: text; * – Vendor: vendor name – format: text; * – Qty: unit quantity – format: whole number, 0; * – Client category: IND (individual), PRO (professional) – format: text; * – Client type: N (new), EX (existing) – format: text; * – Client residence zone: Ci (City), Di (District), C (County), S (State), OS (Outside State) – format: text; **Figure 2.27.** _An example of the range of cells for the "Sales" table_ "Products" table: * – Reference: FF NNN (family, n°) – format: whole number, 00 000; * – Designation: product label, "Product A" to "Product F" – format: text; * – Net UP: unit price before tax – format: _($* #,##0.00_); * – Packaging: number of products per unit of sales – format: whole number, 0; * – Availability: number of days prior to delivery (IM: immediate, nD: x days, nW: x weeks) – format: text; **Figure 2.28.** _An example of the range of cells for the "Products" table_ ### 2.3.2. _Creating data tables_ We will now transform our two cell ranges into data tables: * – switch to one of the cells of the "Sales" cell range; * – select the INSERT tab; * – under TABLES on the ribbon, click on the TABLE icon; * – a dialog box, CREATE TABLE, will open. Confirm that the range indicated covers the entire cell range and click on the OK button (Figure 2.29); * – repeat the same actions for the second cell range ("Products"); * – select the DESIGN tab; * – under PROPERTIES, enter the table name: "Products" instead of the name created by default; * – after having selected a cell from the "Sales" table, repeat the same actions and re-name it. **Figure 2.29.** _Creating a table_ **Figure 2.30.** _The two tables: "Sales" (on the left) and "Products" (on the right)_ ### 2.3.3. _Relationships between tables_ Now that the tables have been created, we must now link them (using relationship or link) through a shared column, referred to here as "Reference". Effectively, in the "Sales" table, entering a product reference makes it possible to find out information relating to that product, whether this is its unit price before tax, its packaging or its availability: * – move the cursor to one of the tables; * – select the DATA tab; * – under DATA TOOLS, click on the RELATIONSHIPS icon; * – a dialog box will open – click on the NEW button; * – a new dialog box, CREATE RELATIONSHIP, will appear; * – in the drop-down menu, TABLE, select "Sales"; * – in the drop-down menu, RELATED TABLE, select "Products"; * – in the drop-down menu COLUMN (FOREIGN), select "Reference"; * – in the drop-down menu RELATED COLUMN (PRIMARY), select "Reference"; COMMENT 2.5.– The two tables can have columns (fields) with different names, but they can still be linked provided that they are the same type. The same principle applies to relational databases. **Figure 2.31.** _The dialog box for creating a relationship_ * – click on the OK button; * – the dialog box will close and your new relationship will appear in the MANAGE RELATIONSHIPS) box (Figure 2.32); **Figure 2.32.** _The new relationship_ * – click on the CLOSE button. ### 2.3.4. _Using multiple tables to create a pivot table_ Now that we have these two linked tables, we would like to show the pivot table from Figure 2.33. **Figure 2.33.** _The pivot table to be created_ We can see that the quantities, the vendors and the agencies come from the "Sales" table, while the designation of products comes from the "Products" table. The previously created relationship establishes a link between the two tables using the "Reference" column. In order to produce a dashboard summarizing sales, carry out the following instructions: * – move your cursor to the "Sales" table; * – select the INSERT tab; * – under TABLES, click on the PIVOT TABLE icon; * – a dialog box will open – confirm that you have "Sales" in the TABLE/RANGE field; * – under LOCATION, enter the cell defining the location destination for your pivot table; * – tick ADD THIS DATA TO THE DATA MODEL in order to take into account the two tables as well as their relationship (Figure 2.34); **Figure 2.34.** _Creating the pivot table using multiple tables_ * – click on the OK button to confirm. The fields area of the pivot table should look like the one in Figure 2.35. In the ACTIVE tab, you should be able to see your two tables; **Figure 2.35.** _The fields area of the pivot table showing the two active tables: "Products" and "Sales"_ * – put the "Agency" and "Vendor" fields in the COLUMNS area; * – put the "Designation" field in the ROWS area; * – put the "Qty" field in the Σ VALUES area; * – rename the different items: table, row, header column and format the pivot table (Figure 2.36); **Figure 2.36.** _The renamed headers: "Qty sold", "Designation" and "Agency"_ * – move your cursor over the pivot table, select the DESIGN tab; * – under LAYOUT, click on the SUBTOTALS icon and select DO NOT SHOW SUB TOTALS in order to make them disappear for each of the agencies. ## 2.4. Limits and constraints with calculated fields We will re-use our first database, only now we will imagine that we want to delete the Net Total column, regarding it as unnecessary since it can be replaced by a calculated field in a pivot table. The Net Total column is the result of a row by row calculation multiplying the product Quantity x Unit price before tax. The final table should look like the one in Figure 2.37. **Figure 2.37.** _The table to be obtained_ In the following section, I will show you a solution for tackling this issue while avoiding the pitfalls involved with a pivot table calculator. At first glance, the solution to the problem seems rather straightforward. Take the following steps: * – move the "Designation" of products into the ROWS section; * – move the "Quantity" and the "Unit price before tax" into the Σ VALUES section; * – create a calculated field called "Net Total", corresponding to the "Quantity" multiplied by the "Unit price before tax"; * – move the latter into the Σ VALUES section; * – in the table, replace the headers for the columns with "Designation", "Total qty", "Net unit price" and "Net Total"; * – select all of the numerical values from the table, switch to the HOME tab, then select CURRENCY from the drop-down menu in the NUMBER section of the ribbon. Although the steps taken appear logical, the results displayed are incorrect. **Figure 2.38.** _The resulting table from our operations. The values obtained are inconsistent_ In reality, there has been no mistake on the part of the pivot table calculator. In the "Net unit price" column, it simply adds the "Net unit price" of the product as many times as there are lines containing this information. In the "Net Total" column, it multiplies the "Net unit price" by the quantity. For instance, for the first row: _85_ × _$3,720.00 = $316,200.00_. It then follows that the column totals are also inconsistent. In order to resolve this issue, the total for the "Net unit price" should not be kept in the Σ VALUES section but instead it should be changed to an average. The average of a set of equal values (here this is the unit price of a product) is identical to one of these values. In terms of the calculated field, the formula must be modified so that it can calculate using the average of the unit price before tax. **Figure 2.39.** _The modified formula for calculating the "Net Total"_ This simple example shows the limits of pivot tables in certain specific cases. In principle, it is generally more useful, less risky and easier to integrate a calculation by adding a column to the corresponding table in the database. The values contained in this column can be easily used within a pivot table. COMMENT 2.6.– The solution that I propose for this example would not work if the net unit price of a product changed over time, given that it would no longer be represented by the average for the entirety of the given period. ## 2.5. Conclusion In this chapter, I have shown some of the possible ways of using this excellent tool, the pivot table calculator, in Microsoft Excel. In doing so I have left out a number of other possibilities and functions, whether linked to pivot tables or not, most notably the potential for importing databases, analyzing scenarios, validating and consolidating data, etc. I would invite you to investigate further by consulting the Bibliography and the Internet links provided at the end of this book. 1 A concept introduced by the British mathematician and statistician Karl Pearson in 1904 that involves crossing two characters from a population and presenting their combined result. 2 The vocabulary "tables", "relationships", "requests" and "cardinalities" is specific to the operation and use of databases connected to what we refer to as relational algebra. In the Bibliography at the end of this volume there are studies and Internet links relating to this subject. # 3 Scheduling and Planning Using a Project Manager ## 3.1. Reminders and information In this chapter, I will show you how to build a project using the Microsoft Project 2013 project manager. The aim will be to allow you to discover the potential of this type of program and possible interactions with other tools. It is not my intention to teach you how to use all of the features of this manager, given that a volume like this one has not been designed for such a purpose. The way in which this information will be presented to you will be based on the concepts explored in detail in Chapter 5, Volume 1. To this we will add resource implementation and management, awareness of the over-allocation of resources and opportunities for reducing and leveling in order to meet imposed constraints, as well as the monitoring of the project. These studies will be based on real-life examples, taken from the industry. Through these means, I hope to be able to show you the full range of this program's capabilities for managing and monitoring one or several projects within a company. With a touch of nostalgia, I still remember how hard it was and how long it took to do the same thing some decades ago. Everything contained in this chapter can easily be partly or fully adapted for use with other project managers, such as those mentioned in section 10.3.2 of Volume 1 of this work. ## 3.2. Example: designing and building a machine-tool ### 3.2.1. _Scenario_ The company, MecaTools, specialists in custom-made machine tools, have been asked by one of their clients to design a hydraulic press for stamping aluminum plates. In order to carry out this order, they have been given a design brief specifying the necessary technical characteristics for the machine. The design and the construction, as well as tests and client approval will be carried out exclusively in their workshops. For this purpose, the board has appointed a project manager who will be responsible for scheduling and planning the work to be carried out. After having analyzed the list of specifications provided by the client, the project manager worked with a support team to draw up a precedence table showing the main tasks to be carried out. **Table 3.1.** _Tasks and predecessors_ _Task_ | _Designation_ | _Duration_ | _Predecessor_ ---|---|---|--- A | Defining the design specification | 4wks | – _Design_ B | Functional design | 3wks | A C | Detailed design | 4wks | B D | Mechanical design | 2wks | C E | Hydraulic design | 2wks | C F | Automatic computer design | 1wks | C _Prototype construction_ G | Mechanical construction | 7wks | D H | Assembling the hydraulic system | 4d | E, G I | Assembling the sensors and PLC | 3d | F, G J | Wiring (electronic, sensors, field network, etc.) | 4d | H, I K | Developing and coding PLC application | 4wks | F L | Developing and coding computer application | 5wks | F M | Linking network to information systems | 1d | J, L N | Integrating mechanics, hydraulics, automation, etc. | 6d | I, J, K _Tests and checks_ O | Network test | 2d | M, N P | Testing and checking the prototype | 1wks | O, Q Q | Technical documentation | 2wks | C _Marketing_ R | Finalizing technical documentation | 2d | P, Q S | Marketing material | 1wks | P, Q T | Client presentation and approval | 1d | R, S The team attached to this project is as follows (the equipment and the raw materials used are not taken into account during the planning stage, with this managed separately by the MecaTools CAPM). The hourly costs given are the average hourly costs, including tax, for an employee or a service. **Table 3.2.** _Resources_ Name | Service | No. | Hourly rate ($/h) | Calendar ---|---|---|---|--- Project manager | Management | 1 | $ 52.00 | Schedule 1 Mechanical project assistant | Production | 1 | $ 38.00 | Schedule 1 Hydraulic project assistant | Production | 1 | $ 38.00 | Schedule 1 Computer automation project assistant | Production | 1 | $ 41.00 | Schedule 1 Design office (5 people) | Production | 1 | $ 215.00 | Schedule 2 Mechanical engineer | Production | 1 | $ 42.00 | Schedule 3 Electrotechnical engineer | Production | 1 | $ 44.00 | Schedule 3 Hydraulic engineer | Production | 1 | $ 42.00 | Schedule 3 Software engineer | Production | 1 | $ 44.00 | Schedule 3 Programmer | IT | 2 | $ 35.50 | Schedule 2 Fitter | Production | 5 | $ 18.00 | Schedule 3 Technician | Production | 4 | $ 24.50 | Schedule 3 Secretary-editor | Administration | 1 | $ 20.00 | Schedule 4 Marketing (3 people) | Administration | 1 | $ 160.00 | Schedule 4 Commercial services (3 people) | Administration | 1 | $ 190.00 | Schedule 4 Logistics (2 people) | Administration | 1 | $ 158.00 | Schedule 4 Quality department (3 people) | Production | 1 | $ 144.00 | Schedule 3 Team leader | Production | 2 | $ 30.00 | Schedule 3 The working hours for the business and personnel (these are independent of the different services) are as follows: * – MecaTools factory hours: Monday to Friday – 7:00 am to 8:00 pm (annual holidays: 25th July 2015 to 9th August 2015 inclusive); * – Schedule 1: Monday to Friday – 8 am to 12:30 pm and 1:30 pm to 6 pm; * – Schedule 2: Monday to Friday – 8 am to 12 pm and 1:30 pm to 5:30 pm; * – Schedule 3: Monday to Friday – 8 am to 12 pm and 1:30 pm to 5:30 pm; * – Schedule 4: Monday to Friday – 8 am to 12 pm and 2 pm to 5:30 pm. The allocation of resources, determined by the project manager, is given in Table 3.3. **Table 3.3.** _Allocation_ Name | Allocation ---|--- Project manager | A, B, C, G, N, O, P, T Mechanical project assistant | A, B, D Hydraulic project assistant | A, B, E Computer automation project assistant | A, B, F Design office (5 people) | B, C, G Mechanical engineer | B, C, D, G, N, P, T Electrotechnical engineer | B, C, F, I, J, K, N, P, T Hydraulic engineer | B, C, E, H, N, P, T Software engineer | B, C, F, J, L, M, N, O, P, T Programmer 1 | K, P Programmer 2 | L, P Fitter 1 | H, M, N, P Fitter 2 | G, H, N Fitter 3 | N, M Fitter 4 | J, M Fitter 5 | I, J Technician 1 | G, J, N, O, P Technician 2 | G, J, N, O, Q Technician 3 | I, M, P Technician 4 | I, M, Q, R Secretary-editor | A, B, C, Q, R Marketing (3 people) | S Commercial services (3 people) | A, S, T Logistics (2 people) | C, G, N Quality control (3 people) | N, P, Q, S, T Team leader 1 | H, N Team leader 2 | I, N The start date for the project is fixed as being 1st June 2015 at 8:00 am. ### 3.2.2. _Creating and configuring the project_ We will start by creating the project calendar, that is the factory hours – Monday to Friday, 7:00 am to 8:00 pm. **Figure 3.1.** _Creating the "Factory schedule" calendar_ We will include the period where the factory is closed for annual holidays in the calendar exceptions, as well as public holidays (07/4/15, 9/7/15, 10/12/15, 11/11/15, 26/11/15, 12/25/15 and 01/01/16). **Figure 3.2.** _The exceptions in the factory calendar_ We will also change the options: * – the week begins on a: Monday; * – default start time: 8:00 am; * – default finish time: 6:00 pm; * – hours per day: 7.5; * – hours per week: 37.5; * – days per month: 20. **Figure 3.3.** _The project calendar options_ We will now modify the project information, that is the start date and the calendar. **Figure 3.4.** _Project information_ Once these parameters have been entered, we will save the project under "MecaTools.mpp". ### 3.2.3. _Entering tasks and durations_ In addition to the tasks specified in the precedence table, we will add a "Project launch" task, with a duration of 0 days that will act as a start task as well as an "End of the project" task, also with a duration of 0 days, which will complete it. Four main recap tasks are defined: "Design", "Prototype construction", "Tests and checks" and "Marketing", each containing several standard tasks. In order to carry out this work, the INDENT and OUTDENT TASKS functions in the ribbon will be used, found under the TASK tab in the SCHEDULE section. The planning mode for tasks is set to "automatic mode" (TASK tab, TASKS section, AUTO SCHEDULE icon in the ribbon). You can see the result obtained in Figure 3.5. **Figure 3.5.** _The main recap tasks and traditional tasks entered into Microsoft Project_ It might seem strange that the length for a task such as "Design" is automatically calculated at 20 days (recap task) despite the fact that it starts on 06/01/15 at 8:00 am and finishes on 06/16/15 at 3:00 pm, slightly fewer than 16 calendar days. The same applies for other tasks where the duration has been manually entered. For example, the "Assembling sensors and PLC" task has a duration of three days but starts on 06/01/15 at 8:00 am and ends on 06/02/15, just less than two calendar days. In reality, this is no error. Our project calendar "Factory schedule" features a working day (see Figure 3.2) that starts at 7:00 am and finishes at 8:00 pm, which is 13 hours long. If we look again at our two tasks, we can calculate by looking at the default options in Figure 3.3, which gives 7.5 h per day: * – "Design": 20 days, therefore _(20_ × _7.5)/13 ≈ 11.538d = 11d + ) 0.538d = 11d + 0.538_ × _13 ≈ 11d + 7h_ to which we will add four unworked days (two Saturdays + two Sundays), or _11d + 4d + 7h = 15d +7h_. We can verify (with working days starting at 8am): _06/01/15 8:00 am + 15d 7h = 06/16/15 3:00 pm_ ; * – "Assembling sensors and PLC": three days, therefore _(3_ × _7.5)/13 ≈ 1.73d = 1d + 0.73d = 1d + 0.73_ × _13 ≈ 1d + 9.5 h_. We can verify (with working days starting at 8 am): _06/01/15 8:00 am + 1d 9.5h = 06/02/15 5:30 pm_. ### 3.2.4. _Entering predecessors_ We will continue building our project by adding the antecedents for each of the tasks. A Task column (Text1) can be added to allow us to note the letters corresponding to the different tasks and to make it easier to input predecessors. Once completed, this will give us the table and the Gantt chart shown in Figure 3.6. **Figure 3.6.** _The table featuring the filled "Task" and "Antecedents" columns_ ### 3.2.5. _MPM network visualization_ It is possible to visualize this whole project using an MPM network via the NETWORK DIAGRAM icon in the ribbon, under VIEW. In this display mode, it is also possible to make modifications to the network, particularly relating to adding or deleting eventual links. Using the zoom functions makes it possible to see certain sections of the network in greater detail. The visible data may vary, by default, but it will include the name of the task, the start date, the end date, its number, its duration and its resources, if they have been allocated. **Figure 3.7.** _A detailed look at some tasks from the "MecaTools" project_ **Figure 3.8.** _The MPM network (or task network) corresponding to the "MecaTools" project_ The dotted lines mark the page edges (depending on the default printer settings) and indicate how it will be divided during printing. In our example, the network will be spread across 15 A4 pages. ### 3.2.6. _Calculating slacks_ With Microsoft Project, calculating slack is straightforward – all that is required is to complete the table to the left of the Gantt chart with columns for "Free slack" and "Total slack". These are expressed by default in units similar to those used for duration. **Figure 3.9.** _The table, to the left of the Gantt chart, to which the two columns: "Free slack" and "Total slack" have been added_ It is also possible to show slack on a Gantt chart by configuring style bars. We will now move on to entering resources in the Microsoft Project resources table. **Figure 3.10.** _The Gantt chart showing free and total slack. Below is shown the window for configuring style bars_ ### 3.2.7. _Entering resources_ Before entering resources, we will need to create the necessary calendars, "Timetable 1" to "Timetable 4" (see section 3.2.1). To make it easier to create, we can copy elements of the calendar from the "Factory timetable" calendar, which will allow us to keep public holidays and the annual holiday period. **Figure 3.11.** _Creating resource calendars using a copy of the "Factory schedule" calendar_ When several resources have the same function, we will differentiate them and each of them will be represented on a single row. By default, if no capacity is given, each of the resources is considered as working at 100% on the project. The value of the capacity is often linked to the fact that a resource can be shared between several projects and can therefore have a capacity of somewhere between 0 and 100% for any given project. The design brief did not specify any hourly rate for overtime and so one hasn't been entered. As with the majority of cases, when we are dealing with a labor resource, the allocation of cost is proportionate (to the time spent on the project). Figure 3.12 shows the resources table. **Figure 3.12.** _The resources table_ It should be noted that this table gives initials that will be useful a bit later on when displaying resources on the Gantt chart. ### 3.2.8. _Allocating resources_ We will now specify what resources will be allocated to each of the tasks. The program will automatically recalculate the data depending on the constraints imposed (schedule, cost, slack, charges, potential over-use, etc.). To make the allocations, we will use the RESOURCE NAMES column in the Gantt chart view. The RESOURCE INITIALS column has been added and it will be displayed behind each bar in the chart. **Figure 3.13.** _The table with the "Resource names" and "Resource initials" columns_ In Figure 3.13, note that task durations have been calculated as well as dates. The same applies for the free and total slack. In the indicators Column i on the left, we notice small logos in the shape of red characters marking several rows (tasks G, J, M, N and Q). Their role is to indicate over-allocation of resources. These problems will need to be resolved in order to maintain a consistent project while trying to keep within the restrictions. **Figure 3.14.** _The new slack calculated and the Gantt chart showing resource initials_ It is rare to have a complex project without detecting evidence of over-allocation. Microsoft Project has a number of tools to resolve these issues. ### 3.2.9. _Resolving over-allocations_ In order to solve the problem posed by over-allocations, there are a range of solutions available: * – rescheduling the task for the next date the resource is available; * – replacing this resource with another available resource that can perform the same work; * – taking on another resource to carry out the work (add a resource); * – rescheduling the task by adjusting the slack. Using the Team Planner or the resource use table, we can examine the periods of over allocation for each resource in detail. These are outlined in red, across from each of the relevant resources. The time axis located in the upper part allows us to determine the dates and the periods for which the normal workload has been exceeded (linked to the schedule that the resource has to follow). In our example, in Figure 3.15, we can see an over-allocation for the "Computer engineer", "Fitter 1", "Fitter 3" and "Technician 2" resources. **Figure 3.15.** _The team planner. We can see the periods of over-allocation for the "Computer engineer", "Fitter 1" and "Fitter 3" resources_ For the first three, the time intervals where there is an over-allocation are as follows: * – Monday 12/28 from 10:00 am to 11:00 am and 1:00 pm to 5:00 pm; * – Tuesday 12/29 from 8:00 am to 9:00 am. On the resource use table, we can see these same over-allocations in more detail, along with the actual number of work hours to be carried out. **Figure 3.16.** _The resource use table featuring the number of hours for each resource_ By configuring the display, we can obtain other information. This is shown in Figure 3.17, where, for each resource and each task, the following elements will appear: "Work", "Over-allocation", "Cost", and "Remaining availability". We will remove our "software engineer", from task no. 13, "Wiring (electrical, sensors, field network, etc.)" because, following a discussion with their colleagues, it turns out that the same work can be carried out without them. Once this has been removed, the over-allocation for task no. 13 will disappear. In task no. 21, "Technical documentation", we will replace "Technician 2" with "Technician 3" who can carry out the same work and who is available on that date. **Figure 3.17.** _A more detailed display showing the resource use table_ As a result, the over-allocation for task no. 10, "Mechanical construction" will disappear. Indeed, "Technician 2" was also used during this same period and can now focus exclusively on this task. **Figure 3.18.** _The over-allocations in tasks no. 10, 13 and 21 have disappeared_ There are now only two tasks left showing over-allocation: no. 16, "Network computer system" and no. 17, "Mechanical, hydraulic, computer integration". "Computer engineer", "Fitter 1" and "Fitter 3" are the over-allocated resources. In order to solve this problem, we will ask the program to reschedule task no. 16 for the next available date (Figure 3.19). **Figure 3.19.** _Rescheduling task no. 16 for the next available date_ Once this operation has been carried out, everything is as it should be, and there is no longer any over-allocation. **Figure 3.20.** _There are no remaining over-allocated tasks_ We can now consider this project to have been properly scheduled. ### 3.2.10. _Viewing the project timeline_ In order to obtain a more general view of the "MecaTools" project, it is possible to attach a simple or more detailed timeline to the project. For our example, we have chosen to put the recap tasks in legend form (above the time axis) and to display the other tasks in detail. The critical tasks have been differentiated using different background colors. **Figure 3.21.** _The detailed timeline for the "MecaTools" project_ ### 3.2.11. _Using WBS coding_ The Work Breakdown Structure (WBS) is a means by which we can divide a project hierarchically with the tasks broken down into different levels. Today, this is often referred to as a project management flowchart. It was the US Department of Defense who developed this concept in the 1950s before it was later adopted by various companies. Its aim is to make project organization easier. With Microsoft Project, we can use a form of coding based on the WBS principle, which can also be personalized. Its structure is based on an initial main code that represents the project itself by default. For our "MecaTools" project, we will create a code whose main prefix will be "1", followed by a series of ordered numbers. Using the WBS tool from the ribbon, under the PROJECT tab, we will create the code structure (Figure 3.22). **Figure 3.22.** _The window for creating the WBS code structure_ Next, we will add a WBS column in the table linked to the Gantt chart. **Figure 3.23.** _The task table and its WBS number column_ In Figure 3.23, we can see the hierarchical coding that we have defined. This is automatically applied in ascending order by level depending on the importance of the task (recap or not). ### 3.2.12. _Generating dashboards and reports_ There is still the possibility of editing different dashboards in order to ensure that the project is monitored and presented. To add to this, we can also generate reports to provide an overview of the use of resources, the cost of tasks, etc. Below, you will find some examples of possible dashboards and reports. Microsoft Project has a number of possibilities for creating different types of dashboards and graphs using raw data from the project or a pivot table of data that can be exported to a spreadsheet such as Microsoft Excel for further use. #### 3.2.12.1. _Tasks/work time dashboard_ This table is based on displaying task use. It is possible to open a task to view the time details depending on the resources, as Figure 3.24 shows with the task "Mechanical construction". **Figure 3.24.** _Table displaying work time for each of the tasks_ #### 3.2.12.2. _Resources/work time dashboard_ This follows the same principle as the previous table, but is guided by resources, with the possibility of seeing details for each of the tasks. See the resource "Mechanical engineer" from Figure 3.25. **Figure 3.25.** _Table showing the work time for each of the resources_ #### 3.2.12.3. _Visual and chart reports_ Using the report generator allows us to create the chart in Figure 3.26, comparing the work time for each of the resources to their availability. To get this result, we had to extract the data in order to create a histogram, made by crossing multiple data (pivot table). When the chart is formatted, it is possible to save it in Microsoft Excel as an HTML page (in order to use it on a website) or even as an Open Document Spreadsheet (ODS), a document format for spreadsheets). **Figure 3.26.** _A pivot table generated by the "Visual reports" tool in Microsoft Project 2013_ Figure 3.27 shows the Microsoft Excel spreadsheet that allowed us to create the previous chart. **Figure 3.27.** _The Microsoft Excel spreadsheet, created in Microsoft Project, that allowed us to generate the chart in Figure 3.26_ ## 3.3. Project monitoring Once the project is underway, the project manager will be responsible for monitoring it. Each change made, whether this is to tasks or to resources, is automatically registered and the scheduling is entirely recalculated (if the automatic scheduling method is activated for the relevant task(s)). As time passes and the project progresses through the calendar, a task can be selected and given a completion percentage using the burndown tools available in the ribbon under the TASK tab in the SCHEDULE group. **Figure 3.28.** _The burndown and scheduling tools available in the ribbon under the TASK tab_ The project can also be managed with an appropriate burndown, by specifying a status date (PROJECT tab, STATUS DATE tool in the ribbon) then by updating the project using the UPDATE PROJECT tool in the STATUS group. In this instance, Microsoft Project considers all the tasks as having been completed up to this point (by default). **Figure 3.29.** _The tools for managing the status date under the PROJECT tab_ The burndown in the task completion is visible on the Gantt chart. The task bars have a bold line down the middle indicating burndown. **Figure 3.30.** _Here we can see the burndown (bold horizontal line in the middle of the task bars)_ To conclude, it can be observed that the bars in the Gantt chart, which correspond to each of the tasks, are interactive, and can be adjusted to move the task along the timeline (cursor in the shape of a crossed arrow), stretched to extend the duration of the task (cursor in the shape of an arrow pointing right will appear at the end of the bar), or given a burndown (cursor in the shape of a % sign and a triangle will appear at the start of the bar). Naturally, each modification is carried out instantaneously and the project is recalculated as a result, if the automatic scheduling mode has been activated for the relevant task (Figure 3.31). **Figure 3.31.** _The functions of the different shapes of cursor that appear when hovering over a bar representing a task in a Gantt chart_ ## 3.4. Conclusion There are various other observations we could make on the functionalities available with Microsoft Project. However, I think that the elements presented here show the main possibilities available with the program. I have intentionally left out the question of multi-project management, a form of management using sub-projects and resource sharing. To develop this further, to learn about these possibilities and to discover more, I would advise you to consult the Bibliography and the list of internet links included at the end of this book. # 4 Road Traffic Simulation ## 4.1. Before we start Unlike the previous chapters, here I will introduce several pieces of free simulation software before finishing with an example developed using AnyLogic. Why was this choice made? It was made in accordance with the wealth of options available to the editors. There is a vast range of software available, covering one or several types of models, and these are often quite complex and difficult to master. They require an excellent knowledge of the theory of road networks, infrastructures, signaling, land topography and various other concepts in order to create a model that will satisfy the design brief while staying in keeping with the right approach. In the space of just one chapter, it would be difficult to explain all of these elements to the reader and to apply them within a chosen application. I would advise you to consult section 4.3 from Chapter 10 of Volume 1 of this work to obtain an overview of the possibilities available with the main applications available on the market and to download and use the trial versions to allow you to form your own opinions. We will deal with several examples and in these I will focus on certain functions that will then enable the reader to discover key aspects of road traffic management. For each example, I will provide a brief overview of the application. I will also provide links to websites where you will be able to download these programs in the internet links section of the bibliography at the end of this work. ## 4.2. Ring road This program is available online at1: www.traffic-simulation.de. The software is the creation of Martin Treiber, a specialist in traffic modeling and the author of several works that can be found in the bibliography. This application provides an excellent approach to congestion problems and their consequences: slowing down, blockages, the build-up of vehicles. Slight changes to any of the parameters will have a significant impact on traffic flow, in the short or the long term. **Figure 4.1.** _The website of Martin Treiber's simulator "Ring road"_ The role of each of the sliders positioned above the simulation ring is given below: * – _Timewarp_ : multiplier timescale (from 0.1 to 20 times); * – _Density_ : density, number of vehicles per kilometer and per road; * – _Scale_ : scale of the window of the simulator (from 0.6 to 5 pixels/meter); * – _Truck fraction_ : percentage of trucks relative to other vehicles (from 0 to 50%); * – _Desired speed v0_ : vehicle speed (from 18 to 144 km/h); * – _Time gap T_ : time gap between vehicles (from 0.6 to 3 seconds); * – _Minimum gap s0_ : space between vehicles (from 0.5 to 5 meters); * – _Max acceleration_ : maximal acceleration of vehicles (from 0.3 to 3 m/s2); * – _Comf deceleration_ : comfortable deceleration of vehicles, i.e. without emergency braking, in normal conditions (from 0.5 to 5 m/s2). While running the application, the user can refer to or consult the links available at the right of the display window for more information. Three traffic models are also presented: * – the _acceleration model_ based on the Intelligent Driver Model (IDM) developed by Treiber, Hennecke and Helbing in 2000; * – the _lane-changing model_ based on the Minimizing Overall Braking Induced by Lane (MOBIL) changes model by Kesting, Treiber and Helbing; * – _Boundary conditions_ , which is based on the conditions at the limits of the traffic area chosen for the study for periodic cases (circular or ring circuit) or road sections that are not required to be periodic. At the time of writing, some features of the application are not yet active, including road closure and speed limits. ### 4.2.1. _A simulation example_ Let's start with a simulation using the parameters in Figure 4.2. **Figure 4.2.** _The parameters for simulation no. 1_ With these sliders we can observe that the traffic remains fluid although reductions in speed can occur. If we are to increase the vehicle density from 25 to 50, a congestion appears, which could be considered a blockage. By reducing speed to 60 km/h and the density to 35 veh/km/lane with a gap between vehicles of 1.0 m, traffic will become fluid again and will remain within the blockage limits. We can see the priority influence of density on traffic flow. Other variables, such as the speed or the distance between vehicles are less significant, although they still contribute to the phenomenon. ## 4.3. RoadTrafficSimulator This program was developed by Artem Vokhin in 2014 and is available to download at2: _github.com/volkhin/RoadTrafficSimulator_. It is based on the traffic models IDM and MOBIL mentioned in the previous section. To use it you will require a web browser such as Mozilla Firefox, Microsoft Internet Explorer, Safari, Google Chrome, etc. It was developed in CoffeeScript3 and HTML54. You can design your own network or even manage it automatically and view traffic flow within a model incorporating crossings with traffic lights. **Figure 4.3.** _The application RoadTrafficSimulator in use with its control interface at the top right_ Several parameters can be adjusted using the control interface: * – _World_ : opens the drop-down menu containing the options _save, load, clear and generateMap_ ; * – _Save_ : save the current model; * – _Load_ : load a saved model; * – _Clear_ : delete the model; * – _generateMap_ : automatically generates a random model; * – _carsNumber_ : specifies the number of vehicles (from 0 to 200); * – _instantSpeed_ : snapshot of average speed for all vehicles in the model; * – visualizer: opens the drop-down menu containing the _running_ and _debug_ options; * – _running_ : launches (ticked) or stops (unticked) the simulation; * – _debug_ : displays the trajectories of vehicles at intersections; * – _scale_ : modifies the scale of the model (from 0.1 to 2); * – _timeFactor_ : accelerates or slows down the simulation (from 0.1 to 20); * – _lightsFlipInterval_ : modifies the rhythm of traffic lights (from 0 to 400); * – _Close Controls_ : Minimizes and closes the control interface window; * – _Open Controls_ : Opens the control interface window. Using the scroll wheel on the mouse allows you to zoom in or out on the model (double-use with the **SCALE** adjustment of the interface). Right-clicking followed by a drag and drop will move the model in the window. A grid made up of points will formalize a square grid that will still be found at the bottom of the window of the model. ### 4.3.1. _Constructing a model_ Once you have downloaded and decompressed RoadTrafficSimulator, open the RoadTrafficSimulator folder and double-click on the index.html folder. A model should appear, generated by default. Before you begin you can adjust the sliders in order to familiarize yourself with the interface and to see the influence this has on the existing road network. The vehicles are represented by small colored rectangles and each street will feature four lanes. The traffic lights at each intersection are represented by small green triangles indicating the direction and the priority of traffic. **Figure 4.4.** _Two intersections with the indicators (green triangles) representing the traffic lights. For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ Strictly speaking, there are two stages to building a model: * – start by deleting the existing model. Click on **CLEAR** in the configuration interface (make sure that **RUNNING** is ticked, otherwise the deletion will not be taken into account); * – hold down the SHIFT key on your keyboard and click seven times on different areas in the window to create intersections for your future model (see Figure 4.5); **Figure 4.5.** _The 7 intersections created for our model_ * – click on the intersections that you have created, hold down the SHIFT key on your keyboard and, while maintaining a left-click, drag to connect to another intersection. A road with two lanes should appear; * – repeat the same steps in order to create each of the sections of the network from Figure 4.6; **Figure 4.6.** _Our network once the different intersections have been connected_ * – click on **SAVE** in the interface in order to save your model. No dialog box will appear but the model will have been saved. The next time you launch the application, this is the model that will appear. Clicking **LOAD** will also bring up this model, which will become the default model. ### 4.3.2. _Activating the simulation from the model_ In the interface, specify a number of vehicles using the **CARSNUMBER** cursor. Your simulator should start automatically if the **RUNNING** option is ticked. By varying the number of vehicles and the rhythm of the traffic lights, **LIGHTSFLIPINTERVAL** , you will be able to see the queues of vehicles and the overall snapshot speed, **INSTANTSPEED** , for all vehicles present in your network. The aim is to reach a high overall snapshot speed while avoiding congestion and blockages at intersections. **Figure 4.7.** _Blockage and congestion of traffic lanes around an intersection (traffic jam)_ ## 4.4. Intersection simulator This application was developed in Java by Kresimir Kovacic and simulates junctions with the management of traffic lights. It is possible to modify various parameters and a graph will give a real-time display of the average waiting time in traffic routes. This software is distributed under the Creative Commons license and is available to download at5: _sourceforge.net/projects/traffic-simulator/_. A right-click on the "intersection_simulator.jar" folder will launch the program. COMMENT 4.1.– In order for this application to function properly on your machine, Java must be installed. If you don't have Java on your system, it is available to download for free at _www.java.com/en/_. If this address doesn't work, use a search engine and search for "Java". **Figure 4.8.** _The Intersection simulator program window_ The display window is divided into five main sections: * – the graphic simulation zone, on the left, that shows the junction at which we can view the circulation of vehicles and the different indicators; * – the parameter table, on the right, where we can specify the values of the different variables; * – the time management cursor, at the bottom left, that allows us to speed up, slow down or stop the simulation; * – the graph area, beneath the parameter table, that displays the lane management histogram; * – the set of interface commands beneath the histogram, which contains the number of cycles carried out by the simulation and the five buttons available to the user. Let's now look in more detail at the different parameters in the table: **Figure 4.9.** _The parameter table_ * – each of the four columns represents one of the directions at the intersection: **DOWN** (bottom), **RIGHT** (right), **UP** (top), **LEFT** (left); * – the first row, **TRAFFIC LIGHT** , is for the main light of the chosen direction. The value represents the rhythm at which the lights change; **Figure 4.10.** _The TRAFFIC LIGHT system for the bottom lane (Down)_ * – the second row, **LEFT SIGN** , is for the additional light for the extra lane. Its value represents the rhythm at which the lights change; **Figure 4.11.** _The TRAFFIC LIGHT system and LEFT SIGN for the bottom lane (Down)_ * – the **ADDITIONAL ARROW** row adds an arrow indicating direction when it is possible to turn. Its value represents how long it will remain activated; **Figure 4.12.** _The ADDITIONAL ARROW, shown to the right of the TRAFFIC LIGHT system_ * – the **DIRECTION PROBABILITY** row governs the probability of how vehicles will be distributed across the different lanes; * – the **DENSITY (PER MIN)** row specifies the number of vehicles arriving per minute. An interval can be determined using a minimal value (on the left) and a maximal value (on the right); * – the **OUTPUT TRACKS** row specifies the number of exit lanes, 1 or 2, for each direction; * – the **TRACK TYPE** row specifies the three possible directions that vehicles can take. **LEFT & UP/RIGHT** to go left, or straight on and right together. **LEFT/UP & RIGHT** to go left and straight on together, or to go right. **LEFT/UP & UP/RIGHT** to go left and straight on together, or to go straight on and right together. * – the **INPUT TRACKS** row specifies the number of entry lanes, 1 or 2, for each direction. COMMENT 4.2.– Please note that the **OUTPUT TRACKS** and **INPUT TRACKS** parameters have matching functions. As a result, certain combinations are logically impossible. Beneath the table there is a histogram featuring a continuous display of the average waiting time in seconds for each direction. **Figure 4.13.** _The histogram showing average waiting times_ The number of vehicles waiting at each direction is shown on the right within the graphic simulation zone. **Figure 4.14.** _Here we can see the number of vehicles waiting on the right-hand side for each direction. In this example, 3 at the bottom, 99 on the right, 41 at the top and 8 on the left_ We will now look at the function of each of the five buttons beneath the histogram: * – **RESET** : Resets the simulation and takes on the new parameters once they have been entered. * – **EXPORT PARAMETERS** : Saves the parameters entered into the table in TXT format, under your chosen name. A dialog box will open to confirm that your parameters have been saved. * – **IMPORT PARAMETERS** : Import the parameters from an exported file. A dialog box will open to confirm that the chosen folder has been imported. * – **EXPORT GRAPH** : Saves the graph from the simulation as a ZIP file containing a PNG image, " _Graph.png"_ , representing the histogram and a file, _"Simulation_results.txt"_ , in TXT format, that will contain the results of the simulation. **Figure 4.15.** _An example of a TXT file extracted from an exported ZIP file, containing the results of the simulation_ * – **EXIT** : exit the simulator. Finally, moving the cursor over the graph simulation zone will allow you to vary the speed, from a complete stop **STOP** to up to 16 times real speed (once). Once you have understood the use for these parameters and the different features of the application, it becomes very easy to simulate an intersection, including its different lanes and traffic lights. ## 4.5. Green Light District (GLD) This program is a traffic simulator that allows you to create your own road network by incorporating different types of road with multiple traffic lanes and intersections controlled by traffic lights. It was developed in Java at the Institute of Information and Computing Sciences at the University of Utrecht in the Netherlands. It is under license of the GNU General Public License version 2.0. The concept behind the creation of GLD was to create a simulator based on the "intelligent" management of traffic lights. Imagine that each car stopped at an intersection communicates its position in the queue and its final destination to a global system for triggering signals. The latter would then be able to select the optimal solution for reducing the waiting time for vehicles in the short and long term and would apply this for their entire journey, which would include one or several intersections controlled by traffic lights. The overall control of the management of traffic lights is based on a distributed multi-agent system where mutual communication and cooperation ensures the best possible coordination. GLD features several types of traffic light controllers, standard or training, in order to test and compare a range of solutions relating to the flow of vehicles in a network. Furthermore, it is possible to find out the type of vehicle – car, bus or bike – and use this information in accordance with statements defined by the experimenter. Furthermore, the system is able to "learn", allowing it to become increasingly efficient over time. It is available to download at6: _sourceforge.net/projects/stoplicht/_. Although it does not present all of the features of the most recent version of the application, the documentation is available to download as a compressed file, " _gld_rel07_docs.zip_ " at: _sourceforge.net/projects/stoplicht/files/OldFiles/gld_rel07_docs.zip/download_. The specifications of the software, version 0.9.2, are available to download at: _sourceforge.net/projects/stoplicht/files/OldFiles/gld_specs_0.9.2.zip/download_. The version provided is not compiled, and you will need to install a Java compiler if you haven't already. You will then be able to compile sources. Information on how to install the Java compiler can be found in Appendix 2 of this work. ### 4.5.1. _GLD compilation_ After downloading GLD, you should have a 570.6 Ko ZIP file named " _gld_rel131_source.zip"_. Version 1.3.1 is the most recent. Decompress the file, open the folder " _gld_rel131_source_ ", and you should have a text file, " _very_quick_howto_build_and_run.txt_ " and a folder " _gld_ ". This version of GLD was developed using an older version of Java (pre 1.5), and it is necessary to specify this aspect during compilation, otherwise you will have errors caused by a variable known as " _enum_ ", unless you are using an older version of Java. Open the folder _"gld_rel131_source"_ , then enter the command: `javac –source 1.4 gld/*.java` and confirm by pressing ENTER. **Figure 4.16.** _The command for launching the compilation in Apple OSX (at the top) and in Microsoft Windows (at the bottom)_ You should obtain a result similar to the one in Figure 4.17. **Figure 4.17.** _Result after compilation in Apple OSX (at the top) and in Microsoft Windows (at the bottom)_ ### 4.5.2. _Launching the GLD_ GLD is made up of two main applications: the editor "GLDEdit" and the simulator "GLDSim". Using the editor, it is possible to build your network by determining the lanes and intersections and then confirming your model. **Figure 4.18.** _The Green Light District editor_ This can be launched using the command `"java gld.GLDEdit"` on your command prompt. **Figure 4.19.** _The editor launch file, in Microsoft Windows using the command prompt (at the top) and in Apple OSX using Terminal (at the bottom)_ The simulator will, among other actions, open the model developed with the editor, position the vehicles in your network, assist you with the animation of the simulation, determine statistics and provide you with different options for managing traffic lights. **Figure 4.20.** _The "GLDSim" simulator in Green Light District_ This can be launched using the command: `"java gld.GLDsim"` on your command prompt. **Figure 4.21.** _The command for launching the simulator, in Microsoft Word using the command prompt (at the top) and in Apple OSX using Terminal (at the bottom)_ ### 4.5.3. _The editor toolbar_ The GLD editor features a main toolbar with the following functions (Figure 4.22): **Figure 4.22.** _The GLD editor toolbar_ * – A: Create a new model, **WIDTH** and **HEIGHT** ; * – B: Open an existing model. GLD files are ". _infra_ " type; * – C: Save a model. The extension should be _".infra"_ type; * – D: Model scale from 25 to 250 %; * – E: Centre the model in the window; * – F: Move the model in the window; * – G: Zoom in on the model; * – H: Select an item; * – I: Create an intersection. In this instance a drop-down menu will appear at the right of the toolbar, enabling you to select the type of intersection ( _Edge node; Traffic lights; No signs; Net-tunnel_ ; * – J: Create a road linking two nodes; * – K: Add a lane to an existing link; * – L: Open the dialog box for the properties of the selected item; * – M: Help. COMMENT 4.3.– * – In order for help to function, you will need to move the "docs" folder, which contains the ".html" files for the previously downloaded documentation into the "gld" folder (see section 4.5). * _–_ To access the specifications from help, you will need to create a file "specs" in the "docs" folder and move the content from the "gld_specs_0.9.2" inside it (see section 4.5). As with the editor, the simulator also has its own toolbar. **Figure 4.23.** _The GLD simulator toolbar_ * – A: Open an existing model. GLD files are _".infra"_ type; * – B: Save a simulation. The extension should be _".sim"_ type; * – C: Model scale from 25 to 250%; * – D: Centre the model in the window; * – E: Move the model in the window; * – F: Zoom in on the model; * – G: Select an item; * – H: Open the drop-down menu for selecting vehicle type: **CAR** , **BUS** or **BICYCLE** ; * – I: **STEP** – Move the simulation one step forward; * – J: **RUN** – Launch the simulation; * – K: **PAUSE** – Pause the simulation; * – L: **STOP** – Stop the simulation; * – M: Choose the simulation speed: **LOW** , **MEDIUM** , **HIGH** , **MAXIMUM** ; * – N: Open the dialog box for the properties of the selected item; * – O: Help. ### 4.5.4. _An example using GLD_ We will now create a simple model using GLD. Open _"GLDEdit"_. The network that we will set up is the one shown in Figure 4.24. **Figure 4.24.** _The road network for our example, featuring 4 intersections, F1 to F4. For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ It includes four intersections, F1, F2, F3 and F4, which are all controlled by traffic lights. Every road has five lanes and there are five entries and exits for vehicles. By default, the lanes will feature every type of vehicle. #### 4.5.4.1. _Creating a model_ COMMENT 4.4.– The capital letters between brackets in the text describing how to create a model refer to Figure 4.22. This will occur as follows: * – in the GLD editor, in order to display the grid and to correctly position the different items of the network, open the **OPTIONS** menu and select **TOGGLE GRID** ; * – click on the icon for creating intersections (I), select the type _"Traffic lights"_ and position the four nodes (squares with black lines) F1, F2, F3 and F4; * – if there is an error it is possible to delete an element by right-clicking on the latter and selecting **DELETE** ; * – the nodes will be numbered automatically, starting from 0, during creation; * – continue by placing five _"Edge node"_ type intersections (squares with blue lines). These nodes border the model that generate and receive the flow of vehicles; **Figure 4.25.** _The four "Traffic lights" type intersections in GLDEdit_ **Figure 4.26.** _The five "Edge node" type intersections" added to four "Traffic lights" blocks_ * – next, select the type _"No signs"_ and position a change of direction that will link F2 to F4; **Figure 4.27.** _Each intersection block_ * – in the toolbar, select the tool for creating a route between two nodes (J) and create the different junctions; **Figure 4.28.** _The model showing road junctions (in pink). The junctions show the traffic lights set up by default_ * – in the **OPTIONS** menu, select **VALIDATE** and confirm that the model is correct. The **GENERAL CONFIGURATION** window will be displayed. **Figure 4.29.** _The GENERAL CONFIGURATION window displayed when confirming your model_ If this is not the case, an **ERROR** dialog box will open to inform you of the errors and to allow you to correct them. **Figure 4.30.** _An example of a potential error during confirmation_ * – to save your model, open **FILE** , then select **SAVE AS...** * – select a destination folder and enter a name using the extension _".infra"_ , then click on the **SAVE** button. **Figure 4.31.** _Saving a model (in Microsoft Windows), here "MyModel.infra" in the Office folder_ Now that we have created our model, we are now able to use it. #### 4.5.4.2. _Traffic simulation_ Open _"GLDSim"_ and open the model that you have previously created by selecting **FILE** followed by **OPEN**. This should appear within the main window of the simulator. If this is not the case, click on the center the model in the window icon (D) on the toolbar. COMMENT 4.5.– The capital letters, in brackets, refer to Figure 4.23. Lastly, zoom in for a more detailed view of the network. **Figure 4.32.** _The model centered in the "GLDSim" window and enlarged by 150%_ To start a simulation using the default settings, click on the icon for launching a simulation (J) in the toolbar. It is possible to adjust the speed of the simulation by changing it via the dropdown menu (M) from **LOW** to **MAXIMUM**. The simulation can be stopped by clicking on the **PAUSE** icon (K) and restarted by clicking on the **RUN** icon (J). To completely stop the simulation, use the **STOP** icon (L), which will remove all vehicles. You can advance step by step using the **STEP** icon (I). The number of cycles for the simulation will be displayed at the bottom left of the window. The small red squares represent bicycles and the large green rectangles represent buses. The other grey, black, blue, white and green rectangles represent other vehicles. The small green and red circles represent traffic lights. **Figure 4.33.** _The different types of vehicle in the model during the simulation_ You can choose **PROPERTIES** by right-clicking on one of the lanes of the junction between intersections. This will display its properties (Figure 4.34). **Figure 4.34.** _Display showing the properties of a junction lane, in this case "Drivelane 24"_ This shows: * – **DRIVELANE n** : lane number; * – **PART OF** : road the lane junction is part of; * – **LEADS TO** : intersection the vehicles are coming from (gives the direction of traffic); * – **COMES FROM** : intersection the vehicles are heading towards (gives the direction of the traffic); * – **WAITING FOR TRAFFICLIGHT** : number of vehicles waiting in the lane; * – **DRIVELANE ALLOWS AUTOMOBILES** : type of vehicles the lane is designed for; * – Type of vehicles in the lane: located in the left pane. If **SHOW FREE SPACES** is ticked, it is possible to view the free spaces (empty inter-vehicle blocks). Right-clicking on one of the nodes of the intersections will allow you to select **PROPERTIES**. This will display its properties (Figure 4.35) or give a two graph display: **TRACK ROADUSERS THAT CROSSED** displays the number of vehicles crossing the intersection as a function of the time elapsed (number of cycles) and **TRACK JUNCTION WAITING TIME** allows you to view the average waiting time for vehicles at the intersection as a function of the time elapsed (number of cycles). A node at an intersection has the following properties: * – **JUNCTION n** : intersection number; * – **ROAD NORTH** : name and number of the road heading north from this intersection; * – **ROAD EAST** : name and number of the road heading east from this intersection; * – **ROAD SOUTH** : name and number of the road heading south from this intersection; * – **ROAD WEST** : name and number of the road heading west from this intersection; * – **JUNCTION HAS n TRAFFICLIGHTS** : number of traffic lights at this intersection; * – **JUNCTION IS n UNITS WIDE** : number of lanes, in width, available at this intersection; * – **TRACK ROADUSERS THAT CROSSED**: Displays the graph showing the number of vehicles; * – **TRACK JUNCTION WAITING TIME** : Displays the graph showing the average waiting time; * – **AVERAGE WAITING TIME** : displays the average waiting time; * – **SHOW OF LAST 1,000 ROADUSERS** : if ticked, this will display the average waiting time for the last 1,000 vehicles. **Figure 4.35.** _Display showing the properties of a node at an intersection, in this case "Junction 8"_ COMMENT 4.6.– Certain items in these properties windows are written in blue and underlined. These are interactive links that display additional information, in relation to the chosen element. **Figure 4.36.** _Two graphs: average waiting time for vehicles at the intersection as a function of the time elapsed (on the left) and the number of vehicles having crossed the intersection as a function of the time elapsed (on the right)_ The "Edge nodes" have different properties: * – **CONNECTS** : road the node is connected to; * – **WITH** : intersection the road is connected to; * – **WAITING IN QUEUE** : number of vehicles waiting in the line as a function of the type of vehicle ( **ALL** , **CAR** , **BUS** , **BICYCLE** ); * – **SPAWNFREQUENCY FOR** : frequency of vehicles generated as a function of the type of vehicle (between 0 and 1 – from 0 to 100%); * – **SET** : button for confirming the frequency input; **Figure 4.37.** _Display showing the properties of an "Edge node", in this case "Edgenode 0"_ * – **TRACK WAITING QUEUE LENGTH** : length of the queue as a function of time elapsed (number of cycles); * – **TRACK TRIP WAITING TIME** : average waiting time for a journey as a function of time elapsed (number of cycles); * – **TRACK ROADUSERS ARRIVED** : number of vehicles arriving as a function of the time elapsed (number of cycles). **Figure 4.38.** _The graphs available from the "Edge node"_ The three graphs in Figure 4.38 can also be accessed by right-clicking on the node. During a simulation with a model, it is possible to adjust several parameters. We will start by adjusting **SPAWNFREQUENCY FOR** , available in the properties panel for _"Edgenodes"_. As a function of the type, you can enter a value corresponding to the frequency that you wish to see generated by the node. **Figure 4.39.** _The properties panel for the node "Edgenode 0" in our model after modification at the end of roughly 15,000 cycles_ In our model, for example, for the node EDGENODE 0, if you adjust the default values and enter 0.65 for BUS, 0.35 for CAR and 0.0 for BICYCLE (don't forget to confirm by clicking on the SET button), you will obtain the results shown in Figure 4.40, after roughly 10,000 cycles. **Figure 4.40.** _The three statistical graphs for the node EDGENODE 0 in our model after roughly 15,000 simulation cycles_ The most important parameter corresponds to controlling traffic lights at each of the intersections. For this, we have a number of options within the GLD, contained in the **OPTIONS** menu, accessible by selecting **TRAFFIC LIGHT CONTROLLER**. **Figure 4.41.** _The categories of options available for managing traffic lights from the OPTIONS menu_ I would invite you to consult section 5b, TRAFFIC LIGHT CONTROLLERS, in the GLD documentation for details relating to the options available for managing signals. **Figure 4.42.** _Section 5b of the GLD documentation relating to traffic light options_ We will now try to modify the management of lights by selecting a management method based on the largest number of cars, **MOST CARS** , in **SIMPLEX MATHS** and we will compare this to **RANDOM** , again in **SIMPLEX MATHS**. Figure 4.43 shows the results at the end of 2,000 cycles for the average waiting time at the intersections in our model ( **STATISTICS** menu, **TRACK** option, then **AVERAGE JUNCTION WAITING TIME** ). **Figure 4.43.** _The average waiting times at intersections in our model with a random management method (RANDOM – on the left) and using a method with the most cars (MOST CARS – on the right)_ We are able to note striking differences depending on the management method. COMMENT 4.7.– It is possible to configure certain options for managing traffic lights. In this case, a dialog box with the appropriate input fields will appear when the user has made one of these choices. Another parameter is the driving policy, which can be accessed by going to the **OPTIONS** menu and selecting **DRIVING POLICY**. Four options are available: * – **NORMAL SHORTEST PATH** : The vehicle selects the shortest path to go from their departure point to their destination, irrespective of the intersections and the traffic lights that they will have to pass through; * – **LEAST BUSY SHORTEST PATH** : The vehicle will take the shortest path by taking into account the waiting time for each of the lanes, which could be blocked; * – **AGGRESSIVE** : The vehicle will try to limit the journey time between their departure point and their destination; * – **COLEARNING** : The vehicle selects their traffic lane in order to reduce the likely waiting time at the next junction as much as possible. Their choice is based on intelligent, distributed, multi-agent algorithms that enable traffic lights to communicate with each other, for which road users are continuously made aware of the waiting times. This option is only available with certain methods of traffic management (learning). #### 4.5.4.3. _Advanced use of the editor_ We will now return to our editor and take a closer look at its editing features. You can access your editor from _"GLDSim"_ by selecting **OPEN EDITOR** ( **CTRL E** ) from the **OPTIONS** menu. You can also close _"GLDSim"_ and re-open your model using _"GLDEdit"_. We will start by deleting the lanes between the different intersections in our model in order to obtain the network from Figure 4.44. Two traffic lanes were deleted between nodes 7 and 9 as well as 5 and 9. **Figure 4.44.** _My example model showing the lanes deleted between nodes 7, 9 and 5_ In order to delete these nodes, once you have opened the model in the editor: * – right click on the section where you want to delete the lanes and then select **PROPERTIES** ; * – in the list **LANES TO** , select the lane that you want to delete, then click on the **DELETE DRIVELINE n**. **Figure 4.45.** _The dialog box for the properties of the junction and its DELETE DRIVELANE button. Here, the lane "Drivelane 25" in the junction "Road 6" has been selected. We can see the corresponding interactive link, underlined and in blue. For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ If you are unsure of the lane, you can verify it by clicking on the corresponding link, underlined and in blue, and it will be highlighted in green in your model. In this instance, it can be deleted by selecting **DELETE THIS DEVICE**. **Figure 4.46.** _The dialog box for lane properties, here "Drivelane 25", and its DELETE THIS DRIVELANE button_ Repeat the same steps to delete the other three lanes. The GLD editor allows you to restrict lanes to a certain type of vehicle. Let's now modify our model to link green lanes to buses (see Figure 4.47). **Figure 4.47.** _The plan for our model showing the bus lanes (in green). For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ Right-click on the relevant junction, then select **PROPERTIES**. Select the lane in **LANES TO** , then assign it **BUS** using the drop-down list **ALLOWS**. Repeat the same steps twice for the other sections. You should obtain a model similar to the one in Figure 4.48. The lanes restricted to buses will have changed color and should now be orange instead of pink. **Figure 4.48.** _The model featuring orange lanes restricted to buses. For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ Save (menu **FILE** , then **SAVE** or **SAVE AS** ) your model using a new name in order to save your modifications. There is a highly significant configuration that I have not yet introduced, and this relates to the direction cars must travel in at each intersection and for each lane. In the model, these direction indicators (the equivalent of white arrows, painted on the ground, in reality) are in the form of small acronyms within the lanes at the entry to an intersection. In Figure 4.49, we can see these before nodes 5 and 6. They are self-explanatory. They are generated by default when constructing a model but do not necessarily correspond to the way you want it to be. **Figure 4.49.** _A section of the model with nodes 5 and 6 surrounded by their direction indicators_ These can be easily modified using the GLD editor. For example, I am going to change the direction to take when a bus arrives from the south, moving towards intersection 5. Instead of turning left, I want it to continue right towards node 6. Right-clicking on the junction will display its properties. I will then select the lane, in **LANES TO** , for which I will specify only **TURN RIGHT** (tickbox). **Figure 4.50.** _The properties box with the modified direction indicators, TURN RIGHT, ticked, TURN LEFT, unticked, for the lane "Drivelane 12" of junction "Road 9"_ This offers the following possibilities, which can all be combined: * – **TURN LEFT** ; * – **GO STRAIGHT AHEAD** ; * – **TURN RIGHT**. This allows us to obtain the direction indicator logos in Figure 4.51. **Figure 4.51.** _The direction indicators in "GLDEdit"_ Save (menu **FILE** , then **SAVE** or **SAVE AS** ) your model in order to save your changes. #### 4.5.4.4. _Simulating the modified model_ Open your modified model using the simulator and launch the simulation. You should now see the bus traveling on the sections of the route that you have modified. These should also respect the direction indicators that you have specified. **Figure 4.52.** _Here we can note the green buses on the orange lanes, starting at node 4 and turning right at node 5. For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ It might be interesting to have general statistical data for a model – you can access this feature by selecting **SHOW STATISTICS** from the **STATISTICS** menu. Once it has been activated, a window will open featuring the **FILE** and **OPTIONS** menus. In **FILE** , the **EXPORT** option will allow you to export the statistics file in _".dat"_ format, or to close the window. COMMENT 4.8.– A _".dat."_ file is a data file ( _".dat"_ for data). In general, this type of file can be easily opened using a text editor such as Notepad in Microsoft Windows or TextEdit in Apple OSX. It is easy to use this data in Microsoft Excel using copy and paste, although in general these files are designed for use with specific programs. The OPTIONS menu has three main functions: * – **REFRESH (CTRL R)** : refreshes the results in relation to the current simulation; * – **VIEW** : displays a summary of the statistics ( **SUMMARY** ) or a table showing the statistics ( **TABLE** ); * – **SHOW AVERAGE OF** : display the average for all vehicles since the start of the simulation using **ALL ROADUSERS** or for the last 1,000 using **LAST 1000 ROADUSERS.** **Figure 4.53.** _The statistics window in SUMMARY mode (on the left) and TABLE mode (on the right)_ Figure 4.54 gives an example showing part of the data copied and pasted into Microsoft Excel from a _".dat"_ folder, exported by the simulator. These are the main features of GLD. Developers are currently seeking ways to make improvements or to increase its capabilities. Consult the links at the end of this work for further information. **Figure 4.54.** _A ".dat" file (top) and the data in Microsoft Excel (bottom)_ ## 4.6. AnyLogic This program is universal – it can be adapted to practically all domains or, alternatively, a simulation model can be created (see Volume 1, section 10.4.3.4). In this chapter, we will concern ourselves with how it might be used for traffic management. In its 7.3 version, AnyLogic features a _"Road Traffic Library"_ designed specifically for road network models and simulations. In order to do this, the application follows a construction process made up of several stages: * – importing a background map or an image of a plan; * – tracing and configuration of traffic lanes as well as their eventual intersections; * – design and configuration of the organigram for generating and controlling the flow of vehicles; * – adding traffic lights, pedestrian walkways, car parks, public transport vehicles, and configuration; * – 2D simulation; * – 3D simulation; * – results analysis. We will create a short example showing some of these stages in order to give you a chance to assess the program's features, ergonomics and flexibility. ### 4.6.1. _Downloading AnyLogic_ Before we begin, download the free version of AnyLogic at7: www.anylogic.com/downloads. Select your operating system, Microsoft Windows (x32 or x64), Mac OSX or Linux and select "FREE PLE" (Personal Learning Edition). **Figure 4.55.** _The AnyLogic downloads page_ Information on how to active the program is available via a link on the page. ### 4.6.2. _Our example_ For our background image, we will take an aerial view of a city taken from Google Maps showing several streets, with at least one intersection. This will be used for tracing our road network. **Figure 4.56.** _Aerial image from our example (Source: Google Maps)_ #### 4.6.2.1. _Capturing the background image_ The easiest way to obtain your image is to use a screenshot. On Mac: Press CMD SHIFT 4 and the cursor will take the shape of a cross (target). Select the area by dragging and dropping, let go of the click, and a _".png"_ image will appear on your desktop with the name _"Screen Shot YEAR-MONTH-DAY at HOUR.MINUTE.SECOND AM/PM"_. On PC8: Click on the START MENU then enter Snipping Tool in the search bar and confirm by pressing ENTER. Click on the triangle of the drop-down menu NEW in the SNIPPING TOOL dialog box which appears. Select RECTANGULAR SNIP, then, using the mouse to drag-and-drop, specify the area you wish to capture. **Figure 4.57.** _The SNIPPING TOOL dialog box in Microsoft Windows 7_ In the **FILE** menu in the window which opens, select **SAVE AS** then, after having given a name, a file type ( **PNG** or **JPG** ). Once you have specified the storage location, save your image by clicking on the **SAVE** button. #### 4.6.2.2. _Network modeling_ After installation, launch the program, then select **CREATE A MODEL** on the welcome screen. **Figure 4.58.** _The AnyLogic welcome screen_ A dialog box will open. Give your model a name and specify a storage location, then click on **FINISH**. Click on the **PALETTE** tab, located beneath the main toolbar, then select the **PRESENTATION** icon in the vertical toolbar (Figure 4.59). **Figure 4.59.** _The PALETTE tab and its PRESENTATION tools_ In the tools for the **PRESENTATION** palette, select **IMAGE** and drag it into the **MAIN** window inside the rectangular area defined by a marker (Figure 4.60). A dialog box will ask you to select a file. Select your screenshot and click on the **OPEN** button. **Figure 4.60.** _Selecting the captured image to be used as your background. Note the area defined by the marker xy_ Position the image so that its top-left corner is where the marker is (Figure 4.61). Finally, resize the image by pulling at one of the corners. **Figure 4.61.** _The image positioned where the marker is in the MAIN window. We can see the scale indicator at the top_ Above the image, a scale indicator will appear. Once this has been selected, you can expand it or reduce it in order to adapt the scale to your image, if the size correspondence is poor. COMMENT 4.9.– In the main horizontal toolbar, located beneath the menu, there is an option to vary the display scale of your model (from 25 to 4000%) in the drop-down menu next to the magnifying tool (ZOOM IN). In the vertical toolbar in the **PALETTE** tab, select **ROAD TRAFFIC LIBRARY** (black icon in the shape of a small car). Double-click on the **ROAD** tool then click in your image to trace a first street, from point to point (click to click). Double-click to complete your route. COMMENT 4.10.– This route tool works in the same way as the pen tool in certain graphics programs such as Adobe Illustrator. This allows us to create curves (splines, Bézier curves) for routes containing non-rectilinear sections. A dialog box will open, recommending that you change the scale (4 pixels per meter). Confirm by clicking **YES**. Clicking on the route that you have traced will bring up the parameters for the network ( **ROAD NETWORK** ) in the **PROPERTIES** window. It might require several clicks, but you should be able to move, in a loop, from the properties of the road ( **ROAD** ), to those of the image and then the network. **Figure 4.62.** _The properties of the road (ROAD) including its name (in this case, "Avenue Boucicaut") and the number of lanes (in this case, 1 and 1)_ In **ROAD NETWORK** , modify the width of the lanes ( **LANE WIDTH** ). 3.5 m is the standard width. In **ROAD** , name your street using the entry field **NAME** (spaces are not allowed) and specify the number of forward ( **NUMBER OF FORWARD LANES** ) and backward ( **NUMBER OF BACKWARD LANES** ) lanes. You can determine where the lane is forward or backward using the route arrows. **Figure 4.63.** _The route (one lane to the right and one to the left) in our model and its direction (in this instance, from left to right)_ We will now design another road, cutting across the first, similar to the previous road but whose last point (end point of the route) will be positioned on the central line of the road already present (Figure 4.64). This point will define where the two roads cross. Finish by naming the second road and specifying the number of lanes. **Figure 4.64.** _The two roads and the point where the routes cross (green dot). For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ COMMENT 4.11.– In the properties window for a road, you can tick the box ONE WAY to make your road one-way, should you so wish. When creating an intersection, connected roads are divided into several sections. In our example, the first road is split into two parts (Figure 4.65). **Figure 4.65.** _The first road, divided into two sections, on both sides of the intersection_ It will be necessary to bring up the properties for each of the sections of the road, by selecting them, in order to rename them. Generally, for ease of use, we use the cardinal points connected to street names. In my model, for example: * – Section 1 Road 1: "avenue_boucicaut_SOUTH"; * – Section 2 Road 1: "avenue-Boucicaut_NORTH"; * – Road 2: "rue Rhin_Danube". **Figure 4.66.** _The three properties windows for my three road segments: "Avenue_Boucicaut_NORTH", "Avenue_Boucicaut_SOUTH" and "Rue Rhin_Danube"_ #### 4.6.2.3. _Generating and implementing road traffic_ In order to introduce vehicles into our model, we will build several organigrams grouping together the visual features linked to their creation and management. Each of the entryways will have a source of cars traveling in a direction that we will be able to configure. The traffic plan to create is the one in Figure 4.67. **Figure 4.67.** _The traffic plan for our example. For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ You will be able to see that the vehicles arriving from the east can travel north or south, vehicles arriving from the south can travel east or north and vehicles arriving from the north can travel south or east. To specify these constraints, move your cursor either above or below your plan in the **MAIN** window. From the **ROAD TRAFFIC LIBRARY** in the **PALETTE** tab, drag and drop a **CAR SOURCE** block, then a **CAR MOVE TO** block and lastly a **CAR DISPOSE** block. When you have moved them to **MAIN** , it will be possible to create links between those close to each other. COMMENT 4.12.– In order to delete a link, left-click to select it (the surrounding points will become blue) then right-click followed by DELETE. In order to create a link, double-click on the first connecting point (green point) then drag towards the second connecting point (green point) and confirm by left-clicking. This should enable you to obtain the organigram from Figure 4.38 with the three connected blocks. **Figure 4.68.** _The 3 blocks taken from the ROAD TRAFFIC LIBRARY, moved to the MAIN window and connected_ We will now configure each one: * – click on the **CARSOURCE** block, then in the **PROPERTIES** window, select **RATE** in the **ARRIVALS DEFINED** BY field; * – enter 750 **PER HOUR** in **ARRIVAL RATE** ; * – select the north section of your n°1 road for the **ROAD** field; * – in **NAME** , enter "Veh_NORTH". You have just specified that a car will arrive from the north from this vehicle source every 15 seconds. **Figure 4.69.** _The properties of the CAR SOURCE block, now named "Veh_NORTH"_ * – click on **CARMOVETO** to display its properties; * – in the **NAME** field, change the name to "carMoveTo_SOUTH" and in the **ROAD** field, select the section of road located towards the south. **Figure 4.70.** _The properties of the CARMOVETO block, now named "carMoveTo_SOUTH"_ By configuring in this way, you indicate that the vehicles arriving from the north will automatically travel towards the south section of your road. Consider saving your model by selecting **SAVE AS** from the **FILE** menu. Enter a name in **MODEL NAME** , select a storage location in **LOCATION** or by using the **BROWSE** button, then click on the **FINISH** button to confirm. #### 4.6.2.4. _Test no.1 of the model simulation_ It is time now to test the first studies carried out using our model in order to ensure that it is working properly. Select **RUN** from the **MODEL** menu or click on the **RUN** icon (white triangle on a green circle) from the horizontal toolbar. Wait a few seconds. The simulator window, containing a **RUN** button below the name of your model, should appear in the foreground. **Figure 4.71.** _The simulator window featuring its RUN button below the name of the model, in this case "Chalon Boucicaut"_ Click on **RUN** to launch your simulation. You will be able to expand the window in order to see the whole of your model. The main functions of the simulator toolbar are explained in Figure 4.72. **Figure 4.72.** _The main functions of the simulator toolbar_ * – Play/Pause: launch the simulation or restart it after pausing – pause the simulation; * – Playback choice – "until" or "for": drop-down menu enabling you to select normal playback ( **RUN** ), playback until a certain time or date ( **RUN UNTIL** ) or playback for a precise length of time ( **RUN FOR** ), for a chosen unit (years, months, weeks, days, hours, minutes, seconds, milliseconds); * – Step by step: Advance the simulation by one step for each click; * – Stop: stop the simulation and return to the window with the **RUN** button; * – Return to real time: play the simulation in real time; * – Slow down: slow the simulation by a factor equal to a fraction of real time (1/2, 1/5, 1/10, 1/25, 1/50, 1/100, 1/250, 1/500); * – Multiplier acceleration/deceleration: displays the value of the deceleration or acceleration factor; * – Accelerate: accelerates the simulation by a factor equal to a multiple of realtime (2, 5, 10, 25, 50, 100, 250, 500); * – Rapid/standard advance: increase the speed to maximum or return to the previous speed. Vehicles are represented by small colored rectangles. They should travel from north to south. **Figure 4.73.** _Window showing the model during simulation. In this instance, we can see six vehicles (blue, green, cyan, green, green and red) traveling from north to south on road no.1 section 1 and 2. For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ COMMENT 4.13.– When you launch the simulator from the editor, if AnyLogic detects any errors, a dialog box will open with a message informing you of the nature of the problem or problems encountered. These errors often relate to direction, choice of roads or logic within the organigrams. #### 4.6.2.5. _Adding traffic_ We will now concern ourselves with redirecting our vehicles when they reach the intersection. For the purposes of this example, 60% of the traffic will be traveling south and 40% will be traveling east, that is towards road no. 2. In order to apply this restriction, we will use a conditional function for redirecting _(aiguillage)_ vehicles. In the **PALETTE** tab, select the **PROCESSING MODELLING LIBRARY** (icon in the shape of a watch). Drag a block **SELECT OUTPUT** next to your organigram. Now open the **ROAD TRAFFIC LIBRARY** and add a **CAR MOVE TO** block and a **CAR ORDER.** Delete and create the connections in order to obtain the organigram in Figure 4.74. **Figure 4.74.** _The organigram featuring three new blocks_ Click on the new block **CAR MOVE TO** that you have just added in order to display its properties. Rename it "carMoveTO_EAST" and in **ROAD** select road no. 2. Select the **SELECT OUTPUT** block and in properties, enter 0.6 for the **PROBABILITY** field and tick **END OF BACKWARD LANE** for **DESTINATION.** The steps that you have just taken will direct 60% of the vehicles towards the south and 40% towards the east. Save your model (menu **FILE – SAVE** ). NOTE. – It is not necessary for you to change the name of different blocks. However, doing so will make it easier to understand and re-read previously defined operations. #### 4.6.2.6. _Test no. 2 of the model simulation_ In the **MODEL** menu, select **RUN** or click on the **RUN** icon in the horizontal toolbar. Click on the **RUN** button to launch the simulation. You should now see vehicles traveling south and east from the north. **Figure 4.75.** _The model in simulation mode featuring four vehicles (green, blue, cyan, green) traveling south, three (green, blue, magenta) traveling east and one (red) arriving from the north. For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ When configuring the blocks, pay attention to the direction of traffic from its source. In the previous example, vehicles were traveling in a southbound direction from the north (source), meaning that the direction was forward ( **END OF FORWARD LANE** ) in the route chosen for road no. 1 and no. 2. However, when vehicles turned left at the intersection, they traveled along road no. 2, which was designed to travel in a westbound direction, and they were therefore traveling in the opposite direction from the route, meaning that the direction was backwards ( **END OF BACKWARD LANE** ). #### 4.6.2.7. _Finalizing your model_ To finish this short example, we will add two vehicle sources, one from the east and one from the south. We will also create organigrams for traffic management following Figure 4.67 and relaunch the simulation before switching to a 3D simulation and an analysis of the results. Start by creating two more organigrams with the same properties as those shown in Table 4.1. **Table 4.1.** _Properties of the blocks for the two new organigrams_ When finished, you should have three organigrams similar to those in Figure 4.76. **Figure 4.76.** _The three-vehicle management organigrams within our model_ #### 4.6.2.8. _Test no. 3 of the model simulation_ When you launch the model simulation, you should see vehicles traveling from the north, the south and the east. When they reach the intersection they will travel in one of the possible directions, depending on the probabilities entered. **Figure 4.77.** _Arriving from different sources, the vehicles will travel in random directions depending on the probabilities entered when the properties were configured. For a color version of this figure, see_ _www.iste.co.uk/reveillac/modeling2.zip_ #### 4.6.2.9. _Switching to a 3D simulation_ With Anylogic, it is possible to generate a 3D simulation of your model. In the **PALETTE** window, select the **PRESENTATION** library in the vertical toolbar and drag a **3D WINDOW** block under your model. Select the **ROAD TRAFFIC LIBRARY** , drag and drop a **CAR TYPE** block to the left of your **3D WINDOW** block. **Figure 4.78.** _The CAR TYPE block and the NEW AGENT dialog box with CAR selected_ A dialog box – **NEW AGENT** – will open. Click on the **NEXT** button, verify the vehicle model ( **CAR** ), click on **NEXT** and then **FINISH**. A window ( **CAR** ) and its tab will open next to **MAIN** , showing the vehicle that you have selected. In this window you will be able to modify the size of the vehicle using the scale indicator (see section 4.5.2.2). **Figure 4.79.** _The new tab CAR next to the MAIN tab, containing the vehicle and its scale indicator_ Return to the **MAIN** tab, select each of the vehicle source blocks in turn, "Veh_NORD", "Veh_SUD" and "Veh_EAST" for your three organigrams. For each of them, enter the value **CAR** in the **NEW CAR** field, within the **PROPERTIES** window, in the zone **CAR**. **Figure 4.80.** _The NEW CAR field (on the bottom) containing the value CAR, in the properties for the "Veh_NORD" source_ #### 4.6.2.10. _Final test of the model simulation_ Launch the simulator and click on the **RUN** button. In the simulation window, click on the **NAVIGATE TO VIEW AREA** icon and select **[WINDOWS3D]**. **Figure 4.81.** _The simulator toolbar and the NAVIGATE TO VIEW AREA icon, as well as the [WINDOWS3D] option (on the right)_ A 3D model should appear and your simulation should start. In this window, there are several options available for navigation and movement: * – Mouse scroll: zoom in and out; * – ALT + click drag-and-drop: rotate the background map right or left; * – Click + drag-and-drop: up-down-right-left translation. ### 4.6.3. _A last word on AnyLogic_ As I pointed out earlier, Anylogic is a powerful, highly sophisticated simulator, which has been shown to be adaptable to the majority of situations, whether for road traffic management or in other sectors. I could have expanded our example by including traffic lights, public transport vehicles, parking, the management of pedestrians, a detailed analysis of the density and flow of traffic in the form of tables, graphs, etc. However, I will not go any further at this point. The help provided with the program is extensive, so feel free to consult the tutorials, videos and the various examples that are available, as well as the editor's website ( **HELP** menu, then **WELCOME** or **HELP** , then **EXAMPLE MODELS** ). ## 4.7. Conclusion We will end our short overview of traffic simulators at this point. I would suggest that you take some time to search for other tools online using your preferred search engine. Here are a few links9 to get you started: * – sourceforge.net/projects/atsimu/: Traffic Simulation, a microscopic traffic simulator developed by Microsoft Visual C++; * – www.ctr.kth.se/mezzo.php: Mezzo: A mesoscopic traffic simulator; * – sourceforge.net/projects/tsignals/: Traffic Signals, a smart simulator for four-lane intersections; * – sourceforge.net/projects/sumotrafficc/: SUMO Traffic Creator, a road network simulator featuring road maps, among other features. 1 This link was active at the time of writing. Should any problems arise, use your preferred search engine. 2 This line was active at the time of writing. Should any problems arise, use your preferred search engine. 3 CoffeeScript is a programming language created in 2009 by J. Ashkenas that compiles into Javascript. 4 HTML 5.0 is the most recent major version of HyperText Markup Language (HTML), a language for formatting data, that was devised for creating websites. It dates back to 1991 and is based on Standard Generalized Markup Language (SGML). 5 This link was active at the time of writing. Should any problems arise, use your preferred search engine. 6 This link was active at the time of writing. Should any problems arise, use your preferred search engine. 7 At the time of writing, this link is active and the PLE version is free to download. Given the volatility of these links and the fact that the terms and conditions are subject to change, should you encounter any problems, search for "AnyLogic" using your preferred search engine. 8 Using Microsoft Windows VISTA or Windows 7 and above. Otherwise, download a free screenshot program such as: Gadwin PrintScreen, ScreenHunter, ScreenHotPlus, etc. 9 This link was active at the time of writing. Should any problems arise, use your preferred search engine. # Conclusion In this second volume, you have been introduced to various possible ways of using spreadsheets as well as the standard operations and features of a project manager and the different processes available for managing vehicle flow within road networks. Since the arrival of Visicalc1 and Multiplan2, the pioneers of electronic spreadsheets, spreadsheets have undergone a number of evolutions, bringing with them new features, but the fundamental principles remain the same. If you are wondering why this might be, the appearance on the market of the spreadsheet Improv3 might provide us with some answers. Improv wanted to introduce a new way of structuring data alongside functional evolution (multi-level cells for example), but it was a total commercial failure. Only specialists were impressed and aware of its real potential. For the majority of users, spreadsheets are complex tools in terms of understanding and functional logic, and it therefore seems difficult to change their design. Microsoft were fully aware of this, and decided to import Multiplan into a new product, Excel4, which has since gone on to be the most popular spreadsheet on the market. Other editors didn't lose any time and created equivalent products. Although the versions are constantly changing and users are increasingly well-informed, it should be pointed out that the majority of spreadsheets continue to make errors in their calculations (around 3% of cells5). Even if this rate seems to be decreasing as editors pay close attention to fundamental bugs, introduce corrective measures and work on the design of their products, new features appear and these lead to new issues. Often, these errors are due to the users themselves. In some ways this is similar to statistics in general: depending on how they are interpreted, you can make them say whatever you like. By now you will have understood that there is nothing revolutionary on the horizon for the future of spreadsheets. The existence of new rules, new alerts and better developed utilization logic, together with a deeper understanding of the features on the part of users will lead the way for the spreadsheets of tomorrow. In terms of project managers, these are increasingly associated with human resources management tools, thus opening the door to an integration of tools concerning pay and financial applications such as the management of repayments. These are often linked to company management production which itself can form part of an internal Enterprise Resource Planning (ERP6) model. The management of project funding is one of the features currently in vogue, along with the ability to intervene in planning using an internet browser. The major evolutions with this type of software largely relate to the ever-present relationships with the information system by adding tools such as a messaging platform, the possibility of using the Lightweight Directory Access Protocol (LDAP7), connections with Electronic Document Management (EDM8), unique Single Sign-On (SSO9) authentication and links with datamarts10. This second volume only deals with certain subjects relating to the modelling and simulation of flows. I would invite the reader to consult and read Volume 3 of this work to learn more about the management of flows relating to transportation, warehousing, transport, security, checking, the evacuation of personnel, etc. You can also explore software such as ExtendSim, FlexSim or Thunderhead PathFinder. 1 The first genuine spreadsheet was created by Bricklin D., Frankston B. and Fylstra D. in May 1979. 2 Microsoft spreadsheet from 1982. 3 Spreadsheet developed by Lotus in 1991 for the platform NeXTSTEP, then for Microsoft Windows in 1993. 4 Spreadsheet from 1984. One of the references for spreadsheets today, it is part of the Microsoft Office Suite. 5 See the publications by CLEMONT M., _A scalable approach to spreadsheet evolution_ , University of Klagenfurt, March 2003 and by PANKO R., _Spreadsheet research_. 6 Also designed in French under the acronym Progiciel de Gestion Intégré (PGI). 7 Protocol for questioning, modification and online directories based on TCP/IP. This has become the standard and includes a data model, a naming model, a security model and a replication model, designed for the directories. Its structure is based on an attributes-values node tree. 8 Electronic Document Management is also known as the Document Management System and forms part of the _workflow_ which describes and formalizes the different stages of the journey for the management of data flow. 9 The aim of SSO is to centralise authentication in order to allow the user to access all available resources from their workstation and across the whole network. 10 Subset of a data warehouse. # Appendices # Appendix 1 Installing the Solver ## A1.1. Introduction Chapter 1 makes several references to the "Solver" tool in Microsoft Excel. By default, this feature is not always installed and will therefore not appear in the menus, the toolbar icons or the icons featured within the different groups in the ribbon. Below you will find the steps required for proper installation depending on the different version of Microsoft Excel for Microsoft Windows or for Apple Mac OSX. ## A.1.2. Microsoft Excel 1997, 2002 and 2003 for Windows In the TOOLS menu, select ADD-INS. **Figure A1.1.** _The ADD-INS option in the TOOLS menu_ A dialog box will open. Tick "Add-ins..." and click on the OK button. **Figure A1.2.** _The list of add-ins with the "Solver Add-In" to be ticked_ In order to locate the solver click on the TOOLS menu and select SOLVER. **Figure A1.3.** _The option for opening the SOLVER from the TOOLS menu_ ## A1.3. Microsoft Excel 2007–2010 for Windows For Microsoft Excel 2007, click on the Office button (top left). **Figure A1.4.** _Top left – the Office button in Excel 2007_ In the window that opens click on the EXCEL OPTIONS button (bottom right, next to the QUIT EXCEL button). For Microsoft Excel 2010, open the FILE menu and select OPTIONS. A dialog box will open. Select "Adds-Ins" in the list on the left. **Figure A1.5.** _The Excel add-ins featuring the drop-down list MANAGE (bottom right) and the GO button_ Across from the "Manage" field (at the bottom), select "Excel Add-Ins" in the drop-down menu, then click on the GO button. A dialog box for add-ins will open. Select "Solver Add-In" and click on the OK button. **Figure A1.6.** _The dialog box displaying the available add-ins_ The solver is the last tool available (on the right) in the ribbon beneath the DATA tab in the ANALYSIS group. ## A1.4. Microsoft Excel 2013 for Windows In the FILE menu, select OPTIONS in the vertical ribbon located on the left. A dialog box will open. In the list on the left, select ADD-INS. In the section on the right, you should see all of the available add-ins for Microsoft Office, including the one called "Solver Add-In". In the lower section, across from the field "Manage" (at the bottom), select "Excel Add-Ins" from the drop-down menu, then click on the GO button. **Figure A1.7.** _The dialog box showing the list of available add-ins for Microsoft Excel 2013. At the bottom, we can see the "Manage" field along with its drop-down menu and GO button_ A new dialog box, "Add-Ins" should open, showing a list of the available add-ins. **Figure A1.8.** _The "Add-Ins" dialog box_ Select "Solver Add-In" and click on the OK button. COMMENT A1.1. **–** If "Solver Add-In" does not appear on the list, click on the BROWSE button. In the file explorer window that opens, go to "Programs\Microsoft Office\Office15\Library\SOLVER", select the file "SOLVER.XLAM" then click on the OK button. To locate the solver, click on the DATA menu in the ribbon on the right in the ANALYSIS group and you should see the solver icon. **Figure A1.9.** _The ribbon in the DATA menu including the solver icon on the right_ ## A1.5. Microsoft Excel for Mac 2008-2011 In the TOOLS menu, select ADD-INS. In the "Add-ins" dialog box that appears, select "Solver.Xlam" and click on the OK button. **Figure A1.10.** _The dialog box for installing the solver add-in_ COMMENT A1.2. – If "Solver.Xlam" does not appear in the list "Available add-ins", click on the SELECT button, open "Applications", and search in the folder "Microsoft Office 2008" or "Microsoft Office 2011" then the sub-folder "Office" then "Add-ins" and select "Solver.xlam". Click on the OPEN button and it should appear in the list of the "Add-ins" dialog box. To open the solver from a spreadsheet, go to the TOOLS menu and select SOLVER... **Figure A1.11.** _The TOOLS menu and the option SOLVER... (last option on the list)_ # Appendix 2 Installing the Java Development Kit ## A2.1. Why Java? Presented in May 1995 and developed by J. Gosling and P. Naughton of Sun Microsystems, _Java_ is an object-oriented programming language. It is now owned by Oracle which bought Sun in 2009. Java's slogan is WORA " _Write once, run anywhere_ ". By now, you will have understood that one of the main advantages of Java is its _portability_. You take your source code and you compile it once and it can then be used on any platform (Microsoft Windows, Linux, OSX, etc.) Another important advantage is the fact that it is free. When you download Java, you are able to access the Java Runtime Environment (JRE). It is made up of Java Virtual Machine (JVM), standard classes and Java libraries. JVM interprets the Java bytecode, controls how it interacts with the operating system and manages memory. The JVE relates to the running of the Java software and makes it possible to run a Java application. Java Development Kit (JDK) is the development kit for the Java language. It incorporates, among others, the compilation tools and the debugger. JDK contains JRE in order to be able to test the applications developed. ## A2.2. Downloading Download the Java Standard Edition (SE) development kit (JDK) at: www.oracle.com/technetwork/java/javase/downloads/index.html. Be sure to select the appropriate version for your operating system. COMMENT A2.1.– Please note that this address is subject to change. Should this happen, use a search engine to search for JDK. ## A2.3. Testing the presence of the JDK compiler Install JDK. Once it has been installed, open your system's command menu. With the OSX platform, use the application Terminal, located in the "Applications/Utilities" folder. **Figure A2.1.** _The sub-folder "Utilities", located in the "Applications" folder in OSX. Note the application "Terminal"_ Below Microsoft Windows 7, enter "cmd" in "Search programs and files" from the **START** menu (circle featuring the Microsoft Windows logo), at the bottom left, then confirm by pressing ENTER. **Figure A2.2.** _The field "Search programs and files" (on the left) and inputting "cmd" in the same field (on the right)_ In Microsoft Windows XP, from the **START** menu, at the bottom left, go to "Run", type "cmd" in the **OPEN** field in the **RUN** dialog box that will open, then click on the **OK** button. **Figure A2.3.** _The "Run" option from "All programs" and the RUN dialog box featuring the field OPEN containing "cmd"_ You can also access the "Command Prompt" from "All programs" in the "Accessories" folder. **Figure A2.4.** _The "command prompt" option in the "Accessories" folder in Microsoft Windows XP_ COMMENT A2.2.– In Microsoft Windows 8, you can access the RUN command by holding down the Windows button and pressing "R". Once your command menu window is displayed, enter "`javac`" followed by ENTER (open the java compiler). A list of commands for use should appear. **Figure A2.5.** _The command list for use with "javac" from the Microsoft Windows command menu (on the left) and from the OSX Terminal (on the right)_ With OSX, you should not encounter any problems. With Microsoft Windows, if this list doesn't appear and a message saying something along the lines of " _javac has not been recognized as an internal command..."_ , is displayed, this will be because you have forgotten the environment variable " _path_ ". ## A2.4. Creating the environment variable Here is the procedure to follow for resolving this issue: * – go to the Java installation folder, for example: _"C:\ProgramFiles\Java"_ ; * – open the folder of your JDK, for example _"jdk1.8.0_91"_ ; * – then open the folder _"bin"_ ; * – copy the access path for this folder, for example: _"C:\ ProgramFiles\Java\jdk1.8.0_91\bin"_ ; * – right click on your work post, then select **PROPERTIES** ; COMMENT A2.3.– It is also possible to access the system properties via the configuration by selecting **SYSTEM AND SECURITY** , then **SYSTEM** (Microsoft Windows 7) or **SYSTEM** , then the **ADVANCE** tab (Microsoft Windows XP). * – select ADVANCED SYSTEM PARAMETERS then click on the ENVIRONMENT VARIABLE button; * – select the variable " _Path_ " in the list of variable users if it is there, and click on the **MODIFY** button. Otherwise, click on the **NEW** button and give it the name " _Path_ "; * – in the **VARIABLE VALUE** field, if a set of values is already present, add an " **;** " (semi-colon) at the end, then past the path that you have previously copied. Otherwise simply paste the copied path; * – click on the **OK** button to close each of the windows then finish by closing the properties window; * – your `"javac"` compiler should now be operational. **Figure A2.6.** _From the properties of the work post we can see all of the windows for accessing the environment variable "Path" (Microsoft Windows 7)_ COMMENT A2.4.– In order to take into account the modifications relating to the environment variable, you will need to close and relaunch the command menu window. # Glossary Affine function: a function in the form of _y_ = _ax + b_. The variable _a_ is called the leading coefficient and the variable _b_ , _y_ -intercept. A linear function is a straight line. When it goes through the origin, in this particular case ( _y_ -intercept null), we then get a linear function ( _y_ = _ax_ ). Analytical resolution: in this type of problem solving, the approach to the solution is based on a mathematical procedure that provides precise and rapid result(s). In parallel with analytical resolution, we can choose a graphic solution. In linear programming, the simplex method is a type of analytical resolution. Branch and bound: a method that consists of finding the optimum solution to a problem of combinatorial optimization. It is built around the concept of separation (branch) that carves the group of solutions into subsets of a smaller size and optimistic assessment in increasing (bound) these same subsets. BRIC (Brazil, Russia, India and China): acronym designating the four principal developing countries. Canonical form (or standard form): form of a problem in linear programming in which the constraints are expressed by inequations. CAPM (computer-aided production management): software dedicated to managing all of the activities related to production in a business. Here, we can find, in the form of modules, the management of orders, the management of articles, the management of resources, the management of bills or materials and ranges of products, management of planning de fabrication, the management of purchases, etc. Cardinality: a pair of values attached to a relation in the entity-relationship model (relational model). For a relationship (or association) between two entities, two pairs must be specified. The cardinalities express the number of times that the occurrence of an entity can be taken into account in the relationship, at minimum or maximum. There are four typical cardinality pairs: ( _0_ , _1_ ), ( _1_ , _1_ ), ( _0_ , _n_ ) and (1, _n_ ), _n_ being the equivalent of several. Concentration: also known as density. For a traffic model, this is the number of vehicles present on a given length of a route at a defined time. Constraint: factor or condition that an optimization problem must satisfy. CONTRAM: mesoscopic model of road traffic. CPM (critical path method): method for calculating a critical path on a graph for planning tasks. Decision-making aid: a group of techniques based on probability theory, graph theory or even operational research. They offer the opportunity for a human actor to opt for the best possible solution when faced with problems that are mainly industrial, financial or other. Density: for road traffic, density is defined as the number of vehicles per unit length of the roadway. Deterministic algorithm: an algorithm that carries out a predefined process in order to resolve a problem. Dual: in linear programming, the initial problem, called "primal", is associated with another linear problem known as a "dual" problem. In some ways, the "dual" is the symmetrical to the "primal". DynaMIT: mesoscopic model of road traffic. Economic function (or cost function): function to be optimized in the context of linear programming. Fastlane: mesoscopic model of road traffic. Flow: for road traffic, flow is the number of vehicles passing a reference point per unit of time, vehicles per hour. GRH (Gazis, Herman and Rothery): microscopic model of road traffic. Heuristic: refers to a method that proceeds by successive approaches progressively eliminating the alternatives to keep only a limited group of solutions leaning toward optimality. Hybrid: refers to a method of traffic simulation model combining microscopic and macroscopic modes with the possibility, among others, to go from one to the other via a simple change in scale. ITS (Intelligent Transportation Systems): application of NICT designed for transportation. Kirchhoff's Law: also known as the "nodal rule". This is a law that shows the conservation of energy in an electrical circuit. The sum of the intensity of the currents that enter into a node is equal to the sum of the intensities of the currents that come out of it. By extension, this law can be found in operational research, among other things, with the management of floats. Linear function: see _affine function_. LWR (Lighthill, Witham, Richards): macroscopic traffic model known as an equilibrium model. Macroscopic: simulation mode within a traffic model. In this case, the flow approach of the network is global and involves large areas. Maximization: refers to a problem of optimization when its objective must lead toward a maximum. Mesoscopic: intermediate traffic simulation mode between microscopic and macroscopic. Microscopic: simulation mode within a traffic model considering each of the vehicles and their interactions. This mode works on zones with small dimensions (crossings, crossroads, small groups of streets). Minimization: refers to an optimization problem when its goal must must lead toward a minimum. MPM (métra potential method): a method invented by Bernard Roy in 1958. It allows for the representation and optimization of a project in the form of a network-type diagram showing, among other things, the intertask dependencies while reducing delays and by constructing a critical path. With MPM, the tasks are symbolized by nodes (vertices) unlike the PERT method. MST (minimum spanning tree): see _MWST_. MWST (minimum weight spanning tree): a tree that connects all of the vertices of a graph and where sum of the weight of each one of its edges is minimal. Normal distribution: also known as "Gaussian law" or "Gauss Laplace distribution". This is the law of probability that is most often used in statistics. Its curve is known as a "bell curve" due to its shape. It has two parameters: expectancy and a real number that makes it possible to calculate the probabilities of a group of random continuous variables. Objective: this is a shortcut for talking about objective function. This function is the principal criterion for determining the solution of a mathematical optimization problem. ODM (origin/destination model): macroscopic model of road traffic. ODS (open document spreadsheet): file extension and open document format dedicated to spreadsheets based on the ODF (Open Document Format for Office Applications) standard. This format is used, in particular, by "Calc", the spreadsheet from the OpenOffice Suite. OOP (object-oriented programming): computerized programming mode created in the 1960s by O.J. Dahl and K. Nygaard, then continued by A. Kay. It is built around objects that are software modules interacting with each other and representing an idea, a concept or an existing entity in the physical world. Numerous languages such as Java, C++, PHP and Ada using this programming mode. The concept of an object is also present within SE (Software Environments – Microsoft Visual Studio, Netbeans, etc.) in certain modeling tools (UML, DBDesigner, etc.) and in distributed buses (Corba, Pyro, RMI, etc.). PEP (program evaluation procedure): planning method used by the United States Air Force. PERT (program evaluation and review technology or program evaluation research task): project planning method developed by Booz, Allen and Hamilton, near the end of the 1950s, at the request of the Special Projects Office of the United States Navy. It makes it possible to create a connected, directed and weighted graph, where each of the tasks is represented by an arc that joins two vertices. It optimizes the project while taking into account the dependency constraints in order to determine the critical path and tasks. Pivot: also known as the "Gauss Pivot". The pivot is attached to the method of the same name (also called the "Gauss–Jordan elimination"). This is an algorithm that determines the solutions of a system of linear equations. Primal: refers to the initial problem in linear programming. RBDMS (relational database management system): database management system that manages the relationships forming the constraints that guarantee the referential integrity of the data. Relation: equivalent to an association between two entities in a relational model. Link established between two tables within an RBDMS. Relational algebra: this is the logical and mathematical support on which the relational model is based. It offers a group of elementary operations for creating new relations. Retroactive planning: also known as "feedback scheduling". This is an inverted planning method that conceives of a project starting with the end date and then go back toward the beginning. 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All the website provided here were valid at the time of this work going to print, but should any of them fail to work, a quick Google search should enable us to find them. ###### _Graph theory and operational research_ 1. ELSEVIER: European journal of operational research _(in French)_ , www.journals.elsevier.com/european-journal-of-operational-research/ 2. INSA ROUEN: Graph theory and operational research _(in French)_ , <https://moodle.insa-rouen.fr/course/view.php?id=124> 3. ROADEF: French society of operational research and decision aids _(in French)_ , www.roadef.org/content/road/road.htm 4. University of Texas: Operations research models www.me.utexas.edu/~jensen/models/index.html 5. University of Nancy: Maximal flow in a graph _(in French)_ , J.F. SCHEID www.iecn.u-nancy.fr/~scheid/Enseignement/flotmax.pdf 6. IEOR Berkeley: Network flows and graphs www.ieor.berkeley.edu/~ieor266/Lecture14.pdf 7. University of Metz: Modelling maximal flow problems _(in French)_ , <http://ensrotice.sciences.univ-metz.fr/module_avance_thg_voo6/co/modelflotmax.html> 8. ENSTA: Introduction to discreet optimization _(in French)_ , Adam OUOROU <http://wwwdfr.ensta.fr/Cours/docs/MAE41/maxflow_hd.pdf> 9. Tutorials on graphs, paths, trees, flows _(in French)_ <http://idmme06.inpg.fr/~rapinec/Graphe/Graphe/default.html> 10. E-book: Applied Mathematical Programming, Bradley, Hax, and Magnanti (Addison-Wesley, 1977) <http://web.mit.edu/15.053/www/> 11. Article: On the history of the transportation and maximum flow problems, Alexander Schrijver <http://homepages.cwi.nl/~lex/files/histtrpclean.pdf> 12. Introduction to graph theory _(in French)_ , Didier Müller www.apprendre-en-ligne.net/graphes/ 13. CNRS: Graph theory and optimization in graphs _(in French)_ , Christine Solnon <http://liris.cnrs.fr/csolnon/polyGraphes.pdf> 14. INPL: Elements of graph theory and linear programming _(in French)_ , Didier Maquin <http://cours.ensem.inpl-nancy.fr/cours-dm/graphes/Graphesnew.pdf> 15. LABRI (LAboratoire Bordelais de Recherche en Informatique), Introduction to graph theory _(in French)_ , Bruno Courcelle www.labri.fr/perso/courcell/Conferences/GraphesX.pdf 16. Graph theory _(in French)_ , <http://theoriedesgraphes.com/> 17. Optimization and complexity: An extensive set of tutorials _(in French)_ , Huet <http://doc.ium.bz/S6/Optimisation%20et%20complexit%C3%A9/cour/> 18. GeoGebra: The calculating software for functions, geometry, algebra etc. Site for resources and downloads <http://www.geogebra.org> 19. GeoGebra: A tutorial written in English by Marc Renault <http://webspace.ship.edu/msrenault/tutorial/> 20. GeoGebra: New figures to see and make with GeoGebra _(in French)_ , <http://rdassonval.free.fr/geogebra/> ###### _Databases and relational algebra_ 1. University of Paris 8: Database, relational algebra _(in French)_ , Rim Chaabane www.ai.univ-paris8.fr/~lysop/bd/seance5-ModeleRel-suite.pdf 2. ENST: The relational model and algebra _(in French)_ , www.enst.dz/Cours/LeModele_relationneletAlgebre_relationnelle.pdf 3. Introduction to SQL language _(in French)_ , Alexandre Mesle <http://alexandre-mesle.com/enseignement/sql/index.html> 4. What is an SGBDR? _(in French)_ , Fabien Celaia <http://fadace.developpez.com/sql/coddsgbdr/> ###### _Tables, Pivot Tables and VBA with Microsoft Excel_ 1. Excel practice, free VBA tutorial _(in French)_ www.excel-pratique.com/fr/vba.php 2. Documentation for VBA developers, Microsoft _(in French)_ , <https://msdn.microsoft.com/fr-fr/office/ff688774.aspx> 3. Excel exercise – Relations between tables _(in French)_ , www.excel-exercice.com/excel2013/relation-entre-les-tables/ 4. How to create a spreadsheet using Excel _(in French)_ , WikiHow <http://fr.wikihow.com/créer-un-tableau-avec-Excel> 5. Paris-Dauphine University: VBA initiation for Excel _(in French)_ , Philippe Bernard www.master272.com/finance/GP_L3/docs/VBA.pdf 6. Towson University: Excel 2013: PivotTables and Macros, Pamela J. Taylor <https://www.towson.edu/adminfinance/ots/trainingdoc/customguide/Excel2013/Excel%202013_PivotTables%20and%20Macros_studentFINAL.pdf> 7. College of Business Administration, Kansas State University: Conducting Data Analysis Using a Pivot Table, Brian Kovar <http://info.cba.ksu.edu/bkovar/PivotTableTutorial.pdf> 8. Spreadsheets in Excel 2007 _(in French)_ <http://silkyroad.developpez.com/excel/tableau/> 9. AgroParisTech: Using lists of data with Excel 2007 _(in French)_ , Michel Cartereau www.agroparistech.fr/mmip/mc/bazar/envoi.php?nom_fichier=cours-listes-excel2007.pdf ###### _Flow simulation_ 1. ExtendSim, flow simulation software, editor's website www.extendsim.com 2. A download of the demo version of ExtendSim <https://www.extendsim.com/prods_demo.html> 3. FlexSim, flow simulation software, editor's website <https://www.flexsim.com> 4. Arena, flow simulation software, editor's website <https://www.arenasimulation.com> 5. Witness, flow simulation software, editor's website www.lanner.com 6. SimWalk, simulation software for pedestrian flow, editor's website www.simwalk.com 7. PTV Group, PTV Vissim, traffic simulation software, editor's website www.ptvgroup.com 8. TSS, Aimsun, traffic simulation software, editor's website www.aimsun.com 9. Caliper, TransModeler, traffic simulation software, editor's website www.caliper.com/transmodeler/ 10. AnyLogic, traffic simulation software, editor's website www.anylogic.com 11. Simio, flow simulation software, editor's website www.simio.com 12. Simul8, flow simulation software, editor's website www.simul8.com 13. SFPE, Society of Fire Protection <http://www.sfpe-chapitre-francais.fr/> (French website) <http://www.sfpe.org/> (American website) ###### _Project management_ 1. Sciforma, project management software, editor's website www.sciforma.com 2. Visual Planning, project management software, editor's website <http://www.visual-planning.com> 3. Microsoft Project, project management software, editor's website <https://products.office.com/fr-fr/project/project-and-portfolio-management-software> 4. GanttProject, project management software, editor's website www.ganttproject.biz 5. The Wikipedia page devoted to project management software, including an enormous list of applications _(in French)_ , <http://fr.wikipedia.org/wiki/Logiciel_de_gestion_de_projets> # Index * Σ VALUES * 3D mode * 3D model ## **A, B** * acceleration * acceleration model * accumulation * add-in * ALIGNMENT * allocation of resources * ANALYZE * analyzing scenarios * AnyLogic * AUTO SCHEDULE * average * boundary conditions ## **C, D** * calculated fields * calendar * sections * capacity * CAPM * cardinalities * CEILING * CHARTS * CoffeeScript * compilation * CONDITIONAL FORMATTING * congestion * consolidating * CONSTRAINTS * constraints * Creative Commons * critical path * dashboards * DATA BARS * data tables * Database Management System (DBMS) * DataPilot * DATE FILTERS * date format * deceleration * density * dynamic programming ## **E, F** * editor * FIELDS, ITEMS AND SETS * FILTER * filtering * fluidity * FORMAT AXIS * FORMAT CELLS ## **G, H, I** * Gantt diagram * gap * between vehicles * GLDEdit * GLDSim * GNU General Public * Google Maps * histogram * crossing multiple data * HTML5 * IDM * importation * INDENT * INSERT SLICER * intersection simulator ## **J, L, M** * Java * Java compiler * LABELS * labor resource * lane-changing model * limits * linear programming * MANAGE RELATIONSHIPS * matrix * maximal flows * MecaTools * mesoscopic * Microsoft Project 2013 * MOBIL * MODULE * monitoring * MPM * MPM network * multiple databases * multiple tables ## **N, O, P** * NETWORK DIAGRAM * OpenOffice * operational research * organigrams * OUTDENT * over-allocation * PERT * Pivot table * PIVOT TABLE OPTIONS * planning * PowerPivot * predecessors * project configuring ## **R, S** * relationship * relationships * RELATIONSHIPS * reports * visual reports * reschedule * RESOURCE INITIALS * resources * Ring road * Road Traffic Library * RoadTrafficSimulator * SCHEDULE * scheduling * segment * shedules * simulator * slack * free slack * total slack * slowing down * SOLVER * spreadsheets * SUB TOTALS * SUMO ## **T, U, W** * Team Planner * TOTALPRODUCT * TOTALS AND FILTERS * traffic * Signals * simulators * transport * model * tuples * UNITS * WBS coding * Work Breakdown Structure (WBS) **2016** ANDRÉ Michel, SAMARAS Zissis _Energy and Environment (Research for Innovative Transports Set - Volume 1)_ AUBRY Jean-François, BRINZEI Nicolae, MAZOUNI Mohammed-Habib _Systems Dependability Assessment: Benefits of Petri Net Models (Systems Dependability Assessment Set - Volume 1)_ BLANQUART Corinne, CLAUSEN Uwe, JACOB Bernard _Towards Innovative Freight and Logistics (Research for Innovative Transports Set - Volume 2)_ COHEN Simon, YANNIS George _Traffic Management (Research for Innovative Transports Set - Volume 3)_ MARÉ Jean-Charles _Aerospace Actuators 1: Needs, Reliability and Hydraulic Power Solutions_ REZG Nidhal, HAJEJ Zied, BOSCHIAN-CAMPANER Valerio _Production and Maintenance Optimization Problems: Logistic Constraints and Leasing Warranty Services_ TORRENTI Jean-Michel, LA TORRE Francesca _Materials and Infrastructures 1 (Research for Innovative Transports Set - Volume 5A) Materials and Infrastructures 2 (Research for Innovative Transports Set - Volume 5B)_ WEBER Philippe, SIMON Christophe _Benefits of Bayesian Network Models (Systems Dependability Assessment Set – Volume 2)_ YANNIS George, COHEN Simon _Traffic Safety (Research for Innovative Transports Set - Volume 4)_ **2015** AUBRY Jean-François, BRINZEI Nicolae _Systems Dependability Assessment: Modeling with Graphs and Finite State Automata_ BOULANGER Jean-Louis _CENELEC 50128 and IEC 62279 Standards_ BRIFFAUT Jean-Pierre _E-Enabled Operations Management_ MISSIKOFF Michele, CANDUCCI Massimo, MAIDEN Neil _Enterprise Innovation_ **2014** CHETTO Maryline _Real-time Systems Scheduling_ _Volume 1 – Fundamentals_ _Volume 2 – Focuses_ DAVIM J. Paulo _Machinability of Advanced Materials_ ESTAMPE Dominique _Supply Chain Performance and Evaluation Models_ FAVRE Bernard _Introduction to Sustainable Transports_ GAUTHIER Michaël, ANDREFF Nicolas, DOMBRE Etienne _Intracorporeal Robotics: From Milliscale to Nanoscale_ MICOUIN Patrice _Model Based Systems Engineering: Fundamentals and Methods_ MILLOT Patrick _Designing Human–Machine Cooperation Systems_ NI Zhenjiang, PACORET Céline, BENOSMAN Ryad, REGNIER Stéphane _Haptic Feedback Teleoperation of Optical Tweezers_ OUSTALOUP Alain _Diversity and Non-integer Differentiation for System Dynamics_ REZG Nidhal, DELLAGI Sofien, KHATAD Abdelhakim _Joint Optimization of Maintenance and Production Policies_ STEFANOIU Dan, BORNE Pierre, POPESCU Dumitru, FILIP Florin Gh., EL KAMEL Abdelkader _Optimization in Engineering Sciences: Metaheuristics, Stochastic Methods andDecision Support_ **2013** ALAZARD Daniel _Reverse Engineering in Control Design_ ARIOUI Hichem, NEHAOUA Lamri _Driving Simulation_ CHADLI Mohammed, COPPIER Hervé _Command-control for Real-time Systems_ DAAFOUZ Jamal, TARBOURIECH Sophie, SIGALOTTI Mario _Hybrid Systems with Constraints_ FEYEL Philippe _Loop-shaping Robust Control_ FLAUS Jean-Marie _Risk Analysis: Socio-technical and Industrial Systems_ FRIBOURG Laurent, SOULAT Romain _Control of Switching Systems by Invariance Analysis: Application to Power Electronics_ GROSSARD Mathieu, REGNIER Stéphane, CHAILLET Nicolas _Flexible Robotics: Applications to Multiscale Manipulations_ GRUNN Emmanuel, PHAM Anh Tuan _Modeling of Complex Systems: Application to Aeronautical Dynamics_ HABIB Maki K., DAVIM J. Paulo _Interdisciplinary Mechatronics: Engineering Science and Research Development_ HAMMADI Slim, KSOURI Mekki _Multimodal Transport Systems_ JARBOUI Bassem, SIARRY Patrick, TEGHEM Jacques _Metaheuristics for Production Scheduling_ KIRILLOV Oleg N., PELINOVSKY Dmitry E. _Nonlinear Physical Systems_ LE Vu Tuan Hieu, STOICA Cristina, ALAMO Teodoro, CAMACHO Eduardo F., DUMUR Didier _Zonotopes: From Guaranteed State-estimation to Control_ MACHADO Carolina, DAVIM J. Paulo _Management and Engineering Innovation_ MORANA Joëlle _Sustainable Supply Chain Management_ SANDOU Guillaume _Metaheuristic Optimization for the Design of Automatic Control Laws_ STOICAN Florin, OLARU Sorin _Set-theoretic Fault Detection in Multisensor Systems_ **2012** AÏT-KADI Daoud, CHOUINARD Marc, MARCOTTE Suzanne, RIOPEL Diane _Sustainable Reverse Logistics Network: Engineering and Management_ BORNE Pierre, POPESCU Dumitru, FILIP Florin G., STEFANOIU Dan _Optimization in Engineering Sciences: Exact Methods_ CHADLI Mohammed, BORNE Pierre _Multiple Models Approach in Automation: Takagi-Sugeno Fuzzy Systems_ DAVIM J. Paulo _Lasers in Manufacturing_ DECLERCK Philippe _Discrete Event Systems in Dioid Algebra and Conventional Algebra_ DOUMIATI Moustapha, CHARARA Ali, VICTORINO Alessandro, LECHNER Daniel _Vehicle Dynamics Estimation using Kalman Filtering: Experimental Validation_ GUERRERO José A, LOZANO Rogelio _Flight Formation Control_ HAMMADI Slim, KSOURI Mekki _Advanced Mobility and Transport Engineering_ MAILLARD Pierre _Competitive Quality Strategies_ MATTA Nada, VANDENBOOMGAERDE Yves, ARLAT Jean _Supervision and Safety of Complex Systems_ POLER Raul _et al_. _Intelligent Non-hierarchical Manufacturing Networks_ TROCCAZ Jocelyne _Medical Robotics_ YALAOUI Alice, CHEHADE Hicham, YALAOUI Farouk, AMODEO Lionel _Optimization of Logistics_ ZELM Martin _et al_. _Enterprise Interoperability–I-EASA12 Proceedings_ **2011** CANTOT Pascal, LUZEAUX Dominique _Simulation and Modeling of Systems of Systems_ DAVIM J. Paulo _Mechatronics_ DAVIM J. Paulo _Wood Machining_ GROUS Ammar _Applied Metrology for Manufacturing Engineering_ KOLSKI Christophe _Human–Computer Interactions in Transport_ LUZEAUX Dominique, RUAULT Jean-René, WIPPLER Jean-Luc _Complex Systems and Systems of Systems Engineering_ ZELM Martin, _et al_. _Enterprise Interoperability: IWEI2011 Proceedings_ **2010** BOTTA-GENOULAZ Valérie, CAMPAGNE Jean-Pierre, LLERENA Daniel, PELLEGRIN Claude _Supply Chain Performance / Collaboration, Alignement and Coordination_ BOURLÈS Henri, GODFREY K.C. Kwan _Linear Systems_ BOURRIERES Jean-Paul _Proceedings of CEISIE'09_ CHAILLET Nicolas, REGNIER Stéphane _Microrobotics for Micromanipulation_ DAVIM J. Paulo _Sustainable Manufacturing_ GIORDANO Max, MATHIEU Luc, VILLENEUVE François _Product Life-Cycle Management / Geometric Variations_ LOZANO Rogelio _Unmanned Aerial Vehicles / Embedded Control_ LUZEAUX Dominique, RUAULT Jean-René _Systems of Systems_ VILLENEUVE François, MATHIEU Luc _Geometric Tolerancing of Products_ **2009** DIAZ Michel _Petri Nets / Fundamental Models, Verification and Applications_ OZEL Tugrul, DAVIM J. Paulo _Intelligent Machining_ PITRAT Jacques _Artificial Beings_ **2008** ARTIGUES Christian, DEMASSEY Sophie, NERON Emmanuel _Resources–Constrained Project Scheduling_ BILLAUT Jean-Charles, MOUKRIM Aziz, SANLAVILLE Eric _Flexibility and Robustness in Scheduling_ DOCHAIN Denis _Bioprocess Control_ LOPEZ Pierre, ROUBELLAT François _Production Scheduling_ THIERRY Caroline, THOMAS André, BEL Gérard _Supply Chain Simulation and Management_ **2007** DE LARMINAT Philippe _Analysis and Control of Linear Systems_ DOMBRE Etienne, KHALIL Wisama _Robot Manipulators_ LAMNABHI Françoise _et al_. _Taming Heterogeneity and Complexity of Embedded Control_ LIMNIOS Nikolaos _Fault Trees_ **2006** FRENCH COLLEGE OF METROLOGY _Metrology in Industry_ NAJIM Kaddour _Control of Continuous Linear Systems_ # **WILEY END USER LICENSE AGREEMENT** Go to www.wiley.com/go/eula to access Wiley's ebook EULA.

