gebhart/patrepeval huggingface dataset:
Pan-3C Protease Inhibitor Rupintrivir Binds SARS-CoV-2 Main Protease in a Unique Binding Mode (2021)

Rupintrivir targets the 3C cysteine proteases of the picornaviridae family, which includes rhinoviruses and enteroviruses that cause a range of human diseases. Despite being a pan-3C protease inhibitor, rupintrivir activity is extremely weak against the homologous 3C-like protease of SARS-CoV-2. In this study, the crystal structures of rupintrivir were determined bound to enterovirus 68 (EV68) 3C protease and the 3C-like main protease (M<sup>pro</sup>) from SARS-CoV-2. While the EV68 3C protease-rupintrivir structure was similar to previously determined complexes with other picornavirus 3C proteases, rupintrivir bound in a unique conformation to the active site of SARS-CoV-2 M<sup>pro</sup> splitting the catalytic cysteine and histidine residues. This bifurcation of the catalytic dyad may provide a novel approach for inhibiting cysteine proteases.
Increased disparity for minor histocompatibility antigens as a potential cause of increased GVHD risk in marrow transplantation from unrelated donors compared with related donors. (1991)

Patients transplanted with marrow from an HLA-phenotypically identical unrelated donor have a much higher risk of acute graft-versus-host disease (GVHD) than patients transplanted from an HLA-genotypically identical sibling. Much of this increased risk may be due to disparity for antigens encoded by genes within the MHC. Although the development of molecular genetic methods for HLA-typing may enable better matching between unrelated donor/recipient pairs, the extent to which GVHD risk might be decreased remains uncertain because disparity for minor histocompatibility antigens encoded by genes outside the MHC also causes GVHD. By application of fundamental population genetics, it can be demonstrated that the disparity for minor histocompatibility antigens is substantially greater between unrelated individuals than between family members. These findings imply that even with improved HLA-matching, unrelated marrow transplantation will carry more risk of GVHD than transplantation from a related donor.
MEIOTIC GENE CONVERSION MUTANTS IN SACCHAROMYCES CEREVISIAE. I. ISOLATION AND CHARACTERIZATION OF pms1-1 AND pms1-2 (1985)

The pms1 mutants, isolated on the basis of sharply elevated meiotic prototroph frequencies for two closely linked his4 alleles, display pleiotropic phenotypes in meiotic and mitotic cells. Two isolates carrying recessive mutations in PMS1 were characterized. They identify a function required to maintain low postmeiotic segregation (PMS) frequencies at many heterozygous sites. In addition, they are mitotic mutators. In mutant diploids, spore viability is reduced, and among survivors, gene conversion and postmeiotic segregation frequencies are increased, but reciprocal exchange frequencies are not affected. The conversion event pattern is also dramatically changed in multiply marked regions in pms1 homozygotes. The PMS1 locus maps near MET4 on chromosome XIV. The PMS1 gene may identify an excision-resynthesis long patch mismatch correction function or a function that facilitates correction tract elongation. The PMS1 gene product may also play an important role in spontaneous mitotic mutation avoidance and correction of mismatches in heteroduplex DNA formed during spontaneous and UV-induced mitotic recombination. Based on meiotic recombination models emphasizing mismatch correction in heteroduplex DNA intermediates, this interpretation is favored, but alternative interpretations involving longer recombination intermediates in the mutants are also considered.
Document Thumbnail Visualization for Rapid Relevance Judgments: When do They Pay Off? (1998)

In a recent experiment, Kaugars (1989) developed a document visualization system that displayed the results of a keyword text search as a set of small graphical representations (thumbnails) of the top 20 retrieved documents laid out in one window and a single document viewer in a second window (See Figure 1). Document thumbnails presented color-coded highlighting indicating positions and identities of search terms in the document, and the single document viewer showed a fish-eye view of the document focused on multiple regions defined by the sentences holding search terms. He compared this system to another more traditional system that represented documents as lists of short titles and a simple scrolled window document viewer. The users judged 8 sets of documents in accordance with relevance judgments supplied with 8 selected TREC-6 topics. The documents and topics were all pre-selected for the users who had no part in selecting query terms or interacting with the retrieval software. Kaugars found that people were faster and better at making relevance judgments for a fixed set of retrieved documents when using the thumbnail/fish-eye system.
Bioimpedance at the Bedside (2015)

