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The president just met with animal breeders in California, but, perhaps more importantly, animal rights activists in the state. According to the Chronicle, the Biden administration has asked the Supreme Court to reinstate the hog producers' lawsuit against Proposition 12, a law setting minimum cage standards for hogs, chickens and veal calves. The companies that filed the complaints â the National Pork Producers Council and the National Farm Bureau Federation â argue the law interferes too much with transnational trade. The administration, for what it's worth, argues that the courts shouldn't have dismissed the lawsuit, not that the law itself is unconstitutional.
The law, which received 64% voter approval, required producers to provide at least 24 square feet of floor space for each breeding pig, one square foot for each laying hen and 43 square feet of floor space ground for calves reared for calf. It further banned California sales of meat products from animals held in smaller cages. Wayne Pacelle, president of the nonprofits Animal Wellness Action and the Center for a Humane Economy, told the the Chronicle, "It is shocking that the Biden administration is attacking the rights of states to enact anti-cruelty and food safety laws that do not exist at the federal level."
This Chinese restaurant in Berkeley is closing
A note appeared in the window of Shen Hua, a College Avenue favorite for nearly 25 years, last weekend: owner Edward Chu let fans know that Sunday, June 26 will be the last day of service. The memo cites the continued challenges of the past two years as motivation to quit. SFGATE reports that Chu was born and raised in San Francisco and opened the northern Chinese-style restaurant in 1998.
Sacramento's outdoor dining plan approved by the city
The Sacramento City Council agreed to an updated and expanded outdoor dining plan on Tuesday, June 22. Sacramento Bee writes that the outdoor dining program allows restaurants to retain their COVID-era parklets and outdoor amenities, as long as businesses seek âreputable permits,â which should be further detailed by a website. support that the city plans to launch on July 1. The new program will last until 2023 at the earliest.
4th of July celebration at this Filipino-Californian restaurant
Abaca will be the place to be on the San Francisco waterfront on Independence Day. The team will roast a whole pig, lechon-style, and serve slushies alongside a full menu including Monterey squid paella and smoked chicken palabok, while a DJ keeps things going lively throughout the case. There will be two places available for the 4th of July dinners, at noon and 1 p.m., S'mores will be available on request.
Take part in this Inner Sunset DIY dinner
Queens, the Korean convenience store on 9th Avenue, lets its fans know via instagram to pull up a stool this Friday, June 24, for a bowl or two of budae jeongol, cooked at the table â by you â and to your liking (hence the DIY part of the dinner equation). The store calls it a Standing Friday Party, which runs from 5 p.m. to 9 p.m., so if you don't catch a reservation this week there is always July.

subset: commoncrawl


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Because to write, one must truly suffer.
Juan Rulfo QuotesShowing all quotes
I am talking about misery and all of its implications.Topics in UncategorizedTags in Misery
Juan Rulfo (3)
|16th May, 1917
|7th January, 1986
|Photographer, Screenwriter, Writer
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Tax Evasion: Shakira May Face Eight-Year Jail Term
Tax Evasion: Shakira May Face Eight-Year Jail Term
Global music superstar Shakira, might face prison sentence of more than eight years following the rejection of a plea deal on accusations of tax evasion.
Spanish prosecutors in Barcelona disclosed this on Friday as they demanded a fine of nearly 24 million euros ($24.5 million) from the 45-year-old singer, whom they accuse of defrauding the Spanish tax office out of 14.5 million euros on income earned between 2012 and 2014.
The"Hips don't Lie" songstress, who has sold over 60 million albums, rejected a plea deal on Wednesday, saying in a statement through her lawyers that she was "absolutely certain of her innocence" and had decided to let the case go to court, "confident" that her innocence would be proven.
A formal referral to court has not yet been announced, neither has a trial date been set.
Lawyers for Shakira, one of the biggest names in the global music industry, say an agreement remains possible until the start of any trial.


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The Top 5 Best Dating Sites For Seniors
Before being able to use eHarmony, each individual needs to go through the registration process. The process is fairly quick and simple, so you'll spend little of your time on this step. Once you're finished signing up, you can explore the countless features eHarmony offers to its members. Other dating groups on Facebook include those for peoplewho are recently divorcedor for meetingother singles in their 50s, 60s and 70s.
The app expects you to preview through hundreds of profiles to make the list of our favorites. The best free online dating sites in the UK are sites like We Love Dates. This site is free to register, create a profile, add photos , search for singles and send an introductory message. Compared to the mentioned German online dating sites above, dating apps take a lot less effort to sign up. There is no personality test and scientific matching algorithm.
Most of the site's features are free, which means you don't have to upgrade to send/receive messages or see who checked out your profile. These Bumble profile tips will help you turn those matches into dates. OkCupid is one of the more popular dating sites out there and is definitely worth your time if you live in a decent-sized city. Most of the users are in their mid-20s to 30s… a.k.a. perfect for you.
Tinder profiles are pretty basic and include some photos and bios which is why Tinder isn't recognized as a serious relationship matchmaker. However, some people are still able to find serious relationships on the app. If you are looking to have some fun, AdultFriendFinder is the site for you. This dating website has been around since 1996 and allows users to connect with others for casual or niche dating. It has about 96 million active users and does not have a matching system.
To use eharmony properly, you will need to pay for a membership – but they encourage you to 'try before you buy' for free initially. With the free trial, you can answer eharmony's questionnaire, see your matches and send icebreakers – so you can try for free and see what you think. Membership starts at £8.95 per month, but that's if you sign up for two years, with a shorter subscription bumping up the monthly price. We all know that dating can be expensive at the best of times, especially if you're going out for dinner and drinks on the reg, and these days free dating sites can be hard to come by. With so many dating sites and apps now offering subscription schemes, it can feel like the cost of dating is just racking up.
To help you out as you begin to use online dating sites, we did extensive research to find the best dating sites on the market, and this review guide takes an in-depth look at each of them. "Inner Circle is a global dating app where people meet their match. It's a community for ambitious single people who know what they want." This exceptional dating site was created in 2012 by the founder David Vermeulen. At the time he was recovering from a terrible heartbreak at the end of a long-term relationship. Dating is difficult enough for the average person, it adds an extra layer of complication for single millionaires.


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Built in 1895, this historic home site of Gail Borden, Jr., inventor of evaporated milk, has been completely restored and re-imagined. Fully furnished 4/3.5 has successfully hosted vacation rental guests who praise the accommodations. A large primary suite boasts a luxurious spa with claw foot tub and roomy shower to melt away that stress. The game room (foos ball table included) has a coffee/wine bar to compliment your entertaining events. The expansive driveway provides plenty of off-street parking for guests and/or residents. The three story carriage house located directly behind the Borden House is new construction. The Open Concept design feels larger than the 1,000 sq. ft. 2/2. Modern furnishings, horizontal railing, loft and large garage make this a desirable addition to the historic house. The Home is being sold fully furnished with a few exclusions. Take a virtual tour of the front home by clicking the virtual tour tab.
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Listing Agent: David Herrin Courtesy of: LMI Group, LLC All information is subject to change and should be independently verified. Copyright© 2022, HOUSTON REALTORS® INFORMATION SERVICE, INC. All Rights Reserved by Houston Association of REALTORS® Updated: 19th August, 2022 2:06 PM (UTC)


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PUBG Mobile India Latest Update: The launch of PUBG Mobile India has been delayed in the country for reasons yet unknown. The delay has left PUBG Corporation officials worried and they are now keen to meet the Indian government officials to get an approval for the launch of PUBG Mobile India.
