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A steam train puffing its way through regional New South Wales is delighting young and old and being used to educate schoolchildren about Australia's rail heritage and its role in their own history.
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Children from two small schools in central west New South Wales jiggle up and down excitedly as local amateur photographers set up their tripods and they all wait for the 3642 to arrive.
Their anticipation reaches fever pitch as the engine puffs into tiny Stuart Town station amid a cloud of snow white steam and lets out an ear-splitting toot.
Their teachers remind the children to stay behind the yellow line and remember the train safety lesson they did in their class earlier in the week.
Operations Manager for Transport Heritage New South Wales, Daniel Page, says they have good reason to be excited by the train which is a coal-fired 36 Class express passenger steam locomotive.
"It was built in 1926 and in its heyday it really was the fastest and grandest locomotive on the rail."
He explains that the 3642 was used to haul freight and express trains between Sydney and Newcastle and other regional destinations and at one point was based in the central west city of Bathurst.
The train is operated by Transport Heritage New South Wales, a not-for-profit company, which was established in 2013 with state government funding.
Based at Sydney's Eveleigh Railway yards, its role is to look after the state's transport heritage including rolling stock, artefacts and rail buildings.
"Today's a special day for our collection because we're taking our museum out on the tracks into central west New South Wales," explains Mr Page.
Some of the group's funding comes through running tourist trips, but another component of its operations is education.
School groups are allowed to take rides on the train and experience the rattle and hiss of a restored steam train, complete with first and second class carriages.
This is integral to its plan of teaching young Australians about the role the railways played in the nation's development, particularly in country areas.
"We're on Stuart Town station today and it's not quite the station it was in its heyday but really without the railways a lot of these towns wouldn't have existed," said Mr Page.
"Just about everything that needed to be transported in the early 20th century was brought by train.
"From mail to cattle and other livestock, timber and supplies for construction sites, even the railwaymen's pay was moved by rail; before electronic banking we were transporting cash."
Transport Heritage provides a series of online lesson plans and has interactive activities to get children and teachers interested in trains, particularly steam engines.
On this leg of a two week tour of central New South Wales tour, 33 students from two tiny country schools, Mumbil Public and Stuart Town Public have boarded the train for an hour long ride.
"It's a great way for the kids to interact with other small schools for a starter but also see how the train system connects this whole area together," said Michael Sturman a teacher at Mumbil Public School.
"A lot of them haven't been on too many trains in their life."
"Growing up in the bush, I actually grew up in this area, you're used to having to travel long distances and the railway's a big part of that."
"So it is important that the children learn the history of the rails."
For Andrew, 11, this was his first steam train trip but it's made a big impression.
"Sort of fast, very loud and don't stand right in front of it because if you didn't block your ears you'd almost burst an eardrum," he said.
Andrew says at school earlier Mr Sturman gave them a lesson on how steam engines work and he recites it clearly and concisely.
"The boiler room that makes fire it boils up water that makes steam turn some pistons."
"That was my original theory actually," Andrew said.
It's clear Daniel Page and the other volunteers with Transport Heritage get a lot of joy out of seeing the children's excitement on the 3642.
But more than that, they hope it will have a long term legacy and perhaps sow the seeds for the next generation of rail buffs.
Transport Heritage New South Wales's Great Western Tour is on 13-23 August running from Westmead in Sydney to as far out as Nyngan.


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Addison Lee is trying to shake off its image as a London-focused taxi service and re-establish itself as a ride-hailing app that works around the world. Today, the company announced a "digital global service" that anyone can use to book minicabs in over 100 cities worldwide. In some locations, that will mean Addison-owned vehicles, but in others your trip will be handled by one of its 5,000 affiliate partners. Addison Lee, in short, wants to be the app that lives on your home screen — a reliable and convenient alternative to Uber, Lyft and similar taxi hire services.
Addison Lee's private minicab app goes global
Sponsored Links
It's a long-awaited expansion. Addison Lee bought executive car service Tristar in June 2016, boosting its affiliate network in the US and abroad. Seven months later, it acquired Flyte Tyme, a US car service business that offers airport transfers, event transportation, shuttle services and black car operations. It then snapped up Tandem, a booking and fleet management specialist, and revealed plans to launch a branded car service in New York. (Vehicles started rolling out in Manhattan late last year.) Addison's focus, clearly, is in North America and the UK — but with an affiliate network, it can scale up (or down) its business and dabble with a global user base.
As part of today's announcement, Addison Lee has committed £65 million ($90 million) to boosting its minicab fleet in London and the Big Apple. In the English capital, the company will introduce 1,300 Ford Galaxy people carriers, over 500 Mercedes vehicles, 30 Vauxhal Vivaro vans and 15 500cc Honda motorcycles. In New York, the expansion will include 350 Chrysler 300s, 150 Lincoln Continentals, 10 Cadillac Escalades, 10 Chevrolet Suburbans and 6 Grech Ford F-550 minibuses. It's a sizeable investment, but one that could prove meaningless if the app doesn't take off.

subset: commoncrawl


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My Bebe
Collection by Anna Meade
8 Keepsake Crafts That Honor the Memory of Loved Ones
They may be gone, but they're never forgotten.
Collar Keepsake - A Photo Frame for Your Pet's Collar.
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Distributive Education Clubs of America (DECA)
The mission of DECA is to enhance the co-curricular education of students with interest in marketing, management and entrepreneurship. This organization helps students develop skills and competence for marketing careers, build self-esteem, experience leadership and practice community service.
DECA is committed to the advocacy of marketing education and the growth of business and education partnerships. DECA, a national association of marketing education students, provides members with educational and leadership development activities to merge with the education classroom instructional program.
DECA utilizes on-the-job experience, chapter projects, and program of competitive events in specific marketing occupational areas. These events emphasize academic excellence as building blocks for successful marketing and management careers, demonstrating the direct relationship between marketing education and the real needs of business industry. Each year more than 110,000 students participate in the competitions on the local, state and international levels.
Students enrolled in Marketing I and II are given the opportunity to become a member of Parkway Central's well respected DECA club. The Parkway Central Marketing Program and DECA organization involves nearly 200 students and is sponsored by Susan Hoffman and Cara Weiss. As a member of DECA, students will acquire knowledge and skills that will enable them to compete against other schools in the spring during DECA competition. They may compete in DECA competition at the local, state and international level. This year, state competition will be held at the Lodge of the Four Seasons in Lake of the Ozarks. National DECA is held in various cities, including Orlando, Florida; San Francisco or Anaheim, California; Denver, Colorado; and Nashville, Tennessee.
Sponsor: Mrs. Lueken


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Permeable resin driveways come with a lot of advantages, and everyone who chooses this solution falls in love, especially with the aesthetic point of the whole idea.
As we've already said, resin surfaces can become an eye candy, and it can stand out a lot in your area compared to other surfaces that you can find on the market.
The fact that this surface is also porous is catchy because a lot of people have grown sick and tired of puddles and flooding in both commercial and residential areas as well.
Anyway, only after deciding that they want a resin driveway people to start wondering about the installation process and what exactly it involves.
It's essential to set things straight before you grab the final deal, just so that you will know what exactly to expect.
So, here are the most frequently asked questions regarding the installation process of a resin driveway.
FAQ before installation
Do I require planning permission to alter my driveway or to install a brand new one?
Fortunately, the answer to this question is that in most cases, you will not need any kind of permission in order to be able to install a permeable resin driveway.
On the other hand, it's important to know that different councils have different rules and it's best to contact yours in order to find out for sure.
Does a resin bound surface comply with SuDS regulations?
We've already said various times that it does, but we cannot highlight this enough.
It's important to choose a company which offers resin surfacing that's SuDS (sustainable drainage system) compliant in order to be able to enjoy all the benefits that come from this. Such a surface allows water to go back into the ground and it will prevent flooding.
What features should I look for in a resin bound surface?
You will have to make sure that the resin surface that you're choosing prevents stone migration, cracking, color change, UV degradation and that the team you're choosing to work with will offer great workmanship.
Don't forget the importance of your pre-installed base.