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Automated synthesis of the generic peptide labelling agent N-succinimidyl 4-[(18)F]fluorobenzoate and application to (18)F-label the vasoactive transmitter urotensin-II as a ligand for positron emission tomography. The objectives of this work were to develop an automated production of N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]-SFB) and to test whether the vasoactive peptide urotensin-II (U-II) could be labelled by conjugation with [(18)F]-SFB. A TRACERlab MX(FDG) synthesizer including an HPLC unit was used. The MS Excel synthesis sequence and the standard disposable FDG cassette were modified to allow the synthesis of [(18)F]-SFB. U-II was subsequently conjugated with [(18)F]-SFB, and the resulting (18)F-labelled peptides were characterised using in vitro ligand binding assays. [(18)F]-SFB was successfully synthesised in the TRACERlab MX(FDG) in 44.3+/-2.5% (n=25) radiochemical yield in 98 min. [(18)F]-SFB (8-12 GBq) has been produced with specific activities in the range of 250-350 GBq/mumol and a radiochemical purity >95%. [(18)F]-SFB was subsequently used to label U-II. Two radiolabelled products, [(18)F]-(Glu(1))-U-II and [(18)F]-(Lys(8))-U-II, were formed in an isolated radiochemical yield from [(18)F]-SFB of 5.2+/-0.3% and 29.0+/-3.7%, respectively (n=7). Radioligand binding assays revealed that [(18)F]-(Glu(1))-U-II had retained subnanomolar affinity. Binding to human skeletal muscle (n=3) was concentration dependent and saturable with K(d)=0.84+/-0.51 nM, B(max)=0.69+/-0.14 fmol/mg protein and Hill slope (nH)=1.03+/-0.12. [(18)F]-SFB has been synthesised using the TRACERlab MX(FDG) module, allowing production of up to 8-12 GBq of [(18)F]-SFB with specific activities of 250-350 GBq/mumol. [(18)F]-SFB was used for the labelling of U-II. In vitro characterisation demonstrated that [(18)F]-(Glu(1))-U-II had retained desirable binding properties and may be suitable as a positron emission tomography radioligand for the imaging of the U-II receptor.

