gebhart/patrepeval huggingface dataset:
The sequence organization of the long arm pseudoautosomal region of the human sex chromosomes (1994)

We have analysed the sequence organization of the pseudoautosomal region at the telomeres of the long arms of the human sex chromosomes and shown that it is 320 kb long. A LINE sequence is present on both the X and Y chromosomes immediately adjacent to the breakpoint in homology suggesting that the homology arose as a result of an ectopic recombination event mediated by LINE sequences originally present in non-homologous stretches of X and Y chromosomal DNA. This led to the translocation of sequences from the X chromosome telomere onto the Y chromosome and created a new pseudoautosomal region.
Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study (2015)

This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥ 1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥ 1.3. The null hypothesis was that ≤ 15% of patients gain such benefit. Overall, ≥ 1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1-6 (median: 4) actionable biomarkers per patient. After MP, patients received 1-4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥ 1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC.
A Novel Biodegradable Gene Carrier Based on Polyphosphoester (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Novel Biodegradable Gene Carrier Based on PolyphosphoesterJun Wang, Hai-Quan Mao, and Kam W. LeongView Author Information Johns Hopkins Singapore, Singapore 117597 Department of Biomedical Engineering Johns Hopkins University School of Medicine Baltimore, Maryland 21205 Cite this: J. Am. Chem. Soc. 2001, 123, 38, 9480–9481Publication Date (Web):September 1, 2001Publication History Received21 April 2001Published online1 September 2001Published inissue 1 September 2001https://pubs.acs.org/doi/10.1021/ja016062mhttps://doi.org/10.1021/ja016062mrapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views2431Altmetric-Citations227LEARN 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:Degradation,Gene delivery,Genetics,Polymers,Toxicity Get e-Alerts
Relationships between Leg Power, Leg Strength, Knee Valgus and Trunk Endurance with Hip Pain in Dancers (2015)

The hip is a common site of pain and injury in dancers. The purpose of this study is to explore the relationships between leg power, leg strength, knee valgus and trunk endurance with anteriolateral hip pain. Nine collegiate-aged dancers currently in a university dance program (age = 20±1 yrs, height = 64.8±4.5 in, weight = 131.2±12.8 lbs) reported, on a Visual Analog Scale, their level of pain at rest and while dancing. The dancers’ countermovement jump (CMJ), squat jump (SJ) and anterior, posterior and bi-lateral trunk endurance were then assessed. The CMJ and SJ assessments, as measures of lower body power and strength, respectively, were conducted on a contact mat (Just Jump, Probotics, Huntsville, AL). During the CMJ, knee valgus was evaluated by filming the participant (120 fps) from the frontal view. The CMJ with the highest jump score was used to measure the greatest amount of knee valgus collapse, defined as the angle from the ASIS, middle of the patella and center of the tibiotalar joint. Moderate Pearson’s product-moment correlations were observed between age (r = 0.48), posterior trunk endurance (r = -0.48) and the ratio between right lateral and anterior trunk endurance (r = 0.42) with hip pain while resting. Moderate correlations were found between leg power (r = -0.43), leg strength (r = -0.54), the ratio between right and left lateral trunk endurance (r = -0.46), and the ratio between left lateral and posterior trunk endurance (r = 0.46) with hip pain while dancing. Increasing leg power and strength as well as addressing asymmetries, particularly in the trunk musculature, may decrease the pain associated with dancing; further research is needed to explore these relationships.
Humanized Monoclonal Antibodies Derived from Chimpanzee Fabs Protect against Japanese Encephalitis Virus In Vitro and In Vivo (2008)

Japanese encephalitis virus (JEV)-specific Fab antibodies were recovered by repertoire cloning from chimpanzees initially immunized with inactivated JE-VAX and then boosted with attenuated JEV SA14-14-2. From a panel of 11 Fabs recovered by different panning strategies, three highly potent neutralizing antibodies, termed Fabs A3, B2, and E3, which recognized spatially separated regions on the virion, were identified. These antibodies reacted with epitopes in different domains: the major determinant for Fab A3 was Lys(179) (domain I), that for Fab B2 was Ile(126) (domain II), and that for Fab E3 was Gly(302) (domain III) in the envelope protein, suggesting that these antibodies neutralize the virus by different mechanisms. Potent neutralizing antibodies reacted with a low number of binding sites available on the virion. These three Fabs and derived humanized monoclonal antibodies (MAbs) exhibited high neutralizing activities against a broad spectrum of JEV genotype strains. Demonstration of antibody-mediated protection of JEV infection in vivo is provided using the mouse encephalitis model. MAb B2 was most potent, with a 50% protective dose (ED(50)) of 0.84 microg, followed by MAb A3 (ED(50) of 5.8 microg) and then MAb E3 (ED(50) of 24.7 microg) for a 4-week-old mouse. Administration of 200 microg/mouse of MAb B2 1 day after otherwise lethal JEV infection protected 50% of mice and significantly prolonged the average survival time compared to that of mice in the unprotected group, suggesting a therapeutic potential for use of MAb B2 in humans.
Interferons in multiple sclerosis (1995)