Recent reports suggested that the Ministry of Electronics and Information technology (MEITY) has not given PUBG Corporation or any other entity in India permission to restart operations. This news has arrived as a disappointment for several PUBG fans in the country. However, officials from the newly formed company in India have officially asked MEITY to hold a meeting where they can discuss various aspects of the PUBG Mobile India launch.
According to the latest updates, PUBG executives have been repeatedly requesting the ministry to hold a meeting. However, PUBG's request has yet to be approved by the ministry.
With the increasing demand, PUBG Corporation is desperate to relaunch this game in India. If they have the opportunity to meet the ministery officials, it will be clarified whether PUBG Mobile India will be launched in the country or not. Considering the current situation, it will not be easy for PUBG to relaunch the mobile game before January or February 2021 and that too will depend on the government stance.
The development comes amid the central government banning a bunch of Chinese apps one after another citing security concerns. At present, a banned company cannot simply operate by floating a new company. This also applies to Tik Tok or other mobile game.
To lift the ban, PUBG Corporation decided to stop authorising the PUBG Mobile franchise to China-based Tencent Games in India. However, PUBG Corp is preparing to launch an Indian version of PUBG game.
No response from ministry on PUBG officials' meeting request
The MEITY has not responded yet to the request of PUBG officials to hold a meeting, sources have said.
According to InsideSport, it's been more than four weeks now since the company officials have requested ministry officials for a meeting. Sources close to the company officials have informed InsideSport that MEITY is yet to respond to the request.
"Government is yet to respond to the request for the meeting. The game promoters are ready to comply to all norms set by the Indian government – but no response has comeback from the MEITY office", told a source close to the game operators.


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Everyday Ageism: FEMAIL columnist CHRISTA D'SOUZA, admits she's torn about the word 'wrinklies' being banned from Scrabble
- There has been a crackdown on hate speech in the Scrabble community
- Christa D'Souza says 'wrinklies' being banned makes her want to scream
- British columnist argues there are other words which need to be banned
It's the last tolerated prejudice. But Femail's had enough. It's time we called out those day-to-day moments when we're patronised for no longer being young...
If you are part of the Scrabble community you will know there's been a crackdown on hate speech.
One such word which may come to be banned is 'wrinklies', that is, the nickname given to those of us whose skin is not as elastic as it was in our youth.
Christa D'Souza (pictured) said the word 'wrinklies' being banned from Scrabble makes her want to throw her hands in the air and scream
On the one hand I want to throw my hands in the air and scream 'Come on!' There are words which definitely need to be banned, I do not need to list them here, but 'wrinklies'? What next?
More insulting to me, somehow, is the new rule that proper nouns — names of people, companies and brands — now count in Scrabble. Honestly, you were never allowed to do that in my day. On the other hand, as I was scrutinising my face yesterday and noticing how many more lines I have, it suddenly felt like a gracious gesture.
I don't know if the word 'wrinkly' features in a book, film or show, but maybe they should also ban the word from Charades. Imagine someone stabbing their finger at your eyes or neck as they acted it out? Maybe I'm losing my sense of humour here. But then if millennials are allowed to be humourless, why can't 60-plussers? Wrinklies can be woke too, y'know.
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The provisional conference programme is now available and registration is open at: https://www.bathspalive.com/online/article/IVACS
Our keynote speakers are: Dr Ivor Timmis : Vernacular Voices from the Vaults: historical perspectives on spoken grammar Prof Alison Sealey : "If we use 'human' in a very loose context it's very dehumanizing" Macro, meso and micro contexts in corpus-assisted discourse analysis
It looks set to be a very interesting conference with a good line up of papers. Our conference dinner is in the iconic setting of the Pump Rooms next to the Roman Baths with the conference itself taking place on Bath Spa University's beautiful Newton Park campus.
I look forward to welcoming you to Bath.
Róisín Ní Mhocháin r.nimhochain at bathspa.ac.uk
IVACS 2016 Conference OrganiserAward Leader MA TESOLInstitute for EducationBath Spa University
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Apple has added two more exclusive offers for .Mac members — a free coy of ArcSoft's PhotoStudio X and a 20 percent discount on ArcSoft's Panorama Maker. PhotoStudio X (US$79.99 value) is photo-editing software that lets you remove backgrounds, add text, and apply a variety of special effects to enhance your photos. ArcSoft's Panorama Maker, which lets you merge three or more pictures into a panoramic image, is available for US$29.99 with the .Mac discount (regularly $39.99). Both offers are available until Feb. 18, 2004.
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Armed carjacking occurs at Second, Chalmers streets
February 1, 2022
Post updated on Feb. 1 at 4:53 p.m.
On Tuesday afternoon, an armed carjacking occurred at the intersection of Second and Chalmers streets. The suspects were arrested within the hour and the situation has been resolved, according to an Illini Alert.
An Illini-Alert was sent at 3:54 p.m., urging people to use caution and avoid the area.
Another Illini-Alert was sent at 4:10 p.m., stating that the suspects left the area and it was safe to resume normal activities.
Editor's note: This is an ongoing story. Stay with The Daily Illini for updates.


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Expression of SAMHD1 and its mutation on prognosis of colon cancer
- Authors:
Affiliations: Translational Medical Centre, Wuxi No. 2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, Jiangsu 214002, P.R. China, Department of Pathology, Wuxi No. 2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, Jiangsu 214002, P.R. China
- Published online on: July 8, 2022 https://doi.org/10.3892/ol.2022.13423
- Article Number: 303
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Colon cancer is a common type of digestive system malignancy worldwide (1,2). Cancer statistics from 185 countries show that 1,104,100 novel cases and 883,200 mortalities were caused by colon cancer in 2018 (3). The incidence rate was ranked fourth and the mortality rate was ranked second among all types of cancer worldwide (3). With improved living standards and diet, the incidence of colon cancer has increased owing to high-fat diet and insufficient food fiber (4). Colon cancer is most common where the rectum and sigmoid colon connect, and it is more common in male compared with female patients (5). Prognosis and treatment of colon cancer is important. Current clinical treatment of colon cancer is based on surgery, radiotherapy and chemotherapy, but the five-year survival rate has not greatly improved (6). Mutations in Kirsten rat sarcoma virus (KRAS) is a diagnostic biomarker and therapeutic target of colon cancer (7). Therefore, determining the molecular mechanism of colon cancer prognosis is crucial to develop gene therapy.
The only dNTP hydrolase in eukaryotes, SAMHD1, is involved in multiple pathological processes (8). SAMHD1 serves a key role in preventing virus transcription and replication by hydrolyzing dNTP, thus protecting host cellular genome integrity (9). As an intrinsic host restriction factor, SAMHD1 exploits deoxynucleoside triphosphohydrolase (dNTPase) activity to resist human immunodeficiency virus 1 (10). Literature has shown that SAMHD1 is primarily involved in apoptosis and proliferation through hydrolyzing nucleic acids (11,12). Although some consider SAMHD1 to serve only as a dNTPase, others hypothesize that SAMHD1 can be used not only as dNTPase but also as RNase. Therefore, this remains controversial (8,13). SAMHD1 is also known as Aicardi-Goutières syndrome (AGS) gene because multipoint mutations in SAMHD1 cause familial autoimmune AGS (14–17). SAMHD1 is affected by post-translational modifications, such as phosphorylation, acetylation and methylation, which primarily affect its ability to prevent viral infection (18–22). For example, phosphomimetic mutation of T592E causes notable destabilization of the active tetrameric form of SAMHD1 and a ~3-fold decline in dNTPase activity (9). However, the T592V variant does not disrupt the crystal structure of SAMHD1, thus its dNTPase activity is not affected (9). Furthermore, SAMHD1 is acetylated on K405 by acetyltransferase arrest defective protein 1, which increases its dNTPase activity in vitro (21).
