gebhart/patrepeval huggingface dataset:
Expression of the E4 gene is required for establishment of soft-agar colony-forming rat cell lines transformed by the adenovirus 12 E1 gene (1984)

Rat 3Y1 cells were transfected with recombinant gARC ( pSV2gpt carrying the adenovirus 12 early region 1 [E1] gene), and focus formation was observed in monolayer cultures after culture of cells in gpt-selective medium (Eagle medium containing 10% fetal calf serum, xanthine, thymidine, aminopterin, and mycophenolic acid) for 10 days, followed by focus formation. Transformed E1Y cell lines were then established from these foci. The E1Y cells were transformed morphologically similarly to cells transformed with intact adenovirus 12 DNA but formed no colonies in soft-agar culture and induced tumors in transplanted rats only after a long incubation period. For the establishment of completely transformed cells, 3Y1 cells were transformed with combinations of gARC , pE3 (pBR322 carrying the adenovirus 12 E3 gene), and gE4 ( pSV2gpt carrying the adenovirus 12 E4 gene) DNA. E1- 3Y cells (3Y1 cells transformed with gARC and pE3 DNA), E1- 4Y cells (3Y1 cells transformed with gARC and gE4 DNA), and E1-3- 4Y cells (3Y1 cells transformed with gARC , pE3 , and gE4 DNA) were established. These transformed cell lines were compared for growth in Eagle medium with 2 or 10% fetal calf serum, colony formation in soft-agar culture, and tumor growth in rats transplanted with the transformed cells. Several transformed cell lines of E1- 4Y and E1-3- 4Y cells showed colony formation in soft-agar culture and abundant expression of the E1B gene. T antigen f was seen by immunofluorescence as flecks in these cells, in which the E4 gene was transcribed, but was not seen in E1Y cells, suggesting that T antigen f was encoded by the E4 gene. The suggestion was confirmed by the observation that T antigen f was detected in COS-1 cells transfected singly with gE4 DNA by immunofluorescence with polyclonal and monoclonal antibodies. Transcription of the E4 gene was confirmed in gE4 -transfected COS-1 cells. T antigen f, one of the E4 gene products, was identified as a polypeptide of molecular weight 11,000 (E4- 11K ) by immunoprecipitation with monoclonal antibodies. The above results also suggest that expression of the E4 gene gives cells the advantage of forming colonies in soft-agar culture. A tendency was noticed for E1B gene expression to be enhanced by E4 gene expression. The relationship between enhancement of colony formation in soft-agar culture and enhancement of E1B gene expression is discussed.
Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers (2009)

Cancer of the esophagus is of two main types, each with distinct etiological and pathological characteristics. Esophageal squamous cell carcinoma (ESCC) is predominant type of esophageal cancers worldwide comprising almost 95% of cases. While ESCC is prevalent in the developing world, esophageal adenocarcinoma is commonly seen in the developed country, usually in association with Barrett's esophagus. In spite of its higher prevalence, ESCC has not been studied as intensively as esophageal adenocarcinoma. ESCC and esophageal adenocarcinoma are common cancers worldwide with poor survival rate among patients mainly because both of these cancers lack early biomarkers of identification. Molecular mechanisms contributing to initiation and progression of esophageal squamous cell carcinoma are still poorly understood. Development of DNA microarray technology allows high-throughput identification of gene expression profiles in cancers. In order to identify molecules as candidates for early diagnosis and/or as therapeutic targets, we analyzed the mRNA expression profiles of 20 cases of ESCC using whole genome DNA microarrays. A total of 2,235 genes were differentially regulated in the tumors as compared to the corresponding adjacent normal epithelium of which 881 were significantly upregulated. We validated two molecules that were not previously reported to be overexpressed in ESCC, oral cancer overexpressed 2 (ORAOV2) and fibroblast activation protein (FAP), by immunohistochemical labeling of tissue microarrays and archival tissue sections and found that they were overexpressed in 98% (116/118) and 68% (79/116) of cases, respectively. By gene enrichment analysis, we identified significant downregulation of several genes in the arachidonic acid metabolic pathway. Overall, using this approach we have identified a number of promising novel candidates that can be validated further for their potential to serve as biomarkers for ESCC.
Randomized Comparison of Low Molecular Weight Heparin and Coumarin Derivatives on the Survival of Patients With Cancer and Venous Thromboembolism (2005)

