gebhart/patrepeval huggingface dataset:
Function and clinical relevance of kallikrein-related peptidases and other serine proteases in gynecological cancers (2014)

Gynecological cancers, including malignant tumors of the ovaries, the endometrium and the cervix, account for approximately 10% of tumor-associated deaths in women of the Western world. For screening, diagnosis, prognosis, and therapy response prediction, the group of enzymes known as serine (Ser-)proteases show great promise as biomarkers. In the present review, following a summary of the clinical facts regarding malignant tumors of the ovaries, the endometrium and the cervix, and characterization of the most important Ser-proteases, we thoroughly review the current state of knowledge relating to the use of proteases as biomarkers of the most frequent gynecological cancers. Within the Ser-protease group, the kallikrein-related peptidase (KLK) family, which encompasses a subgroup of 15 members, holds particular promise, with some acting via a tumor-promoting mechanism and others behaving as protective factors. Further, the urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor-1) seem to play an unfavorable role in gynecological tumors, while down-regulation of high-temperature requirement proteins A 1, 2 and 3 (HtrA1,2,3) is associated with malignant disease and cancer progression. Expression/activity levels of other Ser-proteases, including the type II transmembrane Ser-proteases (TTSPs) matriptase, hepsin (TMPRSS1), and the hepsin-related protease (TMPRSS3), as well as the glycosyl-phosphatidylinositol (GPI)-anchored Ser-proteases prostasin and testisin, may be of clinical relevance in gynecological cancers. In conclusion, proteases are a rich source of biomarkers of gynecological cancer, though the enzymes' exact roles and functions merit further investigation.
Screening of Homogeneous Catalysts by Fluorescence Resonance Energy Transfer. Identification of Catalysts for Room-Temperature Heck Reactions (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTScreening of Homogeneous Catalysts by Fluorescence Resonance Energy Transfer. Identification of Catalysts for Room-Temperature Heck ReactionsJames P. Stambuli, Shaun R. Stauffer, Kevin H. Shaughnessy, and John F. HartwigView Author Information Department of Chemistry, Yale University P.O. Box 208107, New Haven, Connecticut 06520-8107 Cite this: J. Am. Chem. Soc. 2001, 123, 11, 2677–2678Publication Date (Web):February 22, 2001Publication History Received1 December 2000Published online22 February 2001Published inissue 1 March 2001https://pubs.acs.org/doi/10.1021/ja0058435https://doi.org/10.1021/ja0058435rapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views6384Altmetric-Citations204LEARN 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 (2)»Supporting Information Supporting Information SUBJECTS:Catalysts,Chemical reactions,Fluorescence resonance energy transfer,Heck reaction,Ligands Get e-Alerts
Aryl−Aryl Bond Formation One Century after the Discovery of the Ullmann Reaction (2002)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAryl−Aryl Bond Formation One Century after the Discovery of the Ullmann ReactionJwanro Hassan, Marc Sévignon, Christel Gozzi, Emmanuelle Schulz, and Marc LemaireView Author Information Laboratoire de Catalyse et Synthèse Organique, UMR 5622, Université Claude Bernard Lyon 1, CPE, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France, and Laboratoire de Catalyse Moleculaire, UPRESA, CNRS 8075, Institut de Chimie Moléculaire d'Orsay, Université Paris-Sud, 91405 Orsay Cedex, France Cite this: Chem. Rev. 2002, 102, 5, 1359–1470Publication Date (Web):March 8, 2002Publication History Received9 July 2001Published online8 March 2002Published inissue 1 May 2002https://pubs.acs.org/doi/10.1021/cr000664rhttps://doi.org/10.1021/cr000664rresearch-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views43479Altmetric-Citations3379LEARN 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 SUBJECTS:Anions,Aromatic compounds,Catalysts,Cross coupling reaction,Reaction products Get e-Alerts
Enzymatic Synthesis of Nucleobase-Modified Single-Stranded DNA Offers Tunable Resistance to Nuclease Degradation (2018)