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Q: Flutter: Text field cursor doesn't go down after a new line creation I'm using Text Field widget for text editing: new TextField( controller: _controller, maxLines: null, ), The problem: when I start a new line, the cursor doesn't go down until I start typing a text. Here is the screenshot: My question: How to make cursor go down to a new line as soon as it is created? A: According to: Github The _paintCaret method in /lib/src/rendering/editable.dart has to be modified and the maxLines parameter in the textField has to be null. It worked for me, hoping to be a temp workaround. /// MODIFIED: void _paintCaret(Canvas canvas, Offset effectiveOffset) { assert(_textLayoutLastWidth == constraints.maxWidth); final Offset caretOffset = _textPainter.getOffsetForCaret(_selection.extent, _caretPrototype); final Paint paint = new Paint()..color = _cursorColor; //final Rect caretRect = _caretPrototype.shift(caretOffset + effectiveOffset); var textLength = 0; var inputString = ''; if (text.children != null) { for (var ts in text.children) { textLength += ts.text.length; inputString += ts.text; } } else if (text.text != null) { textLength += text.text.length; inputString += text.text; } final Rect tmpRect = _caretPrototype.shift(caretOffset + effectiveOffset); Rect caretRect = new Rect.fromLTRB(tmpRect.left, _viewportExtent - 2.0 - tmpRect.height, tmpRect.right, _viewportExtent - 2.0); if ((tmpRect.top.abs() - caretRect.top.abs()).abs() > 10) { caretRect = new Rect.fromLTWH(0.0, caretRect.top, caretRect.width, caretRect.height); } if (_selection.extentOffset != textLength){ caretRect = tmpRect; } if (caretRect.left != 0 && inputString[_selection.extentOffset - 1] == '\n') { _selection = new TextSelection.fromPosition(new TextPosition(offset: _selection.extentOffset)); caretRect = _caretPrototype.shift(caretOffset + effectiveOffset); } canvas.drawRect(caretRect, paint); if (caretRect != _lastCaretRect) { _lastCaretRect = caretRect; if (onCaretChanged != null) onCaretChanged(caretRect); } }