Administering or neutralizing a single cytokine is currently considered to represent a promising approach to therapeutic intervention in the immune network in autoimmune diseases. In this article, evidence from animal model experiments is reviewed: intervention in such models can have results opposite to those in the clinical disease; and intended neutralization of a cytokine by the administration of anticytokine antibodies can enhance as well as block in vivo cytokine activity. In experimental autoimmune encephalitis in mice, a model system for multiple sclerosis, administration of interferon gamma (IFN-gamma) was found to reduce disease severity and, concordantly, administration of anti-IFN-gamma antibodies was found to aggravate disease. These experimental data are, however, in sharp contrast to the reports on clinical trials, in which IFN-gamma administration was followed by disease relapses. Administration of a neutralizing anti-interleukin-6 (IL-6) antibody to mice to block in vivo activity of IL-6 resulted in increased rather than decreased serum titers, an effect that was found to be due to formation of immune complexes whose elimination from the body is retarded.
Time‐dependent electrochemical characterization of the corrosion of a magnesium rare‐earth alloy in simulated body fluids (2007)

The electrochemistry of the corrosion process of a magnesium rare-earth-alloy is studied in detail in simulated body fluid (m-SBF) over the first 5 days. The aim is to investigate the corrosion mechanism under in vitro conditions. For this purpose we also used electrolytes that contain only some of the components of SBF, they were compared to SBF to investigate the influence of the different ions in SBF. The influence of albumin on the corrosion process was studied with a solution containing m-SBF and albumin in physiological concentration. For this study, impedance spectroscopy series measurements were performed. Additional results were gained from polarization curves. We conclude from the study that the corrosion resistance is significantly lower in m-SBF than in simple isotonic NaCl-solution. Albumin may form a blocking layer on the surface in the first hours of exposure. The formed corrosion layers consisting of amorphous apatite have only a low protective ability. Further results show that the corrosion processes in SBFs follow a linear time-law. The results elucidate critical factors and mechanisms of the electrochemical corrosion process of magnesium rare-earth alloys in SBFs, this understanding is crucial for a successful application of Mg alloys in biomedical applications.
Diuretics. II. Alkoxymercuration by Mixed Anion Salts of Mercury (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDiuretics. II. Alkoxymercuration by Mixed Anion Salts of MercuryCalvert W. Whitehead and John J. TraversoCite this: J. Am. Chem. Soc. 1958, 80, 9, 2182–2185Publication Date (Print):May 1, 1958Publication History Published online1 May 2002Published inissue 1 May 1958https://pubs.acs.org/doi/10.1021/ja01542a037https://doi.org/10.1021/ja01542a037research-articleACS PublicationsRequest reuse permissionsArticle Views299Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
T84 cell receptor binding and guanyl cyclase activation by Escherichia coli heat-stable toxin (1987)

Escherichia coli heat-stable enterotoxin (STa) induces intestinal secretion by binding to enterocyte receptors and activating the guanylate cyclase-guanosine 3',5'-cyclic monophosphate (cGMP) system. The intermediate steps between binding of STa and secretion are poorly understood, due in part to the lack of a convenient system to study the effects of STa at the cellular level. To establish such a model, we investigated the binding of 125I-STa, STa activation of guanylate cyclase, and STa-induced increase in cGMP production in a well-characterized human colonic cell line, T84. Binding was specific, linear with cell number, and time, temperature and pH dependent, and reversible. ST may also be internalized by these cells. Addition of unlabeled STa competitively inhibited binding of 125I-STa. These parameters closely resemble those described in intact rat enterocytes and cell-free membrane preparations. STa stimulated guanylate cyclase and cGMP production in a dose-related manner. The similar dose-response relationships for binding, guanylate cyclase stimulation by STa, and cGMP production suggest that the guanylate cyclase-cGMP system is coupled to ST occupancy of specific receptors. These data, together with the fact that STa induces chloride secretion from T84 cells suggest that T84 cells are a suitable and convenient system to study the cellular mechanism of action of STa.
Dissonant Politics in Mubarak’s Egypt (2005)

For years now political scientists have been asking questions about why the Middle East remains one of the world’s least democratic regions. Given the recent Middle East war and the United States’ current project to build a democracy in Iraq, the question seems more significant than ever.Yet the topic continues to puzzle researchers around the globe as they contribute to a growing body of possible explanations for the phenomenon.While these explanations vary widely in form, they also reflect a constant and underlying question regarding what factors inhibit the formation of sustainable Middle Eastern democracies. This paper examines one such model in the context of contemporary Egypt to test its relevance to events actually occurring in the Arab world.
Effect of a Triplex-Binding Ligand on Parallel and Antiparallel DNA Triple Helixes Using Short Unmodified and Acridine-Linked Oligonucleotides (1994)