The loss of muscle mass is a defining characteristic of malnutrition, and there is ongoing interest in the assessment of lean tissue at the bedside. Globally, bioimpedance techniques have been widely appreciated for their noninvasiveness, safety, ease of use, portability, and relatively low cost compared with other clinically available methods. In this brief update, we review the 3 primary types of commercially available bioimpedance devices (single- and multiple-frequency and spectroscopy) and differentiate the underlying theory and current applications of each. We also address limitations and potential opportunities for using these devices at the bedside for clinical assessment. Mixed reports in the validation literature for all bioimpedance approaches have raised questions about absolute accuracy to estimate whole body composition in clinical populations, particularly those with abnormal fluid status and/or body geometry in whom underlying method assumptions may be violated. Careful selection of equations can improve whole body estimates by single- and multiple-frequency techniques; however, not all devices will allow for this approach. Research is increasing on the use of bioimpedance variables including phase angle and impedance ratio as potential markers of nutrition status and/or clinical outcomes; consensus on reference cut-points for interpreting these markers has yet to be established. Novel developments in the bioimpedance spectroscopy approach are allowing for improved fluid management in individuals receiving dialysis; these developments have implications for the clinical management of other conditions associated with fluid overload and may also provide enhanced whole body estimates of lean tissue through new modeling procedures.
Protection From Obesity in Mice Lacking the VLDL Receptor (2001)

It has previously been reported that mice lacking the VLDL receptor (VLDLR-/-) exhibit normal plasma lipid levels and a modest decrease in adipose tissue mass. In the present study, the effect of VLDLR deficiency on profound weight gain was studied in mice. Obesity was induced either by feeding of a high-fat, high-calorie (HFC) diet or by crossbreeding mice onto the genetically obese ob/ob background. After 17 weeks of HFC feeding, VLDLR-/- mice remained lean, whereas their wild-type littermates (VLDLR+/+) became obese. Similarly, the weight gain of ob/ob mice was less profound in the absence of the VLDLR. Moreover, VLDLR deficiency led to increased plasma triglycerides after HFC feeding. The protection from obesity in VLDLR-/- mice involved decreased peripheral uptake of fatty acids, because VLDLR-/- mice exhibited a significant reduction in whole-body free fatty acid uptake, with no clear differences in food intake and fat absorption. These observations were supported by a strong decrease in average adipocyte size in VLDLR-/- mice of both obesity models, implying reduced adipocyte triglyceride storage in the absence of the VLDLR. These results suggest that the VLDLR plays a role in the delivery of VLDL-derived fatty acids into adipose tissue.
The cyclic diguanylic acid regulatory system of cellulose synthesis in Acetobacter xylinum. Chemical synthesis and biological activity of cyclic nucleotide dimer, trimer, and phosphothioate derivatives. (1990)

An unusual compound, cyclic-bis(3'----5') diguanylic acid (c-di-GMP or cGpGp), is involved in the regulation of cellulose synthesis in the bacterium Acetobacter xylinum. This cyclic dinucleotide acts as an allosteric, positive effector of cellulose synthase activity in vitro (Ka = 0.31 microM) and is inactivated via degradation by a Ca2(+)-sensitive phosphodiesterase, PDE-A (Km = 0.25 microM). A series of 13 analogs cyclic dimer and trimer nucleotides were synthesized, employing a phosphotriester approach, and tested for the ability to mimick c-di-GMP as activators of cellulose synthase and as substrates for PDE-A. Seven of the synthetic compounds stimulate cellulose synthase activity and all of these activators undergo the Ca2(+)-inhibited degradation reaction. The order of affinities for synthase activators is cGpGp approximately cdGpGp approximately cGp(S)Gp (S-diastereomer) greater than cIpGp greater than cdGpdGp greater than cXpGp greater than cIpIp greater than cGp(S)Gp (R-diastereomer). Three cyclic dinucleotides of negligible affinity for either enzyme are cApAp, cUpUp, and cCpCp. This same order of affinities essentially pertains to the analogs as inhibitors of PDE-A activity, but at least one cyclic dinucleotide, cXpXp, which does not bind to cellulose synthase, is also a substrate for the degradation reaction, demonstrating that although the two enzymes share a similar, high degree of specificity for c-di-GMP, their cyclic dinucleotide binding sites are not identical. Phosphodiester bonds of activators in which an exocyclic oxygen is replaced with an atom of sulfur (cGp(S)Gp isomers) resist the action of PDE-A, and such derivatives may be prototypes for synthetic non-hydrolyzable c-di-GMP analogs.
Multicasting streaming media to mobile users (2003)

