gebhart/patrepeval huggingface dataset:
The TLR3 signaling complex forms by cooperative receptor dimerization (2008)

Toll-like receptors (TLRs) initiate immune responses by recognizing pathogen-associated molecules, but the molecular basis for recognition is poorly understood. In particular, it is unclear how receptor-ligand interactions lead to the initiation of downstream signaling. Here, we describe the mechanism by which TLR3 recognizes its ligand, double-stranded RNA (dsRNA), and forms an active signaling complex. We show that dsRNA binds saturably, specifically, and reversibly to a defined ligand-binding site (or sites) on the TLR3 ectodomain (TLR3ecd). Binding affinities increase with both buffer acidity and ligand size. Purified TLR3ecd protein is exclusively monomeric in solution, but through a highly cooperative process, it forms dimers when bound to dsRNA, and multiple TLR3ecd dimers bind to long dsRNA strands. The smallest dsRNA oligonucleotides that form stable complexes with TLR3ecd (40-50 bp) each bind one TLR3ecd dimer, and these are also the smallest oligonucleotides that efficiently activate TLR3 in cells. We conclude that TLR3 assembles on dsRNA as stable dimers and that the minimal signaling unit is one TLR3 dimer.
Hypoxia-Inducible Factor 1 Alpha Contributes to Cardiac Healing in Mesenchymal Stem Cells-Mediated Cardiac Repair (2012)

Mesenchymal stem cells (MSC) are effective in treating myocardial infarction (MI) and previous reports demonstrated that hypoxia improves MSC self-renewal and therapeutics. Considering that hypoxia-inducible factor-1 alpha (HIF-1α) is a master regulator of the adaptative response to hypoxia, we hypothesized that HIF-1α overexpression in MSC could mimic some of the mechanisms triggered by hypoxia and increase their therapeutic potential without hypoxia stimulation. Transduction of MSC with HIF-1α lentivirus vectors (MSC-HIF) resulted in increased cell adhesion and migration, and activation of target genes coding for paracrine factors. When MSC-HIF were intramyocardially injected in infarcted nude rats, significant improvement was found (after treatment of infarcted rats with MSC-HIF) in terms of cardiac function, angiogenesis, cardiomyocyte proliferation, and reduction of fibrotic tissue with no induction of cardiac hypertrophy. This finding provides evidences for a crucial role of HIF-1α on MSC biology and suggests the stabilization of HIF-1α as a novel strategy for cellular therapies.
Mutations altering the cleavage specificity of a homing endonuclease (2002)

The homing endonuclease I-CreI recognizes and cleaves a particular 22 bp DNA sequence. The crystal structure of I-CreI bound to homing site DNA has previously been determined, leading to a number of predictions about specific protein-DNA contacts. We test these predictions by analyzing a set of endonuclease mutants and a complementary set of homing site mutants. We find evidence that all structurally predicted I-CreI/DNA contacts contribute to DNA recognition and show that these contacts differ greatly in terms of their relative importance. We also describe the isolation of a collection of altered specificity I-CreI derivatives. The in vitro DNA-binding and cleavage properties of two such endonucleases demonstrate that our genetic approach is effective in identifying homing endonucleases that recognize and cleave novel target sequences.
Quinoxaline chemistry. Part 5. 2-(R)-benzylaminoquinoxalines as nonclassical antifolate agents. Synthesis and evaluation of in vitro anticancer activity. (1997)

Thirty-one quinoxalines bearing a substituted benzylamino group on position 2 and various substituents on position 3,6,7 and 8 of the heterocycle were prepared in order to evaluate in vitro anticancer activity. Preliminary screening performed at NCI on twenty-two compounds showed that most derivatives exhibited a moderate to strong growth inhibition activity on various tumor panel cell lines between 10(-5) and 10(-4) molar concentrations. Interesting selectivities were also recorded between 10(-8) and 10(-5) M.
Healing of Microdefects in SSZ-13 Membranes via Filling with Dye Molecules and Its Effect on Dry and Wet CO2 Separations (2018)