We synthesized long, nucleobase-modified, single-stranded DNA (ssDNA) using terminal deoxynucleotidyl transferase (TdT) enzymatic polymerization. Specifically, we investigated the effect of unnatural nucleobase size and incorporation density on ssDNA resistance to exo- and endonuclease degradation. We discovered that increasing the size and density of unnatural nucleobases enhances ssDNA resistance to degradation in the presence of exonuclease I, DNase I, and human serum. We also studied the mechanism of this resistance enhancement using molecular dynamics simulations. Our results show that the presence of unnatural nucleobases in ssDNA decreases local chain flexibility and hampers nuclease access to the ssDNA backbone, which hinders nuclease binding to ssDNA and slows its degradation. Our discoveries suggest that incorporating nucleobase-modified nucleotides into ssDNA, using enzymatic polymerization, is an easy and efficient strategy to prolong and tune the half-life of DNA-based materials in nucleases-containing environments.
HLA-B35 is associated with accelerated progression to AIDS. (1992)

To investigate the influence of HLA specificities on the rate of progression and outcome of human immunodeficiency virus (HIV) infection, we performed (a) a case-control study in 1989-1990 of HIV-seropositive individuals stratified by both risk behavior and ethnic background, (b) a longitudinal cohort study of HIV-infected male homosexuals enrolled in 1981-1982, and (c) an analysis of individuals with a diffuse infiltrative CD8 lymphocytosis syndrome. In the case-control study, there was a significantly higher frequency of HLA-B35 among intravenous drug users, but not homosexuals, who developed illnesses meeting the case definition for AIDS compared with asymptomatic HIV-positive controls, regardless of ethnic status. In the longitudinal study, HLA-B35-positive homosexuals had a significantly increased rate of progression to AIDS and decreased survival over a 7-year period compared with those without this specificity. Finally, there was a significantly decreased frequency of HLA-B35 in individuals with the diffuse infiltrative lymphocytosis syndrome, a clinically and genetically distinctive disorder occurring in HIV infection in which a low rate of progression to opportunistic infections was found. The high rate of salivary and lacrimal gland lymphoma in this group suggests that there is dissociation between the presence of HLA-B35 and the development of particular AIDS-defining conditions. We conclude that HLA-B35 is a risk factor for more rapid progression to AIDS, particularly opportunistic infections and Kaposi's sarcoma, operating in groups with high rates of newly acquired HIV infections such as New York City male homosexuals in 1981-1982, and intravenous drug users in 1989-1990.(ABSTRACT TRUNCATED AT 250 WORDS)
Functionally inactive S. aureus alpha-toxin containing a single amino acid substitution: potential usefulness as a vaccine. (1994)

Substitution of His-35 with arginine in staphylococcal alpha-toxin leads to loss of its membrane perturbating properties in vitro. In this study, we report that the inactive mutant toxin is also devoid of toxic properties when injected intravenously into rabbits. Whereas a single application of native toxin at a dose of 20 micrograms/kg proved uniformly lethal within 3 hours (n = 3), all animals receiving 20, 100 or 200 micrograms/kg mutant toxin (n = 3 for each group) remained in unaltered, healthy states over a 15 day period of observation. Furthermore, all animals receiving inactive toxin developed antibody titers on day 10-15. No dose dependency was noted in the tested range. Thus, the site-directed alpha-toxin mutant (His-35:Arg) is an excellent vaccine candidate.
Nonviral Aβ DNA vaccine therapy against Alzheimer’s disease: Long-term effects and safety (2006)