We have used DNase I footprinting to investigate the effect of a triplex-binding ligand on the formation of intermolecular DNA triple helices at target sites that have been cloned into longer DNA fragments. In the presence of a triplex-binding ligand (N-[2-(dimethylamino)ethyl]-2-(2-naphthyl)quinolin-4-ylamine ), the concentrations of T5C5 and C5T5 required to generate DNase I footprints at the target sites A6G6.C6T6 and G6A6.T6C6, respectively, are reduced by at least 100-fold. Complexes with the acridine-linked oligonucleotides Acr-T5C5 and Acr-C5T5 are stabilized to a much lesser extent and produce footprints at concentrations similar to those of the unmodified oligonucleotides in the presence of the ligand. The stabilizing effects of acridine modification or the addition of a triplex-binding ligand are not additive. The position and length of the footprints produced by Acr-T5C5 and T5C5 at the target sequence A6G6.C6T6 are unaffected by the ligand. In contrast, footprints at the target site G6A6.T6C6 appear 3-4 bases shorter in the presence of the ligand, when viewed from the pyrimidine strand, and 1-2 bases longer on the purine strand. These results are explained by suggesting that the compound binds at T.AT triplets and prevents the transmission of any DNA structural changes into the flanking duplex. The compound has a smaller stabilizing effect on short antiparallel triplexes consisting of G.GC and T.AT triplets. Binding of Acr-G5T5 to A6G6.C6T6 is enhanced slightly by the compound, which increases the apparent footprinting site, probably by preventing fraying at the 3'-end of the third strand. The compound does not promote the binding of G5T5 to A6G6.C6T6 or that of Acr-T5G5 and T5G5 to G6A6.T6C6.
Phosphotyrosyl Peptides Block Stat3-mediated DNA Binding Activity, Gene Regulation, and Cell Transformation (2001)

Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic signaling proteins that participates in normal cellular responses to cytokines and growth factors. Frequently, however, constitutive activation of certain STAT family members, particularly Stat3, has accompanied a wide variety of human malignancies. To identify small molecule inhibitors of Stat3, we investigated the ability of the Stat3 SH2 domain-binding peptide, PY*LKTK (where Y* represents phosphotyrosine), to disrupt Stat3 activity in vitro. The presence of PY*LKTK, but not PYLKTK or PFLKTK, in nuclear extracts results in significant reduction in the levels of DNA binding activities of Stat3, to a lesser extent of Stat1, and with no effect on that of Stat5. Analyses of alanine scanning mutagenesis and deletion derivatives of PY*LKTK reveal that the Leu residue at the Y+1 position and a substituent at the Y-1 position (but not necessarily Pro) are essential for the disruption of active Stat3, thereby mapping the minimum active sequence to the tripeptide, XY*L. Studies involving bead-coupled PY*LKTK peptide demonstrate that this phosphopeptide directly complexes with Stat3 monomers in vitro, suggesting that PY*LKTK disrupts Stat3:Stat3 dimers. As evidence for the functional importance of peptide-directed inhibition of Stat3, PY*LKTK-mts (mts, membrane translocating sequence) selectively inhibits constitutive and ligand-induced Stat3 activation in vivo. Furthermore, PY*LKTK-mts suppresses transformation by the Src oncoprotein, which has been shown previously to require constitutive Stat3 activation. Altogether, we have identified a minimal peptide that inhibits Stat3 signaling and provides the conceptual basis for use of this peptide as a lead for novel peptidomimetic drug design.
Cotransformation and gene targeting in mouse embryonic stem cells. (1991)

We have investigated cotransformation in mammalian cells and its potential for identifying cells that have been modified by gene targeting. Selectable genes on separate DNA fragments were simultaneously introduced into cells by coelectroporation. When the introduced fragments were scored for random integration, 75% of the transformed cells integrated both fragments within the genome of the same cell. When one of the cointroduced fragments was scored for integration at a specific locus by gene targeting, only 4% of the targeted cells cointegrated the second fragment. Apparently, cells that have been modified by gene targeting with one DNA fragment rarely incorporate a second DNA fragment. Despite this limitation, we were able to use the cotransformation protocol to identify targeted cells by screening populations of colonies that had been transformed with a cointroduced selectable gene. When hypoxanthine phosphoribosyltransferase (hprt) targeting DNA was coelectroporated with a selectable neomycin phosphotransferase (neo) gene into embryonic stem (ES) cells, hprt-targeted colonies were isolated from the population of neo transformants at a frequency of 1 per 70 G418-resistant colonies. In parallel experiments with the same targeting construct, hprt-targeted cells were found at a frequency of 1 per 5,500 nonselected colonies. Thus, an 80-fold enrichment for targeted cells was observed within the population of colonies transformed with the cointroduced DNA compared with the population of nonselected colonies. This enrichment for targeted cells after cotransformation should be useful in the isolation of colonies that contain targeted but nonselectable gene alterations.
Distributed Active Decoupling Capacitors for On-Chip Supply Noise Cancellation in Digital VLSI Circuits (2006)