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Granulocyte macrophage colony-stimulating factor (GMCSF) can mediate antitumor effects by recruiting natural killer cells and by induction of tumor-specific cytotoxic T-cells through antigen-presenting cells. Oncolytic tumor cell–killing can produce a potent costimulatory danger signal and release of tumor epitopes for antigen-presenting cell sampling. Therefore, an oncolytic adenovirus coding for GMCSF was engineered and shown to induce tumor-specific immunity in an immunocompetent syngeneic hamster model. Subsequently, 20 patients with advanced solid tumors refractory to standard therapies were treated with Ad5-D24-GMCSF. Of the 16 radiologically evaluable patients, 2 had complete responses, 1 had a minor response, and 5 had disease stabilization. Responses were frequently seen in injected and noninjected tumors. Treatment was well tolerated and resulted in the induction of both tumor-specific and virus-specific immunity as measured by ELISPOT and pentamer analysis. This is the first time that oncolytic virus–mediated antitumor immunity has been shown in humans. Ad5-D24-GMCSF is promising for further clinical testing. Cancer Res; 70(11); 4297–309. ©2010 AACR.
New approaches are needed for the treatment of metastatic solid tumors. One strategy is oncolytic viruses, which selectively replicate in and kill tumor cells (1–3). Replication leads to effective local amplification and the virus could also enter the bloodstream for transduction of the same tumor or metastases.
Oncolytic replication is an immunogenic phenomenon, and recent preclinical and clinical evidence suggests that antitumor efficacy is partially mediated by the immune response (4, 5). Adenoviruses are among the most advanced cancer gene therapy platforms and their safety and efficacy has been validated in several randomized studies (6–9). With regard to oncolytic adenoviruses, a few dozen trials have been performed and although there is anecdotal evidence of activity in most trials, overall single-agent efficacy has been nonimpressive. This is partially due to the attenuated nature of the few agents tested thus far. However, even such early generation viruses seem quite effective when combined with standard therapy (10). In the only randomized study performed thus far, combining oncolytic adenovirus to chemotherapy doubled the response rate (8).
Adenoviruses are quite immunogenic (11), and recent preclinical data suggests that this might be a key aspect of their antitumor activity (4). In part because of the lack of suitable animal models, the combination of oncolytic adenoviruses and immunotherapy has not been explored in detail. However, it is known that the replication-deficient adenovirus is a useful vaccination agent due to its unparalleled capacity for gene delivery, high titer production, and immunogenicity (12). Nevertheless, because the antitumor immune response induced by adenovirus replication per se is usually not sufficient for clinical responses, arming oncolytic viruses with immunostimulatory molecules is attractive.
Although regularly present at tumors, the frequency and activity of CD8+ T cells is often too low to mount an effective response. This might be caused partly by the immunosuppressive environment of tumors (13). However, preclinical data suggests that by increasing costimulatory "danger" signals, immunosuppressive mechanisms could be overridden (4, 13, 14). Oncolytic replication provides strong danger signals and lysis of tumor cells releases tumor-associated antigens for sampling (15). Nevertheless, this may be insufficient in the absence of specific activation of antigen-presenting cells (13).
Granulocyte macrophage colony-stimulating factor (GMCSF) is among the most potent inducers of antitumor immunity (16). It acts through several mechanisms, including direct recruitment of natural killer cells and antigen-presenting cells such as dendritic cells (17, 18). GMCSF could also specifically activate dendritic cells at the tumor site to increase their expression of costimulatory molecules to enhance cross-priming and T-cell activation rather than cross-tolerance. Although these effects are well studied in preclinical systems, and there is emerging data from cancer vaccine trials, the immunologic aspects of oncolytic viruses in cancer patients are not well understood. For example, given the dogma of tumor immunosuppression, it is unknown if oncolytic viruses could induce virus- or tumor-specific T-cell responses.
Here, we generated an oncolytic adenovirus armed with GMCSF. Following preclinical testing, 20 patients with advanced and treatment-refractory solid tumors were treated. This is the first time that antitumoral immunity has been shown to result from oncolytic virus treatment of human cancer patients.
Materials and Methods
Ad5-D24-GMCSF was generated and amplified using standard adenovirus preparation techniques (19). Briefly, human GMCSF (Invitrogen) was amplified with specific primers featuring insertion of specific restriction sites SunI/MunI. GMCSF was then subcloned into pTHSN and subsequently recombined with an Ad5 rescue plasmid to generate pAd5-D24-GMCSF. This plasmid was linearized with PacI and transfected into A549 cells for amplification and rescue.
All phases of the cloning were confirmed with PCR and multiple restriction digestions. The shuttle plasmid pTHSN-GMCSF was sequenced. The absence of wild-type E1 was confirmed with PCR. The E1 region, transgene, and fiber were checked in the final virus with sequencing and PCR. To this end, viral DNA was extracted and PCR and sequencing was performed to analyze the integrity of the fiber and GMCSF cDNA. All phases of the virus production were done on A549 cells to avoid risk of wild-type recombination. GMCSF is under the E3 promoter, which results in replication-associated transgene expression starting ∼8 hours after infection. E3 is intact except for deletion of 6.7K/gp19K.
The biodistribution of adenovirus is determined by the capsid and Ad5-based viruses have been studied extensively previously (20). Toxicity studies with oncolytic Ad5-based adenoviruses have been performed previously in mice, hamsters, and cotton rats (20). Ad5-D24-E3 and Ad5Luc1 have been published previously (19).
Cell lines
Hamster pancreatic carcinoma–derived cell line HaP-T1 was kindly provided by Dr. Ruben Hernandez-Alcoceba (Pamplona, Spain). The kidney hamster–derived cell line HaK was courtesy of Prof. William S.M. Wold (St. Louis, MO). These cell lines were maintained in 10% DMEM with 1% pen/strep and 1% l-glutamine. Human transformed embryonal kidney cell line 293 was purchased from Microbix, and human lung adenocarcinoma cell line A549 and TF1 were from the American Type Culture Collection.
All animal protocols were reviewed and approved by the Experimental Animal Committee of the University of Helsinki and the Provincial Government of Southern Finland. Syrian hamsters (Mesocricetus auratus) were obtained from Taconic at 4 to 5 weeks of age and quarantined for at least 1 week prior to the study. Nude mice were purchased from Taconic. The health status of the animals was frequently monitored and as soon as any sign of pain or distress was evident, they were killed.
Nineteen patients with advanced metastatic tumors refractory to conventional therapies were treated with a single round of Ad5-D24-GMCSF (Table 1). Inclusion criteria were solid tumors refractory to conventional therapies, WHO performance score 3 or less, and no major organ function deficiencies. Exclusion criteria were organ transplant, HIV, severe cardiovascular, and metabolic or pulmonary disease (e.g., symptomatic coronary heart disease, uncontrolled blood pressure). Written informed consent was obtained and the study was completed according to Good Clinical Practice guidelines and the Declaration of Helsinki. This compassionate use scheme was evaluated by the Medicolegal Department of the Finnish Ministry of Social Affairs and Health and the Gene Technology Board.
Treatment protocol
Patients received a single round of treatment with Ad5-D24-GMCSF on day 0. Virus administration was performed by ultrasound-guided intratumoral or intracavitary (ovarian cancer, mesothelioma) injection, and one fifth of the dose was given i.v. The starting dose of 8 × 109 viral particles (VP) was chosen based on safety results published by others (1, 5–9, 21). Subsequently, the dose was escalated to 1 × 1010, 3.6 × 1010, 1 × 1011, 2 × 1011, 2.5 × 1011, 3 × 1011, and 4 × 1011 (Table 2). Patients were monitored for 24 hours in the hospital and for the following 4 weeks as outpatients. Follow-up for survival was performed for a maximum of 18 months. Physical assessment and medical history were done at each visit. Side effects were recorded according to CTCEA 3.0. Because many cancer patients have symptoms due to disease, preexisting symptoms were not scored if they did not become worse. However, if the symptom became more severe, e.g., pretreatment grade 1 changed to grade 2 after treatment, it was scored as grade 2.
Tumor size was assessed by contrast-enhanced computer tomography scanning typically performed at 6 weeks. Maximum tumor diameters were obtained and in some liver metastatic cases, Hounsfield units (density estimate) could also be counted (22). Response Evaluation Criteria in Solid Tumors (RECIST) were applied to overall disease, including injected and noninjected lesions. These criteria include complete response, partial response (>30% reduction in the sum of tumor diameters), stable disease (i.e., no response/progression), and progressive disease (>20% increase; refs. 23, 24). Serum tumor markers were also evaluated when elevated at baseline. The same percentages were used except that 12% to 29% reductions are indicated as minor responses.
A panel of three different proinflammatory cytokines (interleukin-6, interleukin-8, and tumor necrosis factor-α) were analyzed by BD Cytometric Bead Array Human Soluble Protein Flex Set (Becton Dickinson) according to the instructions of the manufacturer. In addition, subjective symptoms were collected by the treating physicians. For all patients, serum levels of GMCSF were also measured.
Neutralizing antibody titer
293 cells were seeded at 1 × 104 cells/well on 96-well plates and cultured overnight. Next day, cells were washed with DMEM without FCS. Serum samples were incubated at 56°C for 90 minutes to inactivate complement, and a 4-fold dilution series (1:1 to 1:16,384) was prepared in serum-free DMEM. Ad5luc1 (20) was mixed with serum dilutions and incubated at room temperature for 30 minutes. Thereafter, cells in triplicates were infected with 100 VP/cell in 50 μL of mix, and 100 μL of growth medium with 10% FCS was added 1 hour later. Twenty-four hours postinfection, cells were lysed and luciferase activity was measured with Luciferase Assay System (Promega) using TopCount luminometer (Perkin-Elmer). To evaluate the effect of neutralizing antibodies in the serum of patients treated with Ad5-D24-GMCSF, luciferase readings were plotted relative to gene transfer achieved with Ad5luc1 alone. The neutralizing antibody titer was determined as the lowest degree of dilution that blocked gene transfer by >80%.
Determination of virus in serum samples
Total DNA was extracted by adding 3 μg of carrier DNA (polydeoxyadenylic acid; Roche) to 400 μL of serum and using the QIAamp DNA mini kit. Extracted DNA was eluted in 60 μL of nuclease-free water and DNA concentration was measured by spectrophotometry. PCR amplification was based on primers and probe targeting the E1A region flanking the 24 bp deletion (forward primer, 5′-TCCGGTTTCTATGCCAAACCT-3′; reverse primer, 5′-TCCTCCGGTGATAATGACAAGA-3′; and probe onco 5′FAM-TGATCGATCCACCCAGTGA-3′MGBNFQ). In addition, a probe complementary to a sequence included in the 24 bp region targeted for deletion was used to test the samples for the presence of wild-type adenovirus infection (probe wt 5′VIC-TACCTGCCACGAGGCT-3′MGBNFQ).
The real-time PCR conditions for each 25 μL reaction were as follows: 2× LightCycler480 Probes Master Mix (Roche), 800 nmol/L of each forward and reverse primer, 200 nmol/L of each probe, and 250 ng of extracted DNA. PCR reactions were carried out in a LightCycler (Roche) under the following cycling conditions: 10 minutes at 95°C, 50 cycles of 10 seconds at 95°C, 30 seconds at 62°C, 20 seconds at 72°C, and 10 minutes at 40°C. All samples were tested in duplicate. TaqMan exogenous internal positive control reagents (Applied Biosystems) were used in the same PCR runs to test each sample for the presence of PCR inhibitors. A regression standard curve was generated using DNA extracted from serial dilutions of Ad5-D24-GMCSF (1 × 108—10 VP/mL) in normal human serum. The limit of detection and limit of quantification for the assay were 500 VP/mL of serum. Positive samples were confirmed by real-time PCR using LightCycler480 SYBR Green I Master mix (Roche) and primers specific for adenovirus and GMCSF sequences (forward primer, 5′-AAACACCACCCTCCTTACCTG-3′; and reverse primer, 5′-TCATTCATCTCAGCAGCAGTG-3′).
ELISPOT and flow cytometry analysis
Peripheral blood mononuclear cells (PBMC) were isolated by Percoll gradient according to standard protocols. Cells were immediately frozen in CTL-CryoABC serum-free media (Cellular Technology, Ltd.) for further ELISPOT and flow cytometry analyses. ELISPOT was purchased as a service from Proimmune (Oxford, United Kingdom). For adenovirus ELISPOT, cells were stimulated with the HAdV-5 Penton peptide pool, which consists of 140 peptides, each 15 amino acids long and overlapping by 11 amino acids. For survivin, BIRC5 PONAB peptide was used. It consists of a pool of 33 peptides, each 15 amino acids long and overlapping by 11 amino acids.
Flow cytometry analysis was performed on a Becton Dickinson instrument (FACSCalibur). The following antibodies were used: human CD3 PerCP-labeled (Becton Dickinson), human CD8 clone LT8 FITC-labeled (Proimmune), and for survivin, Pro5 Pentamer A*0201-LMLGEFLKL PE-labeled (Proimmune). For adenoviruses, a custom-made PE-labeled tetramer was ordered from Glycotope A*0201-GLRYRSMLL. Monoclonal antibody W6/36 (Mabtech) was used to selectively block MHC class I presentation.
Statistical analysis
Statistical tests were performed with SPSS 15.0 and GraphPad Prism version 4.00 for Mac (GraphPad Software). Mann-Whitney test was used in the animal experiments. t tests were used to assess significance in the in vitro assays.
In vitro and in vivo characterization of Ad5-D24-GMCSF
Ad5-D24-GMCSF was generated by replacing viral gp19k and 6.7k with GMCSF (Supplementary Fig. S1A). This strategy couples transgene expression with viral replication to ensure high expression of the transgene at the tumor site (25). The virus replicates in a tumor-selective manner, thus resulting in low systemic expression of GMCSF. The tumor specificity of the virus was achieved with a 24 bp deletion, which abrogates the retinoblastoma (Rb)-binding site of E1A. Previous reports have shown that this results in selective virus replication in cells with p16-Rb pathway defects, including most if not all human cancers (19).
Ad5-D24-GMCSF had oncolytic potency in all tested cell lines, and in most cases, we observed no significant differences between Ad5-D24-E3 and Ad5-D24-GMCSF (Supplementary Fig. S2A–C). Therefore, replacement of gp19k and 6.7k with GMCSF did not seem to reduce the oncolytic potency of the virus significantly.