It was recently demonstrated that amyloid beta (Abeta) peptide vaccination was effective in reducing the Abeta burden in Alzheimer model mice. However, the clinical trial was halted because of the development of meningoencephalitis in some patients. To overcome this problem, anti-Abeta antibody therapy and other types of vaccination are now in trial. In this study, we have developed safe and effective nonviral Abeta DNA vaccines against Alzheimer's disease. We administered these vaccines to model (APP23) mice and evaluated Abeta burden reduction. Prophylactic treatments started before Abeta deposition reduced Abeta burden to 15.5% and 38.5% of that found in untreated mice at 7 and 18 months of age, respectively. Therapeutic treatment started after Abeta deposition reduced Abeta burden to approximately 50% at the age of 18 months. Importantly, this therapy induced neither neuroinflammation nor T cell responses to Abeta peptide in both APP23 and wild-type B6 mice, even after long-term vaccination. Although it is reported that other anti-Abeta therapies have pharmacological and/or technical difficulties, nonviral DNA vaccines are highly secure and easily controllable and are promising for the treatment of Alzheimer's disease.
Mechanism of Cellular Uptake of Highly Fluorescent Conjugated Polymer Nanoparticles (2010)

Conjugated polymer nanoparticles are formed by precipitation of highly fluorescent conjugated polymers to form small nanoparticles with extremely bright fluorescence. We characterized cellular uptake and cytotoxicity of 18 ± 5 nm PFBT conjugated polymer nanoparticles in J774A.1 cells. Significant nanoparticle uptake was observed, indicating efficient nanoparticle entry into cells, even for short (1 h) incubations. The high fluorescence of these nanoparticles allows extremely low loading concentrations; PFBT nanoparticle fluorescence in cells could be detected with loading concentrations of 155 pM (270 ppb). Cellular uptake slows at low temperature, consistent with endocytic entry. Nanoparticles colocalize with Texas Red dextran and are trafficked to lysosomes, as demonstrated by the location of nanoparticle fluorescence in perinuclear organelles that also stain with an anti-LAMP-1 antibody. Inhibition of uptake by phosphoinositide 3-kinase inhibitors implicates macropinocytosis as the operative endocytic mechanism. No significant cytotoxic or inflammatory effects could be observed, making PFBT nanoparticles attractive probes for live cell imaging.
Purification and properties of .ALPHA.-glucosidase from Penicillium oxalicum. (1977)

Penicillium oxalicum produced two forms of glucoamylase and an α-glucosidase. The α-glucosidase has been isolated from the mycelia in an electrophoretically homogeneous form, and its properties have been investigated. The enzyme had a pH optimum at 3.5 with maltose as substrate. The enzyme hydrolyzed maltose, maltotriose, phenyl α-maltoside, isomaltose, panose, isomaltotriose, amylose, and soluble starch liberating glucose, but not sucrose. The Km value for maltose was 1.232mM. Phenyl α-maltoside was hydrolyzed to glucose and phenyl α-glucoside by the enzyme. Isomaltose was the main transglucosylation product from maltose and soluble starch. It was found that the enzyme liberated α-glucose from amylose.
Embryonic expression of the human 40-kD keratin: evidence from a processed pseudogene sequence. (1988)

Analysis of the cytoskeletal components of early murine embryos has detected expression of two keratin proteins, K#8 and K#18, at the 4-8-cell stage. Comparable data for human embryos do not exist, although several processed pseudogenes corresponding to K#8 and K#18 have been discovered in the human genome. Because only genes that are expressed in pre-germ-line and germ-line cells can give rise to processed pseudogenes, the existence of human K#8 and K#18 processed pseudogenes is prima facie evidence for expression of keratins K#8 and K#18 in the early human embryo. We have cloned and determined the complete sequence of a processed pseudogene corresponding to another acidic human keratin. Comparison of its sequence with known sequences of other mammalian keratins indicates that the pseudogene arose from a reverse transcript of a correctly initiated and terminated functional human K#19 gene. This implies expression of K#19 keratin in addition to K#8 and K#18 in the early human embryo. We have proposed previously that K#19 evolved specifically to redress unbalanced production of various basic keratins, and our current evidence, that it is expressed at an early stage of development, implies that K#19 may fulfill this same role during human embryogenesis.
Cell phone Mini Challenge: Node-link animation award animating multivariate dynamic social networks (2008)

This article describes the visualization tool developed for analysing a dynamic social network of phone calls, for the VAST 2008 mini challenge. The tool was designed to highlight temporal changes in the network, by animating different network visual representations. We also explain how animating these network representations, helped to identify key events in the mini challenge problem scenario. Finally, we make some suggestions for future research and development in the area.
Large-Scale Analysis of Glycoproteins by LC-MS Method (2006)