Content distribution in general, and multicasting in particular, over a wired network to static hosts can be realized by placing proxies and gateways at several parts of the network. However, if the end hosts are mobile over heterogeneous wireless access networks, one needs to consider many operational issues such as network detection, handoff, join and leave latency, and desired level of quality of service, as well as caching and load balancing. This article surveys a set of protocols and technologies that offer multicast-based services for streaming multimedia in a mobile environment. It also brings forth some of the issues related to mobile content distribution in the wireless Internet that may be helpful during its deployment by application service providers.
Substituted 1,3-Dipropylxanthines as Irreversible Antagonists of A1 Adenosine Receptors (1994)

This report describes the synthesis of 29 xanthines containing a chemoreactive chloroaryl, beta-chloroethylamino, alpha,beta-unsaturated carbonyl, bromoacetyl, 3-(fluorosulfonyl)benzoyl, or 4-(fluorosulfonyl)benzoyl group as part of an exocyclic 1-, 3-, or 8-substituent. The xanthines inhibited the binding of [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]CPX) to the A1 adenosine receptor (A1AR) of DDT1 MF2 cells at IC50s in the low-nanomolar to low-micromolar range. Seven of the 29 analogues irreversibly inhibited the binding of [3H]CPX without changing the KD of that ligand; five were 1,3-dipropylxanthines having the following reactive groups as 8-substituents: (bromoacetamido)methyl (24), (bromoacetamido)ethyl (25), (bromoacetamido)propyl (26), [4-(fluorosulfonyl)benzamido]methyl (33) or 3-[[4-(fluorosulfonyl)benzoyl]oxy]cyclopentyl (42). Both 8-cyclopentyl-3-[3-[[4- (fluorosulfonyl)benzoyl]oxy]propyl]-1-propylxanthine (53) and 8-cyclopentyl-1,3-bis[3-[[4- (fluorosulfonyl)benzoyl]oxy]propyl]xanthine (55) inhibited [3H]CPX binding irreversibly. Five of the ligands, including 26, 33 (IC50 = 49 microM), and 53 (IC50 = 9 microM), antagonized the binding of [3H]NECA to the A2aAR of PC12 cells, but unlike binding to the A1AR, binding to the A2aAR was completely reversible. The potency of 33 (IC50 = 2 microM, 72% loss of CPX binding at 1 microM) and 53 (IC50 = 0.01 microM, 74% loss of CPX binding at 0.05 microM) and their selectivity for the A1AR suggest that those two ligands may be useful in studies of the structure and function of that receptor.
An Intramolecular Switch Regulates Phosphoindependent FHA Domain Interactions in Mycobacterium tuberculosis (2009)

Forkhead-associated (FHA) domains have gained considerable prominence as ubiquitous phosphothreonine-dependent binding modules; however, their precise roles in serine and threonine kinase (STK) pathways and mechanisms of regulation remain unclear. From experiments with Rv1827, an FHA domain-containing protein from Mycobacterium tuberculosis, we derived a complete molecular description of an FHA-mediated STK signaling process. First, binding of the FHA domain to each of three metabolic enzyme complexes regulated their catalytic activities but did not require priming phosphorylation. However, phosphorylation of a threonine residue within a conserved amino-terminal motif of Rv1827 triggered its intramolecular association with the FHA domain of Rv1827, thus blocking its interactions with each of the three enzymes. The solution structure of this inactivated form and further mutagenic studies showed how a previously unidentified intramolecular phosphoswitch blocked the access of the target enzymes to a common FHA interaction surface and how this shared surface accommodated three functionally related, but structurally diverse, binding partners. Thus, our data reveal an unsuspected versatility in the FHA domain that allows for the transformation of multiple kinase inputs into various downstream regulatory signals.
Visualization of RecA-DNA Complexes Involved in Consecutive Stages of An In Vitro Strand Exchange Reaction (1984)

