gebhart/patrepeval huggingface dataset:
Drug-Induced Thrombosis—Experimental, Clinical, and Mechanistic Considerations (2007)

Awareness of the dangers of drug-induced thrombosis has recently been heightened and led to demand for improved testing methodology. For example, reports indicating that some selective inhibitors of cyclooxygenase-2 (COX-2) increase the risk of myocardial infarction and atherothrombotic events caused the withdrawal of rofecoxib from global markets and the issuance of warnings concerning the usage of other COX-2 inhibitors. Drugs may exert a prothrombotic state by a variety of mechanisms--those affecting the vessel wall, the blood flow, and/or different blood constituents. Our review serves as an update to that of Gerhard Zbinden published in 1976 by presenting recently acquired data that more fully elucidate the different mechanisms by which drugs are believed to induce thrombogenic effects and discussing new methods used to detect these without losing sight of the classical pathology of thrombosis. We offer correlations between experimental findings and clinical data and conclude that, because drugs may induce a prothrombotic state by a variety of mechanisms, they should be tested for these using appropriate experimental methods and animal models.
Conversion of type I 4:6 to 3:5 β‐turn types in human acidic fibroblast growth factor: Effects upon structure, stability, folding, and mitogenic function (2005)

Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil superfold, a protein architecture that exhibits a characteristic threefold axis of structural symmetry. FGF-1 contains 11 beta-turns, the majority being type I 3:5; however, a type I 4:6 turn is also found at three symmetry-related locations. The relative uniqueness of the type I 4:6 turn in the FGF-1 structure suggests it may play a key role in the stability, folding, or function of the protein. To test this hypothesis a series of deletion mutations were constructed, the aim of which was to convert existing type I 4:6 turns at two locations into type I 3:5 turns. The results show it is possible to successfully substitute the type I 4:6 turn by a type I 3:5 turn with minimal impact upon protein stability or folding. Thus, these different turn structures, even though they differ in length, exhibit similar energetic properties. Additional sequence swapping mutations within the introduced type I 3:5 turns suggests that the turn sequence primarily affects stability but not turn structure (which appears dictated primarily by the local environment). Although the results suggest that a stable, foldable beta-trefoil protein may be designed utilizing a single turn type (type I 3:5), a type I 4:6 turn at turn 1 of FGF-1 appears essential for efficient mitogenic function.
Alternating current polarography in the harmonic multiplex mode. Use of digital signal conditioning with the Fast Fourier Transform algorithm (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlternating current polarography in the harmonic multiplex mode. Use of digital signal conditioning with the Fast Fourier Transform algorithmDonald E. Glover and Donald E. SmithCite this: Anal. Chem. 1973, 45, 11, 1869–1877Publication Date (Print):September 1, 1973Publication History Published online1 May 2002Published inissue 1 September 1973https://pubs.acs.org/doi/10.1021/ac60333a012https://doi.org/10.1021/ac60333a012research-articleACS PublicationsRequest reuse permissionsArticle Views74Altmetric-Citations24LEARN 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-Alertsclose Get e-Alerts
Cloning and expression of two different genes from Streptococcus dysgalactiae encoding fibronectin receptors. (1992)

Binding of bacteria to fibronectin has been implicated as a mechanism of bacterial adhesion to the host tissue. In this report we have analyzed the binding of a strain of Streptococcus dysgalactiae to fibronectin. The cells bind to a site in the NH2-terminal domain of the protein via trypsin-sensitive cell surface components. Furthermore, a lysate prepared by sonication of streptococcal cells contained fibronectin-binding proteins that inhibit the binding of the ligand to intact bacteria. When the proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted to an Immobilon-P filter, and probed with 125I-labeled fibronectin, a 140-kDa fibronectin-binding protein was identified along with a number of smaller binding proteins. A genomic DNA library was constructed and screened for the expression of fibronectin-binding proteins. Two clones were isolated and shown to contain unrelated inserts by restriction mapping and cross-hybridization experiments. The two encoded proteins were also immunologically distinct although both bound to the same region of the fibronectin molecule, and both effectively inhibited the binding of 125I-fibronectin to bacterial cells. Immunological analyses showed that only one of the two proteins tentatively identified as fibronectin receptors was expressed in detectable quantities in the Streptococcus dysgalactiae strain under the culture conditions employed.
The RecordLinkage Package: Detecting Errors in Data (2010)