このレビューでは、レクチンカラムによる糖ペプチドの捕集、酵素反応による糖鎖付加位置特異的安定同位体標識法、及びLC-MSショットガン法によるタンパク質大規模解析法を組み合わせ、生体に存在する糖タンパク質を糖鎖結合部位も含めて大規模に同定する方法とその応用について紹介する。
DRPLA gene (Atrophin-1) sequence and mRNA expression in human brain (1996)

Dentatorubral pallidoluysian atrophy (DRPLA, Smith's disease) is one of five disorders currently known to result from expansion of a CAG trinucleotide repeat encoding glutamine. The reported full length cDNA sequence encodes a serine repeat and a region of alternating acidic and basic amino acids, as well as the glutamine repeat. We now report the nucleic acid and deduced amino acid sequences of the open reading frame of this gene, obtained from a series of independently isolated and sequenced cDNA clones. Eight nucleotide differences from the originally published sequence result in a change of 34 amino acids, most prominently in the region of alternating acidic and basic residues. Northern analysis and in situ hybridization indicate that atrophin-1 mRNA is expressed in multiple brain regions. The level of mRNA expression as determined by in situ hybridization in a DRPLA-diseased brain is indistinguishable from the level observed in a matched control brain. These results indicate that the correlation between atrophin-1 expression and regions of pathology in DRPLA is at best partial, and that the expanded allele does not cause a major loss of mRNA expression. The pathology of the disorder may therefore arise from the altered structure and function of the abnormal protein.
Shear stress inhibits smooth muscle cell migration via nitric oxide-mediated downregulation of matrix metalloproteinase-2 activity (2005)

Vascular smooth muscle cell (SMC) migration is a hallmark of intimal hyperplasia (IH), the progression of which is affected by hemodynamic conditions at the diseased site. The realization that SMCs are exposed to blood flow in both denuded vessels (direct blood flow) and intact vessels (interstitial blood flow) motivated this study of the effects of fluid flow shear stress (SS) on SMC migration. Rat aortic SMCs were seeded onto Matrigel-coated cell culture inserts, and their migratory activity toward PDGF-BB when exposed to SS in a rotating disk apparatus was quantified. Four hours of either 10 or 20 dyn/cm2 SS significantly inhibited SMC migration to the bottom side of the insert. This inhibition was associated with downregulation of SMC matrix metalloproteinase (MMP)-2 activation. Four hours of 10 dyn/cm2 SS also drastically increased SMC production of NO. A NO synthase inhibitor (N(G)-nitro-L-arginine methyl ester; 100 microM) abolished the shear-induced increase in SMC NO production as well as the inhibition of migration and MMP-2 activity. A NO donor (S-nitroso-N-acetyl-penicillamine; 500 microM) suppressed SMC migration via the reduction of both total and active MMP-2 levels. Addition of 10 microM MMP-2 inhibitor I to inserts significantly reduced SMC migration. Western blots showed no effect of 4 h of 20 dyn/cm2 SS on SMC production of PDGF-AA, another chemical known to suppress SMC migration. Thus it appears that SS acts to suppress SMC migration by upregulating the cellular production of NO, which in turn inhibits MMP-2 activity.
Mass Spectrometric Characterization of the Glycosylation Pattern of HIV-gp120 Expressed in CHO Cells (2000)