It is quite challenging to avoid microdefect formation during hydrothermal growths and/or calcination processes, while manufacturing high-quality zeolite membranes in a reproducible manner. Even less than 1% of defects, which generally provide nonselective pathways, will considerably worsen the intrinsic, high molecular sieving-based separation performance of a continuous zeolite membrane. Herein, we propose a simple and reliable method for blocking defects using water-soluble dye molecules, which were originally used for the visualization of nonzeolitic, defective structures in a zeolite membrane. Because the dye molecules are ∼1 nm in size, they cannot diffuse into the zeolitic pores and selectively access the defects. For the demonstration of dye-based defect healing, we chose a siliceous chabazite type SSZ-13 zeolite membrane (pore size = 0.37 × 0.42 nm2) with some degree of defects and investigated the effect of defect healing on the final CO2 separation performance. Because the defects were gradually filled by the dye molecules, both CO2/N2 and CO2/CH4 separation performances were concomitantly increased. Intriguingly, the CO2 perm-selectivity test with ternary mixtures including H2O vapor (the third largest component in the flue and natural/shale/bio gas streams) in the feed diminished CO2 separation performance. This could be ascribed to inhibited transport of the fast permeating species, here CO2, from the adsorbed H2O molecules on the dye-treated and water-friendly (relatively hydrophilic) membrane surface. On the contrary, the intact, siliceous (water-repelling or hydrophobic) SSZ-13 membranes showed improved CO2 perm-selectivities in the presence of H2O vapor, seemingly due to defect blocking by the physisorbed H2O molecules.
Aurora Kinase Inhibitors - Rising Stars in Cancer Therapeutics? (2010)

Standard therapeutic approaches of cytotoxics and radiation in cancer are not only highly toxic, but also of limited efficacy in treatment of a significant number of cancer patients. The molecular analysis of the cancer genomes have shown a remarkable complexity and pointed to key genomic and epigenomic alterations in cancer. These discoveries are paving the way for targeted therapy approaches. However, although there are a large number of potential targets, only a few can regulate key cellular functions and intersect multiple signaling networks. The Aurora kinase family members (A, B, and C) are a collection of highly related and conserved serine-threonine kinases that fulfill these criteria, being key regulators of mitosis and multiple signaling pathways. Alterations in Aurora kinase signaling are associated with mitotic errors and have been closely linked to chromosomal aneuploidy in cancer cells. Several studies have shown amplification and/or overexpression of Aurora kinase A and B in hematologic malignancies and solid tumors. Over the past several years, Aurora kinases have become attractive targets. Several ongoing clinical trials and bench-based research are assessing the unique therapeutic potential of Aurora-based targeted therapy.
Seroprevalence of Ehrlichia canis, Ehrlichia equi , and Ehrlichia risticii in Sick Dogs from North Carolina and Virginia (2000)

Ehrlichia canis, E. equi, and E. risticii seroprevalence was determined by microimmunofluorescent antibody testing (IFA) in a sequential population of 1,845 sick dogs admitted during a 1-year period to the North Carolina State University Veterinary Teaching Hospital. A seroreactor was defined by a reciprocal IFA titer of > or =80 to E. canis, E. equi, or E. risticii antigens. Of the 48 IFA seroreactors, 44 dogs were seroreactive to E. canis, 21 to E. equi, and 0 to E. risticii. Seventeen dogs reacted to both E. canis and E. equi antigens. There was concordance of E. canis IFA and western immunoblot (WI) test results for 36/44 dogs. Because of cross-reactivity of E. canis sera with E. equi antigens, WI was of less utility to confirm E. equi exposure. After elimination of E. canis seroreactors, there was concordance of 2/4 E. equi IFA and WI test results. Based upon a retrospective review of medical records, ehrlichiosis was diagnosed in 10/48 (21%) IFA seroreactive dogs, 9 of which were confirmed positive by WI. Of the remaining 38 IFA seroreactors, 29 also were confirmed by E. canis or E. equi WI. These results indicate that (1) ehrlichiosis was not diagnosed in the majority of serologically confirmed cases, (2) based upon E. canis and E. equi WI analysis, IFA testing was not specific (21% false positive), (3) E. canis sera cross-react with E. equi antigens, and (4) serologic evidence of E. risticii infection was lacking in the dog population studied.
Understanding the Linux Kernel (2000)

