gebhart/patrepeval huggingface dataset:
Direct Observation of Protonation State Modulation in SARS-CoV-2 Main Protease upon Inhibitor Binding with Neutron Crystallography (2021)

The main protease (3CL M<sup>pro</sup>) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is an essential enzyme for viral replication with no human counterpart, making it an attractive drug target. To date, no small-molecule clinical drugs are available that specifically inhibit SARS-CoV-2 M<sup>pro</sup>. To aid rational drug design, we determined a neutron structure of M<sup>pro</sup> in complex with the α-ketoamide inhibitor telaprevir at near-physiological (22 °C) temperature. We directly observed protonation states in the inhibitor complex and compared them with those in the ligand-free M<sup>pro</sup>, revealing modulation of the active-site protonation states upon telaprevir binding. We suggest that binding of other α-ketoamide covalent inhibitors can lead to the same protonation state changes in the M<sup>pro</sup> active site. Thus, by studying the protonation state changes induced by inhibitors, we provide crucial insights to help guide rational drug design, allowing precise tailoring of inhibitors to manipulate the electrostatic environment of SARS-CoV-2 M<sup>pro</sup>.
Decreased SLIM1 Expression and Increased Gelsolin Expression in Failing Human Hearts Measured by High-Density Oligonucleotide Arrays (2000)

Altered expression of the genes identified in this study may contribute to development of the heart failure phenotype and/or represent compensatory mechanisms to sustain cardiac function in failing human hearts.
Detecting microstructural properties of white matter based on compartmentalization of magnetic susceptibility (2012)

The microscopic structure of neuronal tissue is crucial to brain function, with axon diameter, axonal density and myelination directly influencing signal conduction in the white matter. There is increasing evidence that these microstructural properties alter signal in magnetic resonance imaging (MRI) driven by magnetic susceptibility of different compartments (e.g., myelin sheaths and iron-laden cells). To explain these observations, we have developed a multi-compartmental geometric model of whitematter microstructure. Using a single set of literature parameters, this forward model predicts experimentally observed orientation dependence and temporal evolution of the MRI signal. Where previous models have aimed to explain only the orientation dependence of signal phase, the proposed approach encapsulates the full repertoire of signal behavior. The frequency distribution underlying signal behavior is predicted to be a rich source of microstructural information with relevance to neuronal pathology.
Overview of the Multiview and 3D Extensions of High Efficiency Video Coding (2015)

The High Efficiency Video Coding (HEVC) standard has recently been extended to support efficient representation of multiview video and depth-based 3D video formats. The multiview extension, MV-HEVC, allows efficient coding of multiple camera views and associated auxiliary pictures, and can be implemented by reusing single-layer decoders without changing the block-level processing modules since block-level syntax and decoding processes remain unchanged. Bit rate savings compared with HEVC simulcast are achieved by enabling the use of inter-view references in motion-compensated prediction. The more advanced 3D video extension, 3D-HEVC, targets a coded representation consisting of multiple views and associated depth maps, as required for generating additional intermediate views in advanced 3D displays. Additional bit rate reduction compared with MV-HEVC is achieved by specifying new block-level video coding tools, which explicitly exploit statistical dependencies between video texture and depth and specifically adapt to the properties of depth maps. The technical concepts and features of both extensions are presented in this paper.
Tumors: Wounds That Do Not Heal (1986)

SOLID tumors are composed of two discrete but interdependent compartments: the malignant cells themselves and the stroma that they induce and in which they are dispersed.1 , 2 In tumors of epithelialcell origin — carcinomas — a basement membrane is often interposed between the tumor cells and the stroma, but in other types of tumors, malignant cells directly abut on or intermingle with stromal elements.1 , 3 An appreciation of tumor stroma is essential to an understanding of the biology of tumor growth; all solid tumors, regardless of their site of origin, require stroma if they are to grow beyond a minimal size of . . .
Butaclamol-like neuroleptic agents: Synthesis of 1-(11H-dibenz[b,f]-1,4-oxathiepin-11-yl)methyl-4-isobutylpiperidin-4-ol and of some related compounds (1985)

