gebhart/patrepeval huggingface dataset:
The mouse mammary carcinoma 4T1: characterization of the cellular landscape of primary tumours and metastatic tumour foci (2007)

The murine mammary carcinoma 4T1 causes a leukemoid reaction with profound granulocytosis coincident with the production of tumour-derived growth factors. Here, we study the evolving cellular landscape of primary tumours and metastatic tumour foci and correlate haematopoietic cell infiltration with the production of tumour-derived chemokines. Flow cytometric analysis of enzyme digested primary tumours at different times after transplantation revealed a progressively increasing CD45(+) haematopoietic cell infiltrate consisting predominantly of CD11b(+) myeloid cells. Most of these cells had an F4/80(+)/CD11c(+) phenotype, many of which also stained Gr-1(+). Smaller numbers of Gr-1(+)CD11b(+) granulocytes and lymphoid cells were also identified. Progressive increases in Gr-1(+) granulocytes were observed in enzymatic digests of livers and lungs with metastatic tumour foci. Cultured 4T1 tumour cells expressed mRNA transcripts for the myeloid cell chemokines RANTES, MCP-1 and KC, and enzymatically digested cells from primary 4T1 tumours partially depleted of CD45(+) cells expressed transcripts for these chemokines and also MIP-1alpha and MIP-1beta. These data demonstrate that 4T1 tumour-bearing mice have mixed myeloid cell infiltrates of primary tumours and granulocytic infiltrates of metastatic organs. This pathologic presentation correlated with the expression of tumour-derived chemokines.
Structural and Electronic Snapshots during the Transition from a Cu(II) to Cu(I) Metal Center of a Lytic Polysaccharide Monooxygenase by X-ray Photoreduction (2014)

Lytic polysaccharide monooxygenases (LPMOs) are a recently discovered class of enzymes that employ a copper-mediated, oxidative mechanism to cleave glycosidic bonds. The LPMO catalytic mechanism likely requires that molecular oxygen first binds to Cu(I), but the oxidation state in many reported LPMO structures is ambiguous, and the changes in the LPMO active site required to accommodate both oxidation states of copper have not been fully elucidated. Here, a diffraction data collection strategy minimizing the deposited x-ray dose was used to solve the crystal structure of a chitin-specific LPMO from Enterococcus faecalis (EfaCBM33A) in the Cu(II)-bound form. Subsequently, the crystalline protein was photoreduced in the x-ray beam, which revealed structural changes associated with the conversion from the initial Cu(II)-oxidized form with two coordinated water molecules, which adopts a trigonal bipyramidal geometry, to a reduced Cu(I) form in a T-shaped geometry with no coordinated water molecules. A comprehensive survey of Cu(II) and Cu(I) structures in the Cambridge Structural Database unambiguously shows that the geometries observed in the least and most reduced structures reflect binding of Cu(II) and Cu(I), respectively. Quantum mechanical calculations of the oxidized and reduced active sites reveal little change in the electronic structure of the active site measured by the active site partial charges. Together with a previous theoretical investigation of a fungal LPMO, this suggests significant functional plasticity in LPMO active sites. Overall, this study provides molecular snapshots along the reduction process to activate the LPMO catalytic machinery and provides a general method for solving LPMO structures in both copper oxidation states.
Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. (1998)

Epidemiological and laboratory studies suggest that nonsteroidal antiinflammatory drugs reduce the risk of colon cancer and that the inhibition of colon carcinogenesis is mediated through modulation of prostaglandin production by cyclooxygenase (COX) isozymes (COX-1 and -2). Overexpression of COX-2 has been observed in colon tumors; therefore, specific inhibitors of COX-2 activity could potentially serve as chemopreventive agents. Our recent study indicated that celecoxib (SC-58635), a specific COX-2 inhibitor, suppressed colonic aberrant crypt foci formation induced by azoxymethane in rats and led us to investigate more specifically the chemopreventive potential of this compound using colon tumors as end points. Five-week-old male F344 rats were fed the control diet (modified AIN-76A) or an experimental diet containing 1500 ppm celecoxib. Two weeks later, all animals except those in the saline-treated groups received s.c. injections of azoxymethane (15 mg/kg of body weight) once weekly for 2 weeks. All groups were kept on their regimen until the experiment was terminated, 50 weeks after carcinogen treatment. Colon tumors were evaluated histopathologically. Remarkably, dietary administration of celecoxib inhibited both incidence and multiplicity of colon tumors by about 93 and 97%, respectively. It also suppressed the overall colon tumor burden by more than 87%. The degree of tumor inhibition was more pronounced with celecoxib than it was with previously evaluated nonsteroidal anti-inflammatory drugs. The results of this study provide evidence, for the first time, that a specific COX-2 inhibitor, celecoxib, possesses strong chemopreventive activity against colon carcinogenesis.
Human monoclonal anti-phospholipid antibodies selectively bind to membrane phospholipid andβ2-glycoprotein I (β2-GPI) on apoptotic cells (2000)