This new edition covers Version 2.6 of the Linux kernel, which has seen significant changes to nearly every kernel subsystem, particularly in the areas of memory management and block devices. Understanding the Linux Kernel provides a guided tour of the code that forms the core of all Linux operating systems. Beyond the functioning of the code, the book explains the theoretical underpinnings for why Linux, and many other operating systems, do things the way they do
Inguinal hernia repair: totally preperitoneal laparoscopic approach versus Stoppa operation: randomized trial of 100 cases. (1997)

In a prospective randomized trial comparing the totally preperitoneal (TPP) laparoscopic approach and the Stoppa procedure (open), 100 patients with inguinal hernias (Nyhus IIIA, IIIB, IV) were followed over a 3-year period. Both groups were epidemiologically comparable. In the laparoscopic group, operating time was significantly longer (p = 0.01), but hospital stay (3.2 vs. 7.3 days) and delay in return to work (17 vs. 35 days) were significantly reduced (p = 0.01). Postoperative comfort (less pain) was better (p = 0.001) after laparoscopy. In this group, morbidity was also reduced (4 vs. 20%; p = 0.02). The mean follow-up was 605 days, and 93% of the patients were reviewed at 3 years. There were three (6%) recurrences after TPP, especially at the beginning of the surgeon's learning curve, versus one for the Stoppa procedure (NS). For bilateral hernias, the authors suggest the use of a large prosthesis rather than two small ones to minimize the likelihood of recurrence. In the conditions described, the laparoscopic (TPP) approach to inguinal hernia treatment appears to have the same long-term recurrence rate as the open (Stoppa) procedure but a real advantage in the early postoperative period.
Optimization of abiotic conditions suitable for the production of biodiesel from Chlorella vulgaris (2011)

The present study reports the production of fatty acids by microalgae under the influence of light and dark condition. Microalgae are renewable resource containing rich lipids in their body and has the potential to refill the partial energy demands in an eco-friendly way. We isolated an indigenous green alga ( Chlorella vulgaris ) as a potent source for biodiesel. To get better yield of biofuel, the growth of the microalgal isolate was optimized with the addition of nutrients and salts under light and dark conditions. The lipid fractions were extracted from the biomass through solvent extractions and the fractions were analyzed for biodiesel under GC-MS. The percentage of lipids synthesized from C. vulgaris under light and dark conditions were analyzed and compared. The algae from dark sample shows rich in saturated fatty acid (capric acid, lauric acid&myristic acid) and considerable amount of PUFA (hexadecatrienoic acid, stearidonic acid, eicosapenaenoic acid, docosahexaenoic acid) when compare to algae grown under light. So the algae grown in dark condition is an excellent source for high yield of saturated fatty acids.
Systemic Effects of Orally Administered Interferons and Interleukin-2 (1999)

Orally administered interferons (IFN-alpha, IFN-beta, and IFN-gamma) have been shown to exert a number of systemic effects. Orally administered IFNs exert dose-dependent suppressive effects on the peripheral white blood cell (WBC) count. The suppression of the peripheral WBC count is mediated by a suppression of the function of the bone marrow, as measured in an in vitro bone marrow colony-forming assay. The peripheral WBC and bone marrow suppressive effects of orally administered IFNs are at least as potent as those occurring with parenterally administered IFNs. However, the mechanism by which orally administered IFNs exert these peripheral WBC suppressive and bone marrow suppressive effects differs significantly from that of parenterally administered IFNs: orally administered IFN is not detectable in the serum, the effect of orally administered IFN is not blocked by circulating antibody, the effect of orally administered IFN can be adoptively transferred by injection with peripheral white blood cells from donor mice, and the effect of orally administered IFN develops more slowly than that of parenterally administered interferon. Orally administered IFN-alpha employed alone and in synergistic combination with intraperitoneally administered IFN-gamma can exert an antitumor effect. Finally, orally administered interleukin-2 can exert a suppressive effect on both the peripheral white blood cell count and on the bone marrow. These observations suggest that the oral route may be an effective and novel mechanism for the efficacious administration of IFNs and other lymphokines/cytokines.
Identification of the Copper Regulon in Saccharomyces cerevisiae by DNA Microarrays (2000)