Previous studies have shown that SAMHD1 is associated with development of several types of cancer, including lung and colon cancer (20,23). SAMHD1 mRNA and protein expression levels have been shown to be decreased in lung adenocarcinoma tissue compared with adjacent normal controls, which suggests that the SAMHD1 promoter is highly methylated in lung adenocarcinoma, leading to decreased SAMHD1 expression (20). The decrease of SAMHD1 activity is caused by frequent mutations of SAMHD1 gene in colon cancer cells (23), which suggests that the decrease of SAMHD1 activity is associated with an increased risk for colon cancer compared with other types of cancer. A total of 164 unique mutations in SAMHD1 from a variety of cancer tissues are listed in the catalogue of cancer somatic mutations, which indicates that SAMHD1 mutation is more frequent in cancer (24). SAMHD1 mutations at residues 123, 143, 145, 201, 209, 254, 369 and 385 lead to decreased function of endogenous SAMHD1 protein and disrupt nucleotide metabolism in myeloid cells, leading to carcinogenesis (15). However, the effect of SAMHD1 on colon cancer prognosis is not clear. The present study aimed to determine expression of SAMHD1 in colon cancer and the effect of its dNTPase function on cell apoptosis and proliferation to provide potential biomarkers for prognosis of colon cancer.
Materials and methods
Dataset access and information
The Gene Expression Omnibus (GEO) database was searched (ncbi.nlm.nih.gov/geo; GSE41258). Perl (strawberry-perl-22.214.171.124-64bit; strawberryperl.com/releases.html) command was used to convert the genetic probe IDs in the matrix documents to the platform's genetic symbols to acquire a matrix document encompassing formal symbols. All datasets were normalized using the limma R package (R for Windows 4.1.0 Setup and http://www.rstudio.com). The entire genetic expression data underwent log2 transformation.
Dataset analysis
Gene differential analysis [|LogFC|>1, adjusted P-value (FDR) <0.05] was performed by comparing tumor tissue with controls using limma R package. A volcano plot (R for Windows 4.1.0 Setup; rstudio.com) was created to present the fold-change and P-values of differentially expressed genes (DEGs) using limma R package.
Protein-protein interaction (PPI) network construction
Core genes were obtained from PPI network [Search Tool for the Retrieval of Interacting Genes/Proteins (STRING); string-db.org/] and Cytoscape software (Cytoscape_3_8_2_windows_64bit; cytoscape.org/download.html) was used to plot the net diagram. Each node denotes a protein or gene (25); edges between nodes denote molecular interactions.
Patient information
The present study was approved by the Ethics Committee of Wuxi No. 2. People's Hospital (Wuxi, China; approval no. 20180706). The patients were recruited between January and November 2020. For all patient-derived tissues, written informed consent was obtained. A total of 184 patients (sex, 98 male and 86 female; age, 19–87 years) with colon cancer and 45 adjacent normal tissues (sex, 23 male and 22 female; age, 19–85 years) were included.
Colon cancer tissue were collected to assess tumor morphology as part of routine surgery. Inclusion criteria were as follows: i) Colon cancer diagnosed by histopathological examination; ii) imaging examination confirmed that there was one or more measurable lesions; iii) routine blood examination, liver and kidney function and ECG were normal and iv) estimated survival time >3 months. Exclusion criteria were as follows: i) Patients with other types of tumor or ii) serious underlying disease.
Immunohistochemistry (IHC)
IHC was performed routinely on all primary colon cancer samples, as previously described (26,27). All samples were fixed in 10% neutral buffered formalin at room temperature for 1 h and maintained at 4°C with 30% saccharose overnight. Subsequently, all biopsy samples were embedded in optimal cutting temperature compound and sectioned in 4-µm thick slices, followed by blocking with 10% normal goat serum (cat. no. abs933; Absin) at 37°C for 60 min. The sections were incubated with SAMHD1 antibody (cat. no. ab128107; Abcam; 1:150) at 37°C for 0.5 h, followed by incubation with HRP-Polymer anti-Mouse/Rabbit IHC kit (cat. no. KIT-5020; MXB; 1:100) at 37°C for 30 min. To visualize the antigen-antibody complexes, sections were counterstained with 0.01% DAB at room temperature for 5 min and hematoxylin at room temperature for 3 min. Slides were washed for 10 min with PBS after every step. All samples were imaged using a CX31 light microscope (Olympus Corporation).
Cell culture and transfection
To eliminate background interference, HT-29 (cas9-SAMHD1) cells were constructed. NCM460 was purchased from American Tissue Culture Colection (Manassas, VA, USA), HT-29 and HT-29 (Cas9-SAMHD1) cells were purchased from Cell Bank of Chinese Academy of Sciences (Shanghai, China) and verified by STR DNA profiling. HT-29 (Cas9-SAMHD1) cells were derived from HT-29 cells, which had previously undergone SAMHD1 gene knockout using CRISPR/Cas9 system. All cells were cultured in McCoy's 5A medium (cat. no. 12330031; Thermo Fisher Scientific, Inc.) supplemented with 10% FBS (cat. no. 16140071; Thermo Fisher Scientific, Inc.), 0.5 mmol/l L-glutamine (cat. no. 25030-024; Thermo Fisher Scientific, Inc.), 0.01 mg/ml insulin (Novo Nordisk A/S), 100 IU/ml penicillin and 100 mg/ml streptomycin (cat. no. DE17-602E; Lonza Group, Ltd.), and all cells were cultured in 37°C and 5% CO2. 100 cm2 Flasks and plates were purchased from Nunc (Thermo Fisher Scientific, Inc.) and 6-well plates were purchased from Corning Life Sciences.
HT-29 (Cas9-SAMHD1) cells were inoculated into a 6-well plate (3×105) and incubated for 12 h prior to transfection in 37°C and 5% CO2. Cells were separated into experimental and control groups with each group containing 3 µg plasmid + 5 µl Lipofectamine® 3000 (cat. no. L3000015, Thermo Fisher Scientific). All plasmids, including Flag-SAMHD1 (WT), Flag-SAMHD1 (Q548A), Flag-SAMHD1 (D137N) and Flag-SAMHD1 (D311A), were purchased from Shanghai GenePharma Co., Ltd. The vector for all plasmids involved in this study was PCNDA4.0. Cells were transfected at 70% confluence at room temperature. A total of 5 µl Lipofectamine 3000 was added to 125 µl DMEM/F-12 and mixed well. In addition, 3 µg DNA plasmid and 5 µl P3000™ reagent were added to 125 µl DMEM/F-12 and mixed well. The two solutions were then mixed, maintained at room temperature for 20 min and added into the wells in a drop-wise manner. Cells were transfected in DMEM/F-12 for 6 h, then DMEM/F-12 was replaced with McCoy's 5A for 18 h. Cells were then harvested for subsequent experiments. According to preliminary results, 20 µg/ml was the most suitable concentration of 5-FU for tumor cells (data not shown).