1-(11 H -Dibenz[ b,f ]-1,4-oxathiepin-11-yl)methyl-4-piperidone ( XIII ), which was obtained from 11 H -dibenz[ b,f ]-1,4-oxathiepin-11-carboxylic acid ( VIII ) in four steps, was treated with isobutylmagnesium bromide and gave the title compound V in addition to the prevailing quantity of the secondary alcohol VI, i.e. the product of reduction. Synthesis of a series of trisubstituted benzyl phenyl sulfide derivatives XVIII-XXIV, XXVI-XXXI is described; these compounds are potential intermediates in the preparation of 11 H -dibenz[ b,f ]-1,4-oxathiepinacetic acids XVI and XVII . Chloromethylation of 11 H -dibenz[ b,f ]-1,4-oxathiepin ( VII ) and two further usual steps gave an acid to which structure XVI is assigned. Compound V is an open model of "oxathiaisobutaclamol" and in agreement with this fact it behaves like a neuroleptic agent: it increases the turnover and metabolism of dopamine in the rat brain striatum which is manifested by a significant rise of homovanillic acid level.
Adipsin and an endogenous pathway of complement from adipose cells. (1992)

The alternative complement pathway is best known for its role in humoral suppression of infectious agents. We have previously shown that adipose cells synthesize adipsin, the mouse homolog of human complement factor D, and that the synthesis of this protein is reduced in several rodent models of obesity. We show here that adipose cells and adipose tissue also synthesize two other essential components of the alternative pathway of complement, factors C3 and B, and activate the proximal portion of this pathway. This activation occurs in the absence of infectious agents and without triggering the terminal, lytic part of this pathway. We demonstrate the production in vitro of several polypeptides characteristic of complement activation that are known to have potent biological activities, including the anaphylatoxin C3a. Cultured adipocytes require stimulation with cytokines to activate complement, while explanted adipose tissue has no such requirement. The adipose tissue from obese mice is deficient in this localized activation of the alternative pathway. These results indicate that complement activation occurs in a localized site, adipose tissue, in normal mice and is impaired in a state of metabolic dysfunction. This suggests a novel function for the proximal portion of this complement pathway related to adipose cell biology or energy balance.
Conjugates of Small Molecule Drugs with Antibodies and Other Proteins (2014)

Conjugates of small molecule drugs with antibodies (ADCs) and with other proteins (protein-drug conjugates, PDC) are used as a new class of targeted therapeutics combining the specificity of monoclonal antibodies (mAbs) and other proteins with potent cytotoxic activity of small molecule drugs for the treatment of cancer and other diseases. A(P)DCs have three major components, antibody (targeting protein), linker and payload, the cytotoxic drug. Recently, advances in identifying targets, selecting highly specific mAbs of preferred isotypes, optimizing linker technology and improving chemical methods for conjugation have led to the approval of two ADCs by Food and Drug Administration (FDA) and more than 30 ADCs in advanced clinical development. However, the complex and heterogeneous nature of A(P)DCs often cause poor solubility, instability, aggregation and eventually unwanted toxicity. This article reviews the main components of A(P)DCs, and discusses the choices for drugs, linkers and conjugation methods currently used. Future work will need to focus on developments and strategies for overcoming such major problems associated with the A(P)DCs.
Effects of low molecular weight heparins on fibrin polymerization and clot sensitivity to t-PA-induced lysis. (1993)

We have previously demonstrated that therapeutic concentrations of unfractionated heparin (UFH) impair fibrin polymerization leading to the formation of clots which are more sensitive to lysis induced by tissue plasminogen activator (t-PA). The aim of this study was to compare the effect of UFH with that of three different low molecular weight heparins (LMWHs) on clot sensitivity to t-PA-induced lysis. Labelled fibrin clots, prepared from plasma containing UFH, Fraxiparine, Reviparine, Enoxaparine or saline, were incubated in phosphate buffer containing t-PA (0.1 and 0.5 microgram/ml) and plasminogen (20 micrograms/ml). The extent of clot lysis was quantified by counting the residual radioactivity of the clots and by measuring D-dimer levels released into the medium. Fibrin polymerization and clot structure were evaluated by means of a turbidimetric assay and by electron microscopic scanning. Pre-incubation of plasma with 0.5 or 1.0 U/ml UFH resulted in a marked dose-dependent acceleration of lysis induced by 0.1 or 0.5 microgram/ml t-PA. In contrast, lysis rates induced by 0.5 microgram/ml t-PA were not modified by pre-incubation of plasma with LMWHs. When exposed to 0.1 microgram/ml t-PA clots formed from plasma containing 0.5-2 IU/ml of Fraxiparine, Reviparine and Enoxaparine showed only a minor increase in lysis rates compared to control clots. There was not a clear dose-response curve with LMWHs. Furthermore, lysis rates obtained with UFH-treated clots were always significantly higher than those seen with LMWHs-treated clots.(ABSTRACT TRUNCATED AT 250 WORDS)
Functional Analysis of 14 Genes That Constitute the Purine Catabolic Pathway in Bacillus subtilis and Evidence for a Novel Regulon Controlled by the PucR Transcription Activator (2001)