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Like words? Ore are you more a fan of pictures? Don't worry, there's something for everyone to enjoy in the conclusion of Valve's new comic, Portal 2: Lab Rat , which is now available for your reading and/or picture-looking pleasure.Also of note for time-keeping enthusiasts: the calendar experts here at Valve have crunched some numbers, and have conclusively decided on 7AM EST, April 19th, 2011, as the exact moment that Portal 2 will be available on Steam. That means you've got a finite and rapidly shrinking window for being able to tell your friends, "Oh, is Portal 2 out now? I wouldn't know. Because Iit." Look us in the eye and tell us this isn't something you'd like to be able to tell your friends. You still can

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The TOJ Roundtable is back. Make sure to give everybody a follow on Twitter and to let us know your opinion down in the comment section below! What are you hoping to see in week 1 of the preseason from the New York Jets? Check out our store on The Loyalist! Joe Caporoso: Let’s put quarterback aside, all eyes should be on the offensive line, which has been a train wreck so far in training camp and wide receiver, which is the least proven position group in the NFL after Quincy Enunwa’s injury (weeps). We know Robby Anderson is going to start but after him, who else steps up? Charone Peake, Jalin Marshall, Chris Harper sound like they will get the first shot. Rookies ArDarius Stewart and Chad Hansen have had quiet camps but will see no shortage of reps and be pushed towards playing time. Can one or two of these guys have a big debut to ease some of the valid concerns about the position? Dalbin Osorio: There are a few things I’m looking forward to seeing, but the two main things are really non-QB related. One, I am looking forward to seeing how the Jets vaunted defensive line rotates with their personnel. Will Head Coach Todd Bowles play his three studs together? Will Sheldon Richardson masquerade as a cornerback? It will be fascinating to see, since this preseason will serve as a showcase to move Richardson I would imagine. Also, will we see Muhammad Wilkerson at full strength after he labored through last season? Lastly, will Leo Williams continue his ascent to his rightful perch as the best 3-4 DE in football? That is what I will be watching on defense. On offense, it is the Elijah McGuire and Chad Hansen show. With the injury to Quincy Enunwa, Hansen becomes the best WR by default; yes, he’s better than Robbie Anderson (he runs better routes and has better hands, despite Anderson having better speed) and he will now be tasked with both stepping up into that big slot and movable X role. Is he up to the task, if he even plays at all? With McGuire, Matt Forte and Bilal Powell are both banged up and he will receive a lot of work. I have a feeling people will be talking about him a lot after this game. Scott Mason: I’d like to see some of the young guys play well. I’d like to see early surprises like Chris Harper continue to build a case for earning a roster spot. But – and forgive me if I sound like a broken record here – what I desperately want more than anything else is to watch Christian Hackenberg play well enough to make the fans a little giddy and give the coaching staff a reason to re-evaluate the #fakenews “competition” they have set up that is clearly rigged with the intention of making McCown the opening day starter. I re-watched some pre-injury Chad Pennington tape over the weekend and it reminded me of how 2002 was easily the most excited I have ever been as a Jets fan as far as thinking about the long term. Having a young QB that really looked to be elite – and I maintain would have been if he hadn’t ruined his shoulder midway through 2004 – is what every Jets fan has been wishing for every Christmas for decades. All I want this pre-season opener is to see some signs that maybe, against all odds, Joe Fileppi is right (Leader of the #Hackhive), and Christian Hackenberg is going to be the QB who finally fulfills those many Christmas wishes. Joe Malfa: I recently advised Jets fans not to panic over reports of the offensive line being completely and utterly dominated by the defensive line in the early stages of training camp. Towards the end of that article, I made clear the importance of the first couple of preseason games. If the Jets’ offensive linemen are inept against a team like the Titans, whose defensive line is nowhere near as talented as the defensive line they square off against every day in practice, it might be time to panic. The team in heading for a 3-13 season, a fate cemented by the loss of Quincy Enunwa, but it would still be nice to get a good look at Christian Hackenberg. If opposing pass rushers are on him before he even has a chance to go through his progressions, he won’t stand a chance. The offensive line, particularly Brent Qvale and Brandon Shell at right tackle, will be under my microscope on Saturday night. I will be looking for a strong showing from this unit, otherwise it may officially be time to panic. Daniel Essen: Excuse my emotion but I’m still recovering from the Quincy Enunwa news. In the Jets first game outside of practice for 2017, I’m hoping to see a positive response amidst the amount of negative mud the Jets seem to be trapped in at the moment. The injury to Quincy Enunwa is a really tough blow for the Jets from a leadership perspective and for an offense that was already struggling to piece simple plays together. Ironically, now would be the perfect time for the few veterans left to keep teammates mentally focused and lead by example on the field as the Jets get closer to the regular season. More tangibly, I’m also hoping the defense comes out strong, particularly in the secondary where several players are scrapping for playing time. I’m hoping Adams and Maybe play the whole first half and maybe a little more to gain some valuable experience. Offensively, I’m eager to see plenty of snaps for the rookies Chad Hansen, ArDarius Stewart, and Elijah McGuire, as they now each have larger roles to play. Also, I expect Hackenberg to play the majority of the game so the Jets can get a good read on what he can do. I’m looking forward to getting a better taste of John Morton’s offense and what his tendencies are, as well. Jake Benaquisto: As it has been for seemingly eternity, the Jets biggest question mark on their roster is the quarterback position. Nobody would be shocked if Josh McCown starts the season as the Jets QB, but at 38 years old, he’s clearly not the long term answer. With this being said, I want to see Christian Hackenberg play at least two quarters in the first preseason contest against Tennessee. The polarizing second year quarterback has reportedly looked much improved in training camp so far, but the coaching staff and front office cannot properly evaluate Hackenberg if he sees a limited amount of live game action. Hackenberg needs to see a fair amount of snaps with the Jets first team offense against a first team defense, instead of playing with a bunch of guys on the roster bubble. If Hackenberg is given an increased amount of reps in the first preseason game and beyond, the Jets will have a much better understanding of his ability, or lack there of, to be their franchise quarterback. David Aitken: Firstly, football is back. Enjoy it! Regardless of how good the Jets are going to be this year, we only get a few months of this. Getting the best feel yet for Christian Hackenberg’s progress is the biggest story for me. The general training camp consensus is a vague “progress” but that has manifested itself so far into being groomed as the backup ahead of Bryce Petty rather than a surefire starting opportunity. This will be his first in-game action – probably extended action – since an all-time horrendous showing in last year’s preseason finale. McCown starting has been the consistent line all camp but an overall strong body of preseason performances from Hackenberg would definitely change that and make this season’s overall outlook a little more hopeful. Michael McLaughlin: Outside of Christian Hackenberg playing well, I’d like the young wide receivers to demonstrate why Jets fans believe they have potential while the rest of the league casts serious doubt on them. The latter viewpoint is not unwarranted given their complete and utter lack of experience, however. And my concern is that we tend to to overrate our own players as fans. Besides Robby Anderson, I am not sure what wide receivers will start. Consequently, any players demonstrating that they could handle such a role would be encouraging. That could be Stewart, Hansen, Peake, Marshall, Wilson or Harper. There are a lot of options, but they’re all unproven. – Photo Credit: NewYorkJets.com Related

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Thinktank predicts half will be renting in their 40s and a third ‘by time they claim pensions’ One in three of Britain’s millennial generation will never own their own home, with many forced to live and raise families in insecure privately rented accommodation throughout their lives, according to a report by the Resolution Foundation. In a gloomy assessment of the housing outlook for approximately 14 million 20- to 35-year-olds, the thinktank’s intergenerational commission said half would be renting in their 40s and that a third could still be doing so by the time they claimed their pensions. Housing minister defends claim of immigration impact on house prices Read more It predicted an explosion in the housing benefits bill once the millennial generation reaches retirement. “This rising share of retiree renters, coupled with an ageing population, could more than double the housing benefit bill for pensioners from £6.3bn today to £16bn by 2060 – highlighting how everyone ultimately pays for failing to tackle Britain’s housing crisis,” the report read. It calls for a radical overhaul of the private rented sector, proposing a three-year cap on rent increases, which would not be allowed to rise by more than the consumer price index, currently 2.5%. The report adds to a growing chorus of demands for rent stabilisation. Jeremy Corbyn called for rent control during his speech at the Labour party conferencelast year. The Resolution Foundation wants “indeterminate” tenancies as the sole form of contract in England and Wales. These would replaced the standard six-month or 12-month contracts demanded by most landlords. The thinktank said this would follow Scotland’s lead, where open-ended tenancies began in December 2017, and is the standard practice in Germany, the Netherlands, Sweden and Switzerland. Children in the rented sector Children in the rented sector Greater security of tenancy is vital as more families are raised in the private rented sector, the report said. The number of privately renting households with children has tripled from 600,000 in 2003 to 1.8m in 2016. “While insecurity in the private rented sector is often seen as an acceptable risk when childless, the disruption it can cause to schooling, friendship groups and support networks once young people have a family is clearly less than ideal,” the thinktank said. It added that public policy had failed to catch up with extraordinary changes in renting: “In 2003, the number of children in owner-occupied housing outnumbered those in the private rented sector by eight to one. That ratio has now fallen to two to one.” However, landlords have reacted vigorously against any suggestion of rent controls. David Cox, the chief executive of the Association of Residential Letting Agents, said: “The last time rent controls existed in this country, the private rented sector shrunk from 90% [of all housing] to 7%. “At a time of demand for private rented homes massively outstripping supply, rent controls will cause the sector to shrink. In turn, this means professional landlords will only take the very best tenants and the vulnerable and low-income people that rent controls are designed to help will be forced into the hands of rogue and criminal operators, who may exploit them.” Resolution’s intergenerational commission is also calling for the UK to tax foreign investors in rented property more heavily, along the lines of Vancouver in Canada and Australia, where external buyers face levies of up to 15%. It also sets out a number of reforms to improve the supply of houses in the UK, including giving local councils more powers to compulsorily acquire land and greater access to finance to build affordable homes. Sign up to the daily Business Today email or follow Guardian Business on Twitter at @BusinessDesk Lindsay Judge, senior policy analyst at the thinktank, said: “Britain’s housing problems have developed into a full-blown crisis over recent decades and young people are bearing the brunt.” She added: “If we want to tackle Britain’s ‘here and now’ housing crisis we have to improve conditions for the millions of families living in private rented accommodation. That means raising standards and reducing the risks associating with renting through tenancy reform and light touch rent stabilisation.”

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Because science: Christian TV Host Rick Wiles claims that meatless burgers are a Satanic plot meant to rewrite human DNA and create a “race of soulless creatures.” Right Wing Watch reports that Wiles, host of TruNews, a television “news” program produced for conservative Christians, believes that “plant-based alternatives to meat and dairy products, is part of a satanic plot to alter human DNA so that people can no longer worship God.” Appearing on his program earlier this week, Wiles said: When you go to your favorite fast food restaurant, you are going to be eating a fake hamburger. You’re going to go to the grocery store and buy a pound of fake hamburger or a fake steak, and you won’t know that it was grown in some big corporation’s laboratory. This is the nightmare world that they are taking us into. They’re changing God’s creation. Why? Because they want to be God. Wiles continued: God is an environmentalist. He takes this very seriously. He created this planet, he created the universe and he’s watching these Luciferians destroy this planet, destroy the animal kingdom, destroy the plant kingdom, change human DNA. Why? They want to change human DNA so that you can’t be born again. That’s where they’re going with this, to change the DNA of humans so it will be impossible for a human to be born again. They want to create a race of soulless creatures on this planet. Wiles is a popular but controversial conservative Christian leader who often makes outrageous and idiotic claims. For example, last October, right before the 2018 midterm elections, Wiles warned his viewers that if Democrats won the election they would slaughter “tens of thousands of Christians.” Yet even though the Democrats did win the House in the midterm election, as of today, there have been no reports of Christians being slaughtered. Another example of Wiles being a conservative Christian idiot: Last summer the Christian TV host warned his followers that MSNBC’s Rachel Maddow was preparing to lead a bloody coup to overthrow the Trump administration. Perhaps even more alarming, last month Wiles told his audience that conservative Christians will “impose Christian rule in this country,” while warning that those who support reproductive rights will spend eternity being “aborted continuously forever” by demons in Hell. Bottom line: Christian TV Host Rick Wiles warns his viewers that meatless burgers are a Satanic plot meant to rewrite human DNA and create a “race of soulless creatures.” The stupid, it burns.

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There Are Right and Wrong Ways of Suffering, Pope Says There are “right” and “wrong” ways to live with suffering, Pope Francis has told an apostolate for the evangelization of the sick. Addressing members of the ‘Apostolate of the Suffering’ and the ‘Silent Workers of the Cross’ in Paul VI Hall of the Vatican May 17, the Pope discussed the attitudes suffering persons…

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The overall goal of this proposed research is to elucidate the molecular details of how chromatin structure contributes to the activation of immunoglobulin (Ig) genes. The study of cultured murine cell lines with defined phenotypes of Ig gene rearrangements and expression will allow discrimination between changes in chromatin structure and composition that occur prior to Ig gene rearrangement and transcription from those which occur as a result of transcription. Specifically, these experiments will address the role that chromatin structure has in 1) B cell commitment to DNA rearrangement, 2) isotype selection during heavy (H) chain class switch, 3) the simultaneous coexpression of Mu and Delta H chains and 4) the control of Ig gene expression by immunoregulatory mechanisms. The research can be divided into two major areas of investigation: i) Definition of B cell stage-specific chromatin alterations along endogenous Ig genes that precede and accompany rearrangement and transcription. ii) The definition of sequences (control elements) responsible for the chromatin alterations by DNA-mediated gene transfer. The general experimental strategy will be to subject the nuclei from B cell lines at different stages of development (either with or without transfected recombinant vectors) to nuclease digestion. The digested chromatin will be fractionated based on its protein composition using a) gel electrophoresis of native nucleoprotein complexes, b) the chromatin's solubility under specific ionic conditions and c) immunological techniques. Each fraction will be analyzed to determine its protein constituents, distribution of Ig gene sequences and attendant chromatin structure. The use of protein-DNA crosslinking reagents and DNAse I or chemical cleavage reagents will allow the localization of contact points between chromosomal proteins and specific regions of Ig genes.

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Lotto Newsletter 'Miss Rose White' opens in Abymill Fethard Players cast of "Miss Rose White" photographed after their opening night's performance in the Abymill Theatre on Wednesday, November 20. The play will continue its run every night to Sunday, November 24. Curtain at 8.15pm and Booking at O’Flynn’s Menswear Tel: (052) 6131254 or 087 1604260. Standing L to R: Geraldine McCarthy, Maeve Moclair. Sitting L to R: Jimmy O'Sullivan, Ann Walsh, Niamh Hayes and Colm McGrath. Piers Gate Town House AccommodationPiers Gate Town House Self Catering Holiday Accommodation has now opened at The Square, Fethard. Situated in the heart of the medieval town and overlooking the town square, you couldn't be based in a more ideal location to start exploring the many wonderful amenities in Fethard and surrounding area. Fethard is unique and accepted as the best example of a small medieval town in Ireland with most of its original town wall intact. A local guide is available to take you on our medieval town trail or if you prefer you can wander around our peaceful town and sample some of the many walks and local hostelries. Fethard is central to some of the finest Irish towns and tourist attractions such as the Rock of Cashel, Cahir Castle, Clonmel Town, Carrick-on-Suir, Thurles all within close driving distance. Our parish is nestled under the famed Slievenamon - mountain of the women - which is easily accessible for walking and exploring. Slievenamon Golf Club is situated three miles from Fethard on the Clonmel road and is one of many golf courses in the vicinity. Coffee Morning in aid of the Philippine disaster There will be a coffee morning in Jolly’s Café, The Square, Fethard, next Saturday November 23, in aid of the Philippine disaster. We appeal to your generosity in these difficult times to help. There are about five people from the Philippines living in our community here in Fethard. One girl’s family were right in the eye of the typhoon and everything they owned is gone. Every euro raised will go directly to the families who need it. So call in and have a coffee next Saturday and lend your support. Thank you. Christmas Bazaar Fethard & District Day Care Centre will hold their annual Christmas Bazaar in the Tirry Community Centre, Barrack Street, on Thursday morning, November 28. In conjunction with the bazaar we are holding a monster raffle and a cake sale. Refreshments will be served. All donations gratefully accepted. Please come along and support our fundraiser. A senior day will also be held at the Day Care Centre on Friday, November 28, from 11am. The chiropodist will be in attendance. All seniors welcome. Unwanted gifts are wanted for school ‘Pop-Up’ shop Pupils from Holy Trinity National School photographed with Christmas Boxes that they prepared for the annual Shoebox Appeal – an Irish project that promises to get your 'Christmas Shoebox' into the hands of a needy child in Eastern Europe. Holy Trinity National School will open a ‘pop-up’ shop on Main Street on Friday, December 6, and Saturday December 7, in conjunction with Fethard Business & Tourism Group’s festive weekend. We ask all members of the community to please donate their unwanted gifts to the school. All proceeds from the sale of these items will provide teaching aids for the children in the classroom. Your unwanted gifts can be dropped into the school and will be greatly appreciated. Fethard & Killusty trip to Medjugorje 2014 Next year’s Fethard & Killusty parish trip to Medjugorje, operated by Joe Walsh Tours, will depart on August 13, 2014, and return on August 20, 2014. A special group rate of €669 per person sharing has been organised which includes seven nights guesthouse accommodation with breakfast and evening meal. There are some single rooms available at an additional cost. Special discounts available for early payment. For further information contact David Woodlock at Tel: (052) 6131077 or 086 2066637. Volleyball team do well in Division A Cup competition Members of the school volleyball teams photographed earlier in the year at training with coach Mr McGree L to R: Mr McGree (coach); Liam Quigley; Aaron Hanlon, Danny O’Regan, Dylan Fenlon and Shane Buckley. On Friday, November 8, our cadette boys travelled to Colaiste Cathail Naofa in Dungarvan for their seeding round to face Davis College (Mallow), Colaiste Mhuire (Thurles) and two schools from the host school. This round determines those schools who progress to compete to the Division A (Cup) competition and those who play in the Division B (Shield) competition at national level. Ably managed by Eoghan Hurley and assisted by Mr McGree, our boys took two straight sets in the first round against Colaiste Cathail Naofa (A) in the first round, winning 25-15 and 25-13, setting the Fethard boys up well for the day and for potential qualification. In the second match, against the weaker Dungarvan team, Eoghan played the majority of his reserve panel, who took the first set comfortably. The second of the two sets, however, saw Dungarvan (B) rally to take the set 28-26 after many set points on both sides. Returning to their first choice players with one or two exceptions, Fethard resumed well to see off Colaiste Mhuire (Thurles) in the next match in two straight sets but were eventually outplayed by a very strong Davis College team in the last of their matches. As the top three teams progress to the cup competition, Fethard comfortably earned second place in the group whilst ensuring that all who travelled on the day were given at least one game. Well done to all who were involved and best of luck in the Division A quarter finals, to take place over the coming weeks. The panel for the day were: Thomas Channon (captain), Shane Buckley, Liam Quigley, Thomas O’Reilly, Danny O’Regan, Nathan Costin, Nathan Thompson, Dominik O’Dwyer, Keith Cronin, Jamie Cahill, Dean Dorney, Dylan Fenlon and Eric Fogarty. Last call for Emigrants Newsletter articles Last call to all secretaries and club correspondents to submit their reports for inclusion in this year's Emigrants Annual Newsletter as soon as possible to Joe Kenny, Rocklow Road. Reports should be typed or emailed to [email protected] Alternatively they can be handed in to Joe Kenny, Rocklow Road, Fethard. We also welcome individual articles (long or short), stories of long ago, funny incidents, photographs, particularly old class photographs or photographs of local characters. The first Fethard Emigrants’ Newsletter was published by the Legion of Mary back in 1959. It is interesting to note that second Newsletter was printed in October 1960, third in July 1961, fourth in December 1961, fifth in December 1962, and sixth in December 1963. We have all the issues from 1965 to the present. We are just missing one Newsletter – 1964 (8 page), which was the first commercially, printed Newsletter by the Sporting Press Clonmel), can anyone oblige? Opening night for ‘Miss Rose White’ Niamh Hayes and Ann Walsh rehearsing for 'Miss Rose White' which opens in the Abymill on this Wednesday, November 20 Fethard Players production of ‘Miss Rose White’ opens in the Abymill Theatre on this Wednesday night, November 20, and will continue its run to Sunday, November 24. Early booking advisable at O’Flynn’s Menswear, Burke Street, Tel: (052) 6131254 or 087 1604260. ‘Miss Rose White’ is set in 1940s New York and a tale of the relationship between two sisters. Rose White is a Jewish woman who changes her name to appear far removed from her Polish heritage. She longs to climb the ladder of success in the large department store where she works. Years ago, her mother and sister had to remain in Poland and were subsequently sent to concentration camps. Good news arrives. The sister is alive and, at last, coming to America. When she enters the country, she is much changed. Rose is forced to share her apartment with a virtual stranger. In time, they slowly warm to each other in this well-written, moving production produced by Austin O’Flynn. The cast includes Niamh Ryan, Jimmy O’Sullivan, Ann Walsh, Colm McGrath, Geraldine McCarthy and Maeve Moclair. Serious Illness Fund AGM Fethard Serious Illness Fund will hold their Annual General Meeting in the Tirry Community Centre at 8pm on Tuesday, November 26. All are welcome to attend. White Heather Harriers The Ballyluskey White Heather Harriers will meet next Sunday, November 24, in Rocklow, and the following Sunday, December 1, at Ballyluskey. Both meets start at 11am. Rosaries for the Holy Souls during November Sunday November 24: Killusty after Mass, Kiltinan Cemetery 3pm, Kilmaclugh Cemetery 3.30pm. Fethard Community Library now open The new community library opening times at the Convent Community Centre are: Tuesdays and Wednesdays from 7pm to 8.30pm; Thursdays from 3pm to 4.30pm. Yearly membership is €5 for adults (over 18) and children and students (under 18) are free. Social Dancing at Fethard Ballroom Dancing at Fethard Ballroom on this Sunday Night, November 24, to the music of ‘Tommy Carroll’. All welcome to come along and enjoy a great night’s entertainment and social dancing. Dancing 9pm to midnight and admission is €7. Killusty Soccer Club A final reminder that Killusty Soccer Club’s sponsored walk takes place this coming Saturday night at 8pm. We are asking walkers to be in Killusty for 7.45pm. Please return cards and money on the night. Fethard Juvenile GAA Club Jesse McCormack, captain of the Fethard U14 team is presented with the cup following his team's victory over Solohead in the U14C County Final on Saturday, September 14. Fethard Juvenile GAA Club held their AGM on Friday night last in the Tirry Centre at 8pm. It was well attended with approximately 20 people present. Andy O’Donovan (outgoing Chairman) gave a very positive annual report and all agreed that the club is heading in a positive direction and if we all work as a team and get involved we will have a great Juvenile Club for years to come. The highlight of the year was our U14 Hurling team who won the South and County title. Cúl Camp this year was a great success, with numerous parents complimenting the club on its organisation and running. A huge thanks was extended to all involved. School training has been re-organised now with a dedicated coach attending every week, but we still need parents to get involved to assist. Thanks was given to those assisting with the GAA School liaison. Coaches were also confirmed for U6, U8, U10, U12 and U14 age groups. We were delighted to put forward Jamie McCormack to the South Board na nOg as one of the South Division Under 15 Football coaches. We are looking to confirm coaches for our U16 teams We really need parents to come on board with assisting U6 coaching on Saturday mornings. So if you can spare the time, or if you stay to watch and don't mind helping, please let the coach know at training. We also appear to be losing a number of young players to other clubs due to their choice of school, or where they play other sports. We ask that parents of players or potential players sign with their local parish club and encourage their children to play with their parish teams. The club is very grateful to Coolmore for their continued support of our club and our sister clubs. This contribution has enabled us to continue to provide our juvenile players with equipment for training and games. New Management team for 2014 Going into 2014, there are a few changes to the Management Committee: Michael Moroney (Chairman), Mick O’Mahony (Vice-Chairman) unchanged, we welcome on board Wendy Donegan (Juvenile Secretary), Mary Godfrey (Assistant Juvenile Secretary), who will be on hand to guide Wendy through her initial tasks at hand, John Neville (Treasurer) and Sean Kiely (Assistant Treasurer), Andy O’Donovan (PRO), a role hasn’t been filled for a number of years with Patricia Fitzgerald being our last PRO. Andy will be assisted by Ann Fleming. Delegates from Fethard Historical Society attended the recent European Walled Towns annual conference which took place in the walled city of Derry at the end of October. The three-day event was part of Derry’s programme of events for ‘Derry, UK City of Culture 2013’. Towns and cities from all over Europe were present, including The Netherlands, Austria, Malta, Italy, Portugal, Greece, Croatia, Latvia as well as Ireland, England and Wales. The Fethard delegation were especially interested in meeting the Welsh townspeople as their walls were being constructed contemporaneously with the Walls of Fethard. This ‘town building’ era was all part of the Anglo-Norman expansion westward into the lands of the Welsh and Irish kingdoms in the 12th and 13th centuries. The Irish Walled Towns Network (IWTN), of which Fethard is a member, received the 2013 EU Europa Nostra award for Cultural Heritage at a ceremony in Derry’s magnificent Guildhall. Michael Starrett, Chief Executive of the Heritage Council, who accepted the award, mentioned Fethard in his acceptance speech. Fethard has received close on one million euro in funding between the Heritage Council, County Council and Fáilte Ireland over the past seven years and this all stemmed from the fact that Fethard has been a very active member of the Irish Walled Towns Network over this time. The annual membership fee of the IWTN is paid by our County Council and Fethard Historical Society ensures that a representative from Fethard attends the various events, seminars and training days that take place throughout the year. Lifford Old Courthouse and Fethard ‘s Tholsel A visit into County Donegal formed part of the conference programme and an interesting visit was made to Lifford Old Courthouse which has been turned into an active tourist reception centre, very similar to the ideas being discussed at present for Fethard’s old Town Hall. Information from Lifford, Lismore, the Hook Lighthouse (centres which have already been visited) and other similar tourist visitor centres will, hopefully, be used to fashion a sustainable ‘Visitor’s Centre’ for the medieval walled town of Fethard in the coming year. St. Rita's Camogie Club AGM St. Rita's Camogie Club will hold their AGM on Friday, November 22, at 8pm sharp in the Tirry Community Centre, Barrack Street, Fethard. The club urge parents, mentors and senior players to attend. Members of St. Rita's Camogie U10 team photographed with Gerry Aherne, Coolmore, presenting a set of jerseys to our chairperson Sharon O'Meara for our U8 and U10 teams. Also in the picture mentors of the U8 and U10 teams. Girls Rugby progressing well Fethard Girls Rugby enjoyed numerous wonderful games recently in Thurles, Mallow and Cashel. The squads are progressing well with a front row of Molly O'Dwyer, Aisling Kelly and Aoife Delaney working well together tackling well throughout and rucking over with great strength. Second row of new comers Lisa Norton and Amy Kirby have proved a great asset to the team with their rucking support and ball recycling. Kora Delaney at Scrum half kept the pressure on with fine tackling throughout and quick ball constantly from Rucks. Fly half Aine Phelan showed clean heels and fine runs on a number of occasions to score for the team. Aobh O'Shea with Amy Thompson and Leah Fox are great centres who put in the tackles and recycle the ball providing great support to the team. Katie Ryan has a great catch and backs this up well with her ball carrying and recycling. Niamh Houlihan with Leah Scott are great backs with fine ball carrying and showing support in the rucks when it counts. Thank to Thurles for allowing us to join them for the 15-a-side game in the Munster leagues. Training on Friday evening at Fethard Community Field at 8pm to 9.15pm. New members from the age of 13 years and up are always welcome and supported. Any inquiries to Polly on 086 3394959. Fethard & District Rugby Club minis report Fethard U7s travelled to Clonmel last Sunday and they played two fine games against the hosts and Galbally. Speedy Charlie Walsh scored a hat trick of tries with fine play by quick tagging from both Sean Fitzgerald and Shane Ryan. Sam Coen is a great recruit to the team with fine ball carrying and quick hands to set-up plenty of tries. Gavin Neville continues to shine with smart thinking in his support to his team mates and working well with Noah O'Flynn whose fearless play makes for exciting viewing. Joseph Fitzgerald is following in his sibling’s footsteps as a great player for ball recycling. Adam Ruttle had a great game and supported his teammates well. Lee Delaney with Harry Barton and Cormac O'Donnell were very good at receiving and tipping off. Keep up the great work everyone. Fethard U8s and U9s played excellent matches on Sunday supporting each other and putting plenty of scores on the board. The U10s, on a lovely sunny morning for rugby in Clonmel, played two strong sides and after an hour of hard fought rugby, a defeated but gallant Fethard contributed to some lovely play. Great tries by Johnny Gleeson, Charlie Cummins and Michael Ryan with strong support play by Jack Cleere, James McCormack, Conor Neville, Luke Dolan, Stuart Luke and Michael Long. Looking forward to a speedy return to fitness of Ben Ruttle and Daniel Boland. Fethard U12s arrived to take on their host and the visiting Galbally team. Clonmel came on first looking big and ready. Fethard have had a run of near misses recently when the hard work wasn't producing the results; today it all came together. Ethan Coen, back from injury, made several strong runs, Ryan Walsh and Eabha Fitzgerald rucked the ball beautifully and Mark McCormack sent the ball spinning out to the backs where Iain Harrington made precise kicks. Eoin Walsh, Declan Hayes and Mathew Gleeson all ran and passed and moved the ball with flair and skill. It was a fine victory for Fethard. We played Galbally next and a great match it was. Long passages of open play from both sides were enjoyed with the ball moving through the hands, across the pitch, back and forth. Sam Quigley-O'Dwyer had his best game yet, driving and hooking superbly. Tom Hayden showed his turbo boost speed and Lucy Murphy fought toe to toe for the ball. Angus MacDonald and Cathal Ryan played exceptionally well in this game, unfortunately they were playing for Galbally who were a couple of players short! However, this seemed to prompt the Fethard team into making tackles and playing the game through the stages, much to the delight of all those watching this was a very enjoyable game to watch and a last minute score tipped it Fethard's way. Fethard & Killusty Community Lotto The numbers drawn on November 13 were: 13, 18, 23 and 27. We had no jackpot winner and no ‘Match Three’ winner so the following drawn tickets received €50 each: Liam O'Connor, Kilnockin, Fethard; P.J. Lonergan, The Square, Fethard; and Majella Daly, c/o Tom Purcell. The three following ‘Lucky Dip’ winners won €50 each: Dan Hickey, Rathmoley, Killenaule; John Connolly, Clonmel; and Pamela Sharpe, Cashel Road, Fethard. Remember you can purchase your lotto ticket online at fethard.com. Buy seven weekly tickets and get one free! Check on the website for lots of special offers. Next week’s draw takes place on Wednesday, November 20. The Jackpot is €6,250 and the Jackpot seller’s prize is €625. All proceeds go towards community work in Fethard. Next weeks jackpot will be €2,200 with the draw taking place in Lonergan’s Bar on Tuesday, November 19. Thanks to all for the continued support and also the people that carry out the draw every week. Laura Stocksborough, captain of the Under 14 Ladies team, is presented with the trophy by Chairman of the Tipperary LGFA, Tommy Campbell, following Fethard's team win in the County League final. (Photo by Kieran Butler) A Feast Fit for a King Looking for a little inspiration to liven up your Christmas menu this year? Then Cloneen Sports and Social Club invite you to Cloneen Hall on Friday, December 6, at 8pm for an evening with celebrity chef Frank Moynihan presenting 2½ hours of Christmas fare. We promise you this is a most enjoyable event and you will not be disappointed. Tickets are only €10 and should be pre-purchased from Noonan’s Shop or Anglim’s Bar in Cloneen. Tickets can also be booked at 087-7587913 or by emailing: [email protected] Frank will be remembered from his time as Food Correspondent on the Gay Byrne Radio Show on RTE1. He has conducted cookery programmes on virtually every local radio show and has written a best selling cookbook ‘A Pinch of This’. So write the date in your diary and secure your ticket in time. Christmas Party Night in Moyglass Moyglass Community Centre will host its annual Christmas Party Night on Saturday, December 7. A three-course meal will be served followed by band and disco with fully licensed bar. Tickets €25 and doors open at 7pm, Meal served at 8.30pm. Enquires to Philip at 087 2544703. Bingo takes place every Sunday night at 8pm with €1,000 prize money. Jackpot of €300. 2011 & 2012 Emigrant’s Newsletter download The 2011 and 2012 Emigrants' Newsletters are now available to download, along with others dating back to 1998. We eventually hope to have all the Newsletters dating back to 1959 available to download.CLICK HERE TO GO TO PAST NEWSLETTERS We ask for your support for this year's Fethard & Killusty Emigrants Newsletter, now in operation for over 50 years and posted free of charge to our emigrants and families living away from home. This year, with emigration again rising steadily, we depend on your continued support to provide this much appreciated service to our parish emigrants. Donations can be handed in to Carmel Rice, Brookhill, Fethard, or Joe Kenny, Rocklow Road, Fethard. All donations of €10 and over will be acknowledged in this year's issue of the Newsletters. Donations can also be made online at the following web address: www.fethard.com/donate/ Fethard Players, who are celebrating their 100th anniversary this year, are putting the finishing touches to a wonderful play ‘Miss Rose White’ by Barbara Lebow, which will be staged in the Abymill Theatre from Wednesday, November 20, to Sunday, November 24. Booking has now opened at O’Flynn’s Menswear, Burke Street, Tel: (052) 6131254 or 087 1604260. Christmas at Clonacody House Digital recollections now online Interview with Johnny Sheehan, St. Patrick's Place, Fethard, one of the interviews by Holy Trinity National School pupils as part of the Muintir na Tire’s recent ‘Digital Recollections’ project. The others can be now viewed at www.digitalrecollections2013.com just click on Holy Trinity National School to see the local recordings. Holy Trinity National School were one of small number of Tipperary schools chosen to participate in Muintir na Tire’s recent ‘Digital Recollections’ project where local people were interviewed by the pupils in a similar fashion as the original 1937 National Schools Folklore Study. This project assumed a more modern feel and instead of a pencil, students would be allocated digital recording devices to conduct the interview process, and on completion of this process, the narratives would be uploaded on to a website. The objectives of this project were twofold. Firstly, both the young and old participating in the project will learn how to use digital recording devices and also the social aspect of the interview process, secondly it educated national school children about the cultures and traditions which reside in their communities, thereby preserving them for future generations. The study encompassed national schools in South Tipperary, given budget constraints the number of schools was confined to 12. The funding for the Digital Recollections Project was awarded by South Tipperary Development Company through the Rural Development Programme. Hundreds of hours of recordings were submitted by the 12 national schools and this website showcases the wonderful work by these national school children and their teachers and hopefully will preserve the culture and traditions of their native communities. The website can be now viewed at www.digitalrecollections2013.com and click on Holy Trinity National School to see the local recordings. Part 2 Interview with Mary and Tony Newport, Congress Terrace Interview with Gus Neville, Kilnockin, Fethard. Interview with Kathleen Kenny, The Green, Fethard. Interview with Mike Burke, Redcity, Fethard. Interview with Joan O'Connor, Main Street, Fethard. Interview with Kathleen McCormack, Monroe, Fethard. Interview with Sarah Mullins, St. Patrick's Place, Fethard. Interview with Mary and Tony Newport, Congress Terrace, Fethard. Interview with Aggie Barrett, Main Street, Fethard. Items for Fethard News and Website Items for inclusion on the weekly Fethard News page on The Nationalist can be emailed before noon on Mondays to [email protected] or delivered by hand to Joe Kenny, Rocklow Road, Fethard. Do you know a company expanding internationally? If so, introduce Ireland by CLICKING HERE