GMCSF secretion in vitro was seen when the virus replicated (Supplementary Fig. S3A), but not when UV-inactivated virus was used (data not shown). To show the functionality of virus-derived GMCSF, we cultured the TF1 cell line (26), whose growth is strictly dependent on fully functional human GMCSF, with either the commercial GMCSF or with supernatant from cells infected with Ad5-D24-GMCSF. Although cells cultured without GMCSF started to die at day 3, the presence of GMCSF or supernatant allowed cells to grow (Supplementary Fig. S3B). GMCSF expression was also observed in tumor-bearing mice (Supplementary Fig. S3C).
In accord with the in vitro results, we did not see any significant difference between Ad5-D24-E3 and Ad5-D24-GMCSF in vivo, suggesting that the expression of the transgene does not impair the efficacy of the virus (Supplementary Fig. S3D). Human GMCSF has no biological activity in mice and thus it did not increase the efficacy of the virus.
To characterize the potency of Ad5-D24-GMCSF in an immunocompetent environment, we grew syngeneic tumors in Syrian hamsters, which have been reported to be semi-permissive for human adenovirus (27). Interestingly, previous data also suggests the activity of human GMCSF in hamsters (28, 29). Tumors were eradicated in animals treated with both Ad5-D24-E3 and Ad5-D24-GMCSF within 16 days (Fig. 1A).
Fifteen days after tumor eradication, hamsters were challenged with the same cell line (HapT1) or a different syngeneic cell line (HaK) without further virus treatment. Interestingly, all animals in which HapT1 tumors had been eradicated with Ad5-D24-GMCSF rejected HapT1 but none rejected HaK tumors, suggesting that GMCSF expression from the virus had enhanced tumor-specific immunity (Fig. 1B and C). In animals in which HapT1 tumors had been eradicated with Ad5-D24-E3, we observed delayed HapT1 tumor growth, suggesting that oncolytic adenovirus replication per se could induce a degree of immunity, but not enough to protect from tumor challenge (Fig. 1B).
Safety of Ad5-D24-GMCSF in cancer patients
Treatments were generally well tolerated up to 4 × 1011 VP, and no grade 4 to 5 side effects were observed (Supplementary Table S1). Most patients experienced grade 1 to 2 flu-like symptoms, including fever (14 of 19), chills (5 of 19), fatigue (7 of 19), and injection site pain (8 of 19). Patient O88 experienced temporary worsening of intestinal function (grade 3 ileus and pain). Intestinal problems are quite common in ovarian cancer patients with peritoneal metastatic disease and this patient had similar symptoms prior to virus administration.
As the levels of certain cytokines (e.g., interleukin-6) have been suggested to predict adenovirus-mediated toxicity (30, 31), it may be of importance that only minor elevations were seen (Supplementary Fig. S4; Supplementary Table S2). Therefore, the doses used might have been well within the therapeutic window for this virus.
Presence of Ad5-D24-GMCSF and GMCSF in serum
Because injected virus is rapidly cleared, the extended presence of virus genomes in serum has been suggested to indicate virus replication (32–35). All patients were negative for Ad5-D24-GMCSF before treatment. Two days or more after treatment, virus was detected in the blood of 15 of 18 cases (Table 2).
Systemic levels of GMCSF were low, which was in accord with the absence of significant effects on total WBC counts, suggesting effective restriction of GMCSF production to the tumor (Supplementary Fig. S4).
Neutralizing antibodies
Neutralizing antibody titers were positive in 8 of 19 cases (42%) at baseline (Table 2). Titers increased within 2 weeks in most patients regardless of viral dose. As suggested by others, no clear correlation was seen between neutralizing antibody titers and viral dose, antitumor activity, or toxicity (8, 32, 34, 36, 37). However, with regard to virus replication and antibody titers, it is interesting that the antibody titer of X49 increased to only 4,096 in 1 week and decreased thereafter, and she had high and persistent amounts of virus in her blood. The patient (I78) who showed the highest serum virus load had no antibodies at baseline, and at 4 weeks, had a titer of only 64. These two cases would seem to suggest that some cancer patients are indeed immunosuppressed to some degree which compromised their antibody production, leading to enhanced virus replication. In contrast, patient C58 also featured high serum virus load, but had antibodies at baseline with an increase to maximum in 1 week.
Efficacy of Ad5-D24-GMCSF
Fifteen patients were evaluable for radiologic responses (Table 2; Fig. 2). Two patients (13%) had complete eradication of all measurable disease (Fig. 2). In addition, five patients (33%) had stabilization of disease progressing before treatment. Therefore, the clinical benefit rate was 47% according to RECIST criteria. The duration of disease stabilization was 98, 106, 490, 398, and 245 days for M3, O12, T19, M50, and R73, respectively. Disease stabilization is a surrogate end point and thus further work is required to evaluate if this translated into actual patient benefits (38).
Previous reports suggest that a decrease in tumor density might correlate with antitumor efficacy (22). This was measurable in two patients, and in both cases, the density decreased (by 4.6% and 27%; Table 2). In addition, a nonmeasurable decrease of the intraperitoneal tumor was detected in one patient (O88). There was no detectable difference in response between injected and noninjected tumors. In fact, noninjected tumors sometimes decreased more clearly than injected lesions (Fig. 2A, patient M50). RECIST criteria takes into account both injected and noninjected tumors and therefore response or stabilization of disease previously progressing suggests a systemic antitumor effect (23, 24). Interestingly, about one third of the treated patients seemed to gain long-term survival (Fig. 2B).
Second treatment with Ad5-D24-GMCSF resulted in rapid tumor reduction
Encouraged by the results in the 19 patients who received Ad5-D24-GMCSF as their first oncolytic virus treatment, we treated one additional patient who had received another oncolytic virus (39) 9 weeks earlier. Subsequent to Ad5-D24-GMCSF treatment, she had a 52% reduction in tumor volume (20% decrease according to RECIST) in only 17 days (Fig. 2A, patient O9). After 24 hours, there was 2,133 VP/mL of Ad5-D24-GMCSF present in her serum (Table 2).
Effect of Ad5-D24-GMCSF administration on WBC compartments
GMCSF levels in the serum were monitored, but increase over baseline was observed in only three patients with a maximum level of 70 pg/mL, suggesting a restriction of GMCSF production in the tumor sites. No increases in WBC were seen (Supplementary Fig. S4). The complete phenotypic panel of circulating WBC was evaluated (Supplementary Table S3). Interestingly, 9 of 10 patients showed an increase in the total number of CD8+ T cells following treatment (Supplementary Fig. S5). Hence, we sought to investigate whether these cells were specific for adenovirus or if Ad5-D24-GMCSF could also stimulate a tumor-specific response.
Adenovirus-specific T-cell response in cancer patients treated with Ad5-D24-GMCSF
The tumor microenvironment has been thought to be immunosuppressive, which might work against induction of immunity at the tumor (15). However, because we saw an increase in total number of CD8+ T cells, and inspired by preclinical data (4, 13), we investigated adenovirus- and tumor-specific T-cell responses. For triggering T cell–specific immune responses, peptides need to be presented as MHC class I by antigen-presenting cells expressing the necessary costimulatory molecules. Interestingly, Ad5-specific ELISPOT suggested a strong activation of T-cell responses (Fig. 3A–D). To clarify the mechanism of the response, we blocked MHC class I presentation with a specific antibody. As expected, this resulted in a reduction of IFN-γ secretion by ELISPOT (Fig. 3A). Therefore, an immune response developed against adenoviruses replicating in tumors, suggesting that the tumor environment might not completely preclude the induction of an immune response.
Tumor-specific immune response
T cells were pulsed with a peptide mix from survivin, which is a classic tumor-associated epitope broadly expressed in a variety of different tumors (ref. 40; Fig. 4A–D). In all patients analyzed, we observed a posttreatment increase in T cells capable of recognizing survivin. When we pretreated the PBMCs with an antibody blocking MHC class I presentation, we observed a reduction of IFN-γ secretion. To deconvolute the peptide pool used in ELISPOT, we performed pentamer analyses in HLA-A2–positive patients (Supplementary Fig. S6). PBMCs from patients before and after the treatment were stained with specific antibodies for CD3, CD8, and survivin and then analyzed by flow cytometry. We observed an increase of T cells specific for survivin, in correlation with the results seen in ELISPOT. There were more antiadenovirus T-cells than antisurvivin T-cells, suggesting that the former is a stronger antigen. Thus, the majority of the overall induction of CD8+ cells was probably due to antiadenovirus T-cells (Supplementary Fig. S6). Nevertheless, the clear relative increase in antisurvivin cells suggests that Ad5-D24-GMCSF was able to also induce antisurvivin reactivity.
Although survivin is widely considered an ideal tumor-associated antigen (40, 41), some reports have also proposed expression by selected normal cells (42). Therefore, whereas induction of antisurvivin T-cells suggests tumor-specific immunity, it does not unequivocally prove it.
Accumulating evidence indicates that a dynamic cross-talk between tumors and the immune system could regulate tumor growth and metastasis (15, 43). Viral oncolysis can be useful as a costimulatory danger signal for helping induce immunity instead of tolerance towards tumor antigens (4, 15). In addition, cell lysis provides an ample supply of antigens for sampling by antigen-presenting cells. Here, we armed a p16-Rb pathway–selective oncolytic adenovirus with GMCSF, which could recruit natural killer cells directly to the tumor. GMCSF could also recruit dendritic cells and stimulate them so that they can return to the lymph node for coordinating the cytotoxic T-cell attack on the tumor.
Recombinant GMCSF has been used in humans for both its mitogenic effect on leukocyte progenitors and for its immunostimulating properties. It has been used as a vaccine adjuvant and as systemic agent for general antitumor immune stimulation (44, 45). Therefore, its safety is well established. However, systemic use for immune stimulation was compromised by side effects related to systemic exposure, whereas efficacy may have been limited because of low local concentrations. Thus, the production of GMCSF locally at the tumor might yield safety and efficacy benefits.
Only gp16k and 6.7k were deleted from the virus genome, therefore retaining most of E3, which is useful for effective oncolysis (46). Also, the 24 bp deletion used to obtain tumor selectivity might be advantageous over the most widely clinically used virus with an E1B55k deletion (dl1520/ONYX-015/H101), because it does not attenuate virus replication in tumor cells (46). It has in fact been proposed that the 24 bp constant region 2 deletion in E1A might actually increase the oncolytic potency of the virus (47). In contrast, replication in normal tissues is minimized (1, 46).
In vitro and in immunodeficient preclinical systems, Ad5-D24-GMCSF was found to be as potent as the same virus without the transgene. However, in the presence of T cells, only Ad5-D24-GMCSF treatment protected animals from subsequent challenge with the same tumor cells. Growth of a different cell line was not compromised by prior tumor eradication with Ad5-D24-GMCSF. These findings suggest that the expression of GMCSF by the virus (Ad5-D24-GMCSF) could induce tumor-specific immunity.
Ad5-D24-GMCSF was well tolerated in patients and signs of efficacy were seen in 63% of the patients, suggesting that Ad5-D24-GMCSF may have antitumor activity in humans. Also, one third of the patients seemed to receive a long-lasting benefit. These data are particularly intriguing considering that these were highly pretreated patients with advanced and often large tumors. In this patient population, a high rate of antitumor activity and long-term survival were unusual.
Despite relatively conservative dosing at doses 10 to 100 fold lower than reported safe in previous studies with other oncolytic adenoviruses (1, 5–9, 21), persistent virus shedding into the serum was seen in 15 of 18 patients. Systemic dissemination of virus from the tumor might allow the transduction of metastases which (together with the immune response) might help explain the antitumor efficacy seen in injected and noninjected lesions. In this study, we used a combination of intravenous and intratumoral injection. However, the optimal dosing schedule has not been studied and thus merits further investigation.
One of the key findings in this article is the emphatic cytotoxic T-cell response induced against adenovirus. As Ad5-D24-GMCSF replicates in a tumor-specific manner, this suggests that the tumor environment is capable of mounting an immune response against tumor epitopes. However, at present, we cannot exclude a low degree of adenoviral gene expression in normal tissues, which might also contribute to antiadenoviral T-cell responses.
Most interestingly, Ad5-D24-GMCSF treatment resulted in an immune response against survivin, a classic tumor-associated epitope. This suggests that the immunologic tolerance typical of tumors could be broken with an approach combining oncolytic virus-mediated cell killing with GMCSF-mediated recruitment and activation of dendritic cell and natural killer cells.
Efficacy gains might be obtained by combining virus with standard treatments. For example, it has been reported that radiation and oncolytic adenovirus could be synergistic (1). The same is true for many chemotherapeutics (10, 48). Moreover, immune suppression could yield benefits by slowing antibody induction or modulating the immunologic tumor environment (49). Tumor load and the associated immunosuppressive tumor environment might act against the virus-mediated antitumor immune response. Therefore, earlier treatment might yield efficacy benefits. Furthermore, as we treated patients only once, it is possible that repeated treatment could increase both the antitumor immune response and the transduction of tumor masses for more effective oncolysis.
In summary, Ad5-D24-GMCSF seems safe for the treatment of human cancer. Further clinical studies are needed to study efficacy in larger numbers of patients and to optimize the treatment schedule. In particular, randomized trials would be needed to more reliably show the benefit of adding GMCSF to oncolytic adenovirus, and to assess the efficacy of the approach in general. Nevertheless, our data suggests that the immune tolerance of the tumor environment can be broken for the induction of an antitumor T-cell response.
Disclosure of Potential Conflicts of Interest
A. Hemminki is a K. Albin Johansson Research Professor of the Foundation for the Finnish Cancer Institute. A. Hemminki is also a founder and a shareholder in Oncos Therapeutics, Inc. The other authors disclosed no potential conflicts of interest.
We thank Saila Eksymä-Sillman, Marina Rosliakova, Satu Nikander, Kylli Skogström, Arja Vilkko, Heini Välijeesiö, Jenni Kylä-Kause, Katri Silosuo, and other Eira/Docrates personnel for help and support.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).
- Received September 26, 2009.
- Revision received March 16, 2010.
- Accepted April 8, 2010.
- ©2010 American Association for Cancer Research.