The ability of an anti-phospholipid (LJ1) and an anti-beta2-GPI (RSP-57) human MoAb to bind to apoptotic but not viable cells was demonstrated in this study. Both MoAbs were derived from patients with systemic lupus erythematosus and anti-phospholipid antibody syndrome. The parallel analysis of the specificity and affinity of four anti-phospholipid human MoAbs suggests that the binding of LJ1 MoAb to apoptotic cells is a specific property of this MoAb. RSP-57 MoAb recognizes apoptotic cells through beta2-GPI which becomes available for binding after the interaction with negatively charged phospholipids. This observation provides evidence that the binding of human anti-phospholipid antibodies to apoptotic cells occurs in both a beta2-GPI-dependent and independent way and involves a restricted group of epitopes. The finding that LJ1 and RSP-57 MoAbs bind apoptotic cells underlines the property of these MoAbs to act as cell membrane markers of apoptosis. Major pathological implications derive from the observation that LJ1 and RSP-57 MoAbs recognize epitopes expressed on 'early' apoptotic cells. The interference with the in vivo clearance and processing of apoptotic cells is a potential pathogenic mechanism of these antibodies.
The role of tenascin-C in tissue injury and tumorigenesis (2009)

The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer.
Capillary blood sampling: the pain of single‐use lancing devices (2000)

Six disposable automatic lancing devices were examined in 50 healthy adult volunteers with regard to pain intensity, blood volume and user safety. Devices with a trigger-linked lancet movement were significantly more painful than those with a preset lancet speed. Residual pain was more frequent after the use of devices with a blade compared to devices with a needle. Only half of the devices reliably produced sufficient blood volumes (> 50 microl). Two of the devices could accidentally be re-used and constitute a hazard for patient and personnel. It is concluded that some of the disposable automatic lancing devices are safe and reliable but none of them causes minimal pain.
QT prolongation through hERG K+ channel blockade: Current knowledge and strategies for the early prediction during drug development (2004)

Prolongation of the QT interval of the electrocardiogram is a typical effect of Class III antiarrhythmic drugs, achieved through blockade of potassium channels. In the past decade, evidence has accrued that several classes of drugs used for non-cardiovascular indications may prolong the QT interval with the same mechanism (namely, human ether-a-go-go-related gene (hERG) K(+) channel blockade). The great interest in QT prolongation is because of several reasons. First, drug-induced QT prolongation increases the likelihood of a polymorphous ventricular arrhythmia (namely, torsades de pointes, TdP), which may cause syncope and degenerate into ventricular fibrillation and sudden death. Second, the fact that several classes of drugs, such as antihistamines, fluoroquinolones, macrolides, and neuroleptics may cause the long QT syndrome (LQTS) raises the question whether this is a class effect (e.g., shared by all agents of a given pharmacological class) or a specific effect of single agents within a class. There is now consensus that, in most cases, only a few agents within a therapeutic class share the ability to significantly affect hERG K(+) channels. These compounds should be identified as early as possible during drug development. Third, QT prolongation and interaction with hERG K(+) channels have become surrogate markers of cardiotoxicity and have received increasing regulatory attention. This review briefly outlines the mechanisms leading to QT prolongation and the different strategies that can be followed to predict this unwanted effect. In particular, it will focus on the approaches recently proposed for the in silico screening of new compounds.
3β-(4-Ethyl-3-iodophenyl)nortropane-2β- carboxylic Acid Methyl Ester as a High-Affinity Selective Ligand for the Serotonin Transporter (1997)

ADVERTISEMENT RETURN TO ISSUELetterNEXT3β-(4-Ethyl-3-iodophenyl)nortropane-2β- carboxylic Acid Methyl Ester as a High-Affinity Selective Ligand for the Serotonin TransporterBruce E. Blough, Philip Abraham, Andrew C. Mills, Anita H. Lewin, John W. Boja, Ursula Scheffel, Michael J. Kuhar, and F. Ivy CarrollView Author Information Chemistry and Life Sciences, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, North Carolina 27709, Neuroscience Branch, National Institute on Drug Abuse (NIDA) Addiction Research Center, P.O. Box 5180, Baltimore, Maryland 21224, and Department of Radiology, Division of Nuclear Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Cite this: J. Med. Chem. 1997, 40, 24, 3861–3864Publication Date (Web):November 21, 1997Publication History Received29 July 1997Published online21 November 1997Published inissue 1 November 1997https://pubs.acs.org/doi/10.1021/jm970492zhttps://doi.org/10.1021/jm970492zrapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views203Altmetric-Citations41LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Alkyls,Central nervous system,Inhibition,Organic compounds,Pharmaceuticals Get e-Alerts
The global distribution of fatal pesticide self-poisoning: Systematic review (2007)