An analytical approach is reported for the characterization of the specific glycans found on highly glycosylated proteins based on a combination of specific proteolysis and deglycosylation combined with two different mass spectrometric approaches, matrix-assisted laser desorption/ionization mass spectrometry, and nanoelectrospray mass spectrometry/tandem mass spectrometry using a hybrid quadrupole-time-of-flight tandem mass spectrometer. The high resolution and mass accuracy of the mass spectrometric data obtained on the hybrid instrument combined with the high parent mass capabilities are shown to be extremely useful in the site-specific assignment of heterogeneous glycans. Using this methodology, 25 of 26 consensus glycosylation sites on HIV-1(SF2) gp120, expressed in Chinese hamster ovary cells, could be assigned. Good correlations between the relative abundances of members of heterogeneous series in the matrix-assisted laser desorption/ionization mass spectra and the nanoelectrospray mass spectra were observed, indicating that the mass spectrometric data reflected the actual abundances of the members of the series. These data were incorporated with molecular modeling based on the solved structure of a mutant truncated, highly deglycosylated gp120 to propose a structural model for the completely glycosylated form.
A Model for Determining Retail Product Category Assortment and Shelf Space Allocation (1994)

We develop a category management model to aid retailers in the space constrained decisions of which products to stock (assortment) and how much shelf space to allocate to those products. The model is formulated as a constrained optimization problem with two basic decision variables: assortment and allocation of space to the items in the assortment. The non-linearities in the objective function and the zero-one decision variables disallow a closed form solution. We develop a heuristic solution procedure based on simulated annealing and test it on a problem with a known optimum. We also apply the technique to a larger problem without a known optimum. Finally, the solution found by simulated annealing is compared against a solution produced using a shelf allocation rule based on share of sales.
Enhancing the Protective Efficacy of Mycobacterium bovis BCG Vaccination against Tuberculosis by Boosting with the Mycobacterium tuberculosis Major Secretory Protein (2005)

Tuberculosis continues to ravage humanity, killing 2 million people yearly. Most cases occur in areas of the world to which the disease is endemic, where almost everyone is vaccinated early in life with Mycobacterium bovis BCG, the currently available vaccine against tuberculosis. Thus, while more-potent vaccines are needed to replace BCG, new vaccines are also needed to boost the immune protection of the 4 billion people already vaccinated with BCG. Until now, no booster vaccine has been shown capable of significantly enhancing the level of protective immunity induced by BCG in the stringent guinea pig model of pulmonary tuberculosis, the "gold standard" for testing tuberculosis vaccines. In this paper, we describe a booster vaccine for BCG comprising the purified recombinant Mycobacterium tuberculosis 30-kDa protein, the major secreted protein of this pathogen. In the guinea pig model of pulmonary tuberculosis, boosting BCG-immunized animals once with the 30-kDa protein greatly increased cell-mediated and humoral immune responses to the protein in three consecutive experiments. Most importantly, boosting BCG-immunized animals once with the 30-kDa protein significantly enhanced protective immunity against aerosol challenge with highly virulent M. tuberculosis, as evidenced by a significantly reduced lung and spleen burden of M. tuberculosis compared with those for nonboosted BCG-immunized animals (mean additional reduction in CFU of 0.4 +/- 0.1 log in the lung [P = 0.03] and 0.6 +/- 0.1 log in the spleen [P = 0.002]). This study suggests that administering BCG-immunized people a booster vaccine comprising the 30-kDa protein may enhance their level of immunoprotection against tuberculosis.
Antioxidants in Human Health and Disease (1996)

Free radicals and antioxidants are widely discussed in the clinical and nutritional literature. Antioxidants are needed to prevent the formation and oppose the actions of reactive oxygen and nitrogen species, which are generated in vivo and cause damage to DNA, lipids, proteins, and other biomolecules. Endogenous antioxidant defenses (superoxide dismutases, H2O2-removing enzymes, metal binding proteins) are inadequate to prevent damage completely, so diet-derived antioxidants are important in maintaining health. Many dietary compounds have been suggested to be important antioxidants: The evidence for a key role of vitamins E and C is strong, but that for carotenoids and related plant pigments is weaker. Interest is also growing in the role of plant phenolics, especially flavonoids. Some antioxidants can exert prooxidant effects in vitro, but their physiological relevance is uncertain. Experimental approaches to the optimization of antioxidant nutrient intake are proposed.
Marijuana and the Cannabinoids (2007)

Although primarily used today as one of the most prevalent illicit leisure drugs, the use of Cannabis sativa L., commonly referred to as marijuana, for medicinal purposes has been reported for more th