Record linkage deals with detecting homonyms and mainly synonyms in data. The package RecordLinkage provides means to perform and evaluate different record linkage methods. A stochastic framework is implemented which calculates weights through an EM algorithm. The determination of the necessary thresholds in this model can be achieved by tools of extreme value theory. Furthermore, machine learning methods are utilized, including decision trees (rpart), bootstrap aggregating (bagging), ada boost (ada), neural nets (nnet) and support vector machines (svm). The generation of record pairs and comparison patterns from single data items are provided as well. Comparison patterns can be chosen to be binary or based on some string metrics. In order to reduce computation time and memory usage, blocking can be used. Future development will concentrate on additional and refined methods, performance improvements and input/output facilities needed for real-world application.
Protective effect of coenzyme Q10 against the adverse reaction of mitomycin C in mouse liver. (1987)

The side effects of mitomycin C (MMC) on liver cells and the protective effectiveness were investigated morphologically, biochemically and histo-cytochemically.Coenzyme Q10 (CoQ10) prevented the cells from inflation, mitochondria swelling and vacuolation of endoplasmic reticulum, which were caused by the administration of MMC. This might be due to CoQ10 preventing the cells from decreasing energy metabolism.The biochemical determination of enzyme activities indicated significant difference between the treatments in 5′-nucleotidase (5′-Nase) activity and in contrast, Mg++-adenosine triphosphatase (Mg++-ATPase) was not found statistically different.The histo-cytochemical observation showed that the activity of 5′-Nase and Mg++-ATPase were decreased by being treated with MMC. But the localization pattern of the enzyme activities was not different from the control when both CoQ10 and MMC were administrated. The present results suggested that CoQ10 could prevent damage caused by antineoplastic agents.
Regulation and Function of the ArabidopsisABA-insensitive4Gene in Seed and Abscisic Acid Response Signaling Networks (2000)

We have characterized developmental, environmental, and genetic regulation of abscisic acid-insensitive (ABI)4 gene expression in Arabidopsis. Although expressed most strongly in seeds, ABI4 transcripts are also present at low levels in vegetative tissue; vegetative expression is not induced by abscisic acid (ABA) or stress treatments. Comparison of transcript levels in mature seeds of ABA-insensitive, ABA-hypersensitive, ABA-deficient, or heterochronic mutants indicates that ABI4 expression is altered in only two of the backgrounds, the ABA-insensitive mutants abi1-1 and abi3-1. To determine whether ABI4 is necessary and/or sufficient for ABA response, we assayed the effects of loss of ABI4 function and ectopic ABI4 expression on growth and gene expression. We examined genetic interactions among three ABA response loci, ABI3, ABI4, and ABI5, by comparing phenotypes of mutants, ectopic expression lines, mutants carrying an ectopically expressed transgene, and the corresponding wild-type lines. Our results indicate some cross-regulation of expression among ABI3, ABI4, and ABI5 and suggest that they function in a combinatorial network, rather than a regulatory hierarchy, controlling seed development and ABA response.
Determinants of tissue delivery for 129Xe magnetic resonance in humans (1996)

Magnetic resonance imaging using laser-polarized 129Xe is a new technique first demonstrated by Albert et. al. (Nature 370, 1994) who obtained a 129Xe image of an excised mouse lung. This paper describes the factors influencing the accumulation of inhaled, polarized 129Xe in human tissue. The resulting model predicts the 129Xe magnetization in different tissues as a function of the time from the start of inhalation, the tissue perfusion rate and partition coefficient for xenon, and the relevant T1 decay times. The relaxation times of 129Xe in biological tissues are not yet known precisely. Substitution of estimated values for these parameters results in an expected signal-to-noise ratio (SNR) from polarized 129Xe MR in the brain of approximately 2% of the equivalent SNR from proton MR.
Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis in Male Mice through Activation of the Wnt/β-Catenin Signaling Pathway (2014)