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Trusted, Effective Treatment for Decaying Matter Fear.
Feelings of dread? Overwhelming thoughts? Rapid heartbeat? Tunnel Vision? Or worse? Since 2002 we have worked with countless folks from all walks of life and we have never met a case of decaying matter fear that could not be overcome.
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Instigators and Risk Factors for Decaying Matter Fear
In most cases, Decaying Matter Fear (although not always) is triggered by an extremely negative encounter from the past. The mind will, in some situations, generate the fear without an apparent cause. By exposing the root cause, you will be able to remedy the problem by easily exchanging harmful triggers. Those at greatest risk include:
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You can also read what the media has to say.
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You can take our 2 minute Decaying Matter Fear Online Test to establish the enormity of the problem for you, but it's really quite straightforward: It is time to do something about the fear, if it is having a significantly negative effect on your life.
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The use of drugs and medication for Decaying Matter Fear is not encouraged in our program because they generally mask the problem, rather than tackling the cause. A pill can sometimes act as a quick fix and may seem to help briefly but will not allow you to be free of the fear.
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text: Make your predictions here! Just enter your goal prediction and it saves automatically. You get 3 complimentary Jokers every game week to use as you wish. When you apply a Joker to a match, it lets you double the points you earn for that match. N.B. You can only use one Joker per match. How To Play