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2012 2011 Thomas Vaughan reads God's Second Book May 14, 2014 All readers of seventeenth century literature know of the great Welsh religious poet, Henry Vaughan, but not all these readers will have read far into the work of his twin brother, Thomas — or perhaps they just know of Jonathan Swift’s accusation that he wrote “the most unintelligible Fustian, that, perhaps, was ever publish’d in any language,” or of Anthony Powell’s references to him as an inspiration for the seedy alchemist Dr. Trelawny in “A Dance to the Music of Time”. Thomas Vaughan is, however, interesting in himself. He was the rector of Llansantfraed near Brecon until he was evicted in 1650 under the provisions of the Act for the Propagation of the Gospel in Wales. The charges against him were more serious than for any other Breconshire incumbent, describing him as ‘a common drunkard, a common swearer, no preacher, a whoremaster and in arms personally against the Parliament’. As I have indicated elsewhere1, there are reasons for thinking that the first and fourth of these charges were justified. The transcription of the British Museum MS Sloane 1741 (AQUA VITAE: NON VITIS) in my edition of “The Works of Thomas Vaughan” (Clarendon Press, Oxford, 1984), available on Oxford Scholarly Editions Online, has been built upon by Donald Dickson’s volume in the Medieval And Renaissance Texts and Studies program, Tempe, Arizona, 2001. In this Dickson provides an interpretation of the alchemical recipes and incorporates some valuable original research on Thomas Vaughan’s wife. There are reasons for believing that the Vaughans’ interest in hermetic philosophy began as early as their schooldays, when they were educated privately by Matthew Herbert. Henry was to repudiate this interest later in life, writing “my false magic, which I did believe, / And mystic lies to Saturn I do give.” Thomas Vaughan, Lumen de Lumine: Facsimile title page in Alan Rudrum (ed.), The Works of Thomas VaughanDo not reproduce without permission. The twins’ shared interest is manifested in Thomas’s treatment of the figure of Thalia, seen in ‘Lumen De Lumine’ (lines 220-32): “I could see between me and the Light, a most exquisit, divine Beauty. Her frame neither long, nor short, but a meane decent Stature. Attir'd she was in thin loose silks, but so green, that I never saw the like, for the Colour was not Earthly. In some places it was fansied with white and Silver Rib- bands, which look'd like Lilies in a field of Grasse. Her head was overcast with a thin floating Tiffanie, which she held up with one of her hands, and look'd as it were from under it. Her Eys were quick, fresh, and Celestiall, but had something of a start, as if she had been puzzl'd with a suddaine Occurrence. From her black Veile did her Locks breake out, like Sun-beams from a Mist” (Thomas Vaughan, Lumen de Lumine: LUMEN DE LUMINE. in Alan Rudrum (ed.), The Works of Thomas Vaughan) The figure of Thalia in Vaughan’s allegorical presentation is not only veiled physically in this description, but is also hidden to the majority of Vaughan’s readers through their spiritual incapacity. Thalia represents not merely nature, but transformed nature, the nature that the alchemists hoped their labours were bringing about, the Paradise that, as Jacob Boehme had argued, was “in the world. . .swallowed up in the Mystery. . . but. . . . not altered in itself.” Thalia’s head was “overcast with a thin floating Tiffanie”. It is a hermetic platitude that the phenomenal world both conceals and reveals the divine nature. Here, insofar as “tiffanie” is a veil it hides or overcasts; but it also reveals, for “tiffany” is etymologically related to “theophany,” as Vaughan was linguistically alert enough to know. Thalia, then, represents the possibility of earth’s transformation, and this conception has a bearing on the endeavours of the alchemists. So, at Thalia’s departure Vaughan-as- protagonist “discover’d certain peeces of Gold, which she had left behind her,” and in Henry’s poem “Regeneration” “the unthrift Sun shot vital gold / A thousand pieces.” She is “the virgin, clad in flowers and green,” of the pre-lapsarian world, in Henry’s “Ascension-Day,” and also the Eternity in which all Nature will rest when death and pain are destroyed. Alan Rudrum fell in love with the poems of Henry Vaughan when he was an undergraduate at King’s College, London; his doctoral dissertation, “Henry Vaughan and the Hermetic Philosophy,” was completed in 1961. His edition of Thomas Vaughan’s “Works” was published by the Clarendon Press in 1984, and was published online in 2012 to Oxford Scholarly Editions Online. His life-partner for the past fifty years has been the Romantics and Victorian scholar, June Sturrock, an alumna of St. Anne’s College Oxford and the dedicatee of Thomas Vaughan’s “Works”.

minipile

NaturalLanguage

mit

Wednesday, May 18, 2011 "There is no kind of dishonesty into which otherwise good people more easily and frequently fall than that of defrauding the government." - Benjamin Franklin *** Gender bias uncovered in children's books with male characters, including male animals, leading the fictional pack - "Since children's books are a "dominant blueprint of shared cultural values, meanings, and expectations," the authors say the disparity between male and female characters is sending children a message that "women and girls occupy a less important role in society than men or boys"... The tendency of readers to interpret even gender-neutral animal characters as male exaggerates the pattern of female underrepresentation... "The persistent pattern of disparity among animal characters may reveal a subtle kind of symbolic annihilation of women disguised through animal imagery""No, this is not a joke. However I still prefer "“The Da Vinci Code” will be the 68th movie since 1960 to feature an evil albino" Asked to choose between bacon and sex, 43 per cent of Canadians would choose...bacon! - "When asked to rank various aromas by preference, 23% of men ranked bacon as number one. And it seems bacon lovers think they are better lovers... Nearly one in four of respondents (23%) from Manitoba and Saskatchewan wondered if 'my partner loves bacon more than me'... Of note - western Canadians are especially enamoured with bacon. Of respondents from British Columbia, 50% said they would give up sex before bacon, versus 37% of respondents from Quebec" Excerpt from 'He's Just Not That Into You' - "Imagine right now that I'm leaping up and down and shaking my fist at the sky. I'm on my knees pleading with you. I'm saying this in a loud voice: "Please, if you can trust one thing I say in this book, let it be this: When it comes to men, deal with us as we are, not how you'd like us to be." I know it's an infuriating concept — that men like to chase and you have to let us chase you. I know. It's insulting. It's frustrating. It's unfortunately the truth. My belief is that if you have to be the aggressor, if you have to pursue, if you have to do the asking out, nine times out of ten, he's just not that into you. (And we want you to believe you're one of the nine, ladies!) I can't say it loud enough: You, the superfox reading this book, are worth asking out"One of the many problems with feminism - you never know which set of mores a woman has. "If she says yes, then she's no lady" Why Successful People Leave Work Early - "Try this for a day: don't answer every phone call. Stop checking your email every two minutes. And leave work early. You'll be astounded at how much more you'll get done. According to a study published in the Psychological Review conducted by Dr. K. Anders Ericcson, the key to great success is working harder in short bursts of time. Then give yourself a break before getting back to work." - "Rice makes you stronger, healthier than bread: study - "In a test on university students, researchers measured how long they can perform exercise after eating rice or bread. The duration of time averaged 456 seconds (with an error margin of 58.3 seconds) for rice, compared with 311 seconds (with an error margin of 41.9 seconds) for bread. The researchers also probed how rice and bread affect the level of blood cholesterol in hamsters with hyperlipidemia. After eight weeks, those fed with rice showed lower levels of fat and cholesterol, researchers said. In the group, accumulation of fat reduced and excretion of bile acid increased" French Women Beauty Secrets - "If you want to be sexy, choose: show the top or show the bottom, but not both at once!... Make-up remains discreet, general appearance is classical rather than obvious, subtlety sexy rather than provocative... being attractive is often a serious advantage over men. So we flirt. The things you can get with a large smile... amazing! In my opinion, to some extend, everywoman does it. But French women are not afraid to admit it. They are not ashamed of using their charm to manipulate men" Michael Caine on Film vs Theatre Acting - "The modern film actor knows that real people in real life struggle not to show their feelings. It is more truthful, and more potent, to fight against the tears, only yielding after all those defense mechanisms are exhausted. If today's actor emulates film, he'd be better off watching a documentary. The same is true of drunkenness. In real life, a drunk makes a huge effort to appear sober... On stage you have the dramatic thrust of the whole play to help you along. In film you shoot isolated moments, probably in the wrong sequence, and you have to constantly crank yourself up to an intense pitch of concentration on every shot" All female sect worships Putin - "Followers are reportedly encouraged to sing upbeat patriotic Soviet songs at 'services' rather than hymns and are said to survive on a Spartan diet of turnips, carrots, peas and buckwheat... "Her so-called teachings are a nonsensical mixture of Orthodoxy, Catholicism, the occult, Buddhism and political information"" Kate Middleton, and the fine art of moulding a new husband - "Liz Fraser, best-selling author of The Yummy Mummy’s Survival Guide, sums up the practice of moulding a newly-wed husband best when she describes it as “stealth training”. She points out that “nothing makes a man dig his heels in more than being asked to do something”... Every female of my acquaintance volunteered her own tried-and-tested covert method of promoting domestic harmony. So here they are – 25 ways for a woman to keep her husband in her thrall"Anyone talking about training women would be slammed as sexist and chauvinist The Mended Spiderweb series - "In the forest and around the house where I was living, I searched for broken spiderwebs which I repaired using red sewing thread... My repairs were always rejected by the spider and discarded, usually during the course of the night, even in webs which looked abandoned" Tai chi improves balance, mental health in elderly - "However, the sport "seems to be ineffective" for treating the symptoms of cancer and rheumatoid arthritis, the authors said. The evidence was contradictory as to whether tai chi improved high blood pressure, type 2 diabetes, cardiovascular disease, muscle strength, osteoporosis and other conditions." "There is no kind of dishonesty into which otherwise good people more easily and frequently fall than that of defrauding the government." - Benjamin Franklin *** Gender bias uncovered in children's books with male characters, including male animals, leading the fictional pack - "Since children's books are a "dominant blueprint of shared cultural values, meanings, and expectations," the authors say the disparity between male and female characters is sending children a message that "women and girls occupy a less important role in society than men or boys"... The tendency of readers to interpret even gender-neutral animal characters as male exaggerates the pattern of female underrepresentation... "The persistent pattern of disparity among animal characters may reveal a subtle kind of symbolic annihilation of women disguised through animal imagery""No, this is not a joke. However I still prefer "“The Da Vinci Code” will be the 68th movie since 1960 to feature an evil albino" Asked to choose between bacon and sex, 43 per cent of Canadians would choose...bacon! - "When asked to rank various aromas by preference, 23% of men ranked bacon as number one. And it seems bacon lovers think they are better lovers... Nearly one in four of respondents (23%) from Manitoba and Saskatchewan wondered if 'my partner loves bacon more than me'... Of note - western Canadians are especially enamoured with bacon. Of respondents from British Columbia, 50% said they would give up sex before bacon, versus 37% of respondents from Quebec" Excerpt from 'He's Just Not That Into You' - "Imagine right now that I'm leaping up and down and shaking my fist at the sky. I'm on my knees pleading with you. I'm saying this in a loud voice: "Please, if you can trust one thing I say in this book, let it be this: When it comes to men, deal with us as we are, not how you'd like us to be." I know it's an infuriating concept — that men like to chase and you have to let us chase you. I know. It's insulting. It's frustrating. It's unfortunately the truth. My belief is that if you have to be the aggressor, if you have to pursue, if you have to do the asking out, nine times out of ten, he's just not that into you. (And we want you to believe you're one of the nine, ladies!) I can't say it loud enough: You, the superfox reading this book, are worth asking out"One of the many problems with feminism - you never know which set of mores a woman has. "If she says yes, then she's no lady" Why Successful People Leave Work Early - "Try this for a day: don't answer every phone call. Stop checking your email every two minutes. And leave work early. You'll be astounded at how much more you'll get done. According to a study published in the Psychological Review conducted by Dr. K. Anders Ericcson, the key to great success is working harder in short bursts of time. Then give yourself a break before getting back to work." - "Rice makes you stronger, healthier than bread: study - "In a test on university students, researchers measured how long they can perform exercise after eating rice or bread. The duration of time averaged 456 seconds (with an error margin of 58.3 seconds) for rice, compared with 311 seconds (with an error margin of 41.9 seconds) for bread. The researchers also probed how rice and bread affect the level of blood cholesterol in hamsters with hyperlipidemia. After eight weeks, those fed with rice showed lower levels of fat and cholesterol, researchers said. In the group, accumulation of fat reduced and excretion of bile acid increased" French Women Beauty Secrets - "If you want to be sexy, choose: show the top or show the bottom, but not both at once!... Make-up remains discreet, general appearance is classical rather than obvious, subtlety sexy rather than provocative... being attractive is often a serious advantage over men. So we flirt. The things you can get with a large smile... amazing! In my opinion, to some extend, everywoman does it. But French women are not afraid to admit it. They are not ashamed of using their charm to manipulate men" Michael Caine on Film vs Theatre Acting - "The modern film actor knows that real people in real life struggle not to show their feelings. It is more truthful, and more potent, to fight against the tears, only yielding after all those defense mechanisms are exhausted. If today's actor emulates film, he'd be better off watching a documentary. The same is true of drunkenness. In real life, a drunk makes a huge effort to appear sober... On stage you have the dramatic thrust of the whole play to help you along. In film you shoot isolated moments, probably in the wrong sequence, and you have to constantly crank yourself up to an intense pitch of concentration on every shot" All female sect worships Putin - "Followers are reportedly encouraged to sing upbeat patriotic Soviet songs at 'services' rather than hymns and are said to survive on a Spartan diet of turnips, carrots, peas and buckwheat... "Her so-called teachings are a nonsensical mixture of Orthodoxy, Catholicism, the occult, Buddhism and political information"" Kate Middleton, and the fine art of moulding a new husband - "Liz Fraser, best-selling author of The Yummy Mummy’s Survival Guide, sums up the practice of moulding a newly-wed husband best when she describes it as “stealth training”. She points out that “nothing makes a man dig his heels in more than being asked to do something”... Every female of my acquaintance volunteered her own tried-and-tested covert method of promoting domestic harmony. So here they are – 25 ways for a woman to keep her husband in her thrall"Anyone talking about training women would be slammed as sexist and chauvinist The Mended Spiderweb series - "In the forest and around the house where I was living, I searched for broken spiderwebs which I repaired using red sewing thread... My repairs were always rejected by the spider and discarded, usually during the course of the night, even in webs which looked abandoned" Tai chi improves balance, mental health in elderly - "However, the sport "seems to be ineffective" for treating the symptoms of cancer and rheumatoid arthritis, the authors said. The evidence was contradictory as to whether tai chi improved high blood pressure, type 2 diabetes, cardiovascular disease, muscle strength, osteoporosis and other conditions."

minipile

NaturalLanguage

mit

Abstract Nerve growth factor (NGF) induces a relatively long-term hyperalgesia in rats, whereas substance P (SP) N-terminal fragments, like SP(1–7), produce a long-lasting antinociception in mice. We used various nociceptive assays to compare the effects of these compounds on pain transmission when injected intrathecally (i.t.) in mice, and to determine whether either compound affects the action of the other. NGF produced thermal hyperalgesia when injected i.t. in mice 24 and 48 hr before testing by the tail-flick assay. During this same interval, NGF elicited no effect on the response to von Frey fibers or on chemically induced nociception measured by the writhing assay. In contrast to NGF, SP(1–7) had no effect on tail-flick latencies but induced antinociception in the writhing assay 24 hr after injection. When administered 2 hr before NGF, SP(1–7) antagonized the thermal hyperalgesic effect of NGF in a dose-related fashion, despite the inability of SP(1–7) to alter tail-flick latency when administered alone. NGF, in turn, antagonized the antinociceptive effects of SP(1–7) in the writhing assay. The d-amino acid-substituted analog, D-SP(1–7), failed to mimic the antinociceptive effect of SP(1–7) or to alter the hyperalgesic effect of NGF, which indicated a stereoselective action of SP(1–7). D-SP(1–7), that inhibits SP(1–7) binding, did reverse the ability of SP(1–7) to antagonize NGF-induced hyperalgesia, consistent with its action as a SP N-terminal antagonist. Mutual antagonism between NGF and SP may reflect modulatory roles of these endogenously occurring peptides during chronic pain when N-terminal metabolites of SP may accumulate. Nerve growth factor and capsaicin, an extract of peppers of the genusCapsicum, produce many opposite effects with respect to their effects on primary afferent C-fiber excitability. NGF is necessary for survival of neonatal DRG cells (Schwartz et al., 1982; Rich et al., 1984). Antagonism of NGF activity by capsaicin may thus account for the toxic effects of capsaicin when injected in neonates. The neurotoxic action of capsaicin on neonatal DRG cells in vivo and in vitro is a widely used approach to eliminate small-diameter primary afferent C-fibers. Although no longer necessary for survival of these cell types in adults, NGF is still required for C-fiber activity and SP synthesis in the adult DRG (Kantner et al., 1986). Consistent with this, NGF-depleted animals contain reduced concentrations of SP in their DRG and spinal cord (Schwartz et al., 1982), whereas SP is elevated after injection of NGF (Kessler and Black, 1980; Ottenet al., 1983). This effect of NGF appears to result from an up-regulation of neuropeptide gene expression (Lindsay and Harmar, 1989; Lindsay et al., 1989). Exogenously administered NGF produces a prolonged hyperalgesia in rats (see review by Lewin and Mendell, 1993). Although the mechanism is unclear, this may involve enhanced synthesis of SP and release of neurotransmitters, such as EAAs from small diameter primary afferent C-fibers associated with nociceptive transmission. Capsaicin elicits an immediate depolarization of primary afferent C-fibers in most species tested (see review by Buck and Burks, 1986). In contrast to NGF, after the transient depolarization of primary afferent C-fibers, the result of capsaicin application is a long-term attenuation of the synthesis and concentration of SP in the primary afferent fibers of adult animals (Harmar et al., 1981), which occurs in a slowly reversible fashion. After capsaicin treatment, there is also a decrease in the ability of a variety of stimuli to induce release of SP from primary afferent C-fibers (Gamse et al., 1981). The ability of capsaicin to eliminate C-fibers in the neonate and to desensitize primary afferent C-fibers in the adult has been proposed to result from the tendency of capsaicin to inhibit the availability and thus the action of NGF in the nuclei of primary afferent C-fibers (Miller et al., 1982). In support of this hypothesis, capsaicin decreases the retrograde axonal transport of NGF (Milleret al., 1982), perhaps by attenuating axonal transport in general, as indicated by a similar inhibition of the transport of horseradish peroxidase along these same fiber types (Taylor et al., 1984, 1985). The exact mechanism by which capsaicin inhibits axonal transport is unclear. One consequence of a decreased availability of NGF at the nuclei of DRG cells would be an attenuated synthesis of SP. Desensitization to the depolarizing action of capsaicin would also be expected to ensue because the ability of capsaicin to induce release of SP from small-diameter primary afferent fiber terminals also appears to depend on the presence of NGF (Winteret al., 1988). We have recently found that release of SP in the spinal cord in response to capsaicin appears to be necessary to produce desensitization of primary afferent fibers and for the antinociceptive action of capsaicin in adult mice (Mousseau et al., 1994;Kreeger et al., 1994). This appears to occur as a result of an accumulation of SP N-terminal fragments, such as SP(1–7), the most commonly occurring N-terminal metabolite of SP in the rat (Nyberget al., 1984; Sakurada et al., 1985). Not only does SP(1–7), injected i.t., mimic the antinociceptive effect of capsaicin, SP N-terminal activity also mediates capsaicin-induced desensitization. This hypothesis was supported by use of D-SP(1–7), ad-amino acid-substituted analog of SP(1–7) that inhibits [3H]SP(1–7) binding in the brain and spinal cord (Igwe et al., 1990a) and attenuates the action of SP(1–7) on SP (Igwe et al., 1990b; Mousseau et al., 1992), NMDA (Hornfeldt et al., 1994) and kainic acid (Larson and Sun, 1992). Pretreatment with D-SP(1–7) was found to prevent the development of antinociception usually observed 24 hr after injection of either capsaicin or SP(1–7). The N- rather than the C-terminus of SP is necessary for antinociception because higher doses of [d-Pro2,d-Trp7,4]SP, a neurokinin antagonist, were required to mimic this effect of D-SP(1–7) (Mousseau et al., 1994). Thus, whereas SP interacts initially and transiently with neurokinin receptors, the N-terminus of this peptide, as well as the N-terminal metabolites, like SP(1–7), appear to produce long-lasting changes in the sensitivity of primary afferent C-fibers to kainic acid- (Larson and Sun, 1994) and capsaicin-induced depolarization (Mousseau et al., 1994) as well as to nociceptive stimulation (Kreeger et al., 1994;Mousseau et al., 1994) via a mechanism that does not involve tachykinin activity. Given the opposite effects of NGF and capsaicin on pain transmission and on the concentration of SP in the dorsal spinal cord of adult mice, we postulated that a dynamic equilibrium may exist between NGF and SP N-terminal metabolites, the apparent mediators of capsaicin-induced antinociception in the adult mouse. We hypothesized that an accumulation of SP N-terminal metabolites serve as feedback inhibitors, antagonizing the hyperalgesic action of NGF along nociceptive pathways in a fashion similar to that of capsaicin. To assess the nature of the interaction, we examined the effects of NGF and SP(1–7) alone, as well as after administration of both compounds on nociceptive activity in the mouse. Changes in thermal nociception were measured by the tail-flick assay in which changes in the latency of withdrawal of the mouse tail from hot water were measured. Because NGF has also been found to induce mechanical hyperalgesia in the rat, we also used von Frey fibers to examine mechanical nociception in the mouse. Changes in chemically induced nociception were measured by the abdominal stretch (writhing) assay in which the number of behaviors are measured during the 5-min interval beginning 5 min after an intraperitoneal (i.p.) injection of acetic acid. The writhing assay was selected as it is very sensitive to antinociceptive compounds of relatively low efficacy, such as non-narcotic analgesics. To further characterize interactions between NGF and SP(1–7), assays were chosen in which SP(1–7) is antinociceptive, NGF has no effect 24 hr after injection i.t. (writhing assay) and injection of SP(1–7) induces no effect, whereas NGF is hyperalgesic (tail-flick assay). Materials and Methods Animals. Male Swiss-Webster mice (20–25 g, Sasco Inc., Omaha, NE; Charles River Lab, Portage, MI) were housed four per cage and allowed to acclimate for at least 24 hr before use. Mice were allowed free access to food and water. Animals were used strictly in accordance with the Guidelines of the University of Minnesota Animal Care and Use Committee and those prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council [DHEW Publication (NIH) 78–23, revised 1978]. Drug administration. All injections were made i.t. in mice at approximately the L5-L6 intervertebral space with a 30-gauge, 0.5-inch disposable needle on a 50-μl Luer tip Hamilton syringe. Intrathecal administration was chosen because this route was previously found to induce hyperalgesia after an injection of NGF (Verge et al., 1992) and antinociception after injection of SP(1–7) (Mousseau et al., 1994; Kreeger et al., 1994). A volume of 5 μl was used for all i.t. injections. Substance P(1–7) was administered in 0.85% NaCl containing 0.01 N acetic acid (pH 3.4) and NGF was administered in saline. Control groups were injected with the vehicle corresponding to each drug. Antinociceptive testing. The abdominal stretch, or writhing assay, was performed by injecting 0.3 ml of 1.0% acetic acid in manually restrained mice. Immediately after injection, animals were placed in a large glass cylinder containing approximately 2 cm of bedding. The number of abdominal stretches occurring in a 5-min interval was counted beginning 5 min after acetic acid. Values are reported as mean (± S.E.M.) for each treatment. Treatments that produced a significant decrease in the number of abdominal stretches were considered to be antinociceptive. Mice were sacrificed immediately after testing. The latency of the tail-flick response to a thermal stimulus was determined by the tail immersion or tail-flick assay. Mice were gently restrained and the tail submerged in the water of a bath maintained at 49°C. Control mice responded by the rapid withdrawal of their tail, with a mean latency of 7.6 ± 0.2 sec (n = 15). A cutoff of 15 sec was used to avoid tissue damage. Animals that reached this cutoff were assumed to be antinociceptive. The mean latency of response for each group of at least eight mice was calculated and compared with control mice tested on the same day. Latencies that were significantly less than control values were considered to be hyperalgesic. Mechanical threshold was assessed by testing flexion reflexes in response to the application of calibrated von Frey hairs to the dorsal side of each hind paw (Lewin et al., 1993). By use of von Frey hairs of increasing diameter, the force of the von Frey hair that produced a consistent (in 100% of applications) withdrawal reflex was taken as the threshold. The mean threshold force for each group of at least eight mice was compared with vehicle-injected control mice tested on the same day. Drugs. Substance P(1–7) was obtained from Peninsula (Natick, MA) and D-SP(1–7) was synthesized by the University of Minnesota Microchemical Facility (Minneapolis, MN). Nerve growth factor (2.5s) was purchased from Sigma Chemical Company (St. Louis, MO). Data analysis. Mean (± S.E.M.) values of the data are presented in the figures. Throughout the experiments, each group represented at least eight mice. Statistical analysis of the results was performed by analysis of variance followed by the SchéffeF-test for multiple comparisons. P values less than 0.05 were used to indicate a significant difference for all tests. Means of the test groups were routinely compared with control values collected the same day. Results Injected i.t., 0.1 μg of NGF decreased the latency of behavioral responses in the tail-flick assay (fig.1A). When compared with animals injected with vehicle only, hyperalgesia induced by NGF was found to be maximal at 24 hr and to persist for 48 hr before returning to control values at 72 hr. An identical hyperalgesia was produced by NGF when tested with a water bath maintained at 53°C (data not shown). In contrast to the hyperalgesic effect of NGF in the tail-flick assay (fig. 1A), injection of this same dose of NGF produced no change in the response to mechanical stimulation with von Frey fibers (fig. 1B). The number of behavioral responses measured in the writhing assay was also unaffected by pretreatment with 0.1 μg of NGF (fig. 1C). Writhing was also unaffected by a higher dose (0.3 μg) of NGF injected either 24 or 48 hr before acetic acid (data not shown). Effect of NGF on nociception when injected in mice. NGF was administered i.t. in mice at a dose of 0.1 μg and tested at the times indicated. (A) Values represent the mean change (±S.E.M.) in latency (sec) of the tail-flick response (latency at the time indicated after injection of NGF minus that immediately before injection) compared with similarly expressed values from vehicle-injected control mice tested on the same day. (B) The effect of NGF on the response to mechanical stimulation was assessed by the response threshold (g) when challenged with von Frey fibers. (C) The effect of NGF, compared with vehicle, on the mean (±S.E.M.) number of behavioral responses produced in the acetic acid-induced writhing assay was determined at the times indicated. Throughout all figures, asterisks indicate a significant (P < .05) difference from vehicle-injected controls. Substance P(1–7), injected at doses ranging from 3 to 100 nmol i.t., produced a dose-related inhibition of writhing responses to an i.p. injection of acetic acid (fig. 2A). However, SP(1–7) produced no antinociceptive effect in the tail-flick assay (49°C) when tested at doses of 1, 10, 30 or 100 nmol 24 hr before testing (data not shown). Injection of 30 nmol of SP(1–7) also failed to affect the tail-flick latency when injected 30 min, 6 or 48 hr before testing (data not shown). Despite the inactivity of SP(1–7) on tail-flick latencies, the thermal hyperalgesic effect produced 24 hr after injection of 0.1 μg of NGF was antagonized in a dose-related fashion by SP(1–7) injected 2 hr before NGF (fig. 2B). A dose of 30 nmol of SP(1–7) was equally effective in antagonizing the action of NGF when administered either 2 hr before or 2 hr after injection of NGF (data not shown). The range of doses of SP(1–7) that effectively inhibit NGF-induced hyperalgesia in the tail-flick assay (fig. 2B) corresponds well to that necessary to inhibit acetic acid-induced writhing behaviors (fig. 2A). Substance P(1–7)-induced antinociception (A) and inhibition of NGF-induced hyperalgesia (B). The antinociceptive effect produced 24 hr after injection of increasing doses of SP(1–7), as indicated by the decreased number of writhing responses, is shown in the top graph. The lower graph indicates that a similar range of doses of SP(1–7) (26 hr), inhibited the hyperalgesic effect produced by 0.1 μg of NGF injected 24 hr before the tail-flick assay. Data are expressed and statistically analyzed as in figure 1. Pretreatment of mice with up to 100 nmol of D-SP(1–7), ad-amino acid analog of SP(1–7), had no effect on tail-flick latencies when administered alone (fig.3). Unlike SP(1–7), 100 nmol of D-SP(1–7) failed to alter NGF-induced hyperalgesia. When administered together with an equivalent dose of SP(1–7), 30 nmol of D-SP(1–7) blocked the inhibitory effect of SP(1–7) on NGF-induced hyperalgesia (fig. 3). Effect of D-SP(1–7) on the ability of SP(1–7) to prevent NGF-induced (1 μg) thermal hyperalgesia and on the effect of SP(1–7) on NGF-induced hyperalgesia. Data are expressed and statistically analyzed as in figure 1. d-Substance P(1–7), the d-isomer of SP(1–7), was injected either alone or coadministered with 30 nmol of SP(1–7) at the doses (nanomoles) and times indicated. Analysis of the dose-related hyperalgesic action of NGF revealed a steep dose-response curve (fig. 4A). These data indicate that 0.1 μg of NGF injected i.t. produces a repeatable and near-maximal hyperalgesic effect. Doses higher than 0.3 μg were not tested because of their low solubility. Although as much as 0.3 μg of NGF had no effect on the number of writhing behaviors induced by an i.p. injection of acetic acid in mice (fig. 1C), increasing doses of NGF inhibited the antinociceptive action of 30 nmol of SP(1–7) (fig. 4A). The dose range of NGF that effectively inhibited SP(1–7)-induced antinociception in the writhing assay (fig. 4B) corresponds well to the range of doses of NGF that induced hyperalgesia in the tail-flick assay (fig. 4A). Dose-response curve for the induction of thermal hyperalgesia (A) and antagonism of SP(1–7)-induced antinociception (B) by NGF as measured by use of the tail-flick and abdominal stretch assays, respectively. NGF was injected at the doses indicated 2 hr after an i.t. injection of 30 nmol of SP(1–7) or vehicle. Data are expressed and statistically analyzed as in figure 1. The ability of SP(1–7) to prevent the hyperalgesic effect of NGF in the tail-flick assay does not appear to result from its sustained presence in the spinal cord on the day of testing. A dose of 30 nmol of SP(1–7) injected i.t. 30 min before testing had no effect on the tail-flick latency and failed to alter hyperalgesia produced by pretreatment (24 hr) with NGF (fig. 5). Effect of pretreatment and post-treatment with SP(1–7) on the hyperalgesic effect of NGF in mice. Hyperalgesia in mice was induced by 0.1 μg of NGF injected i.t. 24 hr before the tail-flick assay. Thirty nanomoles of SP(1–7) were administered i.t. either 26 hr or 30 min before testing in the tail-flick assay. Data are expressed and statistically analyzed as in figure 1. Discussion Administration of NGF to the spinal cord area of mice resulted in the development of hyperalgesia that was similar in time course to that previously described in the rat in response to parenterally administered (Lewin and Mendell, 1993) and i.t. infused NGF (Vergeet al., 1992). The hyperalgesic effect of NGF in mice was evident in the tail-flick assay when tested at either 49 or 53°C, but was not observed when tested by the writhing assay, a measure of chemical pain, or in response to mechanical stimulation by von Frey fibers. These data suggest that the i.t. injection of NGF in mice may provide an economical model of thermal hyperalgesia. The selectivity of the hyperalgesic action of NGF for thermal pain suggests that the mediation of pain evoked by various stimuli differs in either the nature of the neurotransmitter or the population of fibers involved. NGF has been found previously to induce hyperalgesia in rats when tested by mechanical stimulation (Lewin and Mendell, 1993). Our failure to observe such a change reflects a possible difference in either the response of these two species or the approach used by the two laboratories to monitor mechanical pain thresholds. In contrast to NGF, the long-term effect of SP(1–7) administered i.t. in mice was found to be antinociceptive in mice 24 hr after injection when tested by the writhing assay but to have no effect on tail-flick latencies. This is consistent with our previous work which indicated that SP N-terminal activity is antinociceptive when administered 24 hr before the writhing (Kreeger et al., 1994) or hot plate (Mousseau et al., 1994) assays. The formalin assay in the mouse is also sensitive to pretreatment with SP(1–7) 24 hr before testing, resulting in an enhancement of the first phase and an inhibition of the second phase of nociceptive responding (Goettl and Larson, 1996). Thus the action of SP(1–7), like that of NGF, is dependent on the nociceptive assay used. Although the hyperalgesic and antinociceptive actions of NGF and SP(1–7), respectively, are reflected in two different nociceptive assays, they are none-the-less mutually antagonistic, as shown in figures 2 and 4. The ability of each to be modulated by the other suggests a common mechanism for the modulation of thermal and chemical nociception despite different pathways transmitting the two types of nociceptive information. Our data support our original hypothesis that SP N-terminal fragments are capable of inhibiting the hyperalgesic effect of NGF, whereas increased availability of NGF not only causes hyperalgesia, but also antagonizes the antinociceptive action of SP N-terminal fragments. The antagonism between SP N-terminal activity and NGF does not appear to be brought about by a simple and direct competition at a common receptor as D-SP(1–7), which competes with [3H]SP(1–7) binding (Igwe et al., 1990a), did not inhibit the effect of NGF in a fashion that mimics that of SP(1–7). Furthermore, the effects of SP(1–7) were inhibited by D-SP(1–7), which suggests that this N-terminal fragment likely actsvia the D-SP(1–7)-sensitive [3H]SP(1–7) binding site previously characterized in the mouse spinal cord (Igwe et al., 1990a). The mechanism by which SP(1–7) inhibits NGF activity is unclear, but would appear to be SP N-terminal-receptor-mediated. Injection of SP(1–7) also produces acute and transient effects on nociception. For example, relatively low doses of SP(1–7) have been reported to elicit antinociception when administered 30 min before the tail-flick (Stewart et al., 1982) or writhing (Goettl and Larson, 1994) assays in mice. Picomolar doses of SP(1–7) in the rat have also been reported to elicit hyperalgesia in the tail-flick assay at 10 min after injection (Cridland and Henry, 1988). In contrast to the effects of SP(1–7) at 24 hr, SP(1–7) has no effect on either the acute or tonic phase of behavioral responses when administered just 5 or 30 min before the formalin assay (Goettl and Larson, 1996). Thus the ability of SP(1–7) to modulate nociception acutely appears to depend on the nociceptive assay used, the time of injection of SP(1–7) and/or the species tested. Although SP(1–7) can produce an acute antinociceptive effect in a variety of nociceptive assays (see above), the ability of SP N-terminal metabolites to prevent the thermal hyperalgesic effect of NGF does not appear to be caused by a simple antinociception brought about by the continued presence of SP fragments in the spinal cord at the time of the tail-flick test. This conclusion can be drawn from the inability of 30 nmol of SP(1–7) to reverse hyperalgesia in mice pretreated 24 hr previously with NGF, even though this same dose was sufficient to completely block the development of NGF-induced hyperalgesia. These data also support our previous conclusion that the acute antinociceptive effect of SP N-terminal fragments, observed at 30 min after their injection, appears to be mediated by a different mechanism than that producing antinociception 24 hr later (Kreeger et al., 1994). NGF has been shown to be necessary for primary afferent C-fiber activity in response to both noxious stimuli and capsaicin (Winteret al., 1988). Based on the present data, together with the literature, one might speculate that the interaction between NGF and SP N-terminal metabolites plays the following physiologic role in regulating nociceptive activity. Noxious stimulation and/or inflammation may cause an increased synthesis of NGF in the periphery which is then transported to the DRG where it serves to enhance nociception by its effect on transmitter activity. One effect of NGF is to enhance preprotachykinin, and hence SP synthesis. The amount of immunoreactive SP in the dorsal horn has been reported to increase as soon as 1 hr after injection of formalin into the rat paw (Kantneret al., 1985), although the exact mechanism by which this occurs is unclear. Substance P (Schaible et al., 1990;Duggan et al., 1988) and EAAs (Skilling et al., 1988) are released in the spinal cord in response to a variety of noxious stimuli. Release of EAAs may precipitate additional release of SP (Skilling et al., 1990) from descending or intrinsic neurons or from primary afferent C-fibers via activation of NMDA receptors located presynaptically on primary afferents (Liuet al., 1994). In the extracellular space, SP would be readily metabolized by cell surface endopeptidases resulting in an accumulation of N-terminal fragments of SP after noxious stimulation or capsaicin treatment. Although inactive at neurokinin receptors, these peptides may antagonize the action of NGF, thus preventing thermal hyperalgesia in addition to causing antinociception to certain types of chemical stimuli. Continuous exposure to noxious stimulation, on the other hand, might provide sufficient NGF to maintain hyperalgesia as well as inhibit the antinociceptive effect of SP N-terminal metabolites. In summary, NGF induces hyperalgesia in the tail-flick assay, whereas SP(1–7) is antinociceptive in the writhing assay. Although each one alone modulates one type of nociceptive activity and not the other, when present together, NGF and SP appear to serve as functional antagonists of each other in these two models of pain, which suggests a mechanism by which the body may simultaneously regulate nociception and hyperalgesia. Acknowledgments The authors express their sincere thanks to Drs. Julie S. Kreeger, Virginia M. Goettl, Susan L. Giovengo, Yongjiu Cai and Mr. Rubén Velázquez for their editorial assistance in the preparation of this manuscript.