Immunofluorescence (IF)
After placing the cell slide on the 24 well plate, NCM460 normal colon epithelial and HT-29 colorectal cancer cells were inoculated in 24 well plates at a density of 1×105 cells/well. Following 24 h culture at 37°C and 5% CO2, cells were centrifuged and washed with PBS and centrifuged two times at room temperature and 1,000 × g for 5 min. 4% paraformaldehyde was fixed for 20 min and washed with PBS and centrifuged two times at room temperature for 5 min. Cells were fixed with punched with 0.1% Triton X-100 for 10 min and washed with PBS for 5 min at room temperature. Then, 0.1% BSA (cat. no. A8010, Solarbio) was used for blocking at room temperature for 1 h, followed by incubation with SAMHD1 antibody (cat. no. ab128107; Abcam; 1:100) at 4°C overnight and rinsing three times with PBS for 5 min each. Incubation with goat Anti-Mouse IgG H&L (FITC-conjugated; cat. no. ab6785, Abcam) was performed at room temperature in the dark for 1 h, followed by rinsing with PBS three times for 5 min each. The cell nuclei were stained with 10 ug/ml DAPI (cat. no. C0065; Beijing Solarbio Science & Technology Co., Ltd.) for 5 min at room temperature. Next, a drop of sealing agent was added, the film was sealed and imaging with a fluorescence microscope was performed as previously described (28,29). Images were analyzed using Cellsens Standard version 1.9 software (Olympus Corporation; olympus-lifescience.com.cn/zh/software/cellsens/).
Western blotting (WB)
Treated cells were harvested and lysed in RIPA buffering solution (Beyotime Institute of Biotechnology). Protein levels were determined using BCA (Beyotime Institute of Biotechnology). Protein samples (50 µg/lane) from each group were separated using 10% SDS-PAGE, transferred onto PVDF membranes and blocked in BSA. Next, the membranes were immersed in primary antibody at 4°C overnight. The primary antibodies (all Abcam) were as follows: Bax (cat. no. ab53154; 1:1,000), Cleaved-caspase3 (cat. no. ab32042; 1;500), Caspase3 (cat. no. ab32351; 1:1,000), Bcl-2 (cat. no. ab32124; 1:1,000) and Flag (cat. no. ab205606; 1:1,000). The normal band density of GAPDH (cat. no. ab8245; Abcam; 1:1,000) at room temperature for 2 h was used as an internal reference. Then they were rinsed with TBST (0.1% Tween-20, cat. no. ST671, beyotime) three times for 10 min each. Incubation with Rabbit Anti-Mouse IgG H&L (HRP-conjugated; cat. no. ab6728, Abcam, 1:5,000) or goat Anti-Rabbit IgG H&L (HRP, ab6721; Abcam, 1:5,000) was performed at room temperature for 1 h, followed by rinsing with TBST three times for 10 min each. Protein detection was performed using BeyoECL Star (cat. no. P0018AM, beyotime). The bands were quantified using the Image Lab System version 6.1 (Bio-Rad, bio-rad.com/SearchResults?search_api_fulltext=Image+Lab). These assays were performed at least three times, as previously described (30,31).
Cell counting kit-8 (CCK-8) assay
To detect cell proliferation, CCK-8 assays (cat. no. C0037; Beyotime Institute of Biotechnology) were performed. HT-29 (Cas9-SAMHD1) cells at the logarithmic growth stage were collected and digested to prepare HT-29 (Cas9-SAMHD1) cell suspension at room temperature for 1 min by trypsin digestion (cat. no. 25200072, Gibco). Next, 1×104 cells/well were inoculated into 96-well plates. Following 24 h incubation at 37°C and 5% CO2, cell viability in each group was detected prior to transfection. The 200 ng Flag-SAMHD1 (WT), Flag-SAMHD1 (Q548A), Flag-SAMHD1 (D137N) and Flag-SAMHD1 (D311A) plasmids were then transfected into HT-29 (Cas9-SAMHD1) cells. Cell viability was detected 24 and 48 h after transfection. A total of 10 µl CCK-8 solution was added to 90 µl culture medium. The medium was replaced in each well for testing, and cells were incubated at 37°C for 1 h. A microplate reader was used to measure optical density in each well at a wavelength of 450 nm, as previously described (32).
Following 24 h transfection at 37°C and 5% CO2, cell viability in the WT and D137N groups was detected. Cell viability was detected for 24 and 48 h following 20 µg/ml 5-FU treatment in 37°C and 5% CO2, as aforementioned.
Statistical analysis
SPSS 19.0 (IBM Corp.) was used to analyze the data. Differences between multiple groups were analyzed using one-way ANOVA followed by Tukey's honestly significant difference post hoc test. Data are expressed as mean ± SEM. An independent samples t-test was used to assess differences between two groups; χ2 test was conducted to determine differences in proportion. Progression-free survival was determined using the Kaplan-Meier method and survival differences were analyzed using log-rank test. Cox proportional hazards model was used for multivariate analysis of prognostic factors. Two-sided P<0.05 was considered to indicate a statistically significant difference. All assays were performed at least three times.
Identification of DEGs in colon cancer
GSE41258 genetic expression matrix and corresponding annotated files were acquired from GEO database. The dataset, which included 187 patients with colon cancer and 45 adjacent normal tissue, was analyzed using the GPL596 Affymetrix Human Genome U133 Plus 2.0 Array. A total of 6,905 DEGs were identified from the GSE41258 dataset using the R package. DEGs were identified using microarray volcano plots (Fig. 1A). STRING database and Cytoscape were used to construct and visualize a PPI network of DEGs. The location of DEG was visualized by PPI analysis. The KRAS mutation is common in colon cancer (occurring in 30–50% of cases) and has been recognized as a key molecular marker for predicting response to anti-epidermal growth factor receptor monoclonal antibodies, cetuximab and panitumumab in metastatic colon cancer (33). Using the PPI network, SAMHD1 was found to be associated with KRAS and the expression of SAMHD1 is upregulated in colon cancer. The red is up and green is downregulation. (Fig. 1B). A total of 187 patients with colon cancer from the GEO database were divided into high and low KRAS expression groups. SAMHD1 expression was negatively associated with KRAS (Fig. 1C). Cox proportional hazards model was used to analyze the effect of multivariate data (SAMHD1 expression, age, sex and TNM) on patient mortality. Cox proportional hazards regression analysis and survival analysis found that low SAMHD1 expression was a factor that led to patient mortality (Fig. 1D). The survival time of patients with low SAMHD1 expression was significantly shorter compared with that of patients with high SAMHD1 expression (Fig. 1E). According to bioinformatics, low expression of SAMHD1 was associated with poor prognosis.
Figure 1.
Identification of DEGs in colon cancer. (A) DEGs were identified using microarray volcano plots. (B) Using a protein-protein interaction network, SAMHD1 was found to be associated with KRAS. (C) SAMHD1 expression was negatively associated with KRAS (P=0.0035). (D) Cox proportional hazards model was used to analyze the effect of univariate data (SAMHD1 expression, age, sex and TNM) on mortality of patients with colon cancer. (E) Survival analysis showed that the survival time of patients with low SAMHD1 was significantly shorter compared with that of patients with high SAMHD1 expression. DEGs, differentially expressed genes; FC, fold change; KRAS, Kirsten rat sarcoma virus; SAMHD1, sterile α motif and histidine/aspartic acid domain-containing protein 1.