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A platform of influence for the Franco-British Defence community
Since the Lancaster House Treaties in 2010, the Franco-British Council has regularly organised a Defence Conference which has established itself as a networking platform of reference for bilateral relationships in the defence sector. This conference brings together representatives from the most senior level of military, government, industry and academia from both sides of the Channel. Its objectives are to forge new relationships and reinforce mutual understanding between the two countries' defence communities.
The Franco-British Council organises regular Defence Conferences. You can read the report from the latest Defence Conference here.
Our sponsors
You can read reports from previous conferences here: 2016 2015 2014


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Vivo had showcased the world's first in-display fingerprint sensor on a smartphone at the Consumer Electronics Show (CES) 2018. It was expected that the first phone to feature the in-display fingerprint sensor will be Vivo X20 Plus UD. Earlier this month, the smartphone had been spotted on 3C certification listing and later on the smartphone had also received certification from TENAA. Now, Vivo has officially announced that the Vivo X20 Plus with an in-display fingerprint variant will be unveiled to the world on Jan. 24.
The above poster confirms that Vivo is holding the launch event of Vivo X20 Plus in-display fingerprint edition at 751D Park, Beijing, China on Jan. 24 at 7:30 PM local time. However, the poster doesn't reveal the specification and pricing of the smartphone but it is expected to feature quite similar specifications to the X20 Plus regular variant.
The Vivo X20 Plus UD is equipped with a Clear ID 9500 optical under-display fingerprint sensor by Synaptics. It can unlock the device in 0.6 or 0.7 seconds – slightly slower than the regular capacitive fingerprint sensors.Image source – mydrivers
Earlier rumors suggested that the Vivo X20 Plus UD would be carrying a price tag of 3,999 Yuan ($625/ Rs. 39936 approx) but the official price has yet to be revealed.
Talking about the specifications, the Vivo X20 Plus runs on FunTouch OS based on Android 7.1 Nougat operating system. It sports a 6.43" Full-HD+ (2160×1080 pixels) FullView AMOLED display with an 18:9 aspect ratio. The smartphone is powered by a 2.2GHz Qualcomm Snapdragon 660 octa-core processor. It offers 4GB of RAM and 128GB of internal storage which can be further expandable up to 256GB via MicroSD card.
For photography, the Vivo X20 Plus sports a dual-camera setup with a combination of a 24MP primary camera with f/1.8 aperture, OIS, and a secondary 5MP shooter. On the front, it has a 12MP shooter with f/2.0 aperture and soft LED flash.
The smartphone is fueled by a 3800mAh battery with fast charging support. Connectivity options include Dual-SIM support, 4G VoLTE, Bluetooth 5.0, WiFi, GPS, and USB Type-C port. It measures 165.2 x 80.02 x 7.35 mm and weighs 183.1 grams.
For the latest tech news and updates follow TechnoCodex on Facebook, Twitter, Google+. Also, if you like our efforts, consider sharing this news with your friends, this will encourage us to bring more interesting updates for you.


text: Hello. Another Bumblebee. What a pain to work on!!! Nothing went right for me on this thing. Just one of those customs!!! Repaint with base yellow, tequila sunrise pearl flop and chameleon pearl flop. The black is actually called galaxy grey. LED lights and eyes. Had to drill out part of the mounting posts from the shoulder areas. Batteries and holder are from a mouth light thing I got from hot topic. Thanks to len_d69 for the leg switch thread!!! Looks way better. Battle damage of course, but not over board. The funny thing is there is SOOO much moving of parts with this, I had a hard time finding a stationary place for the batteries and switch. Fix? They move. That's right, you can move them around and place them in certain areas under the hood while in bot mode and while in car mod!!! But they hide just fine. I would love to do the hand mod but that is one expensive hand. I am thinking about casting some!!! Please feel free to comment!!!


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Ruins & Rubble is the 4th pack in Aaron's series of dungeon tiles! With 50+ entirely new, high-quality, fully-furnished rooms to build with. Featuring everything from Sacrificial Altars to Water Hazards to Forgotten Tombs, this pack will add some debris and danger to your dungeons! This pack works exceptionally well if you're looking for an overgrown jungle dungeon with an Aztec/Mayan style!
Note: FULLY compatible with ALL of Aaron's packs! Mix the packs for truly MASSIVE dungeons! Simply drag-n-drop and you're ready to play!
License: Roll20 End User License Agreement
(Personal Use Only, Do Not Distribute)


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BAGHDAD, Feb. 16 (UPI) -- Anti-American Iraqi Shiite cleric Moktada al-Sadr announced he's retiring from politics.
Al-Sadr made the announcement Saturday on his website, the New York Times reported Sunday.
"I announce that I will not intervene in politics. No party represents us from now on in Parliament or in any position inside or outside the government," he said.
The offices of his Sadrist Shiite party, the Ahrar bloc, will be shut down and only the charities and educational groups he runs will stay open, he said.
Hundreds of al-Sadr's followers gathered outside his office Sunday to urge him to reconsider his decision, the Times reported.
The 40-year-old has made similar announcements in the past, but changed his mind.


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Here are all of the possible secrets to creating Instagram Highlight Stories for your company's Business Instagram. Let me tell you, it can be a tricky ordeal. Maddening, actually. For about two weeks now, I have been creating a feed of photos for Anthem Branding and establishing them as Instagram Highlight Stories that provide context of who we are and what we do as a business. Through trial, error, and a lot of frustration, I have learned the ins and outs with creating good content within your individualized highlight stories that will showcase your business in the best light.
Hold up. Why are Instagram Highlight Stories even important?
Before you start this step-by-step process, I have to delve into how essential Instagram Highlight Stories is to your social media for your business. According to Hubspot.com, Instagram users spend 20-30 minutes on Instagram stories. That is ample amount of viewer time for a consumer to peruse your merchandise, branding, and products. With Instagram Highlight Stories, the stories stay on your profile for as long as you want. On top of that, Instagram Highlight Stories are one of the few things that consumers see within the first glance of your Instagram page. These stories are a quick snippet of what your business is about, and you want to create specific content to interest and impress your potential customers.
Your Feed
Sometimes you hear millennials going around blabbing about their aesthetic. With all of the tech-savvy, instagram-obssessed millennials out there, how something looks is important. With your business Instagram, the same applies. Narrow down the colors and moods that your Instagram centers around, and apply those looks to your Instagram highlight stories. Specific edits or inspiration images help to create the look you're going for as a business and can be carried throughout your stories.
Cover Photos or Icons
Creating a good cover photo for each Instagram highlight story is important to bring everything together and keep your social media cohesive. You have to keep your cover photo on your Instagram highlight in order for it to stay there forever. If for some reason you want to change your cover photo, then you have to redo this maddening process. That means that you have to put it on your regular story, add it to your highlight, adjust the photo with how you want it in the circle, and then keep it on your highlight feed. Tedious stuff right there.
We decided to create icons for our Instagram Highlight Stories to provide a fun aspect to our social media. Our designer, Lisa Tupy, did an amazing job with fitting our aesthetic and creating icons that were just right for Anthem Branding.
Story All of Your Highlight Stories
Before you are allowed to create an Instagram Highlight, you have to make sure it's on the Instagram archive. That means that every story you want to put on the highlight has to be posted as a story first on your general Instagram account. You can't pull from your camera roll to post on your highlight story. There is no way of getting out this besides posting it on your main story first. Once you put it on your story, DO NOT DELETE IT. The story has to be on there for 24 hours to forever stay on your Instagram Highlight Story. If you delete anything on your main story and it wasn't there for the full 24 hours, then it will be deleted on your Instagram Highlight Story too. I can't reiterate this enough (because I have lost a few years of my life because of this), whatever you do with your main story will screw with your Instagram highlight story.
The Secret to Uploading Multiple Photos
Don't want to have your followers see that you are messing around with your Instagram Story Highlights? Paranoid that posting too many photos on your main story will lose integral followers? Have no fear, there is a way to upload a plethora of photos on your main story without scaring too many people. If you go to your profile and click the gear button that represents "Settings," it will bring you to a page that allows you to invite your Facebook friends, contacts, etc.
If you scroll down past Account and Business Settings, the headers that are in bold, and arrive at Privacy and Security, you will find an option that says "Story Controls."
Click into "Story Controls" and at the top of the page you will find an option that says, "Hide Story From."
This option allows you to click every follower that you want to hide your main story from. Selecting all of your followers will allow you to hide your story from virtually everyone, enabling you to upload as many photos as you want without people knowing. Once you have created all of your highlight stories and wanted the 24 hour period since your last post, you can unhide your story from your followers. Voila, now all of your followers can see a clean set of Instagram Highlight Stories without see the mess that went into creating them.
Create Your Last Story First
Your stories bump more than a classic EDM song. What I mean is that Instagram has made it to where your stories get bumped down after you create them. Figure out the chronological order that you want for your highlight stories. Then, create the last one on the list first. That way your order stays how you want it to look on your account.