The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings.
Experiments on incorporating syntactic processing of user queries into a document retrieval strategy (1988)

Traditional information has relied on the extensive use of statistical parameters in the implementation of retrieval strategies. This paper sets out to investigate whether linguistic processes can be used as part of a document retrieval strategy. This is done by predefining a level of syntactic analysis of user queries only, to be used as part of the retrieval process. A large series of experiments on an experimental test collection are reported which use a parser for noun phrases as part of the retrieval strategy. The results obtained from the experiments do yield improvements in the level of retrieval effectiveness and given the crude linguistic process used and the way it was used on queries and not on document texts, suggests that the approach of using linguistic processing in retrieval, is valid.
Synthesis of 1,2,3,4,5,6-Hexahydropyrrolo[3,4-c]pyrrole Dihydrobromide and 1,2,3,5-Tetrahydro-2-[(4-methylphenyl)sulfonyl]pyrrolo[3,4-c]pyrrole (1995)

Synthesis of the pyrrolo[3.4-clpyrrolederivatives (8) and (9) is reported.Nucleophilic aromatic substitution of the 7-fluoride of 1-cyclopropyl-6.7.8-triiluoro-l,4- dihydro-4-oxoquinoline-3-carboxylic acid (1) by 8 under basic conditions followed by Nmethylation, gives the quinolone antibacterial agent (11) (KR 10755, HK 3140) A majority ofcurrently marketed quinolone antibiotics contain an unsubstituted or substituted piperazine at C-7 of the quinolone nucleus.These agents possess excellent activity against Gram-negative bacteria but only fair activity against important Gram-positive pathogens I Simultaneous presence of a cyclopropyl substituent at N-I, a fluorine at C-6 and a chlorine, fluorine or trifluoromethyl at C-8 of the quinolone nucleus has been found to increase in v i m potency against Gram-positive organisms and overall it, viva but the (most efficient) fluorine at the 8-position is often associated with a number of undesirable effects such as increased phototoxicity and cytotoxicity 2b,3 A plethora of sometimes new4 nitrogenheterocycles have been reacted with tritluorocarboxylic acid (I) in order to optimize the Gram-positive activity and hr vilw efficacy of 2 and to minimize its adverse effects Chen~.Abslr.Online Search (Nov 1, 1994) indicated that the patent only refers to the compound (a), and that the patent is the only reference to the compound (9)
Molecular Orbital View of Chemisorbed Carbon Monoxide (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Orbital View of Chemisorbed Carbon MonoxideGeorge BlyholderCite this: J. Phys. Chem. 1964, 68, 10, 2772–2777Publication Date (Print):October 1, 1964Publication History Published online1 May 2002Published inissue 1 October 1964https://pubs.acs.org/doi/10.1021/j100792a006https://doi.org/10.1021/j100792a006research-articleACS PublicationsRequest reuse permissionsArticle Views6107Altmetric-Citations1737LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
High-Level GPU Programming: Domain-Specific Optimization and Inference (2008)

When writing computer software one is often forced to balance the need for high run-time performance with high programmer productivity. By using a high-level language it is often possible to cut development times, but this typically comes at the cost of reduced run-time performance. Using a lower-level language, programs can be made very efficient but at the cost of increased development time. Real-time computer graphics is an area where there are very high demands on both performance and visual quality. Typically, large portions of such applications are written in lower-level languages and also rely on dedicated hardware, in the form of programmable graphics processing units (GPUs), for handling computationally de-manding rendering algorithms. These GPUs are parallel stream processors, specialized towards computer graphics, that have computational performance more than a mag-nitude higher than corresponding CPUs. This has revolutionized computer graphics and also led to GPUs being used to solve more general numerical problems, such as fluid and physics simulation, protein folding, image processing, and databases. Un-
Abstract A29: Development of liposomal curcumin as a new potential anticancer agent (2009)