Pesticide self-poisoning accounts for about one-third of the world's suicides. Epidemiological and toxicological data suggest that many of these deaths might be prevented if (a) the use of pesticides most toxic to humans was restricted, (b) pesticides could be safely stored in rural communities, and (c) the accessibility and quality of care for poisoning could be improved.
Real-world oriented information sharing using social networks (2005)

While users disseminate various information in the open and widely distributed environment of the Semantic Web, determination of who shares access to particular information is at the center of looming privacy concerns. We propose a real-world-oriented information sharing system that uses social networks. The system automatically obtains users' social relationships by mining various external sources. It also enables users to analyze their social networks to provide awareness of the information dissemination process. Users can determine who has access to particular information based on the social relationships and network analysis.
Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors (2003)

Neuronal precursor cells in the developing cerebellum require activity of the sonic hedgehog (Shh) and phosphoinositide-3-kinase (PI3K) pathways for growth and survival. Synergy between the Shh and PI3K signaling pathways are implicated in the cerebellar tumor medulloblastoma. Here, we describe a mechanism through which these disparate signaling pathways cooperate to promote proliferation of cerebellar granule neuron precursors. Shh signaling drives expression of mRNA encoding the Nmyc1 oncoprotein (previously N-myc), which is essential for expansion of cerebellar granule neuron precursors. The PI3K pathway stabilizes Nmyc1 protein via inhibition of GSK3-dependent Nmyc1 phosphorylation and degradation. The effects of PI3K activity on Nmyc1 stabilization are mimicked by insulin-like growth factor, a PI3K agonist with roles in central nervous system precursor growth and tumorigenesis. These findings indicate that Shh and PI3K signaling pathways converge on N-Myc to regulate neuronal precursor cell cycle progression. Furthermore, they provide a rationale for therapeutic targeting of PI3K signaling in medulloblastoma.
A functional single nucleotide polymorphism at the promoter region of cyclin A2 is associated with increased risk of colon, liver, and lung cancers (2011)

The current results suggested that an SNP (rs769236) at the promoter of CCNA2 may be associated significantly with increased risk of colon, liver, and lung cancers.
Naturally occurring respiratory disease in a kennel caused by Bordetella bronchiseptica. (1977)

The role of Bordetella bronchiseptica as a primary pathogen in nautrally occurring respiratory disease of dogs has been in question since its original isolation in 1911. A study to determine the incidence of B. bronchiseptica in a closed breeding kennel has revealed that the frequency of such isolations is closely associated with mild respiratory disease characterized by a moist, sometimes productive, cough. Infection with B. bronchiseptica usually occurred shortly after weaning and produced illness which lasted for one to two weeks. The organisms, however, continued to be shed for two to three months, and important factor in maintaining the infection in this kennel. Adult dogs sampled at frequent intervals did not harbor B. bronchiseptica in spite of their almost constant exposure to heavily infected pups; immunity to reinfection, therefore, appeared to develop. The involvement of several known canine respiratory viral agents was excluded by virus isolation and serological techniques. It therefore was concluded that B. bronchiseptica was the primary cause of respiratory disease in this large breeding kennel.
World Health Organization and disease surveillance: Jeopardizing global public health? (2014)

Health issues now evolve in a global context. Real-time global surveillance, global disease mapping and global risk management characterize what have been termed 'global public health'. It has generated many programmes and policies, notably through the work of the World Health Organization. This globalized form of public health raises, however, some important issues left unchallenged, including its effectiveness, objectivity and legitimacy. The general objective of this article is to underline the impacts of WHO disease surveillance on the practice and theorization of global public health. By using the surveillance structure established by the World Health Organization and reinforced by the 2005 International Health Regulations as a case study, we argue that the policing of 'circulating risks' emerged as a dramatic paradox for global public health policy. This situation severely affects the rationale of health interventions as well as the lives of millions around the world, while travestying the meaning of health, disease and risks. To do so, we use health surveillance data collected by the WHO Disease Outbreak News System in order to map the impacts of global health surveillance on health policy rationale and theory.
罗伯特·默顿、迈伦·斯科尔斯及衍生品定价的发展 (1999)