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October 12, 2011
Tuesday I had the immense privilege of attending talks and discussion panels at the Forum 2000 Conference that is held every year in Prague. It is an occasion that invites dignitaries, scholars, diplomats, and activists from around the world to discuss current global issues and, as the program clearly states, theories on democracy and the rule of law.
The conference was kicked off on Monday with an opening speech by the first president of the Czech Republic, Vaclav Havel, and continued until today. Yesterday, I attended three 90-minute sessions, all of which related to my potential field of advanced study. I must say, some of the discussion was extremely enlightening, and all of it was very engaging.
The first session was titled "Legal Institutions and Transition." It primarily focused on the rule of law, and how it determines economic and political success in a transition state. One of the panelists was a Russian dignitary and a member of the opposition against Putin. He made the assertion that Russia currently doesn't have a rule of law (as Putin gets the final say on all judicial decisions). This statement certainly had support from other scholars in attendance, and Russia was a central theme throughout the day's discussions. There was some interesting input from the panel in comparing Eastern and Central Europe, and why the latter had more success with transition than the former. They asserted that it was due to a strong and active civil society: such development leads to pressure from below that is necessary to form a form rule of law. One of the questions I was left with was the role of international organizations in promoting the rule of law within certain states. Can there be such a role when it comes to Russia?
My second session dealt with "Corruption and Society," where I listened to the founder of Transparency International, a prominent European NGO focused on corruption in both the private and public sectors. This was a very inspirational talk. It was refreshing for me, anyway, to see well-established and influential figures who were not cynical about corruption, nor were they involved in it. I was troubled, however, at the lack of practical application in their viewpoints. One panelist suggested a global network of anti-corruption states to fight rampant corruption. Question is: how is this feasible? Just another solution for our generation to find, I suppose.
The last session was one that interested me the most, "The Law and the Individual." It addressed an issue that I didn't even know was up for debate: the universality of human rights. As it turns out, there are some scholars, like Bobo Lo, expert on Chinese/Russian relations and human rights, who believe that there will never be a universal code of human rights… the global community is nowhere near a consensus about the implementation of human rights laws because the moral authority of the West, upon which the international community has thus far relied, is being undermined by the financial crisis in the U.S. and the Eurozone as well as the mishandling of military activity in the Middle East.
This was a very gloomy perspective to hear, particularly as someone who is seriously considering devoting their education and passions to the implementation of global human rights standards. Others were more positive: the Arab Spring has demonstrated a commitment to human rights, and such commitment can only ever be an international issue. Plus, collective international condemnation has proven to be an incentive for governments to stop human rights abuses, particularly if the state has something to gain, and lose, in terms of the global scale. I wonder if the future of international criminal justice will play a significant role?
The panel ended with a good quote by the moderator, "We all must struggle against what isn't human." Simple and very much to the point.
Katie Beaver '13 is a Government and History major at the College of William & Mary. She is originally from Howard County, Maryland and is spending a semester abroad in Prague. She is studying politics, religious and ethnic issues, and culture through the Czech and Central European context while abroad, and has developed an active interest in those subjects. She has also had the opportunity to travel to surrounding Central European cities including Vienna, Krakow, Budapest, and Berlin. Katie has blogged about her semester abroad at Czechmate: A Prague Blague.


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For nearly 80 years, Ferrellgas has grown significantly, and we recognize the secret to that success is people. Our leaders draw from their unique expertise, talents, and skills to help plan and execute strategies that keep us on the path toward continued success.
Meet our leadership team.
James E. Ferrell
Chairman, Interim Chief Executive Officer & President
On September 27, 2016, Mr. Ferrell was appointed Interim Chief Executive Officer and President by the Board of Directors of Ferrellgas, Inc. Mr. Ferrell has been with Ferrell Companies or its predecessors and its affiliates in various executive capacities since 1965, including Chairman of the Board of Directors of Ferrellgas, Inc. Under his leadership, Ferrellgas has grown from a small, independently owned propane company to one of the nation's largest propane retailers. Mr. Ferrell is a past President of the World LP Gas Association and a former Chairman of the Propane Vehicle Council. Mr. Ferrell brings to the company significant experience in propane and midstream operations and valuable knowledge of the company's operating history.
Jordan B. Burns
Vice President & General Counsel
Jordan Burns joined the Ferrellgas legal team in 2018 and was promoted to Vice President, General Counsel and Corporate Secretary in December 2018. Prior to joining Ferrellgas, Jordan served as outside counsel to Ferrellgas on a national basis. He attended the University of Kansas, where he earned degrees in both Business Administration and Finance. After working as a Series 7 licensed financial analyst, Jordan attended the University of Missouri-Kansas City School of Law.
Sonny R. Catlett II
Vice President, Ferrell North America
Sonny Catlett joined Ferrellgas in August 2020 as Executive Vice President of Ferrell North America, where he is responsible for acquiring and transporting all raw materials for Ferrellgas and Blue Rhino. Prior to joining Ferrellgas, Sonny served as Sr. Vice President of Operations for HNRY Logistics, concentrating on the automation of supply chain decisions. Sonny attended the University of Missouri, earning his Bachelors and Masters in Business Administration.
William E. Ruisinger
Chief Financial Officer
Bill Ruisinger was appointed the Interim Chief Financial Officer in November 2018. Bill joined the company in August of 2012 as Director of Accounting. Since then he has served as Corporate Controller from 2015 to 2017 and Vice Present, Treasury, Investor Relations and Planning from 2017 to 2018. Prior to joining Ferrellgas, Bill worked for 15 years for Deloitte, which is the world's largest professional services organization.
Mark J. Tucker
Mark Tucker joined Ferrellgas' Blue Rhino division in 2006 as Director of Sales and shortly thereafter moved into the VP of Sales role. He was promoted to Senior Vice President of the Blue Rhino Operating Division in 2014. Prior to joining Ferrellgas, Mark worked a variety of senior sales leadership roles in the consumer packaged goods industry for General Mills, Campbell Soup, and Pinnacle Foods. Mark attended the State University of New York at Geneseo, where he earned a degree in management and marketing.
Tamria A. Zertuche
Chief Operating Officer
Tamria Zertuche came to Ferrellgas in 2004 when the company acquired Blue Rhino, where she was employed as Senior Director of IT. She was promoted to Vice President of IT in 2016 and to Senior Vice President of Business Operations and Chief Information Officer in 2019. Tamria holds an MBA from Colorado State University, and she is currently completing a Doctoral program in Organizational Learning, Performance, and Change at the same institution.
Board of Directors, Ferrellgas Partners
James E. Ferrell, Chairman
Pamela A. Breuckmann
Stephen M. Clifford
Andrew Levison
John R. Lowden
Michael F. Morrissey


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Our mission:
We are a non-profit foundation seeking to empower and celebrate women. We use an approach towards women that encourages participation from the entire community in creating equality and healing through self-expression and communication, self-love and self-care.
We approach equality from another point of view. Equality is directed to men, as through them we reach it towards women.
We believe equality is a must and we will do everything to change our ideas and perception of it.
Healing from past trauma will be done by professional psychologists in the near future, as per now we have healing through meditation, healing through music, healing through food, through letting go, through art.
Self-expression: We offer chats to girls through which anonymously you can express yourself and get advice from a big sister which you've never met, we arrange meetings if you need someone to hang with, that only if you show your identity. So join our chat, log in and meet your secret sister.
Communication: We offer free classes on self-love, self-care.
Join us for the next meeting.
Comments from our community:
Natyra M. – Keep doing your wonderful work helping girls understand their value. 💖
Memaj S. – Your are the greatest supporter…thank you for giving us hope. 💖
Vanessa M. – Sometimes one of your quotes or your posts was the inspiration i needed for the day. Thank you for being here, one woman should always help another💖
Krenare- You are the voice that needs to be heard in this world, you represent how kind and loyal girls are. 💖
Alyssa H. – You helped me get through so much and I am so grateful for you. 💖


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Milan Simulated Diamond pendantPrice - Log In for Wholesale PricingAvailable: In Stock
Timeless design is key with the Milan Simulated Diamond Pendant which is now available from Starlet Jewellery for wholesale purchase. Designed for the understated brides and those seeking a dash...
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Understated beauty is key in the Milan Simulated Diamond Bracelet which guarantees to be a firm favourite amoung brides and bridesmaids. Featuring a flexible row of square-cut simulated diamond stones...
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This is a lemon-scented hybrid cross between GDP and Trainwreck. Developed out of Humboldt County, this strain gives a slight body affect, nicely euphoric and uplifting for those Medical Marijuana patients looking for a positive boost.
An almost equal mix of her parents, this combination offers a sweet purple grape taste, almost immediately followed by a classic Trainwreck sourness/dankness. Tingly!
This extremely potent hybrids resin production begins almost immediately in flower and can cover the entire plant in a dripping blanket of thick crystals.
A powerful pain reliever, the Purple Wreck is the kind of medicine you keep going back to for just one more taste. Violet buds with even darker purple hairs makes this strain also intriguing to the eye.
Grows: Grows indoors, Grows outdoors
Harvest Month: early October
Seed Bank: Grand Daddy Purple
Genetics: Indica / Sativa
Parents: GDP x Trainwreck
Height: N/A
Photoperiod: Photoperiod
Yield: High
Flowering Time: 8 – 9 weeks
Award Winner: False
Avail. As: Regular Seeds
Strain Attributes: Euphoric :: High Yield
Medical Uses: Pain Relief
If you're using this strain for medicinal purposes, please leave your experiences in comments below so others can benefit.