The soil bacterium Bacillus subtilis has developed a highly controlled system for the utilization of a diverse array of low-molecular-weight compounds as a nitrogen source when the preferred nitrogen sources, e.g., glutamate plus ammonia, are exhausted. We have identified such a system for the utilization of purines as nitrogen source in B. subtilis. Based on growth studies of strains with knockout mutations in genes, complemented with enzyme analysis, we could ascribe functions to 14 genes encoding enzymes or proteins of the purine degradation pathway. A functional xanthine dehydrogenase requires expression of five genes (pucA, pucB, pucC, pucD, and pucE). Uricase activity is encoded by the pucL and pucM genes, and a uric acid transport system is encoded by pucJ and pucK. Allantoinase is encoded by the pucH gene, and allantoin permease is encoded by the pucI gene. Allantoate amidohydrolase is encoded by pucF. In a pucR mutant, the level of expression was low for all genes tested, indicating that PucR is a positive regulator of puc gene expression. All 14 genes except pucI are located in a gene cluster at 284 to 285 degrees on the chromosome and are contained in six transcription units, which are expressed when cells are grown with glutamate as the nitrogen source (limiting conditions), but not when grown on glutamate plus ammonia (excess conditions). Our data suggest that the 14 genes and the gde gene, encoding guanine deaminase, constitute a regulon controlled by the pucR gene product. Allantoic acid, allantoin, and uric acid were all found to function as effector molecules for PucR-dependent regulation of puc gene expression. When cells were grown in the presence of glutamate plus allantoin, a 3- to 10-fold increase in expression was seen for most of the genes. However, expression of the pucABCDE unit was decreased 16-fold, while expression of pucR was decreased 4-fold in the presence of allantoin. We have identified genes of the purine degradation pathway in B. subtilis and showed that their expression is subject to both general nitrogen catabolite control and pathway-specific control.
Improvement in Rod and Cone Function in Mouse Model ofFundus albipunctatusafter Pharmacologic Treatment with 9-cis-Retinal (2006)

Disruption of 11-cis-RDHs causes a slowly developing cone dystrophy caused by inefficient cone pigment regeneration. Rod and cone visual function improved significantly in the mouse model of F. albipunctatus after treatment with 9-cis-retinal, suggesting a potential approach to slow the progression of cone dystrophy in affected humans.
Scoring Single-Nucleotide Polymorphisms at the Single-Molecule Level by Counting Individual DNA Cleavage Events on Surfaces (2005)

Single-nucleotide polymorphisms (SNPs) are the most frequent type of human genetic variation. Recent work has shown that it is possible to directly analyze SNPs in unamplified human genomic DNA samples using the surface-invasive cleavage reaction followed by rolling circle amplification (RCA) of the cleavage products. The ability of RCA to produce single-stranded DNA tens of thousands of nucleotides in length from a single cleaved DNA molecule on the surface suggested the possibility of detecting individual cleavage events on the surface. The feasibility of this approach to SNP scoring is shown here. Individual cleavage events on the surface are detected using fluorescence microscopy to visualize the single-stranded DNA product of the RCA reaction labeled with the fluorescent dye SYBR Green I. The surface density of fluorescent features observed is dependent upon the concentration of target DNA. Future reductions of the sample volume and optimization of the reaction conditions offer the potential of being able to perform such analyses on as little as a single copy of genomic DNA target.
T Cell Activation-dependent Association between the p85 Subunit of the Phosphatidylinositol 3-Kinase and Grb2/Phospholipase C-γ1-binding Phosphotyrosyl Protein pp36/38 (1995)