In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mac1. Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions. DNA microarray hybridization experiments revealed a limited set of yeast genes differentially expressed under growth conditions of excess copper or copper deficiency. Mac1 activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1, FRE7, YFR055w, and YJL217w. Two of the last three newly identified Mac1 target genes have no known function; the third, YFR055w, is homologous to cystathionine gamma-lyase encoded by CYS3. Several genes that are differentially expressed in cells containing a constitutively active Mac1, designated Mac1(up1), are not direct targets of Mac1. Induction or repression of these genes is likely a secondary effect of cells because of constitutive Mac1 activity. Elevated copper levels induced the expression of the metallothioneins CUP1 and CRS5 and two genes, FET3 and FTR1, in the iron uptake system. Copper-induced FET3 and FTR1 expression arises from an indirect copper effect on cellular iron pools.
Developing Client/Server Systems Using Sybase SQL Server System 10 (1995)

This book covers the new Sybase SQL Server 11, which has improved administration performance and enhanced networking capabilities. This is a developmental guide that covers stored procedures and triggers, query optimization, the APT workbench and other features that help developers build fast and efficient client/server applications.
2-Pyridinone derivatives: a new class of nonnucleoside, HIV-1-specific reverse transcriptase inhibitors (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2-Pyridinone derivatives: a new class of nonnucleoside, HIV-1-specific reverse transcriptase inhibitorsWalfred S. Saari, Jacob M. Hoffman, John S. Wai, Thorsten E. Fisher, Clarence S. Rooney, Anthony M. Smith, Craig M. Thomas, Mark E. Goldman, Julie A. O'Brien, and Cite this: J. Med. Chem. 1991, 34, 9, 2922–2925Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September 1991https://pubs.acs.org/doi/10.1021/jm00113a036https://doi.org/10.1021/jm00113a036research-articleACS PublicationsRequest reuse permissionsArticle Views397Altmetric-Citations81LEARN 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 optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Environmental Risks of Fungicides Used in Horticultural Production Systems (2010)

Adam Wightwick1,2,3, Robert Walters3, Graeme Allinson3,4, Suzanne Reichman5, and Neal Menzies1,2 1The University of Queensland 2Co-operative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE) 3Department of Primary Industries, Victoria 4Victorian Centre for Aquatic Pollution Identification and Management (CAPIM) 5Royal Melbourne Institute of Technology (RMIT) University Australia
Performance analysis of fast distributed network restoration algorithms (2002)

Six distributed network restoration algorithms are analyzed using a set of important performance metrics and functional characteristics. The functional characteristics are used to explain how these algorithms function and provide insight into their performance. The analysis and simulation results indicate that the two prong network restoration algorithm, which is based on issuing aggregate restoration requests from both ends of the disruption and on an intelligent backtracking mechanism, outperforms the other algorithms.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Pharmacokinetics and Hemodynamic Effects of Intravenous and Intramuscular Dexmedetomidine Hydrochloride in Adult Human Volunteers (1993)

The intramuscular administration of dexmedetomidine avoids the acute hemodynamic changes seen with intravenous administration, but results in similar hemodynamic alterations within 4 h.
Gramicidin S synthetase 1 (phenylalanine racemase), a prototype of amino acid racemases containing the cofactor 4'-phosphopantetheine (1995)