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Immer is a library of persistent and immutable data structures written in C++ - fortran77 https://github.com/arximboldi/immer ====== acemarke Ironically, there's a name clash with a fairly popular immutable update library for JS: [https://github.com/immerjs/immer](https://github.com/immerjs/immer) Looks like the C++ one started first (2016-05 vs 2017-12). ~~~ aidos I assumed it was some sort of port, but they’re totally different things! OT but it’s worth reading the code for immerjs. It’s super small, super clever and shows the power of proxies in js. ~~~ acemarke Yep. Michel Weststrate is a genius, and also an all-around nice guy. I hope to have a chance to meet him in person. (For reference, I'm a Redux maintainer. We now recommend Immer as the best way to write immutable update logic in Redux apps, and use it in our Redux Starter kit package.) ~~~ k3liutZu Immer looks awesome but we're relying on Immutablejs shallow object comparison to stop rendering React components when not needed. When I last checked I could not figure out how to achieve the same thing with Immer. Do you know some reference that addresses this? And if we're here an additional question: since our store data is currently composed of deep immutable JS data structures, do you know of a way to slowly migrate to Immer? I've tried to move parts of the store to Immer, but since the root store obejcts are still Immutable js objects, this didn't go well. ~~~ thebosz ImmerJS is a direct replacement for ImmutableJS. We recently switched from using ImmutableJS in our Redux store to using ImmerJS. We took the approach one reducer at a time. We have multiple reducers and we're using combineReducers (the ImmutableJS one until it was completely converted). We had no issues whatsoever in the change. ImmutableJS doesn't care about plain JS objects (which is what ImmerJS reducers return) so everything worked as expected. React's shallow comparison worked as expected since ImmerJS produces new objects on mutation (just like ImmutableJS). Essentially: there is no case where ImmutableJS is needed. _All_ functionality and benefits are available in ImmerJS which is a much easier to use library. To do the migration, we literally just used the docs on the Github repo. This was back with version 1.0 or something and it wasn't documented very well but we were able to figure it out. The first code example is how to use it with Redux. Also the section on Currying is useful. Edit to add: This is all within the context of web apps, specifically React apps with Redux. I'm sure there's probably __some __places where ImmutableJS is desirable, but I don 't know of any. ~~~ __s "there is no case" is a strong statement. ImmutableJS is generally the wrong tool for the job in a reducer. It's optimized for if you have a single flat object with 1000s of keys. Immer can't implement the same level of structural sharing ~~~ aidos Can you explain this scenario further? I’ve not used immutablejs but I’m familiar with both functional data structure concepts and immerjs. Immerjs just improves the ergonomics updating a native nested structure in a way that the original contents are maintained as much as possible. Because js has dreadful support for equality checks, this definitely comes in useful. ~~~ acemarke Immutable.js implements a specific set of data structures that internally share references. When you add a new field or copy an object, Immutable.js doesn't have to completely recreate things. For small objects this doesn't matter, but for _very_ large objects and arrays, it does improve performance to some extent. With Immer and "hand-written" immutable updates, doing a `{...obj}` or `someArray.slice()` will do a "shallow" copy of the object. This is equivalent to what Immutable.js does in that it keeps all the fields pointing to the same references. However, the JS engine does have to do an O(n) processing of all the individual top-level keys, whereas Immutable.js's internal data structure is O(logN) or something like that. So, for _very_ large objects, it is faster for Immutable.js to make a copy than it is for plain JS data. My take, however, is that \- Most apps will not be dealing with gigantic objects, so there's no perf benefit from using Immutable.js \- Immutable.js is a much larger dependency than Immer \- The fact that Immer works with POJOs _and_ gives you the ability to write trivial "mutative" syntax for updates is a huge improvement over Immutable.js's Java-inspired API So, to me, the only hypothetical use case where Immutable.js would actually be worth it is if your app is consistently dealing with huge objects, _and_ there is truly serious overhead from copying them that needs to be optimized. ------ spraak For some perspective on why the name was probably chosen: 'immer' means 'forever' or 'always' in German ------ ur-whale Could someone provide an actual example use-case for immutable data structures in C++? The linked document only mentions high-level examples, all of which seem to be trivially implementable via mutable data structures and a bit of being careful. Does this buy anything beyond peace of mind that if you pass an immutable DS to another thread, they won't be able to change it? ~~~ stabbles The author has created a text editor which uses immutable data structures s.t. he can do fast undo / redo [1] [1] [https://github.com/arximboldi/ewig](https://github.com/arximboldi/ewig) ~~~ bjoli I saw a demonstration where he copy pasted a file into itself until it was larger than whatever memory he had in the computer. He could still efficiently edit it (the data pointers were duplicated, not the data). Pretty impressive. ~~~ johnisgood Do you have the URL to the video? ------ rgovostes The Clang Static Analyzer uses immutable data structures. Here, for instance, is its immutable list implementation: [https://github.com/llvm/llvm- project/blob/master/llvm/includ...](https://github.com/llvm/llvm- project/blob/master/llvm/include/llvm/ADT/ImmutableList.h) The data structures are used during program state exploration because they are more memory efficient than storing many copies of the program state with small mutations. ------ siempreb There is something about this immutability thing I really don't like. In the authors example it looks like v1[0] is set to 42 (const auto v2 = v1.set(0, 42)), at least that's how you read it because it contains the word 'set', but you have to 'know' that v1 is immutable and is actually not setting the value, but returning it. So IMAO the naming should be better, I like to read code that is not confusing. If this construct, that I actually never needed in my entire career, is handy for undo/redo, why not just have a dead simple undo stack? In what situation is an immutable structure your best choice? ~~~ agumonkey what would be a good word for this ? recreate ? recompute ? with_new ? ~~~ ScottBurson In general, I think verbs should be avoided, when possible, as names of functional operations. For instance, in Java, 'BigInteger.add' should have been 'plus'. Compare: x.add(y); x.plus(y); People have been known to write the first one expecting 'x' to be updated. With the second, I think it's clearer that it's a value that needs to be assigned to a variable. For the operation in question here, I suggest 'with'. This is what I have used in my own functional collections libraries; I think it originated in SETL. ~~~ skohan I am a fan of nouns(or gerunds) for pure functions, and verbs for mutating functions. I.e: x.add(y); // x now equals x + y x.adding(y); // returns x + y without mutating x ------ saagarjha Related: it’d be great if C++ had const constructors, so that we could have true const objects. ~~~ leni536 What would be the utility of such a constructor? You can just initialize const objects with regular constructors. How are these objects not "true" const? ~~~ saagarjha The specific use case I had in mind was a implicit “conversion” constructor that took an immutable object and gave back something that you couldn’t strip the const off of (it’d also take a mutable object and give you a normal thing back). What I have specifically is a class that provides a base set of operations and a subclass that lets you do some modifications, and what I am trying to do is wrap it in C++ with an object that is const depending on which class I am converting (converting object to const wrapper_class and mutable_object, a subclass of object, to just wrapper_class). ~~~ munchbunny > What I have specifically is a class that provides a base set of operations > and a subclass that lets you do some modifications Your object isn't actually immutable, it just doesn't let you directly mutate it. That's a really important distinction. That's a common pattern. In C++, rather than using a subclass for the mutator, use a different (friend) class. The semantics for implicit conversion between two different classes will allow you to accomplish what you are asking for with enforcing no changes from one interface but not the other. ~~~ saagarjha > In C++, rather than using a subclass for the mutator, use a different > (friend) class. Unfortunately I don't control this class :(

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advocating for aleigha – my rare disease story Month: November 2015 There seems to be a really big disconnect between those battling with chronic illness and those who are not. I can’t tell you how many times I hear, “I hope you get better,” or, “get well soon.” The fact is that most of these comments are purely backed with good intention. I mean, usually it’s the right thing to say. Most people get sick and then they get better. But what if you never stop being sick? When I got sick, I never recovered and unless there are some radical changes in research and funding, there is no way that I ever will. So, when I hear people say, “get well” or put off plans for when I am healthy it seems almost like a slap in the face. No need to kick a girl while she’s down. Of course, most times these people mean well or don’t necessarily know what to say or how to act. It’s something they have probably never had to deal with or, sometimes, even heard of. They don’t know and that’s okay. What isn’t okay is when people are informed and make a conscious decision to ignore the facts. There are currently 133 million people in the United States living with at least one chronic illness. While some of these can be managed well, many of them cannot. I, for example, have a slew of rare diseases that have no cure, little research to shed light on management options, and a life-altering (and limiting) prognosis. And even though I have had these life-changing illnesses for over a year, it still amazes me how many people (even those who I am quite close with) assume I am going to get better. It is vitally important that the people in my life make an effort to understand my prognosis in order for them to understand me. So when people refuse to accept that I won’t be getting better anytime soon, it’s sort of like saying I’m not invested enough to care. I’m getting pretty exhausted just writing this, to be honest. So to quickly wrap it up, making an effort to understand and accept those battling with chronic illness is REALLY important. Everyone wants the people in their lives to make an effort and everybody wants to be understood. Now, I’m going to take a nap.

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Pyo Chang-won Pyo Chang-won (born May 3, 1966) is a South Korean politician, with professional expertise in police studies and politics. He is an outspoken, self-taught and self-proclaimed expert on criminal profiling. He stated he wanted "to realize justice through politics", and announced his candidacy for the 2016 parliamentary election. He was elected to the National Assembly as a member of the Minjoo Party. Political activity In 2013, a journalist accused Pyo of plagiarism in his doctoral dissertation, and Pyo in return threatened the journalist with legal action. Later, with a letter from his doctoral advisor, Pyo denied the allegations and claimed the alleged plagiarisms were minor mistakes in citations. In 2016, additional plagiarism was found in his doctoral dissertation, but Pyo's representatives said in response that the issue of Pyo's had already been addressed, and there is no further comment to be made. In November 28, 2016, Pyo made a remark on his political opposition of having the mind of a group rapist, based on neutralization theory. He said on Facebook that 5% of South Koreans, who remain to be supporters of President Park Geun-hye, are rationalizing their political opinion and are no different from group rapists who also rationalize their behavior in accordance with the principles of neutralization theory. Several days later in December 15, 2016, Pyo commented on TV that supporters of Park Geun-hye have similar minds as group rapists. In November 30, 2016, Pyo released a list of politicians who opposed President Park's impeachment, now known as the Pyo Changwon List. This act was called upon by opponents as a direct act against representative democracy, an act of political terrorism, and an act against the right to vote as provided by the Constitution of South Korea. In January 20, 2017, Pyo hosted a galleria at the parliament which included artworks satirizing Park Geunhye. One such artwork was the Dirty Sleep(더러운 잠), which depicted Park Geunhey in the nude. Many women's rights organizations and female-oriented organizations condemned the galleria as degradation of women. The galleria was soon halted and President Moon criticized Pyo for hosting the event. Pyo was put under investigation by the Ethics Committee of the Democratic Party of Korea, and was banned from holding a post within the party for six months. References External links Category:1966 births Category:Living people Category:Members of the National Assembly (South Korea) Category:Minjoo Party of Korea politicians Category:South Korean academics Category:South Korean criminologists Category:South Korean psychologists Category:Criminal psychologists Category:People from Pohang Category:Pyo clan

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Dr. Gibbens, Please LEVY a MAXIMUM FINE against Univ. of Oklahoma for their blatant disregard of the Animal Welfare Act (AWA) when their negligence caused a dog to die in connection to a botched surgery. Their behavior must NOT be tolerated & MUST be punished to the fullest extent of the law. The time is NOW to send a clear message with stiff penalties to these renegade, negligent labs that these behaviors will NOT be tolerated! Animal watchdog group files complaint against OU for negligent dog death By Page Jones, OurDaily.com, January 14, 2016 Stop Animal Exploitation Now! (SAEN) has filed another complaint against OU after the negligent death of a dog at the OU Health Sciences Center in July 2015. SAEN obtained records of correspondence between the university and the National Institutes of Health regarding the death of the dog, according to a press release. In the correspondence, James Tomasek, the OUHSC vice president for research, said the staff was poorly prepared for the dog's surgery and failed to sterilize surgical equipment, follow protocol, properly to administer medication and document post-operative monitoring, according to the correspondence provided by SAEN. Although an investigation was conducted, a definitive cause of death was never found and the study has since been halted. In its complaint, SAEN has called for the maximum penalty against the university, which is $10,000 per infraction/per animal, according to the complaint. Michael Budkie, executive director of SAEN, said the group is requesting the maximum penalty because of previous infractions. “It’s very obvious at the University of Oklahoma (that) there is an obvious pattern of violations, going back several years,” Budkie said. SAEN filed a complaint in 2013 after a dog was improperly euthanized at OUHSC and another after OUHSC was found to be mistreating baby baboons. “This is a much more in-depth, system-wide problem here," Budkie said. OU President David Boren announced in September that the baboon testing facility would be closed over the course of three to four years. Fair Use Notice: This document, and others on our web site, may contain copyrighted material whose use has not been specifically authorized by the copyright owners. We believe that this not-for-profit, educational use on the Web constitutes a fair use of the copyrighted material (as provided for in section 107 of the US Copyright Law). If you wish to use this copyrighted material for purposes of your own that go beyond fair use, you must obtain permission from the copyright owner.

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Rationale and design of GISSI OUTLIERS VAR Study in bicuspid aortic valve patients: prospective longitudinal, multicenter study to investigate correlation between surgical, echo distinctive features, histologic and genetic findings in phenotypically homogeneous outlier cases. Bicuspid aortic valve (BAV) is the most common congenital heart disorder, affecting up to 2% of the population. Involvement of aortic root and ascending aorta (aneurysm or, eventually, dissection) is frequent in patients with pathologic or normal functioning BAV. Unfortunately, there are no well-known correlations between valvular and vascular diseases. In VAR protocol, with a new strategy of research, we analysemultiple aspects of BAV disease through correlation between surgical, echo, histologic and genetic findings in phenotypically homogeneous outlier cases. VAR protocol is a prospective, longitudinal, multicenter study. It observes 4 homogeneous small groups of BAV surgical patients (15 patients each): isolated aortic regurgitation, isolated ascending aortic aneurysm, aortic regurgitation associated with aortic aneurysm, isolated aortic stenosis in older patients (>60years). Echo analysis is extended to first-degree relatives and, in case of BAV, genetic test is performed. Patients and relatives are enrolled in 10 cardiac surgery/cardiologic centers throughout Italy. The aim of the study is to identify predictors of favorable or unfavorable evolution of BAV in terms of valvular dysfunction and/or aortic aneurysm. Correlations between different features could help in identification of various BAV risk groups, rationalizing follow-up and treatment.

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Number of intramuscular adipocytes and fatty acid binding protein-4 content are significant indicators of intramuscular fat level in crossbred Large White x Duroc pigs. Intramuscular fat content is generally associated with improved sensory quality and better acceptability of fresh pork. However, conclusive evidence is still lacking for the biological mechanisms underlying i.m. fat content variability in pigs. The current study aimed to determine whether variations in i.m. fat content of longissimus muscle are related to i.m. adipocyte cellularity, lipid metabolism, or contractile properties of the whole muscle. To this end, crossbred (Large White x Duroc) pigs exhibiting either a high (2.82 +/- 0.38%, HF) or a low (1.15 +/- 0.14%, LF) lipid content in LM biopsies at 70 kg of BW were further studied at 107 +/- 7 kg of BW. Animals grew at the same rate, but HF pigs at slaughter presented fatter carcasses than LF pigs (P = 0.04). The differences in i.m. fat content between the 2 groups were mostly explained by variation in i.m. adipocyte number (+127% in HF compared with LF groups, P = 0.005). Less difference (+13% in HF compared with LF groups, P = 0.057) was noted in adipocyte diameter, and no significant variation was detected in whole-muscle lipogenic enzyme activities (acetyl-CoA carboxylase, P = 0.9; malic enzyme, P = 0.35; glucose-6-phosphate dehydrogenase, P = 0.75), mRNA levels of sterol-regulatory element binding protein-1 (P = 0.6), or diacylglycerol acyltransferase 1 (P = 0.6). Adipocyte fatty acid binding protein (FABP)-4 protein content in whole LM was 2-fold greater in HF pigs than in LF pigs (P = 0.05), and positive correlation coefficients were found between the FABP-4 protein level and adipocyte number (R2 = 0.47, P = 0.02) and lipid content (R2 = 0.58, P = 0.004). Conversely, there was no difference between groups relative to FABP-3 mRNA (P = 0.46) or protein (P = 0.56) levels, oxidative enzymatic activities (citrate synthase, P = 0.9; beta-hydroxyacyl-CoA dehydrogenase, P = 0.7), mitochondrial (P = 0.5) and peroxisomal (P = 0.12) oxidation rates of oleate, mRNA levels of genes involved in fatty acid oxidation (carnitine-palmitoyl-transferase 1, P = 0.98; peroxisome proliferator-activated receptor delta, P = 0.73) or energy expenditure (uncoupling protein 2, P = 0.92; uncoupling protein 3, P = 0.84), or myosin heavy-chain mRNA proportions (P > 0.49). The current study suggests that FABP-4 protein content may be a valuable marker of lipid accretion in LM and that i.m. fat content and myofiber type composition can be manipulated independently.

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PHOENIX (March 17, 2009) — Members of The Humane Society of the United States and other consumers filed a class action lawsuit alleging that Petland, Inc. and the Hunte Corporation are conspiring to sell unhealthy puppy mill puppies to unsuspecting consumers in numerous states. Petland is the nation’s largest chain of pet stores that sells puppy mill dogs and Hunte is one of the country’s largest distributors of factory-produced puppies. The lawsuit, filed in federal district court in Phoenix late Monday, alleges that Petland and Hunte violated federal law and numerous state consumer protection laws by misleading thousands of consumers across the country into believing that the puppies sold in Petland stores are healthy and come from high-quality breeders. Many of the puppies sold by Petland come either directly from puppy mills or puppy brokers such as Hunte, which operates as a middleman between the mills and Petland’s retail stores. “Unscrupulous dog dealers like Petland and Hunte reap massive profits by pushing unhealthy puppies on well-intentioned dog-lovers who would never knowingly buy a puppy mill dog,” said Jonathan Lovvorn, vice president & chief counsel for Animal Protection Litigation at The HSUS. “Families often bear the great expense of veterinary treatment for sick and unhealthy dogs, or the terrible anguish of losing a beloved family pet. This industry has been systematically lying to consumers for years about the source of the dogs they sell, and it’s long past time for a reckoning.” The class action lawsuit is the result of many months of investigative and legal research, and comes after an eight-month investigation into Petland stores by The HSUS that demonstrated a direct link between multiple Petland stores and unscrupulous puppy mills. Numerous other reports have also surfaced of Petland’s allegedly deceptive sales practices, including the marketing and sale of puppies with life-threatening genetic defects and highly contagious parasitic and viral infections. The 34-page complaint includes numerous examples of sick or dying puppies that Petland sold, including: Mainerd, a Boston terrier, was diagnosed with a congenital spinal condition. Some of her vertebrae have not formed completely while others have fused together causing tissue to grow underneath along with possible nerve damage. Mainerd is now receiving steroid treatments for her ailments and may require expensive surgery. Minchy, a miniature pinscher, was sold by Petland at 10 weeks old. He was immediately diagnosed with coccidian, an intestinal parasite that causes diarrhea and weight loss. Minchy was also diagnosed with an inherited disorder, Progressive Retinal Atrophy, which will ultimately lead to permanent blindness. Tucker was sold at four months old. The bloodhound puppy experienced severe separation anxiety and various health problems before developing orbital cancer at only 7 months of age. Patrick, a Pomeranian puppy, was sold at three months old. He suffered from diarrhea and vomiting shortly after arriving at his new home. At 11 months old, Patrick was diagnosed with a genetic disorder, dual luxating patellas, which will require expensive surgery on both of his knees to correct. Puppy mills are mass breeding operations where the health of dogs is disregarded in order to maintain a low overhead and maximize profits. The dogs are often kept in wire cages, stacked on top of each other, with no exercise, socialization, veterinary care, or loving human interaction. They are treated not like family pets, but like a cash crop. Petland denies it supports these substandard breeding facilities, and claims to follow “Humane Care Guidelines” developed in conjunction with the USDA. However, USDA recently informed HSUS in writing that it has no record of any such guidelines. The class plaintiffs are being represented in the case by Saltz Mongeluzzi Barrett & Bendesky, PC; Hagens Berman Sobol Shapiro, LLC; Garen Meguerian, Esq. and lawyers in The HSUS’s Animal Protection Litigation section. The suit requests a jury trial on behalf of the consumer class plaintiffs, and seeks reimbursement of the puppies’ purchase price along with compensation for all related monetary damages for the class members. To learn more about puppy mills, visit humanesociety.org/stoppuppymills. A multi-media release is also available. The Humane Society of the United States is the nation’s largest animal protection organization — backed by 11 million Americans, or one of every 28. For more than a half-century, The HSUS has been fighting for the protection of all animals through advocacy, education and hands-on programs. Celebrating animals and confronting cruelty — On the web at humanesociety.org. It will be ironic if the HSUS, which is widely disliked by many club breeders, ends up successfully taking on mills when the AKC chose to propose very controversially to instead work to give Hunte Corp breeders AKC registration status... The class action suit (which we do not have in Ireland) can be a powerful tool. If successful and it established a case law precedent presumably this could then be used against brokers as well -- and we all know there are some very large scale brokers of trash-bred, un-health tested Irish cavalier imports for example...

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Q: Trying to understand how to solve $f(x,y) = x^{1/3}y^{1/3}$ Image pulled from the textbook: http://puu.sh/BS7Ca/7d4f9697e2.png I understand the definition of a partial derivative by limit, and I also understand the method of computing partial derivatives. However, I am confused about what the textbook is trying to tell me. I do not get the part where it says "we restrict $f$ to the line $y=x...$" and everything after. If someone could explain to me what the restriction means I think I could probably understand the rest. My intuition of the restriction is that only values where $y=x$ are taken on, but that doesn't make sense because the graph of $x^{1/3}$ and $x^{2/3}$ only have values $y=x$ at $x = 0$ and $x = 1...$ A: Note that the graph of $z=f(x,y)$ is a surface compromised of all $$ (x,y,z)$$ such that $z=x^{1/3}y^{1/3}$ On the other hand $x=y$ in three dimensional space is a vertical plane passing through the line $y=x$ The intersection of this vertical plane and the graph of $z=x^{1/3}y^{1/3}$ is a curve which is compromised of all $(x,x,x^{2/3})$ where x is a real number. This curve is the restriction of $z=x^{1/3}y^{1/3}$ with $y=x$.

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With a studio like Marvel, it’s easy to assume that the directors come in, call “action” and “cut,” collect their checks, and walk away. Given the very specific plot points they may need to hit with each entry, it’s not hard for some viewers to believe that the directors bring very little to the table. However, as some filmmakers like James Gunn and the Russo Brothers have proven, under the right circumstances, Marvel Studios is very much willing to follow through with the visions that the directors provide. From the over-the-top comedy to the bone-crunching action scenes, each director brought a lot to the table, and was able to form the story of their respective films to fit their own sensibilities. Such is the case with Thor: Ragnarok director Taika Waititi. The traditionally comedy director was able to form-fit the film to his own personal tastes — at least according to his interview with Collider, that’s the case. Here’s what he had to say: “There were already story ideas when I came on board, but a lot of that changed over the first three or four months. Right from the beginning, [Marvel] wanted to lighten [Thor] a little bit and embrace the adventure aspect of it. The last two films, definitely the last film, were a little darker. Personally I feel if the movie’s called Thor, then Thor should be the best character,. My main focus was making him cool & funny when he needs to be and heroic when he needs to be. If you’ve seen my other films, there’s always a balance between comedy and drama. I think that’s a satisfying story to watch.” This all sounds like the right direction to take Thor in. I especially like the line regarding the main characters being the best part of the film. This is a trait Pixar walked into Toy Story with with the characters of Woody an Buzz, and it certainly served them well. It’s one that also applies for all great story. While a great supporting cast is also crucial to a film’s success, the importance of a lead character cannot be overlooked. This is especially the case with Thor, a character whose ridiculousness should be one the main draws to begin with. Turning this story into a more lighthearted adventure seems like a good move, and it’s great to hear that Waititi’s approach with it all was in line with what Marvel wanted. Do you agree with Waititi that the Thor movies should be more cool and funny than they’ve been in the past? Let us know your thoughts down below! Don’t forget to share this post on your Facebook wall and with your Twitter followers! Just hit the buttons on the top of this page. SOURCE: Collider

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LANSING – Michigan Democratic Party Chair Mark Brewer is calling for redistricting reform after Rep. Marty Knollenberg announced his plans to run for Congress. Rep. Knollenberg currently sits on the Michigan House’s Redistricting Committee, which would allow him to draw the district in which he intends to run. “This major conflict of interest is the latest example of why we need redistricting reform now,” Brewer said. “Elected officials should not draw a district in which they plan to seek future office. That’s wrong and it needs to be changed immediately.” “I have no doubt Republicans like Rep. Knollenberg will try to gerrymander the districts to give Republicans the best chance of winning elections for the next 10 years,” added Brewer. “It’s not fair to the voters and it’s not fair to the process. Redistricting must be done in a fair, unbiased fashion. We believe elected officials should not have the power to design their own districts in order to directly benefit them. It is an obvious conflict of interest and it’s time we reformed the process.”

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Tonsillar lymphoma masquerading as obstructive sleep apnea - pediatric case report. The commonest cause of head and neck malignancy in pediatric patients is lymphoma. A particular case is the tonsillar lymphoma. Even though unilateral tonsillar enlargement represents an ominous sign for neoplasia, clinical manifestations vary and are non-specific. Therefore, a delayed diagnosis is performed which compromises optimal therapy and hinders the prognosis. We present the case of a 5-year-old boy who was initially diagnosed with obstructive sleep apnea, without reported systemic complaints. Asymmetric tonsillar hypertrophy created the premises for performing a tonsillectomy to rule out malignancy. The pathological evaluation of the resected tonsils revealed a malignant non-Hodgkin's lymphoma, with immunophenotypic features consistent with sporadic type Burkitt lymphoma. The aim of this paper is to emphasize the importance of the histopathological examination and of the immunohistochemistry testing for the prompt and accurate diagnosis of all asymmetric tonsillar hypertrophy in children undergoing tonsillectomy. Furthermore, immunohistochemical diagnosis is vital for establishing a personalized multi-agent chemotherapy regimen, which dramatically improves the survival rate. We recommend histopathological evaluation in all children with asymmetric tonsillar hypertrophy undergoing tonsillectomy for various reasons. Needless to say, it is better to be cautious and exclude the presence of tonsillar lymphoma, than to confront with the severe consequences of misdiagnosis.

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Evaluation of a pseudo-R2 measure for panel probit models. A simulation study designed to evaluate the pseudo-R2T proposed in an earlier paper by Spiess and Keller suggests that, for the models considered, this measure represents the goodness of fit not only of the systematic part, but also of the assumed correlation structure in binary panel probit models.

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Hamilton Palace was said to have been the largest non-royal residence in Britain – and 100 years ago, it stood proud. But a century later, there’s not a trace of this once-fine building, the home to the Dukes of Hamilton, the premier peer of Scotland. But how could a building, which was the principal resident of the Hamilton family since 1591, disappear so easily? The origins of Hamilton Palace go back some 500 years when, in the 15th and 16th centuries, the Hamilton family grew in wealth and status. James Hamilton, the 2nd Earl of Arran, acted as the Regent of Scotland when Mary Queen of Scots was a child. He began work on building a new house, as his accounts for this new home listed fine tapestries, seeds for the garden and tame deer to populate its grounds. Mary fled to Hamilton in 1568, after escaping from Lochleven, where she rallied her troops before the battle of Langside. During the political and religious upheavals that followed, both the town and the palace of Hamilton were besieged, burnt and demolished. But the son of the 2nd Earl, Lord John Hamilton, began work on the construction of a new palace in 1591, on a site near the River Clyde, close to the rebuilt burgh of Hamilton. The 17th century resulted in political upheaval as a result of the English Civil War, as both the 1st and 2nd Dukes of Hamilton lost their lives as a result of supporting their king. Anne, the daughter of the 1st Duke, became Duchess of Hamilton in 1651, but Hamilton Palace had been confiscated by Oliver Cromwell, and given over to his army officer. Parliamentarians demanded fines from the gentry, resulting in the sale of land and property, but the restoration of Charles II in 1660 saw the Duchess and her husband, William Douglas, Earl of Selkirk, finding themselves in a better financial position. The Duke and Duchess pursued some grand designs to restyle their home, with Scotland’s leading architect, James Smith, being commissioned in 1682 to transform Hamilton Palace into the largest country home in the land. The north front of the palace was left standing, but its wings were demolished and rebuilt, with offices, stables and kitchens being added. The real highlight of the new construction was the south front, with the entrance featuring a stunning portico, the likes of which had never before been seen in Scotland. With the impressive new exterior in place, in the 1730s, the 5th Duke of Hamilton commissioned William Adam to redesign the principal rooms of the palace. Thomas Clayton, one of the leading craftsmen in Scotland, was commissioned to decorate with his elegant plasterwork. By the mid-19th century, Alexander, the 10th Duke of Hamilton, declared himself as the ‘rightful heir to the Scottish throne’. Accordingly, he wanted a home fit to match his status, and created a true palace. He had major additions made to the building. Glasgow’s leading architect David Hamilton adapted Adam’s designs, and in 1822 work began on a new north front, servants’ wing, and additional offices and stables. A new north front was created, with a dozen stone columns at the entrance. The grand entrance hall was suitably impressive too – a black marble staircase gave access to it, with walls of polished sandstone, and paved with siena and black marble. In 1842, the 10th Duke had begun construction of the Hamilton Mausoleum, as the family vault at the Palace was becoming overcrowded. He died in 1852, aged 54, and along with his predecessors, was interred in the Mausoleum after it was completed in 1958. The 10th Duke was a keen collector of art, and after his death, it was sold off by the family. His collection of paintings, objects, books and manuscripts was sold for £397,562 in July 1882 – the equivalent of almost £10 million today. The 12th Duke of Hamilton was, in 1867, close to financial ruin. Following the sale, the family spent less and less time at their palace. The 13th Duke had offered the palace to the navy during World War I for use as a hospital. By this time, the palace was in a state of severe neglect and needed vast sums of money for restoration. Following the end of the war, the palace’s fate was sealed. Since 1882, the Hamilton family had leased out mineral rights in the grounds of the palace. A large area of coal was left beneath the building to keep it stable. In 1915, seams were being mined through this reserved area, to access a larger area of coal to the south. The colliery company was also given permission to work coal under the palace in the future. The 13th Duke wanted the palace to be preserved in 1919, the same year a second haul of art treasures were sold, and asked the Bent Colliery Company to give up its lease – but it refused. The building’s structural integrity was no longer guaranteed, and Hamilton Palace was sold to demolition contractors in 1921. The demolition of Hamilton Palace took almost a decade. During this time, the west wing was used to house the families of homeless miners. Without their palace, the Hamilton family moved to Dungavel House, which had previously been a shooting lodge on moorland close to Strathaven. Hamilton Palace vanished from sight. But in 1974, when a country park was being built on the site of the palace, construction workers found the vaulted roofs of the former palace cellars. Sadly, for safety reasons, these roofs had to be collapsed and the cellars filled in. However, several metres of iron railings from the palace grounds can be seen on Bothwell Road (the B7071), outside Hamilton College. The dining room from Hamilton Palace can be seen the Museum of Fine Arts, Boston, in the European period rooms, where it remains the only extant, assembled room from the building. Some of the fittings, and photographs of the interior, can be viewed in the Low Parks Museum, which was the old Palace Coachhouse, in Hamilton. The site of the palace is now filled by a number of football pitches, a bowling club and a sports centre, known as the Hamilton Palace Sports Grounds, owned by South Lanarkshire Council. (With thanks to South Lanarkshire Council. Find out more at the Low Parks Museum in Hamilton.)