Tyrosine phosphorylation of cellular proteins is an early and an essential step in T cell receptor-mediated lymphocyte activation. Tyrosine phosphorylation of transmembrane receptor chains (such as zeta and CD3 chains) and membrane-associated proteins provides docking sites for SH2 domains of adaptor proteins and signaling enzymes, resulting in their recruitment in the vicinity of activated receptors. pp36/38 is a prominent substrate of early tyrosine phosphorylation upon stimulation through the T cell receptor. The tyrosine-phosphorylated form of pp36/38 is membrane-associated and directly interacts with phospholipase C-gamma 1 and Grb2, providing one mechanism to recruit downstream effectors to the cell membrane. Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-3-K p85) in an activation-dependent manner. Association of pp36/38 with PI-3-K p85 was confirmed by transfection of a hemagglutinin-tagged p85 alpha cDNA into Jurkat cells followed by anti-hemagglutinin immunoprecipitation. In vitro binding experiments with glutathione S-transferase fusion proteins of PI-3-K p85 demonstrated that the SH2 domains, but not the SH3 domain, mediated binding to pp36/38. This binding was selectively abrogated by phosphopeptides that bind to p85 SH2 domains with high affinity. Filter binding assays demonstrated that association between pp36/38 and PI-3-K p85 SH2 domains was due to direct binding. These results strongly suggest the role of pp36/38 in recruiting PI-3-K to the cell membrane and further support the idea that pp36/38 is a multifunctional docking protein for SH2 domain-containing signaling proteins in T cells.
PC-ORD version 5: A user-friendly toolbox for ecologists (2006)

Abstract Recently, version 5 of PC-ORD, one of the major commercial software packages for multivariate ecological community data analyses, was released. The new version offers a whole range of techniques and methods for analyses of ecological data. It includes modules for different types of ordination and classification, as well as other exploratory techniques such as species-area curve analysis and indicator species analysis. Data are stored in spreadsheets and can be easily manipulated in various ways. In essence, version 5 of PC-ORD offers the user a full toolbox for exploration and analysis of ecological data, packed in a user-friendly environment.
Intelligent Transportation Systems (2010)

The increasing need for mobility has brought about significant changes in transportation infrastructures. Inefficiencies cause enormous losses of time, decrease in the level of safety for both vehicles and pedestrians, high pollution, degradation of quality of life, and huge waste of nonrenewable fossil energy.The scope of this article is to introduce novel functionality for providing knowledge to vehicles, thus jointly managing traffic and safety. This will be achieved through the design of the proposed functionality, which, at a high level, will comprise (1) sensor networks formed by vehicles of a certain vicinity that exchange traffic-related information, (2) cognitive management functionality placed inside the vehicles for inferring knowledge and experience, and (3) cognitive management functionality in the overall transportation infrastructure. The goal of the aforementioned three main components shall be to issue directives to the drivers and the overall transportation infrastructure valuable in context handling.
Bio-hydrogen production from renewable organic wastes (2004)

Methane fermentation has been in practice over a century for the stabilization of high strength organic waste/wastewater. Although methanogenesis is a well established process and methane--the end-product of methanogenesis is a useful energy source; it is a low value end product with relatively less energy content (about 56 kJ energy/g CH{sub 4}). Besides, methane and its combustion by-product are powerful greenhouse gases, and responsible for global climate change. So there is a pressing need to explore alternative environmental technologies that not only stabilize the waste/wastewater but also generate benign high value end products. From this perspective, anaerobic bioconversion of organic wastes to hydrogen gas is an attractive option that achieves both goals. From energy security stand point, generation of hydrogen energy from renewable organic waste/wastewater could substitute non-renewable fossil fuels, over two-third of which is imported from politically unstable countries. Thus, biological hydrogen production from renewable organic waste through dark fermentation represents a critically important area of bioenergy production. This study evaluated both process engineering and microbial physiology of biohydrogen production.
Synthesis of (-)-Δ9-trans-Tetrahydrocannabinol:  Stereocontrol via Mo-Catalyzed Asymmetric Allylic Alkylation Reaction (2007)