Low expression of SAMHD1 in colon cancer
IHC analysis of colon cancer tissue revealed lower expression of SAMHD1 compared with expression in adjacent normal tissue (Fig. 2A and B). The nucleus of healthy tissue exhibited diffuse brown staining, indicating the presence of SAMHD1. However, low SAMHD1 expression was detected in patients with colon cancer. To verify these results, expression levels of SAMHD1 were measured in HT-29 colorectal cancer cells. IF revealed lower SAMHD1 expression in HT-29 compared with NCM460 healthy colonic epithelial cells (Fig. 2C and D), which was consistent with IHC results.
Figure 2.
Low expression of SAMHD1 in colon cancer. (A) Representative IHC staining images and (B) quantitative analysis of colon cancer tissue revealed lower expression of SAMHD1 in colon cancer tissues compared with adjacent normal tissues. (C) Representative immunofluorescence staining images and (D) quantitative analysis revealed significantly lower SAMHD1 expression in HT-29 colorectal cancer cells compared with expression in NCM460 normal colon epithelial cells, which was consistent with IHC. **P<0.01. IHC, immunohistochemistry; SAMHD1, sterile α motif and histidine/aspartic acid domain-containing protein 1.
To determine the association between SAMHD1 expression and clinical features, patients were divided into two groups: Positive (≥5%) and negative (<5%) SAMHD1 expression (Table I). No significant differences in age and sex were observed between the two groups. There was a significant association between SAMHD1 expression and N, T and M stage. These data indicated that SAMHD1 may be a biological marker for diagnosis and prognosis of patients with colon cancer.
D137N mutation of SAMHD1 inhibits apoptosis and promotes proliferation of HT-29 (Cas9-SAMHD1)
Post-translational modification and associated sites of SAMHD1 are presented in Table II. WB showed SAMHD1 expression was significantly lower in the HT-29 (Cas9-SAMHD1) group compared with HT-29 (Fig. 3A and B), which indicated the HT-29 (Cas9-SAMHD1) cell model was successfully constructed. Then, three classical mutation sites of SAMHD1 were selected: Q548A, D137N and D311A (11,12). Q548A is RNase deletion, D137N is dNTPase deletion, D311A is RNase deletion and dNTPase deletion (11,12). WB analysis showed that there was no significant difference in Caspase3, Cleaved-caspase3, Bax and Bcl-2 expression levels between the Q548A and WT groups (Fig. 3C and D). Compared with the WT group, expression levels of Caspase3, Cleaved-caspase3 and Bax significantly decreased, whereas Bcl-2 expression significantly increased in the D137N and D311A groups, which indicated that D137N and D311A groups significantly inhibited the expression of apoptosis-related proteins. CCK-8 results showed that the difference in proliferation between the Q548A and WT groups was not statistically significant (Fig. 3E). Compared with WT group, proliferation increased in the D137N and D311A groups.
Figure 3.
D137N mutation of SAMHD1 inhibits apoptosis and promotes proliferation of HT-29 (Cas9-SAMHD1). (A) Successful construction of HT-29 (Cas9-SAMHD1) model. (B) Semi-quantitative analysis of WB images from (A); GAPDH was used as a positive control. **P<0.01. (C) Representative WB images and (D) semi-quantitative analysis of apoptosis-related protein expression in WT, Q548A, D137N and D311A groups. One-way ANOVA followed by Tukey's honestly significant difference post hoc test was used to evaluate the difference between groups. *P<0.05 vs. WT. (E) Cell Counting Kit-8 assay was used to detect cell viability in the WT, Q548A, D137N and D311A groups at 0, 24 and 48 h. *P<0.05 vs. WT. OD, optical density; SAMHD1, sterile α motif and histidine/aspartic acid domain-containing protein 1; WB, western blotting; WT, wild-type.
5-FU treatment promotes apoptosis and inhibits proliferation of HT-29 (Cas9-SAMHD1)
WB analysis showed that in the WT and D137N groups, Caspase3, Cleaved-caspase3 and Bax expression significantly increased and Bcl-2 significantly decreased over time following 20 µg/ml 5-FU treatment (Fig. 4A and B), potentially promoting cell apoptosis. However, compared with the WT group, Caspase3, Cleaved-caspase3 and Bax expression levels were significantly lower and the Bcl-2 level was significantly higher in the D137N group, suggesting a potentially inhibiting effect on the expression of apoptosis-related proteins. CCK-8 results showed that, following 20 µg/ml 5-FU treatment, proliferation in the WT and D137N groups was significantly decreased over time (Fig. 4C). However, compared with the WT group, viability in the D137N group was significantly higher at each time point.
Figure 4.
5-FU treatment promotes apoptosis and inhibits proliferation of HT-29 (Cas9-SAMHD1). (A) Apoptosis-related protein expression was detected by WB analysis following treatment with 20 µg/ml 5-FU for 48 h. (B) Semi-quantitative analysis of the WB images in (A); GAPDH was used as a positive control. One-way ANOVA followed by Tukey's honestly significant difference post hoc test was used to evaluate the difference between groups. *P<0.05 D137N vs. WT; ΔP<0.05 24 h vs. 0 h; ☆P<0.05 48 h vs. 0 h. (C) Cell Counting Kit-8 assay was used to determine cell viability following 20 µg/ml 5-FU treatment for 0, 24 and 48 h. *P<0.05 vs. WT. 5-FU, fluorouracil; OD, optical density; SAMHD1, sterile α motif and histidine/aspartic acid domain-containing protein 1; WB, western blotting; WT, wild-type.
The human SAMHD1 gene was first cloned from human dendritic cell cDNA in 2000 (34). Its protein expression is induced by IFN-γ (34,35). In addition to being associated with occurrence and development of lung and colon cancer, low-level exogenous SAMHD1 expression leads to a notable decrease in development, proliferation and colony formation of HUT78 human T lymphocyte leukemia cells by promoting apoptosis, and SAMHD1 may be a therapeutic target against cancer involving T lymphocytes (20,23,36). The number of SAMHD1 mutations and expression levels vary between types of so lid cancer, such as lung adenocarcinoma and colon cancer, and affect the efficiency of clinical first-line chemotherapy drug ara-C in leukemia (20,23,37). Multipoint gene mutations of SAMHD1 were detected in leukemia cells, resulting in decreased mRNA and protein expression levels of SAMHD1 (38,39). The sensitivity of THP-1 human myeloid leukemia monocytes, which do not exhibit dNTPase activity of SAMHD1, to anti-metabolites, such as fludarabine, decitabine, cytarabine and clofarabine, has improved (40). SAMHD1 protects cancer cells from anti-nucleoside metabolites, such as ara-C (37,40–42). Certain SAMHD1 mutation results in loss of dNTPase activity, leading to abnormal dNTP accumulation, which causes rapid cancer cell proliferation (43–46) and immune system dysfunction (44). In addition, SAMHD1 may protect cancer cells from DNA replication inhibitors, such as antimetabolite antineoplastic agents (43,47). As a result, SAMHD1 is considered a potential biomarker for the stratification of patients with AML based on response to ara-C and a potential therapeutic agent against ara-C-refractory AML (37). It is hypothesized that a similar phenomenon may occur in colon cancer. Previous studies have found that SAMHD1 mutations increase whole mutation rates in colon cancer cells, and SAMHD1 may be a prognostic marker of colorectal cancer (23,48). D137N (dNTPase deletion) and D311A mutation (RNase and dNTPase deletion) prevent the antiviral activity of SAMHD1, whereas the Q548A mutation (RNase deletion) does not significantly inhibit its antiviral activity (11). The present study analyzed the association between SAMHD1 and KRAS and found that SAMHD1 was expressed at low levels in colon cancer. The effects of three classic SAMHD1 mutations (Q548A, D137N and D311A) on apoptosis and proliferation of colon cancer cells were subsequently assessed. The effect treatment with first-line drug 5-FU against colon cancer cells with D137N mutation is time-dependent.