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Back in the days of the Xbox 360, Microsoft started touting their console as a central media unit for the house. They tried to continue that thinking over with the Xbox One launch but for the most part the focus as of late has been geared more towards gaming. That hasn't meant they've abandoned bringing new media options to the consoles, recently replacing Groove Music with the more popular Spotify. Today, the company announced that Amazon Prime Video will be available at launch on the Xbox One X and is available to Amazon Prime members as well as new customers.
The Amazon Prime Video app is available to download globally on your Xbox One console and will give you access to popular Prime Video exclusive shows like The Tick, The Grand Tour, The Main in the High Castle, American Gods, and more. Some Prime Video titles are also available in 4K UHD and can take advantage of the Xbox One S and Xbox One X 4K output for higher resolution entertainment.
As mentioned above, existing Amazon Prime customers can utilize the service at no additional charge and new subscribers can sign up for a 30-day trial — which may just be long enough to binge through that Amazon show you may be missing out on. The service is available in over 200 countries around the world including the U.S., Canada, Australia, countries across Europe, and more.
What do you think about Amazon Prime Video being available to stream on your Xbox One and the upcoming Xbox One X consoles? Let us know in the comments below or on Google+, Twitter, or Facebook.Source: Major Nelson


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Product Description
Codi 4 In 1 Pedicure Kits:
Individually packed with the right amount of product for a single perfect pedicure! One kit per customer.
Kits Include:
- 25g Of Soak
- 25g Of Scrub
- 25g Of Mud Masque
- 25g Of Cream
- Easy Inventory Management
- Easy Cost Management
- Offer A Full Pedicure Menu Cost Effectively
- Aroma Therapy
- No Harmful Chemicals or Preservatives
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Australia's Clothesline Store
- Clotheslines
- Accessories
- Installation
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- Shop By
$259.00 $290.00 You Save 10% ($31.00)|
or make 4 interest-free payments of $64.75 AUD fortnightly with More info
If you have any questions at all, please contact our friendly team on 1300 798 779.
Hills Portable 170 Clothesline
The perfect portable line for multiple uses and suitable for all living situations. Being a portable unit, the Hills 170 Clothesline can be used anywhere in your house, unit or garage for extra drying space.
With long lines that can handle sheets and towels, this all round drying solution can be used indoors and out and is the perfect height so you don't strain your back.
Made from galvabond steel tough enough for the outdoors, it has 10 lines at 1.8m, total line space of 18m and is backed by the Hills 3-year warranty. The Hills Portable 170 would also be great for a second line, vacation home or caravan.
Please Note: This product is not available at any Bunnings stores.
What's Included With The Portable 170
Useful Links
|Suitable For
|2 - 3 People
|Total Line Space
|Line Length
|Line Width
|Number of Lines
|Leg Width
|Frame Material
|Galvabond Steel
|Length Closed
|Frame Height
|3 Years
|Assembly Required
When you place an order, we will estimate delivery dates for you based on the availability of your items and as a general rule we make every effort to have most orders delivered within 2 - 9 working days from date of order depending on your location within Australia and the product purchased.
Please keep in mind some products are of a 'Made to Order' nature and may take a little longer. Rural and regional areas can take longer, up to approx. 12 - 19 working days.
If you have ordered installation or want to have your new clothesline installed by one of our professional installers, please see the steps below which outline the order/installation process.
Step 1. Place your order online or over the phone by calling 1300 798 779
Step 2. Your order will be processed within 24 hours (Mon - Fri) and the details of your order are then sent to the warehouse and the appropriate installer.
Step 3. Depending on the product you have chosen and your location the clothesline will either be picked up from the warehouse or sent by courier to the installer.
Step 4. Once the clothesline installer has the clothesline and he is ready to do your installation, he will call you directly on the phone number provided to arrange the installation day with you. Please make sure you provide the most contactable phone number/s. The installer will bring the clothesline with him on the day of installation.
Step 5. This process generally takes approx. 1 - 3 weeks depending on seasonal demand.
To view the complete guide to clothesline installation, please click on the following link Clothesline Installation Process
Great! It was fairly simple to set up, the delivery was like, 2 weeks? Or even earlier, I can't remember. Really sturdy and such a perfect height. Low enough for my 9 year old to help with the washing, but high enough so that I never have to bend down or strain my back. Will never go back to cheap washing lines from Kmart/Target again.
Very happy with clothesline. I would recommend this product, good quality and easy to use.
This a wonderful product and a great clothesline, and delivery was prompt. During the COVID restrictions it only took an extra couple of days to arrive from interstate. It can take queen size linen easily, but can also dry king size quilts and sheets by draping it over multiple lines. Make sure you follow the instructions for construction carefully, and having someone check and assist with assembly is recommended. My husband and I made a great team, making construction a lot easier. Make sure when you are fitting the actual line to the clothesline you don't leave too much of a loose end at the starting point on each arm. My advice is fold the line in half and make sure there is enough line to finish, as leaving too little at the end means the last line may unfasten and you need to rethread the line as we did by mistake. My fault for having put a load of washing on and was hurrying up my poor husband as he threaded the line and fastened it by himself before the load finished. This a problem easily avoided if you take your time.
We found both the diagrams and the video confusing and when we got it together it didn't look like the pictures. Still, it's up and working fine generally and easy to move. However if we try to hang a business shirt from the plastic arch between the poles, as advertised, the bottoms drag on the ground.
We had one for 10 years and unfortunately it reached the end of its life cycle when it was blown over in a recent storm. We are thrilled to be able to obtain a new one from Lifestyle recently. Being able to easily move the Clothes line on our patio and inside when needed is great and the finishes on the product protect the floor from marking when moved. We do usually anchor it most times in case of strong winds, as our patio is quite exposed.
Hi Helen, we are glad that you like you new clothesline and thank you for you review.


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Quick Navigation
- What is a director ID number?
- What is the purpose of a director ID number?
- When will the director ID number be approved through parliament?
Illegal business activity, in particular, phoenix activity, where a company director moves assets from a failing company to a new company (phoenix), to avoid paying outstanding debts of the collapsing business, is costing the Australian economy millions of dollars.
The director identification number system will have huge benefits for government agencies for early detection of this illegal activity as well as providing enforcement rulings.
These reforms are part of the bigger picture to simplify national business registers and have been supported by government and industry associations.
Tracking the rise of illegal phoenix activities
In July 2018, the Australian Taxation Office (ATO) in their report, The Economic Impacts of Potential Illegal Phoenix Activity, estimated that illegal phoenix activity in 2015-16, cost Australia between $2.85 billion and $5.13 billion in total.
It also found that phoenix activity had a big impact across numerous sectors of the Australian economy. It was felt by everyday Australians in unpaid wages and entitlements to an estimated $31 to $298 million, and other trading businesses with unpaid trade creditors of between $1,162 million to 3,171 million.
Lastly, with an estimated $1,660 million being the cost to the government in unpaid taxes and compliance costs.
What is a director ID number?
Under the proposal, all directors of companies registered with the Corporations Act will be assigned a unique identifier, called directors identification number, or DIN for short.
To apply for a one-off DIN, the person must show 100-points of documentation to verify their identity. At present, any person can be appointed as director of a company without them knowing.
How will it work?
Any person who is a company director will be required to register with the Commonwealth prior to taking up the directorship of a company. They will be assigned their own director identification number.
This ID number will be used to register each new director appointed and regulators can use this number to track directors across companies, quickly and easily.
The DIN will limit the opportunities for a company and its directors to engage in phoenixing activities through a database of unique registrations.
Under the proposed law changes, the database will be administered through a new registry scheme, which will see ASIC's companies register being merged with the Australian Business Register, currently overseen by the commissioner of taxation.
Under the proposal, there will be civil and criminal penalties for directors who fail to apply for identification numbers, while regulators may also issue infringement notices to those who fail to comply.
New company directors and the DIN
It is being proposed, that newly appointed company directors must apply for a DIN within 28 days of being appointed a director under the Corporations Act (or the CATSI Act) unless they are provided with an exemption or extension by the Registrar.
Existing company directors and the director ID number
Under the new proposal, there will be a transitional period for directors who are already in office. They will have 15 months from the date the new law comes in force, to apply for a DIN.
Once a DIN has been assigned to the director, they must update the company register with this number.
What is the purpose of a director ID number?
The Director's ID number is designed to create a new business registry scheme, which will see two existing company databases merge – ASICs company's register and the Australian Business Register, overseen by the commissioner of taxation.
This central register will provide business registry information to allow Government agencies and databases to:
- better oversee the relationships between individuals and entities,
- track directors associated with unsuccessful companies and
- alert them to high-risk individuals and entities.
Reducing phoenix activities will lead to enormous flow-on effects to the economy, in addition to offering greater data integrity and security, accountability and efficiency in identifying and prosecuting director-related offences.
When will the director ID number be approved through parliament?
The 45th Parliament of Australia was prorogued on 11 April 2019. This means that the Bill to which this event has lapsed. For this event to become law, it would need to be re-introduced into parliament.
Treasurer Josh Frydenberg told the Sydney Morning Herald in July 2019 that the government still supports the business registers policy and the director ID idea, though would not commit to a timeline on reintroducing bills to parliament.
"Legislation to make business data current, accurate and accessible remains Government policy," the treasurer said.
The team at Penguin Management will be monitoring the resurrection of the Bill and its progress. We will inform our clients and all their directors of the upcoming introduction of director id numbers.
Related reading
Business Budgeting
Think of budgeting as the road to your future – a budget will drive your business, provide you and management with the invaluable information you need to navigate the road ahead within your means, handle any problems as they come along so you safely arrive at your destination having made a profit. Read our guide – Better Business Budgeting (How To Plan Your Best Year Yet!)
Business Advisor Or Virtual CFO?
Professional advice is always beneficial, whether your business is starting, expanding, growing, or ending. Who do you turn to for this advice? Our blog – Business Advisor or Virtual CFO: Which is Right For Your Business? – should help!
If you have any questions or concerns about the Director Identification Number, please feel free to talk to your Penguin accountant or contact our office here.
Did you find this article helpful? Let us know in the comments below, or share it with your network.