[reaction: see text] Delta9-THC is synthesized in enantiomericaly pure form, where all of the stereochemistry is derived from the molybdenum-catalyzed asymmetric alkylation reaction of the extremely sterically congested bis-ortho-substituted cinnamyl carbonate in high regio- and enantioselectivity.
Enzyme immunoassay for identification of Vibrio vulnificus in seawater, sediment, and oysters (1991)

Historically, methods used to identify Vibrio vulnificus in environmental samples have been inadequate because isolation and identification procedures are time-consuming and fail to separate V. vulnificus from other bacterial species. We describe an enzyme immunoassay (EIA) and culture techniques which identified V. vulnificus in seawater, sediment, and oysters. The EIA used monoclonal antibody FRBT37 to a species-specific epitope of V. vulnificus. No cross-reactions were observed among 72 non-V. vulnificus strains comprising 34 species and 15 genera. In field trials, the EIA identified correctly 99.7% of 348 biochemically confirmed V. vulnificus isolates. The epitope corresponding to FRBT37 was found in cells lysed by Triton X-100, deionized H2O, and ultrasonication but was not found in culture supernatants, indicating that its location was intracellular. In addition, electron micrographs of V. vulnificus labeled with FRBT37-biotin-avidin-gold showed that epitope FRBT37 reacted with fragments of lysed cells but not whole cells. FRBT37 was expressed when V. vulnificus was cultured in different growth media. The minimum level of detection of the EIA was approximately 2,000 V. vulnificus cells per EIA well. Epitope FRBT37 was labile at 70 degrees C for 30 min. Immunoblot and EIA plate formats reduced assay time and facilitated handling large numbers of test samples.
A Vaulted Biaryl Phosphoric Acid-Catalyzed Reduction of α-Imino Esters:  The Highly Enantioselective Preparation of α-Amino Esters (2007)

A new method for the chiral phosphoric acid-catalyzed reduction of α-imino esters using Hantzsch ester is described. A series of 11 α-imino esters were evaluated, and it was shown that imino substrates derived from substituted aryl and alkyl keto esters could be reduced to the corresponding α-amino ester in excellent yield and in enantiomeric excesses from 94 to 99%. Catalyst loading was 5 mol % in each case, and the reactions were run with toluene as the solvent.
Mutation and protein expression of p53 in acquired immunodeficiency syndrome-related lymphomas (1993)

p53 mutations are found in a variety of neoplasia. B-immunoblastic lymphoma (BIBL) is a rapidly progressive, aggressive lymphoma. As patients with acquired immunodeficiency syndrome (AIDS) live longer, BIBL is becoming an increasing problem. We asked three questions in our study. What is the frequency of p53 mutations in BIBL? Is it more frequent in patients with AIDS? Can immunohistochemical staining of lymph nodes for expression of p53 substitute for mutational analysis of p53 to detect lymphomas with mutated p53? Exons 5, 6, 7, 8 of the p53 gene (hot-spots for mutations) were amplified and examined for mutations by single-strand conformation polymorphism (SSCP) analysis. Altered migration was observed in 7 of 52 BIBL samples. Of these, 4 of 25 were from individuals infected with human immunodeficiency virus (HIV) and 3 of 27 were not infected with HIV. Direct sequencing of amplified material confirmed the presence of mutations in exons 5, 7, 8 of p53. A total of 26 BIBL as well as other lymphoma/leukemia samples, stained strongly by immunohistochemistry with three antibodies directed against human p53. Five of 6 BIBL samples with p53 mutations stained strongly for p53, but 20 lymphoma samples with no detectable p53 mutations also stained strongly for p53. Of note, however, 10 hyperplastic, nonmalignant lymph nodes from individuals either infected or not infected with HIV had negligible staining for p53 protein. In conclusion, p53 mutations occur in about 14% BIBL samples; the frequency of p53 mutations in BIBL in individuals with and without AIDS was similar. Positive p53 immunohistochemistry did not correlate with detectable p53 mutations in the same tissue, but positive immunohistochemical staining for p53 was only found in neoplastic lymph nodes. This latter finding provides a strong warning that p53 immunochemistry with available reagents cannot be used to determine which tumors have mutations of p53.