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--- abstract: 'We present a theory that accurately describes the counting of excited states of a noninteracting fermionic gas. At high excitation energies the results reproduce Bethe’s theory. At low energies oscillatory corrections to the many–body density of states, related to shell effects, are obtained. The fluctuations depend non-trivially on energy and particle number. Universality and connections with Poisson statistics and random matrix theory are established for regular and chaotic single–particle motion.' author: - 'P. Leboeuf$^1$, A. G. Monastra$^2$, and A. Relaño$^3$' title: Fluctuations in the level density of a Fermi gas --- The level density is a characteristic property of every many–body quantum mechanical system. Its precise determination is often a key ingredient in the calculation of different processes, like compound nuclear decay rates, yields of evaporation residues to populate exotic nuclei, or thermonuclear rates in astrophysical processes. The first and main step towards the understanding of the density was given by H. Bethe more than sixty years ago. He considered $A$ noninteracting fermions moving in a mean–field potential. By this model he showed that the number of excited states of the many–body (MB) system contained in a small energy window $dQ$ at energy $Q$, ${\rho_{\text {\tiny MB}}}(A,Q) dQ$, is [@bethe] $$\label{bethe} {\rho_{\text {\tiny MB}}}(A,Q) = \frac{1}{\sqrt{48}\ Q} \exp \sqrt{\frac{2}{3}\pi^2 {\overline{\rho}}\ Q} \ .$$ Here ${\overline{\rho}}$ is the average single–particle (SP) density of states at Fermi energy ${\epsilon_{\text {\tiny F}}}$, and $Q$ is measured with respect to the ground state energy. For a given potential, ${\overline{\rho}}$ is in general a function of $A$. This expression assumes that the excitation energy is, on the one hand, large compared to the SP mean level spacing $\delta = {\overline{\rho}}^{-1}$ and, on the other, small compared to ${\epsilon_{\text {\tiny F}}}$ (degenerate gas approximation). Most of the present knowledge concerning the density of states is based on refinements of Bethe’s result. In Eq. (\[bethe\]) all the information concerning the SP spectrum is encoded in a unique parameter, ${\overline{\rho}}$, that describes its average behavior. The exact dependence of ${\rho_{\text {\tiny MB}}}$ on $A$ and $Q$ is sensitive, however, to the detailed arrangement of the SP energy levels around the Fermi energy. After Bethe’s work, more accurate calculations of ${\rho_{\text {\tiny MB}}}$ were made [@bloch]. Schematic shell corrections related to a periodic fluctuation of the SP density were computed in [@ros] (see also [@bm]), introducing the so–called backshifted Bethe formula. Several modifications of Eq.(\[bethe\]) have been done to match the experimental results. These models take into account, for example, shell effects, pairing corrections and residual interactions [@para], introducing a multitude of coexisting phenomenological parameterizations. The present status of the understanding do not allow to draw a clear theoretical picture of the functional dependence of ${\rho_{\text {\tiny MB}}}$ with $A$ and $Q$. Within an independent particle model we demonstrate, through a general theory, the role played by shell effects in the MB density of states. Superimposed to the smooth growth of the density described by Eq.(\[bethe\]), there are oscillatory corrections. To lowest order, these corrections are directly related to energy fluctuations of the system, that may be expressed in terms of sums over the classical periodic orbits. We make a statistical analysis of the density fluctuations, in particular of their probability distribution, typical size, and temperature dependence [@note]. We show that the amplitude of the shell corrections grows linearly at low temperatures, and decays as $T^{-1}$ when $T \gg E_c /2\pi^2$, where $E_c$ is the energy conjugate to the time of flight across the system (temperature is measured in units of Boltzmann constant). The statistical properties of the density fluctuations strongly depend on the regular or chaotic nature of the underlying classical SP motion. Universal properties for each class (regular or chaotic) are found for $T \ll E_c /2\pi^2$. Besides the fluctuations, we find and discuss corrections to the smooth part of the density in the exponent of Eq.(\[bethe\]). The present analysis considers general properties of fermionic systems. Applications to the specific problem of the nuclear density and to the interpretation of the experimental results will be done in a separate contribution. The MB density of states is defined as $$\label{rhodef} {\rho_{\text {\tiny MB}}}(A,E) = \sum_N \sum_j \delta (A- N) \ \delta \left( E - E_{N,j} \right) \ ,$$ where $E_{N,j}=\sum_i n_{j,i} \epsilon_i$ is the energy of the $j$-th SP configuration of $N = \sum_i n_{j,i}$ particles, $\epsilon_i$ the SP energies, and $n_{j,i}=0,1$ are the occupation numbers. When the SP spectrum consists of equidistant levels separated by $\delta$, e.g. the spectrum of a one dimensional harmonic oscillator, an exact answer to the counting problem exists. The MB excitation energies are integer multiples of $\delta$, each level having a nontrivial degeneracy. It is easy to see that, for a given level defined by an integer, the degeneracy is the same as the number of ways into which the integer can be decomposed as a sum of integers (the partition number). An asymptotic approximation to this well–known mathematical problem was obtained by Hardy and Ramanujan, and later on Rademacher found a convergent series [@hrr]. Expressing it in terms of an expansion in terms of ${\overline{\rho}}Q$, the result reads $$\begin{aligned} \label{shr2} && \log \left( {\rho_{\text {\tiny MB}}}^{\text {\tiny HO}}/{\overline{\rho}}\right) = \sqrt{ \frac{2}{3} \pi^2 {\overline{\rho}}\ Q } - \log \left( \sqrt{48} \ {\overline{\rho}}Q \right) - \\ && \ \ \frac{\pi^2 + 72}{24 \sqrt{6} \pi} ({\overline{\rho}}Q)^{-\frac{1}{2}} - \left(\frac{3}{4 \pi^2}- \frac{1}{24} \right) ({\overline{\rho}}Q)^{-1} + {\cal O} (({\overline{\rho}}Q)^{-\frac{3}{2}}) \nonumber \ .\end{aligned}$$ The first two terms of this expansion reproduce Bethe’s formula. For an arbitrary SP spectrum the computation of the density of excited states of a fermionic system is a difficult combinatorial problem for which no exact solution is known. We expect, however, that Eq. (\[shr2\]) gives correctly the contribution of the average part of the SP spectrum. What we are seeking here are the variations of the MB density due to fluctuations of the SP spectrum with respect to a perfectly ordered spectrum. A convenient way to express an approximate solution is by means of an inverse Laplace transform of Eq.(\[rhodef\]). A saddle point approximation of the resulting integrals yields [@bm; @fow] $$\label{rhosp} {\rho_{\text {\tiny MB}}}(A,E) = {\rm e}^{{{\cal S}}(\mu,T)}/ \ 2\pi \sqrt{|{{\cal D}}(\mu,T)|} \ ,$$ valid in the degenerate gas approximation. The dependence on $A$ and $E$ in Eq. (\[rhosp\]) arises from the saddle point conditions that fix the value of the chemical potential $\mu$ and temperature $T$ of the gas $$\label{spc} {{\cal N}}(\mu, T) = A \ , \;\;\;\;\;\;\;\;\;\;\;\;\;\;\; {{\cal E}}(\mu, T) = E \ .$$ The functions ${{\cal N}}=-\partial \Omega/\partial \mu|_{\scriptscriptstyle T}$ and $$\label{u} {{\cal E}}(\mu,T) = \Omega (\mu,T) + \mu {{\cal N}}(\mu,T) + T {{\cal S}}(\mu,T)$$ are the particle number and energy functions of the gas, respectively, with the entropy ${{\cal S}}(\mu,T) =-\partial \Omega/\partial T|_\mu$ and the grand potential $\Omega = - T \int d\epsilon \rho (\epsilon) \log \left[1+{\rm e}^{(\mu-\epsilon)/T}\right]$, where $\rho (\epsilon) = \sum_i \delta (\epsilon-\epsilon_i)$ is the SP density of states. In terms of the previous functions, the determinant in Eq.(\[rhosp\]) is defined as ${{\cal D}}(\mu,T) = T^3 \left[ \partial {{\cal N}}/\partial \mu|_{\scriptscriptstyle T} \ \partial {{\cal E}}/\partial T|_\mu - \partial {{\cal N}}/\partial T|_\mu \ \partial {{\cal E}}/\partial \mu|_{\scriptscriptstyle T} \right]$. All the necessary quantities involved in the computation of ${\rho_{\text {\tiny MB}}}$ are therefore defined from $\Omega (\mu,T)$. The task consists in the evaluation of the entropy and the determinant at values of $\mu$ and $T$ that satisfy the conditions (\[spc\]). As $A$ and $E$ are varied in Eqs.(\[spc\]), in general $\mu$ and $T$ do not have a smooth and gentle behavior, because the functions ${{\cal N}}$ and ${{\cal E}}$ may have sudden changes due to the discrete nature of the SP spectrum. The difficulty lies in a proper treatment of the smooth part of the variations as well as the fluctuations with respect to it. To this purpose it is convenient to use the semiclassical approximation [@gutz]. The SP density of states is decomposed into the sum of a smooth term (${\overline{\rho}}$, given by a Thomas Fermi approximation or Weyl series) plus oscillatory terms $({\widetilde{\rho}})$, $\rho = {\overline{\rho}}+ {\widetilde{\rho}}$. Taking into account only the smooth part of the SP density of states, the calculation of ${\rho_{\text {\tiny MB}}}$ is relatively straightforward and leads to Bethe’s formula. The oscillatory part depends on the primitive classical periodic orbits $p$ (and their repetitions $r$), ${\widetilde{\rho}}= 2 \sum_p \sum_{r=1}^{\infty} A_{p,r} \cos \left[ r S_p/\hbar+ \nu_{p,r} \right]$. Each orbit is characterized by its action $S_p$, stability amplitude $A_{p,r}$, and Maslov index $\nu_{p,r}$. When inserted into the definition of the grand potential, and after integration with respect to the energy, the fluctuating part of $\Omega$ is given by [@ruj] $$\label{grandosc} \widetilde{\Omega} (\mu,T)= 2 \hbar^2 \sum_p \sum_{r=1}^{\infty} \frac{A_{p,r} ~ \kappa ( \frac{r ~ \tau_p}{{\tau_{\scriptscriptstyle T}}})}{r^2 ~ \tau_p^2} \cos \left( \frac{\scriptstyle r S_p}{\scriptstyle \hbar}+ \nu_{p,r} \right).$$ Here $\tau_p$ is the period of the periodic orbit, and $\kappa (x) = x/\sinh (x) $ is a temperature factor that introduces the time scale ${\tau_{\scriptscriptstyle T}}= \hbar/(\pi T)$ conjugate to the temperature. This expression describes the departures of $\Omega$ with respect to its mean behavior due to the fluctuations of the SP spectrum. By simple derivation of the grand potential the smooth and fluctuating part of all other thermodynamic functions can be obtained. Intensive functions like the chemical potential and the temperature should also be decomposed. We define their smooth parts by the implicit equations $$\label{spc2} {\overline{\cal N}}({\overline{\mu}}, {\overline{T}}) = A \ , \;\;\;\;\;\;\;\;\;\;\;\;\;\;\; {\overline{\cal E}}({\overline{\mu}}, {\overline{T}}) = E \ ,$$ whereas the fluctuating parts are ${\widetilde{\mu}}= \mu - {\overline{\mu}}$ and ${\widetilde{T}}= T - {\overline{T}}$. Using Eqs.(\[spc\]) and the decomposition of the different functions, Eq.(\[u\]) may be rewritten as $$\label{s1} ({\overline{T}}+ {\widetilde{T}}) {{\cal S}}= E - {\overline{\Omega}}(\mu,T) - {\widetilde{\Omega}}(\mu,T) - ({\overline{\mu}}+ {\widetilde{\mu}}) A \ .$$ If $A$ is large, the smooth part of the grand potential can be expanded in power series of ${\widetilde{\mu}}$ and ${\widetilde{T}}$. Keeping terms up to first order, using that in the degenerate gas approximation ${\overline{\Omega}}({\overline{\mu}},{\overline{T}}) \simeq {\overline{\Omega}}({\overline{\mu}},0) - (\pi^2/6) {\overline{\rho}}\ {\overline{T}}^2$, and neglecting variations of ${\overline{\rho}}$, Eq.(\[s1\]) becomes $$\begin{aligned} \label{s2} ({\overline{T}}+ {\widetilde{T}}) {{\cal S}}&=& E - {\overline{\Omega}}({\overline{\mu}},0) + \frac{\pi^2}{6} {\overline{\rho}}\ {\overline{T}}^2 + \overline{{{\cal S}}} ({\overline{\mu}},{\overline{T}}) \ {\widetilde{T}}- \nonumber \\ && {\widetilde{\Omega}}(\mu,T) - {\overline{\mu}}A \ .\end{aligned}$$ This equation is valid for an arbitrary temperature. At zero temperature, the energy of the system is the ground state energy $E_0$, and Eq.(\[s2\]) reduces to $$\label{s3} 0 = E_0 - {\overline{\Omega}}({\overline{\mu}},0) - {\widetilde{\Omega}}(\mu_0,0) - {\overline{\mu}}A \ .$$ ${\overline{\mu}}$ remains constant if variations of ${\overline{\rho}}$ are neglected, but the fluctuating part still depends on temperature. As a consequence the chemical potentials are slightly different. The idea is to subtract Eq.(\[s3\]) from (\[s2\]). Before doing that we first need to properly analyze some of the terms. The difference $E-E_0=Q$ is the excitation energy of the gas, as well as the term $(\pi^2/6) {\overline{\rho}}\ {\overline{T}}^2 =Q$. The latter equation follows from the dependence of the energy on temperature in the degenerate gas approximation, ${\overline{\cal E}}({\overline{\mu}},{\overline{T}}) \simeq {\overline{\cal E}}({\overline{\mu}},0) + (\pi^2/6) {\overline{\rho}}\ {\overline{T}}^2$, and the stationary phase condition (\[spc2\]) for ${\overline{\cal E}}$ (and the corresponding one at zero temperature). It allows to express the temperature in terms of $Q$. Similarly, ${\overline{\mu}}$ is obtained by inversion of ${\overline{\cal N}}({\overline{\mu}},{\overline{T}})$ in (\[spc2\]) which, in the degenerate gas approximation and neglecting variations of ${\overline{\rho}}$, is independent of ${\overline{T}}$. Returning to Eq.(\[s2\]), the term ${\widetilde{T}}({{\cal S}}- \overline{{{\cal S}}} ({\overline{\mu}},{\overline{T}})) = {\widetilde{T}}\widetilde{{{\cal S}}}$ is of second order, and is therefore neglected. After subtraction of Eq.(\[s3\]) and expressing ${\overline{T}}$ in terms of $Q$, the entropy may be expressed as $$\begin{aligned} \label{sdef} {{\cal S}}(A,Q) &=& \sqrt{\frac{2}{3} \pi^2 {\overline{\rho}}\ Q} + \frac{1}{{\overline{T}}} \left[ {\widetilde{\Omega}}({\overline{\mu}},0) - {\widetilde{\Omega}}({\overline{\mu}},{\overline{T}}) \right] \\ &\approx& \sqrt{\frac{2}{3} \pi^2 {\overline{\rho}}\ \left[ Q + {\widetilde{\Omega}}({\overline{\mu}},0) - {\widetilde{\Omega}}({\overline{\mu}},{\overline{T}}) \right]} \ , \label{sdef2}\end{aligned}$$ where, to lowest order, ${\widetilde{\Omega}}$ has been evaluated at $({\overline{\mu}}, {\overline{T}})$ (a similar though improved accuracy is obtained using $\mu$ and $T$, cf. Eq.(\[hro\]) below). Equation (\[sdef2\]) is valid if ${\widetilde{\Omega}}({\overline{\mu}},0) - {\widetilde{\Omega}}({\overline{\mu}},{\overline{T}}) \ll Q$, and puts the result under the form of a backshifted Bethe formula. A more physical interpretation of Eqs.(\[sdef\]) and (\[sdef2\]), that expresses the result in an entirely microcanonical language, is provided by the following connection. It has been shown previously [@lm3; @sev] that, to leading order in an expansion in terms of ${\widetilde{\mu}}$, ${\widetilde{\Omega}}({\overline{\mu}},{\overline{T}}) = {\widetilde{\cal E}}(A,Q)$, where ${\widetilde{\cal E}}(A,Q)$ are the (shell) fluctuations of the energy of the gas at a fixed number of particles and excitation energy. The shell corrections of Eq.(\[sdef2\]) are therefore directly related to the fluctuations of the energy of the system. A similar analysis can be performed for the determinant ${{\cal D}}(\mu,T)$ in Eq.(\[rhosp\]). To leading order we find $$\label{det} {{\cal D}}= \frac{\pi^2}{3} {\overline{\rho}}^2 \ {\overline{T}}^4 = \frac{12}{\pi^2} \ Q^2 \ ,$$ recovering the same form obtained by Bethe ($2\pi \sqrt{{{\cal D}}}=\sqrt{48} \ Q$, see Eq.(\[bethe\])). There exist oscillatory corrections to ${{\cal D}}$, but these are exponentially small compared to those associated with Eq.(\[sdef\]), and we neglect them. Equation (\[sdef\]) is the central result of the paper. It expresses, together with Eq.(\[det\]), the MB density of states in terms of the particle number $A$ and excitation energy $Q$. It decomposes ${{\cal S}}$ into a smooth and a fluctuating part, ${{\cal S}}= {\overline{{\cal S}}}+ {\widetilde{{\cal S}}}$. The smooth part is given by the usual Bethe’s result (corrections to it may be obtained by keeping higher order terms in ${\widetilde{\mu}}$ and ${\widetilde{T}}$ in the expansion). The novelty in Eq.(\[sdef\]) is the additional contribution of oscillatory corrections, ${\widetilde{{\cal S}}}= [{\widetilde{\Omega}}({\overline{\mu}},0) - {\widetilde{\Omega}}({\overline{\mu}},{\overline{T}})]/{\overline{T}}$. They describe shell corrections to the MB density. $\widetilde{\Omega}$ depends on temperature only through the function $\kappa$. The effect of this function is to exponentially suppress the contribution of periodic orbits whose period $\tau_p \gg {\tau_{\scriptscriptstyle T}}$ [@ruj; @lm3]. Since there is no suppression at $T=0$ (because ${\tau_{\scriptscriptstyle T}}\rightarrow \infty$), only orbits whose period $\tau_p \gtrsim {\tau_{\scriptscriptstyle T}}$ contribute to the difference ${\widetilde{\Omega}}({\overline{\mu}},0) - {\widetilde{\Omega}}({\overline{\mu}},{\overline{T}})$. At temperatures such that ${\tau_{\scriptscriptstyle T}}\ll {\tau_{\text{min}}}$, where ${\tau_{\text{min}}}$ is the period of the shortest periodic orbit of the system, the term ${\widetilde{\Omega}}({\overline{\mu}},{\overline{T}})$ becomes exponentially small, and only ${\widetilde{\Omega}}({\overline{\mu}},0)$ remains. The shell correction ${\widetilde{{\cal S}}}$ therefore decays as ${\overline{T}}^{-1}$. This decay contrasts with the more common exponential damping observed in other thermodynamic quantities [@lm3]. The behavior of $\widetilde{\Omega}$ (and therefore of ${\widetilde{{\cal S}}}$) strongly depends on whether $\mu$ or $T$ are varied. As discussed above, a temperature variation modifies the prefactors of the summands in $\widetilde{\Omega}$ (through the function $\kappa$), and therefore produces gentle variations of ${\widetilde{{\cal S}}}$. In contrast, $A_{p,r}$, $\tau_p$ and $S_p$ depend on $\mu$. For large values of $\mu$, $S_p \gg \hbar$ and the dominant variation with the particle number (or any other parameter that modifies the actions) comes from the argument of the cosine function in $\widetilde{\Omega}$. Rapid oscillations of ${\widetilde{{\cal S}}}$ are therefore generically expected when the number of particles is varied. A clearer picture of how the fluctuations behave may be obtained through a statistical analysis. There are two relevant SP scales in the analysis, the mean spacing $\delta$ and the energy conjugate to the shortest periodic orbit, $E_c = h/{\tau_{\text{min}}}$. The ratio $g = E_c/\delta$ is typically much larger than $1$ (for instance, $g\sim A^{2/3}$ in a three dimensional cavity). The most simple property of the fluctuations is $\langle {\widetilde{{\cal S}}}\rangle =0$, where the brackets denote an average over a suitable chemical potential window. This result is valid only to first order in the expansion; it can be shown that higher order terms contribute to a non–zero average. The next non–trivial statistical property is the variance $\langle {\widetilde{{\cal S}}}^2 \rangle$, that may be computed using Eq.(\[grandosc\]). The result is $\langle {\widetilde{{\cal S}}}^2 \rangle = (1/2) \int_{0}^\infty d x \ K(x,{x_{\text{H}}}) \left[ 1 - \kappa (x) \right]^2 /x^4$, where $K(x,{x_{\text{H}}})$ is the rescaled form factor of the SP spectrum (cf Eq.(36) in Ref.[@lm3]). The latter function depends on the rescaled Heisenberg time ${x_{\text{H}}}=h {\overline{\rho}}/{\tau_{\scriptscriptstyle T}}$. It describes system–dependent features for $x$ of the order of ${x_{\text{min}}}= {\tau_{\text{min}}}/{\tau_{\scriptscriptstyle T}}$, while it is believed to be universal for $x \gg {x_{\text{min}}}$. The universality class depends on the regular or chaotic nature of the dynamics, and on its symmetry properties. Taking into account the basic properties of $K(x,{x_{\text{H}}})$, in chaotic systems we find three different regimes for $\langle {\widetilde{{\cal S}}}^2 \rangle$ as a function of ${\overline{T}}$: \(i) Low temperatures $2\pi^2 {\overline{T}}\ll \delta$. In this regime $\langle {\widetilde{{\cal S}}}^2 \rangle = c_4 \pi^2 {\overline{T}}/\delta$, where $c_4 = 0.0609...$. \(ii) Intermediate temperatures $\delta \ll 2\pi^2 {\overline{T}}\ll E_c$. In this regime the size of the fluctuations saturate at a universal constant $\langle {\widetilde{{\cal S}}}^2 \rangle = c_3/\beta$, where $c_3 = 0.1023\ldots$ and $\beta = 1 (2)$ for systems with (without) time–reversal invariance. \(iii) High temperatures $2\pi^2 {\overline{T}}\gg E_c$. The size of the fluctuations decreases with excitation energy, $\langle {\widetilde{{\cal S}}}^2 \rangle = \langle {\widetilde{\Omega}}^2 ({\overline{\mu}},0) \rangle [ 1 - 8 \ {\rm e}^{-2 \pi^2 {\overline{T}}/E_c} ]/ {\overline{T}}^2$. After an exponential transient, a power–law decay $\langle {\widetilde{{\cal S}}}^2 \rangle^{1/2} \propto {\overline{T}}^{-1}$ is obtained. The situation is different in integrable systems, where only two regimes are found. At low temperatures the result is identical to that of chaotic systems. The difference is that now the growth extends up to much higher temperatures, $2 \pi^2 {\overline{T}}\approx E_c$, without saturation. At that temperature the variance of the fluctuations is of order $g$. In integrable systems, the maximum amplitude of the fluctuations is therefore reached at $2 \pi^2 {\overline{T}}\approx E_c$, and its typical size is much larger than in chaotic systems. At high temperatures $2 \pi^2 {\overline{T}}\gg E_c$ the decay is almost identical to that of chaotic systems (the coefficient 8 is replaced by a 12). As shown elsewhere [@lm3], ${\widetilde{\Omega}}({\overline{\mu}},{\overline{T}})$ is dominated, at any ${\overline{T}}$, by the shortest classical periodic orbits. In contrast, the difference ${\widetilde{\Omega}}({\overline{\mu}},0)-{\widetilde{\Omega}}({\overline{\mu}},{\overline{T}})$ depends on orbits whose period $\tau_p {\stackrel{>}{\scriptstyle \sim}}{\tau_{\scriptscriptstyle T}}$. For temperatures $2 \pi^2 {\overline{T}}\ll E_c$ the statistical properties of these orbits are universal, and correspondingly the probability distribution function of ${\widetilde{{\cal S}}}$ is expected to be universal, in the sense that at a given temperature it should only depend on the nature of the underlying classical dynamics (regular or chaotic), and the symmetries of the system. This statement is supported by the fact that in the limit ${\overline{T}}\rightarrow 0$, ${\widetilde{{\cal S}}}\approx - \partial {\widetilde{\Omega}}({\overline{\mu}},{\overline{T}}) /\partial {\overline{T}}$. The probability distribution of the latter quantity was studied in Ref.[@lm3]; it was shown that it coincides at low temperatures with that obtained from a Poisson spectrum for integrable systems and from a random matrix spectrum for chaotic ones. As the temperature is raised, the universality of the probability distribution of ${\widetilde{{\cal S}}}$ will be lost for temperatures of the order or greater than $E_c$, where system specific features are revealed. ![The logarithm of the many-body density of states of $A$ noninteracting fermions in a rectangular billiard of sides $a = \sqrt{(1 + \sqrt{5})/2}$ and $b=a^{-1}$. Dots: numerical computation at three different excitation energies; solid curves: theoretical prediction (\[hro\]); dashed curves: smooth part Eq.(\[shr2\]).](lmr_figure.eps){width="8.5cm" height="7.0cm"} We have checked some of our predictions by a direct numerical counting of the MB density of states in a particular system. Figure 1 shows the results obtained for a gas of about 2000 fermions contained in a two–dimensional rectangular cavity, an integrable system. For each number of particles we compute the MB density of states at three different temperatures, measured in units of $T_{\delta}=\delta/2 \pi^2$ and $T_c =E_c /2 \pi^2$. The theoretical curve is computed according to the expression $$\label{hro} \log ( {\rho_{\text {\tiny MB}}}/{\overline{\rho}}) = \log ( {\rho_{\text {\tiny MB}}}^{\text{\tiny HO}}/{\overline{\rho}}) + [ {\widetilde{\Omega}}(\mu,0) - {\widetilde{\Omega}}(\mu,{\overline{T}}) ]/{\overline{T}}\ ,$$ where ${\widetilde{\Omega}}$ is given by the periodic orbits of the rectangle. Though the results are similar, $\mu$ instead of ${\overline{\mu}}$ is used to obtained a more accurate description of the numerical data. A systematic deviation is observed between theory and numerics if the corrections arising from the exact expression Eq.(\[shr2\]) are not included. Notice the extremely good accuracy of this equation, either for the average value of the density as well as for the fluctuations. The Laboratoire de Physique Théorique et Modèles Statistiques is an Unité de recherche de l’Université Paris XI associée au CNRS. [10]{} H. A. Bethe, Phys. Rev. [**50**]{} (1936) 332. C. Bloch, Phys. Rev. [**93**]{} (1954) 1094. N. Rosenzweig, Phys. Rev. [**108**]{} (1957) 817. A. Bohr and B. R. Mottelson, [*Nuclear Structure*]{}, Vol.I, Benjamin, Reading, Massachusetts, 1969. A. Gilbert and A. G. W. Cameron, Can. J. Phys. [**43**]{} (1965) 1446; A. V. Ignatyuk, G. N. Smirenkin, and A. S. Tishin, Sov. J. Nucl. Phys. [**21**]{} (1975) 255; K. Kataria, V. S. Ramamurthy, and S. S. Kapoor, Phys. Rev. C [**18**]{} (1978) 549; Y. Alhassid, G. F. Bertsch, and L. Fang, Phys. Rev. C [**68**]{} (2003) 044322. All over the text, we may either refer to the excitation energy $Q$ of the system or to its temperature $T$. G. H. Hardy and S. Ramanujan, Proc. London Math. Soc. [**17**]{} (1918) 75; H. Rademacher, Proc. London Math. Soc. [**43**]{} (1937) 241. R. H. Fowler, [*Statistical Mechanics*]{}, Macmillan Company, New York, 1936. M. C. Gutzwiller, J. Math. Phys. [**10**]{} (1969) 1004; R. Balian and C. Bloch, Ann. Phys. (N.Y.) [**69**]{} (1972) 76. K. Richter, D. Ullmo and R. Jalabert, Phys. Rep. [**276**]{} (1996) 1. P. Leboeuf and A. G. Monastra, Ann. Phys. [**297**]{} (2002) 127. P. Leboeuf, [*Regularity and chaos in the nuclear masses*]{}, Lectures delivered at the VIII Hispalensis International Summer School, Sevilla, Spain, June 2003 (to appear in [*Lecture Notes in Physics*]{}, Springer–Verlag, Eds. J. M. Arias and M. Lozano); nucl-th/0406064.

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Self-regulation in older Thai women with self-reported knee osteoarthritis: A path analysis. This study aimed at testing factors influencing coping behavior and health status among older women with knee osteoarthritis. A total of 274 participants completed questionnaires. Model testing revealed that self-efficacy was the most powerful predictor of coping behavior. Illness representation had a significant direct and indirect effect on health status and was a better predictor of health status than were the other variables. Understanding the complex relationships among study variables should help to tailor future interventions to better address the symptoms of osteoarthritis and to promote optimal health in older Thai women who report knee osteoarthritis.

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Q: Search datetime in MySQL I have a MySQL database, there's a table which have column Time's Type is Nvachar(50) and its values is kind like this "05/09/2012 20:53:40:843" *(Month-date-year hour:mins:second:msecond)* Now I want to query to get a record have Time after "10/05/2012 01:00:30 PM". I had code in C# to converted it to "05/10/2012 13:00:30" before making a query. My Query : SELECT * FROM ABCDFEGH WHERE capTime > '05/10/2012 13:00:30' LIMIT 0, 1 But i got no record. So please tell me how can I can make it return record have time after the time above ??? More Info My C# code : string tableName = "ABCDFEGH"; string date = "05/10/2012 13:00:30"; var query = "SELECT * FROM " + tableName + " WHERE capTime > '" + date + "' LIMIT 0, 1"; var cmd = new MySqlCommand(query, connection); MySqlDataReader dataReader = null; try { dataReader = cmd.ExecuteReader(); } I'm so so so so so so sorry. I made a mistake the query must be SELECT * FROM ABCDFEGH WHERE capTime > '05/10/2012 13:00:30' LIMIT 0, 1 This query is successful return the record i need :) But soemhow I have mistyped it into SELECT * FROM ABCDFEGH WHERE capTime > '05-10-2012 13:00:30' LIMIT 0, 1 Sorry again, topic close. But tks for evveryone tried :) A: I recommend using the DATETIME datatype instead of NVARCHAR. Store dates in YYYY-MM-DD HH:MM:SS format, which is the native DATETIME format recognized by MySQL. Also use date literals in the same format. Two reasons for this recommendation: First, DATETIME takes only 8 bytes, instead of up to 150 bytes which is the potential size of a multibyte 50 character varchar. Second, the sort order of DATETIME will be the same as the chronological order. So if you create an index on the Time column, your > comparison can benefit from the index. Your query will be much faster as a result.

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Valley Mall (Hagerstown) Valley Mall is a super-regional shopping mall serving Hagerstown, Western Maryland and nearby communities in West Virginia and Pennsylvania. Valley Mall is the only indoor mall in the Hagerstown Metropolitan Area since the other closed, Martinsburg Mall. Anchor stores include Belk, JCPenney, Onelife Fitness, and Tilt Studio with one vacant anchor last occupied by Macys. Dick's Sporting Goods will be opening up in 2020 where Sears once was located . History Valley Mall, developed by Shopco Development Company of New York City, officially opened its doors on 15 August 1974. It was considered the second mall to open in Western Maryland and the Tri-State Area (the first being its then-sister mall Frederick Towne Mall in Frederick, Maryland, which opened in 1972). The mall opened with 90 stores anchored by Montgomery Ward, Eyerly's, JCPenney, McCrory's, Peoples Drug, Carmike Cinemas 3, and Pantry Pride grocery store. Many changes have come to the mall over the years. Within a short time of opening, Eyerly's became The Bon-Ton, and a partial second floor with mostly small crafts stores opened. In 1995, the mall underwent a major renovation inside, including the removal of the second floor. Also in the 1990s, Peoples Drug and McCrory's closed and were replaced by small shops. Pantry Pride's location became Martin's, and Martin's moved and was replaced by Toys R Us. In 1999-2000, the mall expanded with a new wing to include Old Navy, a food court, Hecht's department store, a 16-screen multiplex, and additional small stores. In 2003, Sears moved from Long Meadow shopping center in northern Hagerstown to replace Montgomery Ward, which closed all of its remaining stores in 2001. In 2006, Hecht's became Macy's as part of the retirement of the Hecht's nameplate. Macy's closed its Valley Mall location in April 2016. On June 22, 2017, it was announced that Sears would be closing as part of a plan to close 20 stores nationwide. The store closed in September 2017. On July 22, 2017, it was announced that Bon-Ton would be closing in February 2018 as it lease expires which will leave JCPenney as the only anchor left, however on October 18, 2018, Belk opened up in the former space of Bon-Ton, making Valley Mall having once again 2 anchor stores since the closure of Bon-Ton. On December 13, 2017, it was announced that the former Macy's would be replaced by a Tilt Studio which opened up in September 2018, and an Onelife Fitness which opened up in January 2019. Dick's Sporting Goods will be replacing the location where Sears once was. References External links Valley Mall PREIT Website Category:Shopping malls in Maryland Category:Shopping malls established in 1974 Category:Buildings and structures in Washington County, Maryland Category:Hagerstown metropolitan area Category:Pennsylvania Real Estate Investment Trust Category:1974 establishments in Maryland

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Post navigation The 5 Pillars of Marriage: Part I, Respect I swear I’m not making this up. The first time I ever laid eyes on my husband I was absolutely in love with him. I mean, head over heels, gah-gah about him. My mother used to tease me about my craziness for him. I guess it was pretty obvious. And the truth is that I’m still gah-gah nutso over him even after 16 years together. He’s an awesome husband and a great dad! He has just one itty bitty, teeny tiny problem. As wonderful of a guy as he is, he just doesn’t possess the genetic makeup that propels someone to keep his house clean. He’s not the sort of guy who takes it upon himself to vacuum, or clean bathtubs, or do laundry, or anything at all. He made for a good bachelor, actually. But one thing he does do around the house- and with consistency- is help wash dishes. And it’s a big help, especially when you’re having to keep up with a party of five three times a day. But when it’s my turn to wash the dinner dishes, I notice that he never loads the dishwasher the way I would want it. I usually (and silently) ask myself, “Why did he put that there? That’s not where it goes!” He probably wonders the same thing about me. Of course, I’ve never confronted him about his obvious inability to load the dishwasher right (tongue firmly in cheek). But it has made me recognize that this same sort of little problem occurs between other couples too and not just mine. Whether it’s how to scramble eggs, or if the toilet seat should be up or down, or how to make up the bed in the morning, one spouse sometimes insists that their way is better. Where does this stubbornness come from? Sometimes it’s taught by our parents and we mimic what we grew up with. Sometimes it’s just an inherent trait that seems to have been a part of you since you were born (any A-type personalities out there?). And sometimes it’s both. Regardless of the what’s and why’s, I believe that challenges in a relationship can all boil down to five key areas that I consider the be the pillars of a great marriage: respect, being a help mate, unity, love, and, above all, communication. Let’s take them one at a time starting with respect. I’ll cover the other four areas in future articles. Respect can have two different emphases depending on if you’re the husband or wife (or boyfriend or girlfriend). Respect is always extremely important no matter who you are. But it happens differently between the sexes it seems. There’s a great book written by Gary D. Chapman called “The 5 Love Languages: The Secret To Love That Lasts” that talks about this. He provides a great bottom line. It’s really simple. Ready for it? Here it is. Men want to be respected first, then everything else comes after it. Women, on the other hand, want love first, then respect comes second (a very close second in my opinion). In Ephesians 5:22, 25, 28, the apostle Paul lays out the plain truth about marriage. He addresses the women first in verse 22 by saying, “Wives, submit to your husband as to the Lord.” I’ve heard so many people take this verse out of context and think that the Bible commands wives to be subservient to their husbands, even thinking that it obligates them to allow abuse. Let’s be completely clear…that is not what Paul is saying. Rather, he’s telling the wives to show proper respect to their husbands because he is the head of the household. Then three verses later he addresses the husbands: “Husbands, love your wives just as Christ also loved the church and gave Himself for her….husbands ought to love their own wives as their own bodies, he who loves his wife loves himself.” Husbands are clearly commanded to love, honor, and respect their wives just as Jesus loves them. The essence of what Paul is saying here is that wives should love their husbands just as they love Christ. With that same kind of love. Because in the family the husband is meant to be symbolic of Christ and the wife is the church. We know Christ adores His church as evidenced by His death on the cross for us. And so the church should honor Him with respect and love in return. Sounds fair. It’s the same in marriages. To do this shows proper respect for each other according to how the Father prescribes it. The Lord will most certainly bless the marriage as both spouses grow and mature together. But what if you don’t feel respected by your spouse? Should you just chuck it all and stay rooted in bitterness and disappointment? Wait for him or her to make the first move? Absolutely not. Every spouse is called to respect the other even if it’s not easy. Any time a relationship is experiencing challenging times, the first step toward healing and growth always has to begin with you. If you are a wife, show respect for your husband’s interests, his time, his concerns, and his daily needs. If you’re a husband, then show respectful affection and attention, both physical and emotional, to your wife so she feels welcomed and accepted by you. Mutual respect is the foundation of any relationship. It shows commitment, patience, and a desire to make the marriage work no matter what. If you start there, the years you go through together will be a lot more bearable as you face future hills and valleys. And chances are good you’ll even agree on how to load the dishwasher. Further Reading John Piper is a highly respected pastor who has been leading men and women to Christ for many years. His website, Desiring God, is rich in wisdom told through short devotionals and books. Read here to find out what he has to say about respect and love within the marriage bonds. I’m so excited you stopped by Steppes of Faith. And I’m even happier that you were encouraged. It’s all for His glory. I’ll be posting the next pillar soon. I hope you can bear with me while I continue to build the website. As you can see, it’s still in its infancy and little tweaks here and there are in the works. I would appreciate any comments you have about it and even suggestions for topics. The more people we can reach for Christ the better! May I Help You Look For Something? Need Prayer? "Again I say to you that if two of you agree on earth concerning anything that they ask, it will be done for them by My Father in heaven. For where two or three are gathered together in My name, I am there in the midst of them." Matthew 18:19

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;===- ./lib/Target/PowerPC/TargetInfo/LLVMBuild.txt ------------*- Conf -*--===; ; ; The LLVM Compiler Infrastructure ; ; This file is distributed under the University of Illinois Open Source ; License. See LICENSE.TXT for details. ; ;===------------------------------------------------------------------------===; ; ; This is an LLVMBuild description file for the components in this subdirectory. ; ; For more information on the LLVMBuild system, please see: ; ; http://llvm.org/docs/LLVMBuild.html ; ;===------------------------------------------------------------------------===; [component_0] type = Library name = PowerPCInfo parent = PowerPC required_libraries = Support add_to_library_groups = PowerPC

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Dave Lucey David J. Lucey (January 20, 1915 – February 20, 1997) was an American football player and coach and a civil servant who served as Massachusetts Registrar of Motor Vehicles from 1972-1974. Lucey played football for the Boston College Eagles from 1937-1939. He was a member of the Eagles team that played in the 1940 Cotton Bowl. After graduation, Lucey accepted the position of head football coach at Saugus High School in Saugus, Massachusetts. In 1947, he returned to Boston College as an assistant football coach. After one season he was named Director of Public Relations. He also coached at Peabody Veterans Memorial High School, St. Mary's High School, and St. John's Preparatory School. Lucey was a friend and fundraiser for Governor Francis W. Sargent. From 1971 to 1972, Lucey was a member of the State Appellate Tax Board. He was the Massachusetts Registrar of Motor Vehicles from 1972 until his retirement in 1974 References Category:Boston College Eagles football players Category:Massachusetts Democrats Category:People from Saugus, Massachusetts Category:People from Rochester, New Hampshire Category:1997 deaths Category:1915 births

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Penstemon cyanocaulis Penstemon cyanocaulis, the bluestem penstemon or bluestem beardtongue, is a perennial plant in the plantain family (Plantaginaceae) found in the Colorado Plateau and Canyonlands region of the southwestern United States. Description Growth pattern It is a perennial plant growing tall. Leaves and stems Stems are smooth with narrow inversely lanceolate leaves. Inflorescence and fruit It blooms from April to July. Dense clusters of tubular, two lipped, long, blue to lavender-blue flowers are on elongations of the stem stalks. Fruits are woody capsules. Habitat and range It can be found in blackbrush scrub, pinyon juniper woodland, and mountain bush communities to in southwestern Colorado and southeastern Utah. Ecological and human interactions "Cyan" + "caul" means "blue" + "stem", referring to the stem color. It is pollinated by bees and other insects. References cyanocaulis Category:Flora of Colorado Category:Flora of Utah

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The New York Times Co. chairman and publisher Arthur “Pinch” Sulzberger Jr. is no longer the highest-paid executive at the company. That title now belongs to Chief Executive Mark Thompson, whose total compensation nearly doubled last year — to $8.7 million, up from $4.5 million. Most of that increase reflects stock awards, which swelled to almost $5 million, from $2.3 million in 2014, according to the company’s shareholder proxy statement filed this week. Thompson’s non-equity incentive plan also more than doubled, to $2.6 million, last year. He pocketed the same base salary of $1 million in 2015, slightly less than Sulzberger’s, the filing showed. Although Sulzberger’s $1.1 million in base pay stayed the same, his overall pay package dipped nearly 15 percent last year, to $5.86 million, due mostly to change in the value of his pension plan. His stock awards were trimmed by 2.7 percent, to just under $2 million, in 2015. On the plus side, his non-equity incentive compensation, which is based on longer-term performance, jumped nearly 18 percent, to $2.7 million, last year. While Sulzberger lost his title as the top-paid executive, he rakes in more than the other members of the Ochs-Sulzberger clan who work at the family-controlled company. His first cousin Vice Chairman Michael Golden had to make do with a pay package of $2.1 million, down from $2.7 million in 2014.

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Prenatal diagnosis of hypomethylation at KvDMR1 and Beckwith-Wiedemann syndrome in a pregnancy conceived by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer. We report prenatal diagnosis of hypomethylation at KvDMR1 and Beckwith-Wiedemann syndrome (BWS) in a pregnancy conceived by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer. A 34-year-old, primigravid woman was referred to the hospital at 21 weeks' gestation because of advanced maternal age and an isolated omphalocele in the fetus. Her husband had the fertility problem of oligospermia. This pregnancy was achieved by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer. Prenatal ultrasound revealed a 2.1 cm × 1.6 cm isolated omphalocele. The woman underwent amniocentesis. Array comparative genomic hybridization and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were applied to the DNA extracted from the uncultured amniocytes. Conventional cytogenetic analysis and high-resolution melting analysis were performed on cultured amniocytes. Array comparative genomic hybridization revealed no genomic imbalance. MS-MLPA analysis revealed H19DMR(IC1) normal methylation and KvDMR1(IC2) hypomethylation. Conventional cytogenetic analysis revealed a karyotype of 46,XX. High-resolution melting analysis using a methylation-specific polymerase chain reaction assay confirmed normal methylation at H19DMR(IC1) and hypomethylation at KvDMR1(IC2). The altered methylation status at 11p15.5 and the phenotype of omphalocele were consistent with the diagnosis of BWS. In case of prenatally detected omphalocele associated with an obstetric history of assisted reproductive technology, a differential diagnosis of BWS should be considered. Methylation assays such as MS-MLPA and methylation-specific polymerase chain reaction using uncultured amniocytes are useful for rapid diagnosis of BWS under such circumstances.

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Q: Dockerfile JBOSS don't access local I'm creating a Dockerfile running a JBOSS EAP 7, see my dockerfile: FROM mlaccetti/docker-debian-java8 # file author / maintainer MAINTAINER "Ronaldo Lanhellas" "[email protected]" USER root RUN apt-get update;apt-get install sudo -y RUN adduser --disabled-password --gecos '' docker RUN adduser docker sudo RUN echo '%sudo ALL=(ALL) NOPASSWD:ALL' >> /etc/sudoers USER docker RUN sudo mkdir -p /opt/jboss/jboss-eap-7.0 COPY jboss-eap-7.0 /opt/jboss/jboss-eap-7.0 ENV JBOSS_HOME /opt/jboss/jboss-eap-7.0 RUN sudo chown -R docker:docker /opt/jboss/*;sudo chmod +x /opt/jboss/jboss-eap-7.0/bin/standalone.sh RUN java -version #RUN sudo apt-get install default-jdk -y CMD sudo sh $JBOSS_HOME/bin/standalone.sh EXPOSE 8080 9990 The jboss-eap-7 start normally, without error in server.log. But trying to access from host machine the address-> http://localhost:8080 i can't access. Edit 1 Looking inside docker container , this is my IP: 1: lo: <LOOPBACK,UP,LOWER_UP> mtu 65536 qdisc noqueue state UNKNOWN group default qlen 1 link/loopback 00:00:00:00:00:00 brd 00:00:00:00:00:00 inet 127.0.0.1/8 scope host lo valid_lft forever preferred_lft forever 44: eth0@if45: <BROADCAST,MULTICAST,UP,LOWER_UP> mtu 1500 qdisc noqueue state UP group default link/ether 02:42:ac:11:00:02 brd ff:ff:ff:ff:ff:ff inet 172.17.0.2/16 brd 172.17.255.255 scope global eth0 valid_lft forever preferred_lft forever But my network (host) is : 192.168.0.x. Why docker don't use same ip as host ou another ip in same network ? I think that it can be the cause of problem. A: You need to publish container᾿s ports, like this: docker run -p 8080:8080 mlaccetti/docker-debian-java8

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Energy assistance The Salvation Army’s Energy Assistance Services (EAS) seeks to walk alongside low-income households to address energy crises. In this process an applicant may be offered bill payment assistance, energy company subsidy program enrollment, and case management services. The goal of these services is to support household financial stability and support the customer in achieving goals they have set for themselves. In most situations, an EAS Case Specialist will meet with an applicant one on one to determine eligibility and to assess the need or opportunity for additional supports. Funding for EAS is provided by a grant from the State of Michigan, partnerships with Consumers Energy, DTE Energy, and Michigan Gas Utilities as well as donations from individuals and other corporations. How It Works Each household that requests utility assistance is given a one-on-one interview conducted by our social services staff. During the interview, individual strengths and needs are identified, including the need for utility assistance. Also at this time, past and current use of community resources are explored and household income and expenses are reviewed. This dialogue leads to the development of a service plan to guide the provision of utility assistance. In all cases, eligibility for services is individually determined by our social services staff, based on the comprehensive assessment. Social services staff members then work directly with the utility companies to assist the household financially and to avoid shut off. The following documents are needed for energy assistance appointments: One form of ID for the applicant such as: Driver’s license State ID Passport or green card Birth certificate Some form of ID for all other household members. Income documentation for the entire household Need documentation for each source of income that includes 45 days prior to the interview. If there is a source of income that is meant to remain the same after the interview date (usually child support, unemployment, etc.), documentation is needed to show how much is supposed to be paid during the 30 days after the interview. If you have questions, please call The Salvation Army's Call Center at (855) 929-1640. The Call Center is available Monday - Friday from 8:00 am to 5:30 pm. If you need energy assistance outside of Call Center hours please contact United Way 2-1-1 at 1-800-887-1107 or https://www.211.org/ Enrollment in Affordable Payment Plans for DTE Energy and Consumers Energy customers is available below. The Salvation Army, an international movement, is an evangelical part of the universal Christian Church. Its message is based on the Bible. Its ministry is motivated by the love of God. Its mission is to preach the gospel of Jesus Christ and to meet human needs in His name without discrimination.

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A partially folded state of hen egg white lysozyme in trifluoroethanol: structural characterization and implications for protein folding. The effect of 2,2,2-trifluoroethanol (TFE) on the solution conformation of hen egg white lysozyme has been investigated using circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) spectroscopy. Addition of TFE to lysozyme at pH 2.0, 27 degrees C, up to a concentration of 15% (v/v) induces only slight changes in the NMR spectrum. However, above this concentration a cooperative transition to a new but partially structured state of the protein is observed. This state shows no structural cooperativity against further denaturation and is characterized by an ellipticity in the far-UV CD greater than that of the native protein. Near-UV CD intensity is dramatically reduced compared with that of the native state, and 1H NMR studies indicate that side-chain interactions are substantially averaged in this denatured state. Solvent proton/deuterium exchange rates for 66 amide hydrogens were measured site-specifically by a combination of amide trapping experiments and 2D 1H NMR. Significant protection from exchange occurs for about 25 backbone amides, the majority of which are located in regions of the protein that are helical in the native enzyme. By contrast, amides located in a second region of the native protein which contains a beta-sheet and one 3(10)-helix as well as a long loop show little protection. This pattern of protection resembles that found in the stable molten globule state of alpha-lactalbumin and in an early kinetic intermediate detected in the refolding of hen lysozyme.