RecA protein, which is essential for general genetic recombination in Escherichia coli, in vitro pairs single-stranded DNA (ssDNA) with homologous double-stranded DNA (dsDNA) and promotes strand exchange (for review and other recombination reactions mediated by RecA, see Radding 1982). This reaction has been shown to require ATP hydrolysis and to be stimulated by the single-strand-binding protein (SSB) (Cox and Lehman 1981). In the presence of the non-hydrolyzable analog of ATP adenosine-5′-O-(3-thiotriphosphate) (ATPγS), dsDNA is found covered with RecA in stable complexes (West et al. 1980; Stasiak et al. 1981; Dunn et al. 1982; Flory and Radding 1982), at a stoichiometry of 1 RecA/3 bp (DiCapua et al. 1982; Dombrowski et al., 1983). These filamentous RecA-DNA complexes are helical, and the dsDNA in the complexes is unwound from 10.5 bp/turn (B-DNA) into 18.5 bp/turn, following the protein helix (Stasiak and DiCapua 1982).
ATR-FTIR Spectroscopy Reveals Bond Formation During Bacterial Adhesion to Iron Oxide (2006)

The contribution of various bacterial surface functional groups to adhesion at hematite and ZnSe surfaces was examined using attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy. When live Shewanella oneidensis, Pseudomonas aeruginosa, and Bacillus subtilis cells were introduced to a horizontal hematite (alpha-Fe(2)O(3))-coated internal reflection element (IRE), FTIR peaks emerged corresponding to bacterial phosphate group binding. These IR peaks were not observed when bacteria were introduced to the uncoated ZnSe IRE. When cells were added to colloidal suspensions of alpha-Fe(2)O(3) at pH 7, spectra included peaks corresponding to P-OFe and nu(COOH), the latter being attributed to bridging of carboxylate at mineral surface OH groups. Selected model organic compounds with P-containing functionalities (phenylphosphonic acid [PPA], adenosine 5'-monophosphate [AMP], 2'-deoxyadenyl(3'-->5')-2'-deoxyadenosine [DADA], and deoxyribonucleic acid [DNA]) produce spectra with similar peaks corresponding to P-OFe when adsorbed to alpha-Fe(2)O(3). The data indicate that both terminal phosphate/phosphonate and phosphodiester groups, either exuded from the cell or present as surface biomolecules, are involved in bacterial adhesion to Fe-oxides through formation of innersphere Fe-phosphate/phosphonate complexes.
Person Reidentification Using Spatiotemporal Appearance (2006)

In many surveillance applications it is desirable to determine if a given individual has been previously observed over a network of cameras. This is the person reidentification problem. This paper focuses on reidentification algorithms that use the overall appearance of an individual as opposed to passive biometrics such as face and gait. Person reidentification approaches have two aspects: (i) establish correspondence between parts, and (ii) generate signatures that are invariant to variations in illumination, pose, and the dynamic appearance of clothing. A novel spatiotemporal segmentation algorithm is employed to generate salient edgels that are robust to changes in appearance of clothing. The invariant signatures are generated by combining normalized color and salient edgel histograms. Two approaches are proposed to generate correspondences: (i) a model based approach that fits an articulated model to each individual to establish a correspondence map, and (ii) an interest point operator approach that nominates a large number of potential correspondences which are evaluated using a region growing scheme. Finally, the approaches are evaluated on a 44 person database across 3 disparate views.
[Treatment of overtime avulsion of scalp with split thickness scalp skin grafting: 7 cases of reports]. (2003)

The limits of time of scalp skin grafting will be prolonged as long as the processes are settled properly to maintain the skin of body.
The Genomic Analysis of Lactic Acidosis and Acidosis Response in Human Cancers (2008)

The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little is known about how cells respond to lactic acidosis and how that response relates to cancer phenotypes. We develop genome-scale gene expression studies to dissect transcriptional responses of primary human mammary epithelial cells to lactic acidosis and hypoxia in vitro and to explore how they are linked to clinical tumor phenotypes in vivo. The resulting experimental signatures of responses to lactic acidosis and hypoxia are evaluated in a heterogeneous set of breast cancer datasets. A strong lactic acidosis response signature identifies a subgroup of low-risk breast cancer patients having distinct metabolic profiles suggestive of a preference for aerobic respiration. The association of lactic acidosis response with good survival outcomes may relate to the role of lactic acidosis in directing energy generation toward aerobic respiration and utilization of other energy sources via inhibition of glycolysis. This "inhibition of glycolysis" phenotype in tumors is likely caused by the repression of glycolysis gene expression and Akt inhibition. Our study presents a genomic evaluation of the prognostic information of a lactic acidosis response independent of the hypoxic response. Our results identify causal roles of lactic acidosis in metabolic reprogramming, and the direct functional consequence of lactic acidosis pathway activity on cellular responses and tumor development. The study also demonstrates the utility of genomic analysis that maps expression-based findings from in vitro experiments to human samples to assess links to in vivo clinical phenotypes.
HIV-associated myocarditis treated with zidovudine (AZT). (1989)