The biosynthesis of the decapeptide antibiotic gramicidin S in Bacillus brevis ATCC 9999 is catalyzed by a multienzyme system consisting of two multifunctional proteins, gramicidin S synthetase 1 and 2, encoded by the grsA and grsB genes, respectively. Gramicidin S synthetase 1 (phenylalanine racemase, EC 5.1.1.11, GS1) racemizes phenylalanine in the thioester-bound stage. The amount of 4'-phosphopantetheine liberated from highly purified GS1 was determined microbiologically using Lacto-bacillus plantarum as the test organism. It matches exactly with the amount of L-[14C]phenylalanine covalently incorporated by GS1 as thioester. The reaction center of GS1 for L-phenylalanine thiolation and racemization was labeled with [3H]iodoacetic acid. After tryptic fragmentation of the 3H-carboxymethylated enzyme, the active site peptide for thioester binding and racemization of phenylalanine was isolated in pure form by multistep methodology and investigated by sequence, amino acid, and mass spectrometric analysis. A 4'-phosphopantetheine carrier was found to be attached to the active site serine of the consensus motif LGGDSI forming the thiolation site of phenylalanine. These specific properties establish GS1 as a prototype of amino acid racemases using 4'-phosphopantetheine as a cofactor and yield further evidence that multiple Pan carriers are involved in gramicidin S formation. Our results are strong evidence for the "multiple carrier model" as a new concept of nonribosomal peptide biosynthesis at protein templates as recently proposed [Stein, T., et al. (1994) FEBS Lett. 340, 39-44].
Controlling Protein Orientation at Interfaces Using Histidine Tags:  An Alternative to Ni/NTA (2005)

A strategy for immobilizing histidine-tagged proteins at surfaces has been developed by using a macrocyclic chelator that enhances the stability and specificity of conventional histidine-tag technology and allows application of this technology to long-term studies including direct electrochemistry.
BCR-ABL-mediated inhibition of apoptosis with delay of G2/M transition after DNA damage: a mechanism of resistance to multiple anticancer agents (1995)

A critical determinant of the efficacy of antineoplastic therapy is the response of malignant cells to DNA damage induced by anticancer agents. The p53 tumor-suppressor gene is a critical component of two distinct cellular responses to DNA damage, the induction of a reversible arrest at the G1/S cell cycle checkpoint, and the activation of apoptosis, a genetic program of autonomous cell death. Expression of the BCR-ABL chimeric gene produced by a balanced translocation in chronic myeloid leukemia, confers resistance to multiple genotoxic anticancer agents. BCR-ABL expression inhibits the apoptotic response to DNA damage without altering either the p53-dependent WAF1/CIP1-mediated G1 arrest or DNA repair. BCR-ABL-mediated inhibition of DNA damage-induced apoptosis is associated with a prolongation of cell cycle arrest at the G2/M restriction point; the delay of G2/M transition may allow time to repair and complete DNA replication and chromosomal segregation, thereby preventing a mitotic catastrophe. The inherent resistance of human cancers to genotoxic agents may result not only by the loss or inactivation of the wild-type p53 gene, but also by genetic alterations such as BCR-ABL that can delay G2/M transition after DNA damage.
Improvement of Glycemic Control in Subjects With Poorly Controlled Type 2 Diabetes (2005)

Glargine is safe and effective in improving glycemic control in a large, diverse population with longstanding type 2 diabetes. A simple subject-administered titration algorithm conferred significantly improved glycemic control with a low incidence of severe hypoglycemia compared with physician-managed titration.
1,25-Dihydroxyvitamin D3and Human Bone-Derived Cells in Vitro: Effects on Alkaline Phosphatase, Type I Collagen and Proliferation* (1986)

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], but not 24,25-(OH)2D3 stimulates the alkaline phosphatase activity of cultured human bone cell populations. The stimulatory effect of the sterol was dose dependent (10(-10)-10(-7) M), evident by 24 h, and observed over a range of cell densities. Analysis of the radiolabeled collagens synthesised by human bone cell cultures indicated the synthesis of predominantly type I collagen. In the presence of 1,25-(OH)2D3, but not 24,25-(OH)2D3, there was a dose-dependent (10(-11)-10(-9) M) increase in radiolabeled proline incorporation into collagenase-digestible protein and in the amount of collagen synthesized, expressed as a percentage of the total protein synthesis. The effect of 1,25-(OH)2D3 was observed over a range of cell densities and appeared to be specific for the synthesis of type I collagen. The stimulatory effect of 1,25-(OH)2D3 on alkaline phosphatase activity and the increase in proline incorporation into collagenase-digestible protein were accompanied by a dose-dependent (5 X 10(-11) to 5 X 10(-8) M) inhibition of bone cell proliferation. These findings suggest that 1,25-(OH)2D3 is an important modulator of the growth and differentiation of human bone cells in vitro. They are also consistent with the possibility that 1,25-(OH)2D3 has direct effects on bone formation in vivo.