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In order for your heart to function properly, it needs all of the above to work efficiently.
Blood is pumped around your body through a network of blood vessels:
Blood vessels have a layer of spiral muscle within their walls. This makes them able to widen or narrow depending on how much blood each part of your body requires. The action on these muscles is a very complex mechanism which is partly controlled by hormones.
How blood flows through your heart
Blood pressure is the measurement of the pressure within the arteries. It plays a vital role in the way your heart delivers fresh blood, containing the oxygen and nutrients required throughout your body, to all the blood vessels.
In order for blood to travel throughout your body, quickly enough, it has to be under pressure. This pressure is created by the relationship between three things:


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Sleep Chaos Love Motherhood Mint 22oz Stainless Steel Tumbler
Sleep Chaos Love Motherhood Mint 22oz Stainless Steel Tumbler
Motherhood Little Sleep Lots of Chaos So Much Love - 22oz tumbler
Professionally engraved on mint 22oz Stainless Steel double wall Tumbler. BPA Free & Non-Toxic. Includes lid & matching straw. Handwash only.
These make great gifts, the perfect birthday, Mother's Day or Christmas gift for that special Mama in your life!
Customer Reviews
I absolutely beyond love this tumbler!!!! One of my most favorite purchases! Almost want to buy another ya know, just in case....


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ATLANTA, July 31, 2017 /PRNewswire/ — Hospitality Staffing Solutions, LLC (HSS), a leading national provider of supplemental and outsourced staffing solutions for the hospitality industry, announced today it has acquired DEZ Staffing, LLC (DEZ Staffing), a successful provider of hospitality and industrial staffing services in the Denver market.
"DEZ Staffing is a perfect fit for our growing organization, from the quality internal management and staff to their operational practices. The DEZ Staffing organization supports a complementary portfolio of clientele to our company, which will greatly expand our presence and service capabilities in the Denverarea and beyond," stated Tim McPherson, CEO of HSS. "The DEZ Staffing brand, branch office and staff members will remain intact as we expand our reach in this wide market area."


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Are you often drowsy during your waking hours and have difficulty with concentration? Are you feeling restless and over-reliant on caffeine? If this sounds familiar, it's very possible that you are suffering from sleep apnea. Large numbers of people receive a sleep apnea diagnosis every passing year, but so many more go about their lives still suffering without a diagnosis or any kind of treatment.
Because the day-to-day symptoms feel more like a nuisance than a giant red flag (headaches, daytime drowsiness, etc.) many people write off these symptoms as something less serious. However, this tendency to hide in plain sight with a variety of smaller symptoms in the short term is exactly what makes sleep apnea so dangerous.
What Is Sleep Apnea?
Sleep apnea is marked by a blockage in the airways that stops normal breathing while you sleep. This can happen hundreds of times every night, with the patient stopping their breathing up to 30 seconds each time, and sometimes even longer. When put in these terms, it's easy to see that cutting off the oxygen supply to the body for so long every night can cause major issues.
There are three basic types of sleep apnea: obstructive, central and complex.
Obstructive sleep apnea happens when there is a blockage in the airway that slows or stops the flow of air. Central sleep apnea is neurological in nature, where the bran is not properly sending signals to control your unconscious breathing. And finally, complex sleep apnea is caused by a mixture of both obstructive and central sleep apnea. This is why it is important for patients to diagnose their sleep apnea, to not only find out that a problem exists but also to learn the nature of the problem and how best to treat it.
Sleep Apnea Testing
The only way to truly diagnose your sleep apnea is to take an in-lab sleep study (or "polysomnogram") or a home sleep test (HST). These tests will also help your physician determine to what degree the sleep apnea is affecting your sleep and overall health. Both methods of testing are painless and simple to administer, usually within a single night. A physician analyzes these measurements to offer a diagnosis. Once you receive your diagnosis, our dentist, Dr. Merrily Sandford, and our team can help you determine the best treatment for your case.
If you think you are suffering from sleep apnea or want to be tested, Dr. Sandford, in conjunction with a qualified sleep physician, can bring you relief and answers with sleep apnea treatment in Austin, Texas. If you would like to get treated, call 512-263-8284 for more information.


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Maverick County Sheriff Tom Schmerber touched base on the fact that the No Texting While Driving Law is a few weeks from going into effect in the State of Texas including in Maverick County.
"The Maverick County Sheriff Department is in preparations to begin enforcing this new law throughout our community. As we all know that a no cell phone use law is set in place in the area of school zones but the No Texting While Driving will be enforceable everywhere that you're driving. Once this law goes into effect on September 1st we will be ticketing people for not following it.
I do recommend that people seriously reconsider their actions behind the wheel. I also do recommend that people consider seek to go hands free on their device use by purchasing a hands free accessory. That is one possible option but if you are detected to be driving and texting at the same time you will be ticketed."
Schmerber does advice the community that as of September 1, 2017 texting while driving will be illegal in Texas including in Maverick County.
Governor Greg Abbott signed the ban into law during June ending a decade-long effort to reduce potential deadly driver distractions across the entire state and its roadways. Texting While Driving will be punishable by a fine of up to $99 for first-time offenders and $200 for repeat offenses.


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The New Elizabeth Hotel
This weekend I was able to check out the new Elizabeth Hotel in Fort Collins for dinner, and it is great! The Emporium, the restaurant in the hotel, while pricey was totally worth it for the quality and quantity of food. It has a very upscale vibe, and the hotel bar, lobby, and restaurant were PACKED on Saturday night. This is clearly the hot new destination in town. I had some friends stay there over the weekend, and the surprising thing was the price was only about $170 per night!
The Elizabeth is a pet friendly hotel, and was developed with McWhinney and Sage Hospitality. It even features something called the Beer and Bike Suite with its now beer tap, beer refrigerator fully stocked, and bikes for the guests to use. I highly recommend checking it out!
Friday Fun Facts!
Dog Friendly Fort Collins
As I was playing in the backyard with my dogs yesterday (Bella the Weimaraner and Haley the Doberman), I thought "I should let dog people know just how cool it is to be a dog in Fort Collins". Fort Collins was voted in the top 10 Dog Friendly Cities in the US by REALTOR.com, they even said that 67% of all households in the Fort own a dog.
Check out links below to some of the activities for you and your pup in Fort Collins. As always, if you have any questions or would ever like to chat please let me know!
Dog Links:
Best Places To Take Your Dog in Fort Collins


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The standard connector plugs used on all AEG's, batteries and associated chargers.
The standard connector plugs used on all AEG's, batteries and associated chargers. The set comprises of one male and one female connector including the pin inserts. We recommend that the wiring is soldered onto the pins rather than just crimping as the current involved is high enough to cause overheating problems and possibly fire if not connected properly.
All images, product contents and specifications listed are based on checks performed when a product is first listed and may differ due to changes over time made by the manufacturer. This includes package contents in regards to any 'extras' provided e.g. Sample BBs.
Items used in images to promote the main item (Holsters, Camo, etc) are not supplied unless listed in the Specification tab under 'Extras'. This includes attached rails, grips, scopes, suppressors etc. If no extras are listed, please assume none are supplied.
Unless otherwise stated in the Specification tab, Battery and Chargers are not suppplied.
Where supplied, Chinese batteries and chargers are warrantied to be not DOA (Dead on Arrival) only. We always recommend swapping out to a better quality battery and charger at the earliest opportunity.
Custom Painted products (Two-Tone) are non-refundable as these are painted to order.
Unless otherwise stated, all products are sold singly.
Any figures used are based on tests performed on the products when they are first listed. These can vary due to changes by the manufacturer, gas pressure, gas used and a number of other factors. All figures should be treated as an approximate guide and used for reference only.
All listed FPS are +/- 5% due to differences from rifle to rifle. If you require a guaranteed FPS, please add an upgrade/downgrade option on to your product (this may cost extra).
No airsoft AEG is warrantied for use with an 11.1v LiPo or higher voltage battery at UK velocities (373fps or lower) unless specifically recommended on the product itself. Use of higher voltage batteries can cause failures and will negate any warranty implied or otherwise.
Wearable Items
We cannot offer a refund or exchange on articles bought and worn skirmishing that you subsequently feel aren't suitable. If in doubt, try the kit on in your house BEFORE you play as soiled items will not be refunded for this reason. Clothing worn next to the skin (Long Johns, Socks etc) cannot be returned for refund if worn at all. For sizing, simply place them next to you before physically putting them on. Would you like to wear someone elses soiled socks?
We cannot offer an exchange on pyrotechnic devices due to device failure or items that have been stored for long periods of time. We are unable to guarantee that the pyrotechnic device has been stored in a moisture free environment or used correctly in accordance with the manufacturers guidelines.
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