Abstract Previously, pre-clinical dose finding tolerance study in a human xenograft pancreatic cancer model of intravenous liposomal curcumin determined 20 mg/kg TIW was to be the optimum dose and schedule for anticancer activity. Follow up pharmacokinetic and dose finding studies in a health rat model evaluated doses up to 40 mg/kg was not associated with weight loss, hematological, serologic, or dose-limiting toxicity. In canine model, a single-dose finding tolerance study ranging from 2 mg/kg up to 40 mg/kg revealed the maximum tolerated dose (MTD) of liposomal curcumin to be 20 mg/kg or 540 uMol/L of curcumin maximal blood concentration. Toxicity observed at this dose level was characterized by a brief single episode of reversible hematuria. The dose limiting toxicity was observed at a single dose of 40 mg/kg of liposomal curcumin. Following dose on day 1, life threatening toxicity followed within 48 hours with the dogs exhibiting irreversible acute hemolysis with hematuria, over 60% blood loss, and associated serologic abnormalities. A control cohort of dogs infused with the same quantity of liposome contained in the 40/mg/kg dose was without ensuing toxicity. These changes suggest the mechanism of hemolysis following 40mg/kg curcumin is due to an oxidant effect. Following acute hemolysis, the iron chelation activity of curcumin could contribute to unremitting anemia by blocking iron reutilization. In conclusion, at concentrations below the canine MTD of 20 mg/kg, curcumin acts as an anti-oxidant, and acts as a pro-oxidant at higher concentrations. The disparity between rodent and canine sensitivity to liposomal curcumin may be due to species differences in pharmacokinetics and/or curcumin metabolism. Ongoing study will define liposomal curcumin pharmacokinetic parameters at the MTD in canine mode as well define tolerability of multiple dosing in dogs. In addition hematological studies are being conducted to determine the mechanism of hemolysis that was observed at higher dose levels and identify potential biomarkers for predicting toxicity. Preliminary data suggests liposomal curcumin will have promising anticancer activity. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A29.
A TLR3-Specific Adjuvant Relieves Innate Resistance to PD-L1 Blockade without Cytokine Toxicity in Tumor Vaccine Immunotherapy (2017)

Cancer patients having anti-programmed cell death-1 (PD-1)/PD ligand 1 (L1)-unresponsive tumors may benefit from advanced immunotherapy. Double-stranded RNA triggers dendritic cell (DC) maturation to cross-prime antigen-specific cytotoxic T lymphocytes (CTLs) via Toll-like receptor 3 (TLR3). The TLR3-specific RNA agonist, ARNAX, can induce anti-tumor CTLs without systemic cytokine/interferon (IFN) production. Here, we have developed a safe vaccine adjuvant for cancer that effectively implements anti-PD-L1 therapy. Co-administration of ARNAX with a tumor-associated antigen facilitated tumor regression in mouse models, and in combination with anti-PD-L1 antibody, activated tumor-specific CTLs in lymphoid tissues, enhanced CTL infiltration, and overcame anti-PD-1 resistance without cytokinemia. The TLR3-TICAM-1-interferon regulatory factor (IRF)3-IFN-β axis in DCs exclusively participated in CD8<sup>+</sup> T cell cross-priming. ARNAX therapy established Th1 immunity in the tumor microenvironment, upregulating genes involved in DC/T cell/natural killer (NK) cell recruitment and functionality. Human ex vivo studies disclosed that ARNAX+antigen induced antigen-specific CTL priming and proliferation in peripheral blood mononuclear cells (PBMCs), supporting the feasibility of ARNAX for potentiating anti-PD-1/PD-L1 therapy in human vaccine immunotherapy.
Mithramycin blocks protein binding and function of the SV40 early promoter. (1989)