Although alcohol effects within the liver have been extensively studied, the complex mechanisms by which alcohol causes liver cancer are not well understood. It has been suggested that ethanol (EtOH) metabolism promotes tumor growth by increasing hepatocyte proliferation. In this study, we developed a mouse model of tumor promotion by chronic EtOH consumption in which EtOH feeding began 46 days after injection of the chemical carcinogen diethylnitrosamine (DEN) and continued for 16 weeks. With a final EtOH concentration of 28% of total calories, we observed a significant increase in the total number of preneoplastic foci and liver tumors per mouse in the EtOH+DEN group compared with corresponding pair-fed (PF)+DEN and chow+DEN control groups. We also observed a 4-fold increase in hepatocyte proliferation (P < 0.05) and increased cytoplasmic staining of active-β-catenin in nontumor liver sections from EtOH+DEN mice compared with PF+DEN controls. In a rat model of alcohol-induced liver disease, we found increased hepatocyte proliferation (P < 0.05); depletion of retinol and retinoic acid stores (P < 0.05); increased expression of cytosolic and nuclear expression of β-catenin (P < 0.05) and phosphorylated-glycogen synthase kinase 3β (p-GSK3β), P < 0.05; significant upregulation in Wnt7a mRNA expression; and increased expression of several β-catenin targets, including, glutamine synthetase (GS), cyclin D1, Wnt1 inducible signaling pathways protein (WISP1), and matrix metalloproteinase-7(MMP7), P < 0.05. These data suggest that chronic EtOH consumption activates the Wnt/β-catenin signaling pathways to increase hepatocyte proliferation, thus promoting tumorigenesis following an initiating insult to the liver.
Sharing of the Interleukin-2 (IL-2) Receptor γ Chain Between Receptors for IL-2 and IL-4 (1993)

The gamma chain of the interleukin-2 (IL-2) receptor is an indispensable subunit for IL-2 binding and intracellular signal transduction. A monoclonal antibody to the gamma chain, TUGm2, inhibited IL-2 binding to the functional IL-2 receptors and also inhibited IL-4-induced cell growth and the high-affinity binding of IL-4 to the CTLL-2 mouse T cell line. Another monoclonal antibody, TUGm3, which reacted with the gamma chain cross-linked with IL-2, also immunoprecipitated the gamma chain when cross-linked with IL-4. These results suggest that the IL-2 receptor gamma chain is functionally involved in the IL-4 receptor complex.
Sealing of micromachined cavities using chemical vapor deposition methods: characterization and optimization (1999)

This paper presents results of a systematic investigation to characterize the sealing of micromachined cavities using chemical vapor deposition (CVD) methods. We have designed and fabricated a large number and variety of surface-micromachined test structures with different etch-channel dimensions. Each cavity is then subjected to a number of sequential CVD deposition steps with incremental thickness until the cavity is successfully sealed. At etch deposition interval, the sealing status of every test structure is experimentally obtained and the percentage of structures that are sealed is recorded. Four CVD sealing materials have been incorporated in our studies: LPCVD silicon nitride, LPCVD polycrystalline silicon (polysilicon), LPCVD phosphosilicate glass (PSG), and PECVD silicon nitride. The minimum CVD deposition thickness that is required to successfully seal a microstructure is obtained for the first time. For a typical Type-1 test structure that has eight etch channels-each 10 /spl mu/m long, 4 /spl mu/m wide, and 0.42 /spl mu/m tall-the minimum required thickness (normalized with respect to the height of etch channels) is 0.67 for LPCVD silicon nitride, 0.62 for LPCVD polysilicon, 4.5 for LPCVD PSG, and 5.2 for PECVD nitride. LPCVD silicon nitride and polysilicon are the most efficient sealing materials. Sealing results with respect to etch-channel dimensions (length and width) are evaluated (within the range of current design). When LPCVD silicon nitride is used as the sealing material, test structures with the longest (38 /spl mu/m) and widest (16 /spl mu/m) etch channels exhibit the highest probability of sealing. Cavities with a reduced number of etch channels seal more easily. For LPCVD PSG sealing, on the other hand, the sealing performance improves with decreasing width but is not affected by length of etch channels.
Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage (2005)