一、引言今年的诺贝尔经济学奖得主罗伯特·默顿和迈伦·斯科尔斯,每人在经济学的许多领域里都做出了很大贡献,但是瑞典皇家科学院秉承尊重特殊贡献的传统,只甄选提名了他们的衍生品定价理论。迈伦·斯科尔斯关于该论题的论文是与费希尔·布莱克合著的,可惜布莱克已于1995年8月去世。费希尔·布莱克和迈伦·斯科尔斯(1973)以及罗伯特·默顿(1973c)关于期权定价的论著,
Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. (1966)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Genital Infection of Female Chimpanzees with Human Immunodeficiency Virus Type 1 (1998)

To develop an animal model for mucosal HIV-1 infection, adult chimpanzees were inoculated without trauma by depositing the virus inoculum at the entrance to the cervical canal with a rigid catheter to which flexible tubing was attached. By this procedure, persistent infections were established in some chimpanzees with various infectious doses of either cell-associated HIV-1LAI(IIIB) (peripheral blood mononuclear cells from an infected chimpanzee) or with cell-free HIV-1 strains representing subtypes B and E, but not with a subtype A strain. Although some animals did not become infected until after the second or third cervicovaginal exposure, one chimpanzee was clearly infected after one exposure by several criteria, including virus isolation, but this animal did not seroconvert. A second chimpanzee appeared to be resistant to infection despite repeated mucosal exposures at irregular intervals. However, lymphocytes from both of these animals exhibited low-level proliferative responses to HIV-1 but not SIV antigens. Despite these apparently abortive or latent infections, after exposure to HIV-1 by the intravenous route, both animals developed systemic infections and seroconverted. Overall, 8 of 10 chimpanzees were infected systemically after one to three cervicovaginal exposures to HIV-1LAI(IIIB). The results indicate that (1) HIV-1 productive infection of female chimpanzees by the cervicovaginal route generally requires more than one exposure, just as with humans; (2) low level infections without seroconversion can be established after mucosal exposure to HIV; and (3) vaccine efficacy studies involving a single virus challenge of immunized chimpanzees by the cervicovaginal route probably will not be possible.
Pfam 3.1: 1313 multiple alignments and profile HMMs match the majority of proteins (1999)

Pfam is a collection of multiple alignments and profile hidden Markov models of protein domain families. Release 3.1 is a major update of the Pfam database and contains 1313 families which are available on the World Wide Web in Europe at http://www.sanger.ac.uk/Software/Pfam/ and http://www.cgr.ki.se/Pfam/, and in the US at http://pfam.wustl.edu/. Over 54% of proteins in SWISS-PROT-35 and SP-TrEMBL-5 match a Pfam family. The primary changes of Pfam since release 2.1 are that we now use the more advanced version 2 of the HMMER software, which is more sensitive and provides expectation values for matches, and that it now includes proteins from both SP-TrEMBL and SWISS-PROT.
Review article: issues in oral administration of locally acting glucocorticosteroids for treatment of inflammatory bowel disease (1998)

Inflammatory bowel diseases are treated in some cases by local administration of anti-inflammatory drugs. Local delivery of drugs in the colon following oral administration may lead to improved efficacy/side-effect profiles and may improve patient compliance. This review covers a number of issues important in the design of oral delivery systems of glucocorticosteroids for local therapy of colonic inflammation. The choice of specific glucocorticosteroids is based on the drug's physicochemical and pharmacological properties. The conditions under which an orally administered glucocorticosteroid (or other drug) must be delivered to treat ulcerative colitis are also discussed. These conditions include variations in local pH, transit throughout the gastrointestinal tract, the potential role of gut microflora, and drug dissolution in both the healthy and diseased large intestine. The effective delivery of topically-active glucocorticosteroids in ulcerative colitis and Crohn's colitis patients is complex, but if successful could improve their usefulness.
SOI Circuit Design Concepts (2002)

Market demand for microprocessor performance has motivated continued scaling of CMOS through a succession of lithography generations. Quantum mechanical limitations to continued scaling are becoming readily apparent. Partially Depleted Silicon-on-Insulator (PD-SOI) technology is emerging as a promising means of addressing these limitations. It also introduces additional design complexity which must be well understood. SOI Circuit Design Concepts first introduces the student or practicing engineer to SOI device physics and its fundamental idiosyncrasies. It then walks the reader through realizations of these mechanisms which are observed in common high-speed microprocessor designs. Rules of thumb and comparisons to conventional bulk CMOS are offered to guide implementation. SOI's ultimate advantage, however, may lie in the unique circuit topologies it supports; a number of these novel new approaches are described as well. SOI Circuit Design Concepts draws upon the latest industry literature as well as the firsthand experiences of its authors. It is an ideal introduction to the concepts of governing SOI use and provides a firm foundation for further study of this exciting new technology paradigm.