Congestive cardiomyopathy has been reported in patients infected with human immunodeficiency virus (HIV). In this report of diffuse lymphocytic myocarditis in a patient who tested positive for HIV antibody after receiving blood from an HIV-positive donor, the patient failed to respond to conventional medical therapy. Although no opportunistic infection or malignancy was observed by electron-and light-microscopic examination of the endomyocardial tissue sample at biopsy, it was decided to give the patient zidovudine (AZT) at a dosage of 200 mg every 4 hours. Definite clinical improvement was noted on repeat right heart catheterization and endomyocardial biopsy 3 months after the initiation of AZT therapy. This case supports the theory that myocarditis can be caused by HIV and suggests that AZT may be useful in the treatment of patients with HIV-associated cardiomyopathy.
Effect of DNT cells on tumor cells (2009)

DNT cells(CD4-CD8-double-negative T cells)ale newly discovered immune cells,whose surface ex press neither CD4 nor CD8 molecules.In recent years,the prognosis and survival quality of tumour patient have been greatly improved through cell immunotherapy.Immunocyte can kill the tumour directly Or through immunoregu lation.The study of DNT cells(double-nnegative T cell)on cancer cells will be of vital significance. 

Key words: 
DNT cells; neoplasms; immunotherapy
Mechanical and Structural Properties of a Novel Hybrid Heart Valve Scaffold for Tissue Engineering (2004)

Hybrid heart valve scaffolds were fabricated from decellularized porcine aortic heart valve matrices and enhanced with bioresorbable polymers using different protocols: (i) dip coating of lyophilized decellularized matrices, and (ii) impregnation of wet decellularized matrices. The following polymers were evaluated: poly(4-hydroxybutyrate) and poly(3-hydroxybutyrate-co4-hydroxybutyrate). Tensile tests were conducted to assess the biomechanical behavior of valve leaflet strips. Suture retention strength was evaluated for the adjacent conduit. A pulse duplicator system was used for functional testing of the valves under physiological systemic load conditions. The properties of the hybrid structures were compared with native, decellularized, and glutaraldehyde-fixed specimens. Mechanisms of the polymer impregnation process were studied with IR spectroscopy, fluorescent microscopic imaging, and SEM. Altogether this study demonstrates the feasibility and improved biomechanical function of a novel hybrid heart valve scaffold for an application in tissue engineering.
Platelet Unresponsiveness to Collagen: Involvement of Glycoprotein Ia-IIa (α2β1 Integrin) Deficiency Associated with a Myeloproliferative Disorder (1995)

Summary We studied a 66-year-old man with a myeloproliferative disorder who presented with a prolonged bleeding time and marked thrombocytosis (platelet count, 3,890 × 109/1). There was no past history of a bleeding disorder. The patient had normal coagulation data. His platelets completely lacked collagen-induced platelet aggregation and adhesion, but showed normal responses to other agonists. All family members tested showed normal platelet aggregation with collagen. Analysis of 125I surface-labeled platelets by two-dimensional SDS gel electrophoresis disclosed absence of the spot corresponding to platelet membrane GPIa (α2) but no other significant deficiencies of major platelet glycoproteins i.e., GPIb, IIb-IIIa, and IV. Immunoisolation studies of the patient’s platelets indicated that neither anti-GPIa nor anti-GPIIa (β1) monoclonal antibody (mAb) isolated any surface membrane proteins corresponding to GPIa. GPVI, a putative collagen receptor, was immunoisolated from the platelets. Indirect immunofluorescence study using flow cytometry confirmed that the patient’s platelets were totally deficient in surface expression of the GPIa-IIa complex (α2β1, integrin). In contrast, phytohemoagglutinin-activated T-lymphocytes from the patient expressed normal concentrations of this complex. The data suggest that our patient had an acquired deficiency of the platelet GPIa-IIa complex, due to a myeloproliferative disorder, which might account for the absence of responsiveness of his platelet to collagen.