The incidence and mortality rate of colon cancer in 2018 ranked fourth (3) in all types of cancer worldwide, which showed that the present research has high clinical value. In addition, a review of The Cancer Genome Atlas found that, among 15 types of cancer with frequent SAMHD1 mutations, mutation rate of SAMHD1 in colon cancer ranked third and frequent mutations in SAMHD1 gene that result in its downregulation have also been found in colon cancer (23). Here, SAMHD1 was differentially expressed between the adjacent normal tissue group and the colorectal cancer group. Therefore, the present study investigated expression of SAMHD1 in colon cancer. In the present study, 6,905 DEGs were identified using R software firstly. The classical colorectal cancer gene KRAS was selected and found different SAMHD1 expression levels in KRAS-L and KRAS-H in colorectal cancer. SAMHD1 and KRAS were found to be negatively associated. Cox proportional hazards regression and survival analyses demonstrated that low expression of SAMHD1 was associated with increased patient mortality. This is consistent with the conclusions of previous studies in AML (49). Therefore, it was hypothesized that SAMHD1 may serve a key role in colorectal cancer. The expression of SAMHD1 in colorectal cancer was assessed in tissue and cells; its mRNA expression was lower in tumor compared with that in adjacent normal tissue. Similarly, compared with NCM460 normal colon epithelial cells, SAMHD1 expression in HT-29 colorectal cancer cells was decreased, which was consistent with the results of bioinformatic analysis. The effect of mutations in the dNTPase functional site of SAMHD1 on proliferation and apoptosis of colon cancer was investigated. Therefore, three previously reported mutation sites of SAMHD1 were selected: Q548A, D137N and D311A (11,12). The Q548A mutation had no significant effect on proliferation and apoptosis of HT-29 cells compared with WT group, whereas D137N and D311A notably promoted proliferation and inhibited apoptosis of HT-29 cells. WT and D137N groups were treated with 20 µg/ml 5-FU for 24 and 48 h. The results showed cell proliferation was inhibited and apoptosis-related protein expressions were promoted in WT and D137N groups over time following 20 µg/ml 5-FU treatment. However, compared with the WT group, cell proliferation in the D137N group was higher and apoptosis-associated protein expression levels were lower following 20 µg/ml 5-FU treatment.
In conclusion, SAMHD1 was expressed at low levels and was associated with prognosis in colon cancer. The dNTPase function of SAMHD1 may inhibit proliferation and promote apoptosis in colon cancer cells. In addition, first-line chemotherapy with 5-FU had a time-dependent effect on colon cancer cells, which may provide novel options for clinical treatment of colon cancer.
Not applicable.
The present study was supported by the Wuxi Health Commission Scientific Research Project (Wuxi, China; grant no. MS201930).
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Authors' contributions
PS conceived and designed the experiments. ZZ and PL performed the experiments, analyzed the data and wrote the manuscript. All authors have read and approved the final manuscript. ZZ and PS confirm the authenticity of all the raw data.
Ethics approval and consent to participate
The present study was approved by the ethics committee of Wuxi No. 2. People's Hospital (Wuxi, China; approval no. 20180706). Written informed consent was obtained from all patients.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
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Keeping Up with Technology in Commercial Real Estate
Key Takeaways from the 2018 Annual Real Property Retreat/California Lawyers Association Real Property Law Section
Session topics ranged from the practical, i.e., "How to Get your Project Approved Under the New Housing Laws," to the intriguing, as in the talk on "Real Estate Reimagined: When Tech and Real Estate Meet," in which the unique needs of a growing segment of commercial real estate (CRE) leasing, the tech start-ups, was discussed. We can vouch for some of the requests being made by these tenants, being a tech company ourselves, with one of the most important requirements being access to free snacks on site!
I was pleased to be part of a panel called "Keeping up with the (Techie) Joneses on day 1 of the conference. We all know that the real estate industry is slowly but surely turning to technology to solve some of their daily challenges, whether it be deal management platforms, or financial/ asset management platforms, or AI software designed to help you extract data, which is what we offer at LEVERTON. I was joined on the panel by Nav Athwal, a former commercial broker and land use attorney turned tech company leader, who founded RealtyShares, a digital platform for online investing in real estate. Michael Sroka, co-founder and CEO of Dealpath, a deal management platform for CRE teams, was the third speaker on the panel that was expertly moderated by Miriam Montesinos, Of Counsel at Pelosi Law Group and Mark Leverette, Partner at BPM LLP.
Listed below are a couple of things that stood out for me the most from our discussion:
1. The CRE law crowd IS interested in adopting new technology but is moving slowly—at least in the US.
At the start of the session, Mark asked attendees how many people were using AI in their offices today. Not one person raised their hand. At LEVERTON, we're speaking at conferences around the world on the topic of AI and real estate weekly, and notice an interesting phenomenon. When it comes to law firms at least, the UK and Europe are a good year to 18 months ahead in terms of adoption.
2. There's a demand for an easier way to raise the capital, manage assets, review leases, etc.
Nav spoke about the passion for tech by Early Adopters, an excellent, "first to adopt" audience descriptor from Geoffrey A. Moore's iconic book on tech marketing, "Crossing the Chasm." People are looking for simpler ways to get their daily work done in CRE and those with a vision and an innovative bent are giving it a try. What's harder for most technology companies to achieve is to reach and influence the larger group, the Early Majority, who are more pragmatists rather than visionaries.
3. For those in CRE, technology needs to be easy to implement, work (of course!) and hold data security in the highest importance.
The panel Q&A focused heavily on perceived risks of using these types of technologies. There must have been some pragmatists in the room! For example, many asked about data security, while others were concerned with the quality checks of crowdsourcing a deal or using AI to review leases. Nav, Mike and I all spoke about how our companies are committed to ensuring quality and data security, and that putting these types of standards and measures in place was the only way to appeal to a larger audience and have as sustainable business in today's world.
4. CRE trends includes the machine learning aspect of AI.
Panelists spoke of machine learning allowing for "the programmatic use of data", which allows for a faster delivery of insights. Being able to conduct analysis on data which has been historically highly unstructured, coupled with the reality that AI can take away some of the more mundane tasks of CRE legal work, like lease review, means this: technology in the CRE space, for those who embrace it, will lead to access and analyze data faster to make smarter decisions.
Now that's not such a bad thing, is it?
For more information on LEVERTON or to request a Demo, please click here.


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text:
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2017; you can also visit the original URL.