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by Charles A month ago, an Iranian general "disappeared" (perhaps along with his family) while in Turkey, and speculation is rampant. Did Mossad or the CIA kidnap him or did he defect? In either case, he is a high-level intelligence source who could expose Iranian inner workings. The Blotter: "This is a fatal blow to Iranian intelligence," said the source, explaining that Asgari knows sensitive information about Iran's nuclear and military projects. Iran called tens of its Revolutionary Guard agents working at embassies and cultural centers in Arab and European countries back to Tehran out of fear that Asgari might disclose secret information about their identities, according to the analyst. There are conflicting reports about how and when Asgari disappeared. The general, according to Turkish and Israeli press reports, arrived in Istanbul from Damascus on Feb. 7. Initial reports speculated he may have been kidnapped because he failed to show up at a hotel that had been booked for him by two non-Turkish men. The source, however, believes Asgari's disappearance was prompted by the detention of five Iranians after the raid on their government's liaison office in Irbil, Iraq in January. Asgari, 63, knew and may have worked with some of the detained men, said the analyst. Asgari's years with the Iranian Revolutionary Guard and the Iranian defense ministry would make him an invaluable source of information. He was reportedly based in Lebanon in the 1990s and was in charge of ties with the Lebanese Shiite group Hezbollah. Ha'aretz and the Jerusalem Post have weighed in, and Ynet reported that the Saudi newspaper al-Watan reported on the disappearance a week or so ago. Makes you wonder if Abdullah and Ahmadinejad discussed the general's disappearance during their summit last week. By way of the New York Post, DEBKA adds this wrinkle: Askari is believed to have taken part - or have links to - the armed group that stormed a U.S.-Iraqi command center in the holy city of Karbala on Jan. 20 and killed five U.S. troops, the Web site said. The attackers wore military uniforms and used vehicles often driven by foreign dignitaries in an attempt to impersonate Americans. A Middle East intelligence source said the United States could not let the outrage stand and had been hunting the general ever since, the Web site said. Of course, it's always good to take Debka with a vat of salt, but it looks like an interesting mystery nevertheless.

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A two- to four-lane roadway providing mobility and access. Collector streets can be found in residential neighborhoods, commercial and industrial areas, and central business districts. Collectors usually have minimal access control, and the right-of-way is typically 80 feet. Collectors are designed to move traffic from local roads to secondary arterials. A method used to characterize the spectral properties of a light source and specify the appropriate light source type in architectural design; light sources of the same color can vary in quality (CRI is used to describe light source quality); lower color temperatures are warmer (yellow/red) while high color temperatures are cooler (blue); the standard unit for color temperature is Kelvin, K (e.g. candlelight is 1500k, daylight at noon is 5500k). Transportation pathway allowing movement between activity centers; a corridor may encompass single or multiple transportation routes and facilities, adjacent land uses, and the connecting street network. Color Rendering Index - A system used to describe the effect of a light source on the color/appearance of an object, compared to a reference source. The index uses a scale from 0-100 and is used as a quality distinction. An extension of the sidewalk or curb line into the parking lane to reduce the effective street width. Also known as curb bulb-outs or neckdowns, curb extensions significantly improve pedestrian crossings by reducing the pedestrian crossing distance, visually and physically narrowing the roadway, improving the ability of pedestrians and motorists to see each other, and reducing the time that pedestrians are in the street. Curb extensions are only appropriate where there is an on-street parking lane. Curb extensions should not extend more than 6 feet from the curb, and must not extend into travel lanes, bicycle lanes or shoulders. The turning needs of larger vehicles, such as school buses, need to be considered in curb extension design.

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Get breaking news alerts and special reports. The news and stories that matter, delivered weekday mornings. WASHINGTON — Speaker Paul Ryan said he doesn’t believe there is a need for Congress to pass any kind of legislation aimed at protecting special counsel Robert Mueller from termination. “I don't think it's necessary,” the Wisconsin Republican said during an interview that aired Sunday on NBC’s “Meet the Press” when specifically asked whether he would bring such a bill to the House floor if it passed the Senate. “I don't think he's going to fire Mueller.” “First of all, I don't think he should be fired,” Ryan reiterated. “I think he should be left to do his job, and I don't think they're really contemplating this. We’ve had plenty of conversations about this. It's not in the president's interest to do that. We have a rule of law system. No one is above that rule of law system.” Ryan’s comments came days after White House press secretary Sarah Huckabee Sanders said President Donald Trump believes it’s within his power to fire Mueller, the former FBI director who is leading the investigation into Russian attempts to interfere in American elections, among other matters. Lawmakers on both sides of the aisle have been adamant that the president should not remove the special counsel. Let our news meet your inbox. The news and stories that matters, delivered weekday mornings. This site is protected by recaptcha The New York Times first reported last week that Trump sought to fire Mueller as recently as December, and NBC News reported that the recent FBI raid on Trump’s personal lawyer Michael Cohen has upended talks for the president to sit down for an interview with Mueller’s team. Ryan's interview also came just as another former FBI director, James Comey, who Trump fired last May, embarks on a media tour to promote his new book, which asserts that Trump is “unethical” and “untethered to truth and institutional values.” Asked whether he believes Comey is a man of integrity, Ryan responded, “as far as I know,” but resisted answering further questions about him. “I've met him two or three times in two or three briefings,” Ryan said. “I don't really know the guy. I'm not trying to be evasive. But what I don't want to do is join some food fight, some book-selling food fight. I don't see any value in that.” Days after announcing his decision to leave Congress at the end of the year, Ryan had only gracious things to say about the president. “We have a good relationship,” he said. “We've gotten a lot done together.” Ryan said Trump was “disappointed” in his decision to leave elected office, “but he understood.” The speaker also rejected the notion that this era in political history could one day be looked back on as a victory of “Trumpism over Ryanism.” “I just don't see it like that,” Ryan said, pointing to progression on two of his priorities over the last year, tax legislation and military funding. But pressed on some policy differences between him and the president, like trade and the role of entitlement spending, Ryan noted “no two people are going to agree on everything.” “We have different styles,” he continued. “We have different ideas. But it's a big tent party. And we represent different corners of the tent.”

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10 A.3d 1276 (2010) COMMONWEALTH of Pennsylvania, Appellee v. Felix David RIVERA, Appellant. No. 344 MDA 2010. Superior Court of Pennsylvania. Submitted August 9, 2010. Filed December 17, 2010. *1278 Vincent J. Quinn, Lancaster, for appellant. Todd P. Kriner, Assistant District Attorney, Lancaster, for Commonwealth, appellee. BEFORE: MUSMANNO, BENDER, and LAZARUS, JJ. OPINION BY LAZARUS, J.: Felix David Rivera appeals from the order dismissing his amended petition under the Post Conviction Relief Act, 42 Pa.C.S.A. § 9541, et seq. After careful consideration, we reverse. On December 8, 1995, Rivera was convicted of indecent assault of a person less than thirteen years of age[1] and was sentenced to five years' probation. On May 15, 2000, a capias was issued for a probation violation and Rivera was committed to Lancaster County Prison.[2] On July 9, 2000, Megan's Law II went into effect. On August 31, 2000, a probation violation hearing was held. At some point in 2006, Rivera was released from incarceration and failed to register his address with the Pennsylvania State Police. Commonwealth v. Rivera, 1015 MDA 2008, at 2 (filed April 20, 2009). He was thereafter charged with failure to comply with registration of sexual offenders pursuant to 18 Pa.C.S.A. § 4915(a). The remaining factual and procedural background has been provided by the PCRA court in its opinion dated February 17, 2010: On May 5, 2008 [Rivera] appeared before the [t]rial [c]ourt for a stipulated bench trial. [Rivera] was found guilty of Failure to Comply with Registration of Sexual Offender Requirements. Immediately following trial, [Rivera] was sentenced to five to ten years' incarceration. On June 3, 2008, [Rivera] filed a timely direct appeal to the Superior Court of Pennsylvania. The Superior Court affirmed the judgment of sentence. . . . On May 28, 2009, [Rivera] filed a Post-Conviction Collateral Relief Act Motion. Counsel was appointed to represent him, and PCRA counsel filed an Amended Petition for Post-Conviction Collateral Relief on July 14, 2009. The [c]ourt held an evidentiary hearing on December 11, [2]009, at which time the [c]ourt ordered both parties to file briefs. Both parties submitted briefs, and [Rivera's request for relief was denied]. PCRA Court Opinion, 2/17/10, at 1-2 (citation omitted). On appeal, Rivera raises the following issue: WHETHER APPELLATE COUNSEL WAS INEFFECTIVE WHEN SHE *1279 WAIVED THE MERITORIOUS ISSUE THAT THE EVIDENCE WAS INSUFFICIENT TO PROVE BEYOND A REASONABLE DOUBT THAT THE DEFENDANT VIOLATED 18 PA.C.S.A. § 4915 WHEN HE WAS NOT SUBJECT TO REGISTRATION UNDER 42 PA.C.S.A. § 9795.1 SINCE HE WAS NOT SERVING AN ORIGINAL SENTENCE OF INCARCERATION AT THE TIME MEGAN'S LAW [II] WENT INTO EFFECT? Brief for Appellant, at 4. This Court's standard of review regarding an order dismissing a petition under the PCRA is whether the determination of the PCRA court is supported by evidence of record and is free of legal error. Commonwealth v. Burkett, 5 A.3d 1260, 1267 (Pa.Super.2010) (citations omitted). In evaluating a PCRA court's decision, our scope of review is limited to the findings of the PCRA court and the evidence of record, viewed in the light most favorable to the prevailing party at the trial level. Id. at 1267. We may affirm a PCRA court's decision on any grounds if it is supported by the record. Id. Our standard of review when faced with a claim of ineffective assistance of counsel is well settled. First, we note that counsel is presumed to be effective and the burden of demonstrating ineffectiveness rests on appellant. Commonwealth v. Thomas, 783 A.2d 328, 332 (Pa.Super.2001) (citation omitted). In order to prevail on a claim of ineffective assistance of counsel, a petitioner must show, by a preponderance of the evidence, ineffective assistance of counsel which, in the circumstances of the particular case, so undermined the truth-determining process that no reliable adjudication of guilt or innocence could have taken place. Commonwealth v. Turetsky, 925 A.2d 876, 880 (Pa.Super.2007). A petitioner must show (1) that the underlying claim has merit; (2) counsel had no reasonable strategic basis for his or her action or inaction; and (3) but for the errors or omissions of counsel, there is a reasonable probability that the outcome of the proceedings would have been different. Id. (citation omitted). The failure to prove any one of the three prongs results in the failure of petitioner's claim. Presently, Rivera was convicted under 18 Pa.C.S.A. § 4915(a)(1)[3] for failing to register as required under 42 Pa.C.S.A. § 9795.1, which provides as follows: § 9795.1. Registration (a) TEN-YEAR REGISTRATION. — The following individuals shall be required to register with the Pennsylvania State Police for a period of ten years: (1) Individuals convicted of any of the following offenses: . . . 18 Pa.C.S. § 3126 (relating to indecent assault) where the offense is graded as a misdemeanor of the first degree or higher. . . . 42 Pa.C.S.A. § 9795.1. Additionally, 42 Pa.C.S.A. § 9795.2 provides, in relevant part, as follows: § 9795.2. Registration procedures and applicability *1280 (a) REGISTRATION. — (1) Offenders . . . shall be required to register with the Pennsylvania State Police upon release from incarceration, upon parole from a State or county correctional institution or upon the commencement of a sentence of intermediate punishment or probation.. . . . . . 42 Pa.C.S.A. § 9795.2 (emphasis added). On appeal of the dismissal of his PCRA petition, Rivera claims that direct appellate counsel was ineffective for failing to raise a sufficiency claim. Specifically, Rivera claims that the registration provisions of Megan's Law II only apply to those convicted on or after the effective date of Megan's Law II or who were incarcerated on a Megan's Law offense on or after the law's effective date. Rivera was convicted of his Megan's Law offense on December 8, 1995 and sentenced to five years' probation. Megan's Law II became effective on July 10, 2000. Rivera was subsequently convicted of probation or parole violations in August 2000, April 2001, November 2001 and January 2003, and was finally released from custody in 2006. As Rivera was only on probation for his sex offense on the effective date of Megan's Law II, he asserts that he was not subject to registration under Megan's Law II and, as a result, could not be guilty of failing to register pursuant to 18 Pa.C.S.A. § 4915. Specifically, Rivera relies upon Section 5 of the enabling legislation for Megan's Law II, which provides as follows: Section 5. This act shall apply as follows: (1) To proceedings initiated on or after the effective date of this act. (2) The reenactment and amendment of 42 Pa.C.S. Ch. 97 Subch. H shall apply to individuals incarcerated or convicted on or after the effective date of this act. (3) This act shall not affect the requirements for individuals registered pursuant to 42 Pa.C.S. Ch. 97 Subch. H prior to the effective date of this act. Act No. 2000-18, Section 5, enacted May 10, 2000 (emphasis added). Rivera also asserts that, even though he was incarcerated subsequent to the effective date of Megan's Law II, that specific period of incarceration was not imposed for his sex crime, but rather for parole and/or probation violations on unrelated charges. Rivera argues that the term "incarcerated" as used in Megan's Law II refers to the original period of incarceration for a sex offense, not a subsequent period of incarceration resulting from a probation/parole violation and/or another crime. He claims appellate counsel's failure to raise this claim on direct appeal amounted to ineffective assistance. The Commonwealth asserts that Rivera became subject to the provisions of Megan's Law II upon its enactment because he was still serving his sex offense sentence at the time and it is irrelevant that his sentence was probationary and not custodial. A review of the record in this matter reveals that direct appellate counsel raised the identical argument on direct appeal that PCRA counsel raises instantly. Specifically, the Pa.R.A.P. 1925(b) Statement of Errors Complained of on Appeal filed by direct appellate counsel raises the following issue for review: 1. The evidence was insufficient to prove beyond a reasonable doubt that Mr. Rivera violated 18 Pa.C.S. 4915. Mr. Rivera was not subject to registration under 42 Pa.C.S. 9795.1. 42 Pa.C.S. 9795.1, which is set forth in 42 Pa.C.S. Chapter 97, Subchapter H, was enacted as part of Act 2000-18, on May 10, 2005 [sic], and became effective sixty days later, on July 9, 2005 [sic]. According to *1281 the provisions of Act 2000-18, "[t]he reenactment and amendment of 42 Pa.C.S. Ch. 97 Subch. H shall apply to individuals incarcerated or convicted on or after the effective date of this act." Act 2000-18, Section 5(2). The Commonwealth did not establish that Mr. Rivera was incarcerated or convicted on or after the effective date of Act 2000-18; therefore, it did not establish that Mr. Rivera was subject to registration under 42 Pa.C.S. 9795.1. Furthermore, even if the Commonwealth did establish that Mr. Rivera was incarcerated on or after the effective date of Act 2000-18 pursuant to a capias and bench warrant which had been issued, alleging that Mr. Rivera had committed a probation violation related to his 1995 conviction for indecent assault, Section 5(2) of Act 2000-18 refers only to persons who were still serving their original sentences of incarceration on the effective date of the act or who were convicted on or after the effective date of the act. Act 2000-18 does not apply to persons who were incarcerated for a probation or parole violation on or after the effective date of the act. Therefore, the Commonwealth did not establish that Mr. Rivera was subject to registration under 42 Pa.C.S. 9795.1, an element of the offense with which he was charged. Statement of Errors Complained of on Appeal, filed 6/26/08, at 1-2. Furthermore, the Statement of Question Presented contained in the Brief filed on Rivera's behalf by direct appellate counsel reads as follows: I. Was the evidence insufficient to prove beyond a reasonable doubt that Mr. Rivera violated 18 Pa.C.S. 4915, where Mr. Rivera was not subject to registration under 42 Pa.C.S. 9795.1? Commonwealth v. Rivera, 1015 MDA 2008, Brief for Appellant, at 4. The Argument section of direct appellate counsel's brief addresses that issue in detail. Id. at 10-19. Clearly, Rivera's instant claim of ineffectiveness must fail. Direct appellate counsel did, in fact, raise the identical issue that Rivera now claims should have been raised, i.e. that the evidence was insufficient to prove a violation of 18 Pa.C.S.A. 4915 because he was not subject to registration under 42 Pa.C.S.A. 9795.1. Thus, counsel cannot be deemed ineffective when the record reflects that she pursued the exact claim that PCRA counsel claims she should have. Nevertheless, we conclude that Rivera is entitled to relief. On direct appeal, a panel of this Court concluded that Rivera had waived his argument because it had not been specifically raised in and passed upon by the trial court. However, we believe that Rivera's issue on direct appeal is non-waivable, as it raises the legality of his sentence. While couched in terms of a sufficiency claim, Rivera's argument actually raises a fundamental question regarding the legality of his conviction and sentence: whether or not he was subject to prosecution under Megan's Law II in the first instance. Of course, a legality claim is not subject to waiver. See Commonwealth v. Edrington, 780 A.2d 721, 723 (Pa.Super.2001) (citation omitted) (illegal sentence can never be waived and may be reviewed sua sponte by court). Thus, we will proceed to address that claim on its merits. As stated above, Rivera grounds his argument on Section 5 of the enabling legislation for Megan's Law II, which provides as follows: Section 5. This act shall apply as follows: (1) To proceedings initiated on or after the effective date of this act. *1282 (2) The reenactment and amendment of 42 Pa.C.S. Ch. 97 Subch. H shall apply to individuals incarcerated or convicted on or after the effective date of this act. (3) This act shall not affect the requirements for individuals registered pursuant to 42 Pa.C.S. Ch. 97 Subch. H prior to the effective date of this act. Act No. 2000-18, Section 5, enacted May 10, 2000 (emphasis added). Rivera asserts that because he was not incarcerated for his sex offense "on or after the effective date" of the act, the Megan's Law II registration requirements do not apply to him. The trial court concluded, based on Commonwealth v. Richardson, 784 A.2d 126 (Pa.Super.2001), that Rivera was, in fact, subject to the requirements of Megan's Law II and, thus, also subject to its penal provisions. The trial court relied on Richardson for the proposition that the registration requirements of Megan's Law are applicable not only to those individuals who were incarcerated on the effective date of the statute, but also to those individuals who were subject to probationary supervision. In Richardson, the appellant had been sentenced to an aggregate of 4 to 10 years' imprisonment on convictions of Involuntary Deviate Sexual Intercourse ("IDSI") and Rape in 1982; he was paroled in March 1986. Thereafter, in June 1987, he was convicted of involuntary manslaughter; as a result, Richardson was recommitted as a convicted parole violator and was given a new maximum date of sentence on his IDSI/rape conviction of July 15, 1993. More than two years later, on October 24, 1995, Megan's Law I was enacted, requiring certain offenders (including those sentenced for IDSI and rape) to register for a period of ten years pursuant to 42 Pa. C.S.A. § 9793,[4] which provided as follows: § 9793. Registration of certain offenders for ten years (a) Registration. — A person convicted of any of the offenses set forth in subsection (b) shall be required to register a current address with the Pennsylvania State Police upon release from incarceration, upon parole from a State or county correctional institution, upon the commencement of a sentence of intermediate punishment or probation or where the offender is under the supervision of the Pennsylvania Board of Probation and Parole at he time of enactment of this section . . . 42 Pa.C.S.A. § 9793(a). At the time Section 9793 became effective, Richardson was imprisoned, although not for any reason related to his sex offense convictions, as his sentence had fully "maxed out" by that time. Nevertheless, upon his release, the Commonwealth advised Richardson of his duty to register pursuant to Megan's Law and Richardson signed an acknowledgement of that requirement. He subsequently failed to report his address and was charged with failure to make the required notification of address change to law enforcement. Richardson filed a pretrial motion contesting the applicability of Section 9793 to him, which the trial court granted on the basis that Richardson's sex offense sentences had been fully served approximately three years prior to the statute's effective date. The Commonwealth appealed, arguing that Section 9793 was applicable "as long as the defendant was incarcerated at the time Megan's Law went into effect, irrespective of the underlying offense, and he had a prior record in which a Megan's Law offense was committed." Richardson, 784 A.2d at 128-29 (emphasis added). *1283 In affirming the trial court's decision, this Court stated that "[t]here is little doubt that the Legislature clearly wants persons convicted of certain sexually violent offenses to register their addresses with the police upon completion of their confinement or probation. However, the underlying statute does not clearly state whether persons who were convicted in the past and who fully served their sentence for those convictions before the statute's enactment must register. Accordingly, we do not find that the trial court erred in dismissing the Commonwealth's case." Id. (emphasis added). We find the trial court's reliance upon Richardson is misplaced. Preliminarily, we note that the passage relied upon by the trial court, that "the Legislature clearly wants persons convicted of certain sexually violent offenses to register their addresses upon completion of confinement or probation," is mere dicta, as Richardson was not a probationer at any period relevant to the Court's determination. As such, the quoted language is not binding on us here. Moreover, Richardson was decided under Megan's Law I, not Megan's Law II — the relevant statute in this case. Examining that law's enabling legislation, which sets forth the applicability of the act, we note: Section 3. The provisions of this act shall be applicable as follows: (1) All offenders convicted of an offense set forth in 42 Pa.C.S. Section 9793(b) before the effective date of this section, who remain under the jurisdiction of the Pennsylvania Board of Probation and Parole or the Department of Corrections, shall be subject to the provisions of this act, with the exception of 42 Pa.C.S. Sections 9794, 9795(A), 9796(A), 9797, 9798 AND 9799.4, which relate to sexually violent predators. (2) All offenders convicted of an offense set forth in 42 Pa.C.S. Section 9793(b) committed on or after the effective date of this section shall be subject to all provisions of this act. Act No. 1995-24, Section 3, enacted October 24, 1995 (emphasis added). Notably, in the language quoted above, the legislature clearly expressed its intent that Megan's Law I provisions apply to all offenders who had previously been convicted of an offense set forth in Section 9793 and were either imprisoned or subject to probation or parole on the effective date of the act. Thus, it was reasonable for the Richardson court to conclude that probationers were required to register. Conversely, however, in Section 5 of the enabling legislation to Megan's Law II, the legislature provided that the law would be applicable only to those offenders "incarcerated or convicted" on or after the effective date of the law. The absence of any reference to "probationers" by the legislature renders Richardson inapposite. Further, based on the language of the Megan's Law I enabling legislation, there can be no question that the legislature knew how to make the law applicable to probationers if it saw fit to do so. It did not do so with Megan's Law II. Thus, we must conclude that, in making Megan's Law II applicable only "to individuals incarcerated or convicted on or after the effective date," the legislature did not intend for its provisions to apply to those serving a probationary term. See Commonwealth v. Cotto, 708 A.2d 806, 811 (Pa.Super.1998) (noting that change in language of statute generally indicates change in legislature's intent) (citation omitted); St. Elizabeth's Child Care Ctr. v. Department of Public Welfare, 600 Pa. 131, 963 A.2d 1274, 1276 (2009) (citation omitted) (when words of statute are clear and free from all ambiguity, they are presumed to be best indication of legislative intent). *1284 Additional evidence of the legislature's intent in this regard can be found in Section 9795.2 of Megan's Law II, which sets forth the applicability of the law's registration provisions and provides, in relevant part, as follows: (a) REGISTRATION. — (1) Offenders . . . shall be required to register with the Pennsylvania State Police upon release from incarceration, upon parole from a State or county correctional institution or upon the commencement of a sentence of intermediate punishment or probation. . . . 42 Pa.C.S.A. § 9795.2(a)(1) (emphasis added). As the wording of the statute indicates, the legislature clearly intended that offenders be required to register at the commencement of their probation and not at some point in the middle of their term. See Barasch v. Pennsylvania Public Utility Comm., 516 Pa. 142, 532 A.2d 325, 332 (1987) ("It is well settled that the legislature cannot be deemed to intend that its language be superfluous and without import"). Rivera's sentence "commenced" approximately 4½ years prior to the law's effective date. Indeed, at the time Megan's Law II went into effect, Rivera's probationary sentence was nearly complete. Thus, Rivera could not possibly have registered at the "commencement" of his probationary term, as Megan's Law II was not in effect at that time. Finally, we must determine whether the term "incarceration" as used in the statute was intended by the legislature to refer only to the original period of incarceration imposed on a sex offense, or whether it could also refer to a period of incarceration imposed pursuant to a probation violation on that sex offense. As this Court stated in Richardson: It is a cardinal rule of statutory construction that if the words of a statute are clear and free from ambiguity, the letter of it is not to be disregarded under the pretext of pursuing its spirit. When the words of a statute are clear and unambiguous, their plain meaning and common usage are to be applied. If the statutory language is unclear, only then may the legislative intent be considered. Furthermore, [i]t is axiomatic that, under the rule of lenity, penal statutes must be strictly construed, with ambiguities being resolved in favor of the accused. Richardson, 784 A.2d at 131 (citations and quotations omitted). After careful review of the statutory language at issue, we conclude that the meaning of the word "incarceration" is ambiguous and that we must, therefore, seek to ascertain the legislature's intent through statutory construction. Section 9791 of Megan's Law II sets forth the legislature's findings and declaration of policy. Specifically, subsection (b) reads as follows: It is hereby declared to be the intention of the General Assembly to protect the safety and general welfare of the people of this Commonwealth by providing for registration and community notification regarding sexually violent predators who are about to be released from custody and will live in or near their neighborhood. 42 Pa.C.S.A. § 9791(b) (emphasis added). This language appears to suggest that the registration provisions are intended to apply to an offender only upon release from a term of imprisonment served as a direct result of a Megan's Law offense. Indeed, to interpret the statute otherwise could lead to an absurd result, whereby a person convicted of a sex offense in 1985 could be re-committed for a burglary twenty years later and, upon release from that sentence, be required to register as a sexual offender pursuant to a law that did not take effect until after his original sex offense *1285 sentence had been fully served. See Richardson, supra. Applying the rule of lenity to our reading of the language, we can arrive at no other conclusion than that the term "imprisonment" was intended by the legislature to apply only to the original term of confinement served pursuant to a conviction for a Megan's Law sex offense. Thus, the term does not apply to Rivera, as his imprisonment resulted from a probation violation on an unrelated offense. For the reasons stated herein, we are compelled to conclude that the provisions of Megan's Law II, specifically 42 Pa. C.S.A. 9795.1 and 18 Pa.C.S.A. 4915, are inapplicable to Rivera and, accordingly, his judgment of sentence must be reversed. Order reversed; judgment of sentence vacated; appellant discharged. Jurisdiction relinquished. NOTES [1] 18 Pa.C.S.A. § 3126(a)(7), a first-degree misdemeanor pursuant to 18 Pa.C.S.A. § 3126(b)(3). [2] From the information available to us, it is unclear why Rivera remained incarcerated for the 3½ month time period between his arrest pursuant to the capias and his violation hearing on August 31, 2000. [3] Section 4915 provides as follows: (a) Offense defined. — An individual who is subject to registration under 42 Pa.C.S.A. § 9795(a) (relating to registration) or an individual who is subject to registration under 42 Pa.C.S.A. § 9795.1(b)(1), (2) or (3) commits an offense if he knowingly fails to: (1) register with the Pennsylvania State Police as required under 42 Pa.C.S.A. § 9795.2 (relating to registration procedures and applicability); 18 Pa.C.S.A. § 4915. [4] Section 9793 was repealed effective July 9, 2000 and subsequently amended effective February 18, 2001 as 42 Pa.C.S.A. § 9795.1.

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In vivo characterisation of parathyroid lesions by use of gamma probe: comparison with ex vivo count method and frozen section results. In this study we hypothesized that if timing of gamma probe-guided parathyroidectomy were individualized according to an optimal-time-to-surgery technique, in vivo characterization of parathyroid lesions would be possible. We compared our findings with an ex vivo counting method ("20% rule") and frozen section results. Thirty-five patients who were referred for surgical treatment of hyperparathyroidism were studied. Maximum parathyroid to thyroid sestamibi uptake ratio (UR(max)) was measured by use of preoperative dynamic scintigraphy. The interval between sestamibi injection and UR(max) was defined as the optimal time to surgery. On the day of surgery, the patients received the same dose of sestamibi and were taken to the operating room at UR(max) as determined by preoperative scintigraphy. Intraoperative in vivo gamma probe counts from parathyroid lesions were compared with in vivo contralateral background thyroid counts (in vivo/Bkg) and to ex vivo parathyroid counts relative to postexcision background of the adjacent normal tissue (ex vivo/Bkg). A total of 70 excised lesions were evaluated. In vivo/Bkg counts obtained from parathyroid adenoma were significantly different from parathyroid hyperplasia (z = -3.093, P = 0.002) and other lesions (z = -3.958, P = 0.0001). By receiver operating characteristic curve (ROC) analysis, we found the cutoff value for the in vivo/Bkg counts ratio to be 103% to differentiate parathyroid adenoma from hyperplasia with a sensitivity, specificity, and accuracy of 82.5, 65, and 74.4%, respectively. On the other hand, sensitivity, specificity, and accuracy of the ex vivo/Bkg method to differentiate parathyroid adenoma from hyperplasia with a cutoff value of 34.7 was found to be 70.8%, 60%, and 65.9%, respectively. The difference between the accuracy of these 2 tests was not significant statistically (P = 0.137). Sensitivity of frozen section to differentiate parathyroid adenoma and hyperplasia was 76.2% and 33.3%, respectively. Patient-specific optimal protocol for timing of sestamibi injection together with in vivo/Bkg method is a useful alternative method in guiding the surgeon to differentiate parathyroid adenoma from parathyroid hyperplasia and other tissues and may help surgeons' decisions during the operation. Combined use of in vivo/Bkg and ex vivo/Bkg methods may give more accurate results than frozen section.

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General intelligence and cognitive profile in women with congenital adrenal hyperplasia (CAH). To investigate possible effects of prenatal androgen exposure on cognitive functions, general intelligence and cognitive profile were studied in 22 women, 17-34 years old, with prenatal virilization due to congenital adrenal hyperplasia (CAH) (21-hydroxylase deficiency) and 22 healthy controls matched for region and date of birth. The tests were selected to measure abilities where gender differences repeatedly had been observed or that had earlier shown differences between CAH subjects and controls. The following cognitive functions were tested: Verbal, Visuo-Spatial, Visuo-Motor, Arithmetical, Logical Inductive abilities, and Field Dependence. Contrary to earlier reports, the mean general intelligence level of the CAH (22) group was significantly lower than the controls' and the earlier observed inferiority for calculation abilities in female CAH subjects was not supported by the results of the present study. A possible verbal disadvantage with significantly inferior results was noted for the two verbal tests for the CAH (22) group. For the 13 CAH/control pairs with equal general intelligence levels, the discrepancy between the inferior verbal vs. visual, arithmetic, and logical category scores was significantly larger for the CAH group than the controls. These results may suggest that CAH women develop a more masculine cognitive pattern under the influence of increased prenatal androgen exposure.

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.TH "OPENSHIFT ADMIN" "1" " Openshift CLI User Manuals" "Openshift" "June 2016" "" .SH NAME .PP openshift admin new\-project \- Create a new project .SH SYNOPSIS .PP \fBopenshift admin new\-project\fP [OPTIONS] .SH DESCRIPTION .PP Create a new project .PP Use this command to create a project. You may optionally specify metadata about the project, an admin user (and role, if you want to use a non\-default admin role), and a node selector to restrict which nodes pods in this project can be scheduled to. .SH OPTIONS .PP \fB\-\-admin\fP="" Project admin username .PP \fB\-\-admin\-role\fP="admin" Project admin role name in the cluster policy .PP \fB\-\-description\fP="" Project description .PP \fB\-\-display\-name\fP="" Project display name .PP \fB\-\-node\-selector\fP="" Restrict pods onto nodes matching given label selector. Format: '<key1>=<value1>, <key2>=<value2>...'. Specifying "" means any node, not default. If unspecified, cluster default node selector will be used. .SH OPTIONS INHERITED FROM PARENT COMMANDS .PP \fB\-\-api\-version\fP="" DEPRECATED: The API version to use when talking to the server .PP \fB\-\-as\fP="" Username to impersonate for the operation. .PP \fB\-\-certificate\-authority\fP="" Path to a cert. file for the certificate authority. .PP \fB\-\-client\-certificate\fP="" Path to a client certificate file for TLS. .PP \fB\-\-client\-key\fP="" Path to a client key file for TLS. .PP \fB\-\-cluster\fP="" The name of the kubeconfig cluster to use .PP \fB\-\-config\fP="" Path to the config file to use for CLI requests. .PP \fB\-\-context\fP="" The name of the kubeconfig context to use .PP \fB\-\-google\-json\-key\fP="" The Google Cloud Platform Service Account JSON Key to use for authentication. .PP \fB\-\-insecure\-skip\-tls\-verify\fP=false If true, the server's certificate will not be checked for validity. This will make your HTTPS connections insecure. .PP \fB\-\-log\-flush\-frequency\fP=0 Maximum number of seconds between log flushes .PP \fB\-\-match\-server\-version\fP=false Require server version to match client version .PP \fB\-n\fP, \fB\-\-namespace\fP="" If present, the namespace scope for this CLI request. .PP \fB\-\-server\fP="" The address and port of the Kubernetes API server .PP \fB\-\-token\fP="" Bearer token for authentication to the API server. .PP \fB\-\-user\fP="" The name of the kubeconfig user to use .SH SEE ALSO .PP \fBopenshift\-admin(1)\fP, .SH HISTORY .PP June 2016, Ported from the Kubernetes man\-doc generator

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Monday, April 30, 2001 This article does a very good job of summarizing the current outrages of the Recording Industry Association of America. The interesting question is whether Professor Felten, knowing that the gist of his research was publically available anyway, sucked the RIAA in by rapidly giving in to their threats and agreeing to censor his scientific research. Certainly the RIAA's panicky response indicates that the leaders of the RIAA are afraid they've been well and truly snookered. Is it possible that the extreme measures now being taken to hurry through various 'free-trade' agreements reflect a realization by the big thinkers of the powers that be that capitalism is finally headed for some kind of apocalyptic 'crisis' (a la Marx) and that the only way to stall this is to turn everything in the world into a commodity? It is probably a sad truth that violence is required to lead to real social change. Why would that be? By definition, progressive social change interferes with the existing power structure. Those on top of the heap will use any means at hand to preserve the status quo. As we recently saw in Quebec, that includes all the violence that is controlled by the state. In the modern world, with information controlled by the major media (owned by the powers that be with a strong bias to the status quo), the only way to get the message out is to create a spectacle, and the only spectacle which can entice the media is to put yourself in a position to be subject to violence at the hands of the police. The police are sophisticated enough to behave themselves whan confronted by non-violent protest, and therefore non-violent protest is ignored by the media. The reporting habits of the major media have made violence necessary. The process of sneaking genetically modified foods into human food continues. Aventis, having 'inadvertently' mixed some of its StarLink corn (approved only for animal food) with corn for human consumption and therefore contaminating the human food supply, now wants relaxation of restrictions on the StarLink corn. What are the chances that the Bush administration will turn down a big corporation? Why should Aventis receive a benefit for its wrongdoing? The only just solution would be to wind up Aventis and use its assets to partially pay for the damage it has caused. Instead, it will almost certainly be allowed to use its 'inadvertence' to futher its long term plan to have us all eating frankenfood. Saturday, April 21, 2001 The most useful part of the Quebec City fandango is that the big fence, tear gas plumes, balaclava-clad protesters, and, best of all, robocop police with swell riot gear, make Canada look like a genuine third-world dictatorship. It is good to keep this in mind when we get full of ourselves about how 'democratic' we are. The other irony of the violence is that the mainstream, NGO-associated protesters will disclaim any connection to the violence, 'nothing to do with us', blah, blah, blah, all the while realizing that without the violence the protests would be ignored by the press and the process of taking over that small sliver of power not yet held by big corporations would continue unabated. If nothing else, the riots serve as a reminder first, of the violence inherent in the state (even one as innocuous as Canada) in aid of money power, and second, of the fact there are still powers other than those wielded by the ruling class. The irony of the riots is that, up to a point, they play into the hands of the ruling class, who can tar all the protesters with the same brush, and thus don't have to go through the tiresome and dangerous process of debating anyone. The problem that the ruling class has is that they have to hire bureaucrats to do their dirty work, and bureaucrats the world over are easily manipulated by threats of inconvenience (their favorite saying is "they don't pay me enough for this"). A little tear gas wafts through the lobby of the luxury hotel, and the bureaucrats suddenly want to get the next first-class flight home, leaving the process of 'negotiating' trade agreements for another resort hotel and another time. This pusillanimity must really steam the rulers of the world. You just can't get good help these days! Sunday, April 15, 2001 I've been reading lots of American nonsense about how the Chinese 'lost' in their recent confrontation with the United States over the spy plane. Somehow the great genius Bush is supposed to have tricked the Chinese by giving what they thought was an apology when it actually was no apology at all. Thus American amour-propre has been saved. This analysis completely misses the point. The Chinese now know that the addled Bush is completely hamstrung in a crisis situation, as he doesn't know how to choose between the advice given to him by his extreme right-wing advisors and the advice given to him by his rabidly insane right-wing advisors. They also know that Americans are still mesmerized by the concept of American hostages. Therefore, all the Chinese have to do to deter future spy planes is merely give the impression that they could bring another one down. All they have to do to get their way with the Bush administration in the future is to put Bush under some pressure where he has to make a decision in a hurry. On top of that they have a nice spy plane to look at. Sunday, April 08, 2001 There are still many unanswered questions about the U. S. spy plane currently in China. Why did it land on Chinese territory instead of in the sea? Why was apparently such a bad job done of destroying secret equipment on board? Was this whole enterprise a method of turning over American military secrets to the Chinese? If so, was this part of the Bush regime's attempt to reignite the Cold War by making China with U. S. secrets a more credible enemy? Will we see a connection made to this incident when new arms sales are made to Taiwan? Tuesday, April 03, 2001 Francis Gary Powers and his U2 were downed in the Soviet Union in May 1960, thus conveniently (for those who make money from war) ending arms reduction negotiations between the United States and the Soviet Union (Khrushchev angrily cancelled Eisenhower's planned trip to Moscow and the Paris Summit Conference was adjourned). Now a U. S. spy plane has apparently been forced to land in China at a time when the current President is clearly making every effort to damage relations with China with a view to reigniting the Cold War. This will allow him to claim that he needs to have a big increase in military spending, thus putting lots of money in the pockets of his friends in the military-industrial complex. It's ironic that Pa George has been lauded for his role in ending the Cold War, while Son George may go down in history as having started it up again!

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