Specific interactions between DNA and transcription factors are necessary for transcription initiation. These interactions provide a potential target for the selective inhibition of eukaryotic gene expression. Mithramycin is a DNA binding antibiotic which, in the presence of Mg2+, binds G-C containing sequences in the minor groove. The SV40 early promoter contains six G-C decanucleotide sequences, which are binding sites for the transcriptional activating factor, Sp1. Each of the six Sp1 binding sites of this promoter is protected from DNAse 1 digestion by mithramycin binding. Mithramycin binding to the G-C rich sequences in the SV40 early promoter prevents subsequent protein binding to these sequences. The gel retardation of the SV40 early promoter fragment incubated with a HeLa cell extract is completely abrogated by pretreatment of the DNA fragment with mithramycin. The functional significance of mithramycin binding is reflected in the ability of mithramycin to block promoter function. Mithramycin inhibits promoter dependent transcription in an in vitro runoff transcription system in a concentration dependent manner. This suggests that mithramycin prevents transcriptional activation of the SV40 early promoter by blocking binding of transcriptional activating proteins to G-C rich promoter regions.
Pathogenicity in mice of herpes simplex virus type 2 mutants unable to express glycoprotein C (1986)

Herpes simplex virus type 2 (HSV-2) mutants that were unable to express glycoprotein C (gC-2) were isolated. Deletions were made in a cloned copy of the gC-2 gene, and recombinant viruses containing these deletions were screened by using an immunoreactive plaque selection protocol. The viruses did not display a syncytial phenotype. Intravaginal inoculation of BALB/cJ mice with one of the HSV-2 gC-2- viruses produced local inflammation followed by a lethal spread of the viral infection into the nervous system in a manner identical to that produced by parental HSV-2 strain 333. Similarly, intracerebral inoculation of DBA-2 mice with the gC-2- virus produced a lethal neurological disease paralleling that caused by HSV-2 strain 333. These results indicate that gC-2 is not required for the spread of HSV-2 infections in mice.
Clinical Trials of Cancer Therapies Targeting Prostate-Specific Membrane Antigen (2007)

Prostate cancer is the most common non-cutaneous cancer of men in the United States and represents their second-leading cause of cancer-related death. Metastatic disease is largely resistant to conventional chemotherapies, and targeted therapies are urgently needed. Prostate-specific membrane antigen (PSMA) is a prototypical cell-surface marker of prostate cancer. PSMA is an integral, non-shed, type 2 membrane protein with abundant and nearly universal expression in prostate carcinoma, but has limited extra-prostatic expression. In addition, PSMA is expressed in the neovasculature of other solid tumors. These findings have spurred development of PSMA-targeted therapies for cancer, and first-generation products have entered clinical testing. Vaccine approaches have included recombinant protein, nucleic acid and cell-based strategies, and anti-PSMA immune responses have been demonstrated in the absence of significant toxicity. Therapy with drug-conjugated and radiolabeled antibodies has yielded objective clinical responses as measured by reductions in serum prostate-specific antigen and/or imageable tumor volume. However, responses were observed in a minor fraction of patients and at doses near the maximum tolerated dose. Overall, these initial studies have provided measured proof of concept for PSMA-based therapies, and second-generation antibody and vaccine products may hold the key to exploit PSMA for molecularly targeted therapy of prostate and other cancers.
Respiratory Syncytial Virus (RSV) Fusion Protein Subunit F2, Not Attachment Protein G, Determines the Specificity of RSV Infection (2003)