The file type is
Teaching computer architecture using an architecture description language
Proceedings of the 2004 workshop on Computer architecture education held in conjunction with the 31st International Symposium on Computer Architecture - WCAE '04
ArchC enables students to perform several experiments using its automatically generated SystemC simulators, covering topics from simple single-cycle (functional) models to pipeline and memory hierarchy ... The simplicity and flexibility of the ADL, along with its simulation features, proved to be an useful tool not only for research, but also for computer architecture education. ... We are also very grateful to all the students and teachers that are using ArchC, for education and/or research, whose feedback has been extremely valuable to the continuous improvement in ArchC tools. ...doi:10.1145/1275571.1275580 dblp:conf/wcae/RigoJAAC04 fatcat:ucsobfersng4hkntn2mch65454
Scalability evaluation in many-core systems due to the memory organization
2016 IEEE International Conference on Electronics, Circuits and Systems (ICECS)
The goal of this paper is to highlight the limitations of shared memory connected through a network-on-chip (NoC) in many-core systems, executing a similar workload with both memory organizations. ... SM has a worst traffic distribution, with hotspots around the SM, and a much higher communication volume compared to DM. ... The main goal is to describe the platform in a high-level abstraction, enabling the designer to explore and to evaluate new architectures with automatic generation software tools and simulators. ...doi:10.1109/icecs.2016.7841216 dblp:conf/icecsys/MadalozzoDAM16 fatcat:qbevxpxcujggzfhruhmzqyxddi
ACCGen: An Automatic ArchC Compiler Generator
2012 IEEE 24th International Symposium on Computer Architecture and High Performance Computing
exploration in early stages of the design. ... They compare, as well, the generated code quality with LLVM and gcc, two well-known open-source compilers. ... We conducted this experiment in an Intel Core 2 Quad Q6600 with 4GB RAM memory. ...doi:10.1109/sbac-pad.2012.33 dblp:conf/sbac-pad/AulerCB12 fatcat:cliw4wd54nfm3ogzhkhwbubeyi
A Methodology and Toolset to Enable SystemC and VHDL Co-simulation
IEEE Computer Society Annual Symposium on VLSI (ISVLSI '07)
Considering a standalone execution, i.e., the processor with an internal memory running the software in the same single core machine mentioned above, compiled with GCC 4.0 with full optimization, the interpreted ... The ArchC Reference Platform The ArchC Reference Platform (ARP) born like a reference model to guide ArchC [1, 2] users on how to ex-plore ArchC 2.0 TLM communications capabilities in order to build ...doi:10.1109/isvlsi.2007.9 dblp:conf/isvlsi/MacielARAA07 fatcat:t7z2heb3bneofma53bvfm4bcbi
Harmless, a hardware architecture description language dedicated to real-time embedded system simulation
Journal of systems architecture
A cycle accurate description of the memory hierarchy (memory cache, memory latency, etc.) is not presented in this paper and is still a work in progress. ... Harmless is 8% faster but does not model the memory hierarchy. Simulation times are in the same order of magnitude. ...doi:10.1016/j.sysarc.2012.05.001 fatcat:oyo7na2ckzbs5oi4vnor3ua4p4
A Combined Optimization Method for Tuning Two-Level Memory Hierarchy Considering Energy Consumption
EURASIP Journal on Embedded Systems
In this paper we combined two optimization methods for tuning both instruction and data cache configurations in a two-level memory hierarchy, where both levels have separate instruction and data caches ... Experiments based on simulations were performed for 12 applications from the Mibench suite benchmark and the combined method achieved better efficiency in 60% of the evaluated cases compared with existing ... Basically, the TECH heuristic is similar to TCaT, but it adopts a reverse exploration order and a different exploration environment based on the Architecture Description Language known as ArchC. ...doi:10.1155/2011/620578 fatcat:qxpi45v4x5gnzeb5gqu4r63ckm
An ESL Approach for Energy Consumption Analysis of Cache Memories in SoC Platforms
International Journal of Reconfigurable Computing
Thus, developing new high-level specification mechanisms for the reduction of the design effort with automatic architecture exploration is a necessity. ... PCacheEnergyAnalyzer has been validated with several applications of Mibench, Mediabench, and PowerStone benchmarks, and results show that it provides analysis with reduced simulation effort. ... This heuristic uses the eCACTI [20] cache memory model to determine the energy consumption of the memory hierarchy. ...doi:10.1155/2011/219497 fatcat:vsdfqvs27ncxtj6v7awxujxsny
An Integrated Open Framework for Heterogeneous MPSoC Design Space Exploration
Proceedings of the Design Automation & Test in Europe Conference
Among them, the difficulty of thoroughly exploring the design space by simultaneously sweeping axes like processing elements, memory hierarchies and chip interconnect fabrics. ... openness and flexibility in terms of design space exploration. 1 ... One axis of exploration involves memory hierarchies, where both the partitioning among local (e.g. caches) and higher-latency memories and the partitioning among private and shared buffers have to be investigated ...doi:10.1109/date.2006.244000 dblp:conf/date/AngioliniCLFFB06 fatcat:kjfkgmhbyfcgrpvfxfvwvbh3qq
Fast Translated Simulation of ASIPs
Doctoral Workshop on Mathematical and Engineering Methods in Computer Science
If the output would be only one single function, then, in the the case of large target application, the function would become uncompilable (e.g. problems with optimizations, problems with virtual memory ... The designer can describe resources, such as memories or registers, instruction set and its behavior. The behavior is described with SystemC functions in shared libraries. ...doi:10.4230/oasics.memics.2010.93 dblp:conf/memics/PrikrylKHK10 fatcat:epql3ez54nfdjpuelszsqdq6nm
Modeling and simulating memory hierarchies in a platform-based design methodology
Proceedings Design, Automation and Test in Europe Conference and Exhibition
Making use of the new architecture description language ArchC, able to capture the processor description as well as the memory subsystem configuration, this environment offers support for system-level ... As a case study, it is presented the memory architecture exploration for a simple image processing application, yet a more robust environment evaluation is performed through the execution of some real-world ... Figure 2 . 2 Memory hierarchy in ArchC. Figure 3 . 3 Performance of media benchmarks. ...doi:10.1109/date.2004.1268953 dblp:conf/date/VianaBRAA04 fatcat:g2hiejwotvfxbphinbrzn6lixq
Generating and evaluating application-specific hardware extensions
architecture in terms of operation set and memory model on custom instruction generation/selection under different input/output constraints. ... YARDstick is a building block for ASIP development, integrating application analysis, custom instruction generation and selection with user-defined compiler intermediate representations. ... Functional and cycle-accurate simulators generated by version 1.5.1 of ArchC can be used with YARDstick without any modifications. ...arXiv:1403.7380v1 fatcat:zqlxls245vd77bs7mrhfaiaz6m
A Framework for Reliability Assessment and Enhancement in Multi-Processor Systems-On-Chip
22nd IEEE International Symposium on Defect and Fault-Tolerance in VLSI Systems (DFT 2007)
versions of the PowerPC, Leon2 and ARM7 RISC processors; • interconnections in terms of bus and Networks-On-Chip; • memory hierarchies including simple memories and caches. ... Then, simulation can be automatically stopped and it is possible to explore the internal state of the architecture and compare it with the state of the golden model. ...doi:10.1109/dft.2007.35 dblp:conf/dft/BeltrameBFMS07 fatcat:by3mdg7yjjafvizv652ar5vnlq
Managing Complexity through Abstraction: A Refinement-Based Approach to Formalize Instruction Set Architectures
Lecture Notes in Computer Science
Current industrial practice is to describe a processor's ISA informally using natural language often with added semi-formal notation to capture the functional intent of the instructions. ... Our method is now being used to formalize the ISA of the XMOS XCore processor with the aim to guarantee that the documentation of the XCore matches the silicon and the silicon matches the architectural ... This allows design development and exploration within a hierarchy of increasingly detailed abstraction levels. ...doi:10.1007/978-3-642-24559-6_39 fatcat:uxwodbnbcvc3dfaf4dpf2swqde
0 Instruction Set Architecture
Digital Design and Computer Organization
The global memory hierarchy has not been taken into account in these processor designs, and is decided in the ASAM project by the macro-level exploration in cooperation with a separate global memory system ... hierarchy. ... 3b 4 Loading information from APEX file ... 5 Initial prototype has 3 issue -slots 6 7 Searching for best 'ed ' fitness solution ... 8 Using ' issue -slot --first ' strategy Listing A.8: Example exploration ...doi:10.1201/b12403-15 fatcat:mygaz2meibgljew5tzvmuw6x5i
Hardware-Accelerated Cross-Architecture Full-System Virtualization
ACM Transactions on Architecture and Code Optimization (TACO)
Hardware virtualization solutions provide users with benefits ranging from application isolation through server consolidation to improved disaster recovery and faster server provisioning. ... For an ARM-based Linux guest system running on an x86 host with Intel VT support we demonstrate application performance levels, based on SPEC CPU2006 benchmarks, of up to 5.88× over state-of-the-art QEMU ... In this example, the MMU is an x86-64 MMU, which has a 4-level hierarchy. Definition 3.7 (Native Page Definition 3.8 (Guest MMU). ...doi:10.1145/2996798 fatcat:kefw3xgczzf7va3kw6opeaatim
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text:
Nice. I 'm putting everything in cash today. I'll probably look like an idiot, but I've had a nice streak and things are starting to look a little too exciteable for me.