Exposure to excessive light induces retinal photoreceptor cell damage, leading to development and progression of various retinal diseases. We tested the effect of geranylgeranylacetone (GGA), an acyclic polyisoprenoid, on light-induced retinal damage in mice. Oral treatment with GGA (1.0 mg/d) for 5 d induced thioredoxin (Trx) and heat shock protein 72 (Hsp72) predominantly in the retinal pigment epithelium (RPE). After white light exposure (8000 lux for 2 h), the percentage of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive photoreceptor cells decreased significantly at 24 and 96 h, and the number of photoreceptor cell nuclei at 96 h and the electroretinographic amplitudes of the a- and b-waves at 4 and 10 d increased significantly in GGA-pretreated mice compared with saline-pretreated mice. Light-induced upregulations of 8-hydroxy-2-deoxyguanosine and 4-hydroxy-2-nonenal-modified protein, markers of oxidative stress, were inhibited by GGA pretreatment. To elucidate the cytoprotective mechanism of GGA and Trx, we used human K-1034 RPE cells and mouse photoreceptor-derived 661W cells. In K-1034 cells, GGA (10 microM) induced intracellular Trx, Hsp72, and extracellular Trx but not extracellular Hsp72. Extracellular Trx (0.75 nM) attenuated H2O2 (200 microM)-induced cell damage in 661W cells. Pretreatment with GGA and overexpression of Trx in K-1034 cells counteracted H2O2 (50 microM)-induced attenuation of cellular latex bead incorporation. Protection of phagocytotic activity through induction of Trx and possibly Hsp72 in RPE cells and elimination of oxidative stress in the photoreceptor layer through release of Trx from RPE cells may be mechanisms of GGA-mediated cytoprotection. Therefore, Trx is a neurotrophic factor released from RPE cells and plays a crucial role in maintaining photoreceptor cell integrity.
A GENERAL REACTION OF AMINO ACIDS (1928)

In the case of proline little or no ketone formation was observed.In every case the evolution of carbon dioxide was noted to accompany ketone formation.An investigation of the structure of the compounds indicated that two CHz.CO groups were present, one being attached to nitrogen in the usual fashion and one attached to carbon in the form of a ketone.The reaction with phenylalanine may be represented as follows:CsHs .
VLA‐4 Molecules on Tumor Cells Initiate an Adhesive Interaction with VCAM‐1 Molecules on Endothelial Cell Surface (1992)

To elucidate the role of VLA-4 (alpha 4 beta 1 integrin) in tumor metastasis, we have transfected cDNA coding alpha 4 subunit into human fibrosarcoma (HT1080) cells. VLA-4-overexpressing HT-VC1 cells exhibited increased ability to interact with known ligands for VLA-4, such as CS1 peptide and VCAM-1 (vascular cell adhesion molecule-1). In addition, the in vitro invasive ability of HT-VC1 cells was augmented and the mRNA for type IV collagenase was increased in HT-VC1 cells. The induction of VCAM-1 molecules on lung endothelial cells of nude mice by tumor necrosis factor-alpha treatment resulted in augmentation of in vivo HT-VC1 cell adhesion to the lung endothelial cells. Thus, the VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cells, that is important for hematogenous metastasis.
Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies (2009)