A distributed active decoupling capacitor (decap) circuit is proposed to suppress the on-chip power supply noise in digital VLSI circuits. Effectiveness on suppressing local supply noise is verified from a 0.18mum test chip using multiple on-chip supply noise generators and supply noise sensors. Measurements show 4-11times boost in decap value over conventional passive decaps for frequencies up to 1 Hz. Decap area reduction of 40% is achieved
Tim4- and MerTK-Mediated Engulfment of Apoptotic Cells by Mouse Resident Peritoneal Macrophages (2014)

Apoptotic cells are swiftly engulfed by macrophages to prevent the release of noxious materials from dying cells. Apoptotic cells expose phosphatidylserine (PtdSer) on their surface, and macrophages engulf them by recognizing PtdSer using specific receptors and opsonins. Here, we found that mouse resident peritoneal macrophages expressing Tim4 and MerTK are highly efficient at engulfing apoptotic cells. Neutralizing antibodies against either Tim4 or MerTK inhibited the macrophage engulfment of apoptotic cells. Tim4-null macrophages exhibited reduced binding and engulfment of apoptotic cells, whereas MerTK-null macrophages retained the ability to bind apoptotic cells but failed to engulf them. The incubation of wild-type peritoneal macrophages with apoptotic cells induced the rapid tyrosine phosphorylation of MerTK, which was not observed with Tim4-null macrophages. When mouse Ba/F3 cells were transformed with Tim4, apoptotic cells bound to the transformants but were not engulfed. Transformation of Ba/F3 cells with MerTK had no effect on the binding or engulfment of apoptotic cells; however, Tim4/MerTK transformants exhibited strong engulfment activity. Taken together, these results indicate that the engulfment of apoptotic cells by resident peritoneal macrophages proceeds in two steps: binding to Tim4, a PtdSer receptor, followed by MerTK-mediated cell engulfment.
Cytokeratins are exposed on the outer surface of established human mammary carcinoma cells (1991)

Normal human mammary epithelial cells and established tumour cells of the same origin express three to eight cytokeratins, which are distributed throughout the cytoplasm in the form of intermediate filaments. The combined use of the iodogen and the two-dimensional gel electrophoresis methods has allowed us to demonstrate the presence of cytokeratins 8, 18 and 19 on the outer surface of established human mammary carcinoma cells, in particular MCF-7 cells, while they were absent from the surface of normal mammary cells in primary culture. By ultrastructural immunocytochemistry, these cytokeratins were localized on blebs formed by the cell surface. Cytokeratins 8, 18 and 19 were also detected in the culture medium of mammary carcinoma cells.
Mapping of the vaccinia virus thymidine kinase gene by marker rescue and by cell-free translation of selected mRNA (1982)

A selective plaque assay that uses thymidine kinase (TK)-deficient human 143 cells was developed to titer mixtures of TK(+) and TK(-) vaccinia virus. With this assay it could be shown that methotrexate-resistant TK(+) virus was formed in cells coinfected with TK(-) virus and wild-type virus DNA. By substituting vaccinia DNA fragments cloned in plasmids for virion DNA, this marker rescue system provided the basis for mapping the TK gene. Of the 15 HindIII fragments, only J could rescue five independently derived TK(-) mutants. This 5000-base-pair (bp) fragment maps approximately 80,000 bp from the left-end of the 180,000-bp vaccinia genome. Marker rescue could be detected with 18 ng or less of plasmid and was proportionate to DNA concentration. The resistance to methotrexate of the TK(+) recombinants was shown to be due to TK synthesis. Evidence that the HindIII J fragment contains the structural TK gene and not a regulatory element was demonstrated by the synthesis of active TK in a cell-free system programmed with mRNA selected by hybridization to the plasmid. Previous studies [Belle-Isle, H., Venkatesan, S. & Moss, B. (1981) Virology 112, 306-317] indicated that mRNAs coding for three immediate early polypeptides with molecular weights of 41,000, 21,000, and 17,000 map within HindIII J. The mapping of the easily selectable vaccinia virus TK gene now opens the way to genetic manipulations that should increase our understanding of vaccinia virus gene expression and facilitate the use of vaccinia virus as an efficient cloning vector for foreign genes.