Nice, congrats Stallion.
Im in a similar spot BS. Heading on vacation after next week so I am taking a little risk off the books
SUNE bros
Still holding onto this thing Stallion? Seems like for every good news story there are 2 bad ones.
SuNE for life . Down 48 percent today
Ouch this thing is terrible just came here to check this thread. The tiny bit I am holding is down like 75%, glad I sold the majority of my position a while ago. What a mess
The ol' buy high sell low
I closed out my position at $1.60. Cost basis: $9.
^can you afford a sbux?
no, a sbux costs $60 now.
Someone put a fork in it.
And this circus ends in a clown show…
I got out at 1.20. I really wanted to love this stock, I really did
does anyone know why Bro changed his username?
guestuser Nov 17th, 2015 4:12pm
- Afghanistan
- Charterholder
- 4,134 AF Points
Is that Bromion? Maybe it had some hint to his personal info.
S&P 400 dropped it today.
GG NT. Now that SUNE is headed to the infamous land of SUNE-Q. Do we have any buyers? Does empirical evidence show that these de-listed companies during re-org that get assigned the letter Q have a sharp bounce back before it drops back down to 0 when the new stock is issued? Is it worth the gamble? I only like gambling when I have Vegas House Odds.


text:
Lessons in Life and Love
The Reality of Love
I think I can probably blame my father for my unrealistic expectations in life. I was his princess and never wanted for anything (note: if you've read my earlier posts you'll know that despite this it wasn't exactly an ideal childhood). I grew up on Disney films and dreams of Prince Charming sweeping me off my feet. Unrealistic? Absolutely. Unusual? Not really! So moving into adulthood meant that romantic relationships weren't exactly going to be the easiest thing for me to m
Back in the Dating Game
I should start by justifying the title I've given this...I currently have an app group on my phone called dating. This is next to the group called games. And sometimes I genuinely confuse the two. Dating in London is HARD! It's why I signed up for MAFS in the first place. The continuous messaging, game playing, waiting twice the amount of time divided by three times the age difference multiplied by the distance between your postcodes before you reply to their message asking y
Decision Day and moving forward
I can't believe it's all come to an end! Last week we watched back the final episode at the production office and it was probably the most emotional of them all! It's very odd watching your life back through the eyes of an edited tv show but it's even weirder watching your breakup reduced to a few lines of text. It's fair to say we've all struggled at points of the show, both recording it and watching it back. Never underestimate the impact of a tv crew in your life and membe


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Conveniently located just across the road from Bolton railway station, the B&M Bolton store features one of the biggest garden...
1 Clayton Grove, Blackburn, Blackburn, Lancashire, BB1 9HJ
At Tom Swinhoe Dry Stone Walling in Waterfoot, we have a wealth of knowledge and experience in Gardeners. Our friendly staff are...
* Gardeners
Crostons Retail PArk, Wood Street, Lancashire, BL8 1LB
1 Gorse Pit, Bury, Lancashire, BL9 7NT
Kernel Horticultural Services are a small, but professional gardening and landscaping concern, delivering a comprehensive range of...
garden services, landscapers, landscape gardener, lawn mowing
Active Way, Lancashire, BB11 1RT
This B&M home store with garden centre in Burnley is a popular addition to this part of Lancashire. If you want affordable...
Wigan Road, Bolton, BL3 4RD
Here at Bolton Garden Centre Garden Centre, we are passionate about plants and all things gardening. We have everything you will...
Victoria Road, Padiham, Burnley, Lancashire, BB12 8TG
7 Fletcher Street, Little Lever, Bolton, Lancashire, BL3 1HW
Irwell Bank Farm, Bury Road, Radcliffe, Manchester, Greater Manchester, M26 2WW
Hall Moss Business Park, Bolton Road, Darwen, Lancashire, BB3 2TT
St James's Road, Blackburn, Lancashire, BB1 8ES
CanvasDesign, Workshop 14, Off Percival Street, Darwen, Lancashire, BB3 1HB
Shaw Street, Bolton, Lancashire, BL3 6HU
Pole Street, Preston, Lancashire, PR1 1DX
119 St. James's Road, Blackburn, Blackburn, Lancashire, BB1 8ES
St James Road, Blackburn, Lancashire, BB1 8ES
126 Seymour Road, BOLTON, BL1 8PU
We offer a wide range of property maintenance services which include garden fencing, garden care, garden clearance and much more....
Garden Services -> Garden Maintenance
New Inn Farm, Dawson Lane, LEYLAND, Lancashire, PR25 5DB
One of the most striving garden nurseries with hundreds of beautiful plant varieties on offer. Specialist for Hedging Plants,...
Brokenstone Road, Darwen, Lancashire, BB3 0LL
1 Wyre Street, Padiham, Burnley, Lancashire, BB12 8DF
Playgroups & Pre-school -> Nursery Schools
Fairfield Street, Accrington, Lancashire, BB5 0LD
Green Lane, Blackburn, Lancashire, BB2 4SR
25 Warner Street, Accrington, Lancashire, BB5 1HN
Community Centres...
Haslingden Old Road, Rossendale, Lancashire, BB4 8RR
King Street, Leyland, Lancashire, PR25 2LE
Garden City Medical Centre, 1a Garden City, Ramsbottom, Bury, Lancashire, BL0 9TN
Derby Barracks Fletcher Street, Bolton, Lancashire, BL3 6NF
Sport Centre, Chester Street, Blackburn, Lancashire, BB1 1DR
38 Peel Mount, Blackburn, Lancashire, BB1 2DU
We have been in the garden business for nearly 17 years and we take great pride in our work. We have expertise in everything from...
Garden Services -> Tree Surgeons
Dawson Lane, Whittle-le-Woods, Chorley, Lancashire, PR6 7DT
Unit 5b Bradley Hall Trading Estate, Bradley Lane, Standish, Wigan, Lancashire, WN6 0XQ


text:
Simple yet solid, the colours on the Nike Dunk Low Gym Red have been around since 1985 with the release of the 'Be True to Your School' pack. Taken from the University...
Style Code: DD1391-602
Condition: Brand New
Delivery: Standard Service
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