Vascular disrupting agents (VDAs) are a relatively new group of 'vascular targeting' agents that exhibit selective activity against established tumour vascular networks, causing severe interruption of tumour blood flow and necrosis to the tumour mass. Microtubule depolymerizing agents form by far the largest group of small molecular weight VDAs many of which, including lead compound disodium combretastatin A-4 3-O-phosphate (CA-4-P), are under clinical development for cancer. Although distinct from the angiogenesis inhibitors, VDAs can also interfere with angiogenesis and therefore constitute a potential group of novel drugs for the treatment of pathological conditions characterized by excessive angiogenesis, in addition to cancer. The endothelial cytoskeleton is the primary cellular target of this family of drugs, and some progress in understanding the molecular and signalling mechanisms associated with their endothelial disrupting activity has been made in the last few years. Susceptibility of tumour vessels to VDA damage is ascribed to their immature pericyte-defective nature, although the exact molecular mechanisms involved have not been clearly defined. Despite causing profound damage to tumours, VDAs fail to halt tumour growth unless used together with conventional treatments. This failure is attributed to resistance mechanisms, primarily associated with cells that remain viable within the tumour rim, and enhanced angiogenesis. The focus is now to understand mechanisms of susceptibility and resistance to identify novel molecular targets and develop strategies that are more effective.
TheSaccharomyces cerevisiae ICL2Gene Encodes a Mitochondrial 2-Methylisocitrate Lyase Involved in Propionyl-Coenzyme A Metabolism (2000)

The Saccharomyces cerevisiae ICL1 gene encodes isocitrate lyase, an essential enzyme for growth on ethanol and acetate. Previous studies have demonstrated that the highly homologous ICL2 gene (YPR006c) is transcribed during the growth of wild-type cells on ethanol. However, even when multiple copies are introduced, ICL2 cannot complement the growth defect of icl1 null mutants. It has therefore been suggested that ICL2 encodes a nonsense mRNA or nonfunctional protein. In the methylcitrate cycle of propionyl-coenzyme A metabolism, 2-methylisocitrate is converted to succinate and pyruvate, a reaction similar to that catalyzed by isocitrate lyase. To investigate whether ICL2 encodes a specific 2-methylisocitrate lyase, isocitrate lyase and 2-methylisocitrate lyase activities were assayed in cell extracts of wild-type S. cerevisiae and of isogenic icl1, icl2, and icl1 icl2 null mutants. Isocitrate lyase activity was absent in icl1 and icl1 icl2 null mutants, whereas in contrast, 2-methylisocitrate lyase activity was detected in the wild type and single icl mutants but not in the icl1 icl2 mutant. This demonstrated that ICL2 encodes a specific 2-methylisocitrate lyase and that the ICL1-encoded isocitrate lyase exhibits a low but significant activity with 2-methylisocitrate. Subcellular fractionation studies and experiments with an ICL2-green fluorescent protein fusion demonstrated that the ICL2-encoded 2-methylisocitrate lyase is located in the mitochondrial matrix. Similar to that of ICL1, transcription of ICL2 is subject to glucose catabolite repression. In glucose-limited cultures, growth with threonine as a nitrogen source resulted in a ca. threefold induction of ICL2 mRNA levels and of 2-methylisocitrate lyase activity in cell extracts relative to cultures grown with ammonia as the nitrogen source. This is consistent with an involvement of the 2-methylcitrate cycle in threonine catabolism.
Superhydrophobic Polymer Multilayers that Promote the Extended, Long‐Term Release of Embedded Water‐Soluble Agents (2013)

Polymer multilayers that exhibit surface and bulk superhydrophobicity are demonstrated to promote long-term release of water-soluble agents (for ca.1 year) when submerged in water. The extremely nonwetting nature of these materials prevents rapid influx of water, addressing a key limitation inherent to polyelectrolytebased multilayers that release imbedded agents quickly. Our results provide new and potentially general principles for the design of surface coatings in the context of controlled release.
Elastic optical networking: a new dawn for the optical layer? (2012)

Optical networks are undergoing significant changes, fueled by the exponential growth of traffic due to multimedia services and by the increased uncertainty in predicting the sources of this traffic due to the ever changing models of content providers over the Internet. The change has already begun: simple on-off modulation of signals, which was adequate for bit rates up to 10 Gb/s, has given way to much more sophisticated modulation schemes for 100 Gb/s and beyond. The next bottleneck is the 10-year-old division of the optical spectrum into a fixed "wavelength grid," which will no longer work for 400 Gb/s and above, heralding the need for a more flexible grid. Once both transceivers and switches become flexible, a whole new elastic optical networking paradigm is born. In this article we describe the drivers, building blocks, architecture, and enabling technologies for this new paradigm, as well as early standardization efforts.