Human respiratory syncytial virus (HRSV) and bovine RSV (BRSV) infect human beings and cattle in a species-specific manner. We have here analyzed the contribution of RSV envelope proteins to species-specific entry into cells. In contrast to permanent cell lines, primary cells of human or bovine origin, including differentiated respiratory epithelia, peripheral blood lymphocytes, and macrophages, showed a pronounced species-specific permissiveness for HRSV and BRSV infection, respectively. Recombinant BRSV deletion mutants lacking either the small hydrophobic (SH) protein gene or both SH and the attachment glycoprotein (G) gene retained their specificity for bovine cells, whereas corresponding mutants carrying the HRSV F gene specifically infected human cells. To further narrow the responsible region of F, two reciprocal chimeric F constructs were assembled from BRSV and HRSV F1 and F2 subunits. The specificity of recombinant RSV carrying only the chimeric F proteins strictly correlated with the origin of the membrane-distal F2 domain. A contribution of G to the specificity of entry could be excluded after reintroduction of BRSV or HRSV G. Virus with F1 and G from BRSV and with only F2 from HRSV specifically infected human cells, whereas virus expressing F1 and G from HRSV and F2 from BRSV specifically infected bovine cells. The introduction of G enhanced the infectiousness of both chimeric viruses to equal degrees. Thus, the role of the nominal attachment protein G is confined to facilitating infection in a non-species-specific manner, most probably by binding to cell surface glycosaminoglycans. The identification of the F2 subunit as the determinant of RSV host cell specificity facilitates identification of virus receptors and should allow for development of reagents specifically interfering with RSV entry.
Multiple Wavelength Anomalous Diffraction (MAD) Crystal Structure of Rusticyanin: a Highly Oxidizing Cupredoxin with Extreme Acid Stability (1996)

The X-ray crystal structure of the oxidized form of the extremely stable and highly oxidizing cupredoxin rusticyanin from Thiobacillus ferrooxidans has been determined by the method of multiwavelength anomalous diffraction (MAD) and refined to 1.9 A resolution. Like other cupredoxins, rusticyanin is a copper-containing metalloprotein, which is composed of a core beta-sandwich fold. In rusticyanin the beta-sandwich is composed of a six- and a seven-stranded beta-sheet. Also like other cupredoxins, the copper ion is coordinated by a cluster of four conserved residues (His85, Cys138, His143, Met148) arranged in a distorted tetrahedron. Rusticyanin has a redox potential of 680 mV, roughly twice that of any other cupredoxin, and it is optimally active at pH values < or = 2. By comparison with other cupredoxins, the three-dimensional structure of rusticyanin reveals several possible sources of the chemical differences, including more ordered secondary structure and more intersheet connectivity than other cupredoxins. The acid stability and redox potential of rusticyanin may also be enhanced over other cupredoxins by a more extensive internal hydrogen bonding network and by more extensive hydrophobic interactions surrounding the copper binding site. Finally, reduction in the number of charged residues surrounding the active site may also make a major contribution to acid stability. We propose that the resulting rigid copper binding site, which is constrained by the surrounding hydrophobic environment, structurally and electronically favours Cu(I). We propose that the two extreme chemical properties of rusticyanin are interrelated; the same unique structural features that enhance acid stability also lead to elevated redox potential.
Burns (2006)

About 250 000 people are burnt each year in the United Kingdom. Of these, almost 112 000 attend an accident and emergency department and about 210 die of their injuries. At least 250 000 others attend their general practitioner for treatment of their injury. A burn results in loss of epidermal integrity of the skin; this article discusses the aetiology and management of various types of burn injury.
Comparison of viable cell counts and fluorescence in situ hybridization using specific rRNA-based probes for the quantification of human fecal bacteria (2000)

Conventional cultivation and fluorescence in situ hybridization (FISH) using 16S rRNA-based probes were compared for the enumeration of human colonic bacteria. Groups of common intestinal anaerobic bacteria were enumerated in slurries prepared from fecal samples of three healthy volunteers. To introduce variation between the samples, they were incubated for 48 h in batch culture (anaerobic) fermenters at 37 degrees C, and pure cultures of Bifidobacterium infantis, Clostridium perfringens, or Lactobacillus acidophilus were added. Samples were taken from the fermenters at different times. Total anaerobes, bifidobacteria, bacteroides, clostridia, and lactobacilli were enumerated by both plating and FISH. The results showed that plate counts of total anaerobes, bifidobacteria, lactobacilli and bacteroides were approximately ten-fold lower than the corresponding FISH counts. Numbers of clostridia were higher using the plating method, probably because the clostridia probe used in FISH analyses was designed to only detect part of the genus Clostridium. The introduced variation in the methods could be detected by both methods and was comparable.