gebhart/patrepeval huggingface dataset:
Drug‐induced Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome: A Concise Review (2004)

An extensive variety of drugs have been associated with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS). Although a direct causal effect has usually not been proven, the cumulative evidence linking several drugs with TTP/HUS is strong. This paper reviews several categories of drugs including antineoplastics, immunotherapeutics and anti-platelet agents that have been reported to induce TTP/HUS. The pathogenesis of drug-induced TTP/HUS and the effectiveness of treatment regimens are also reviewed. A consensus on diagnostic criteria to accurately and consistently diagnose drug-induced TTP is needed.
Statistical performance analysis of signal variance-based dipole models for MEG/EEG source localization and detection (2003)

A set of dipole fitting algorithms that incorporate different assumptions about the variability of the signal component into their mathematical models is presented and analyzed. Dipole fitting is performed by minimizing the squared error between the selected data model and available data. Dipole models based on moments that have 1) constant amplitude and orientation, 2) variable amplitude and fixed known orientation, 3) variable amplitude and fixed unknown orientation, and 4) variable amplitude and variable orientation are considered. The presence of a dipolar source is determined by comparing the fractional energy explained by the dipole model to a threshold. Source localization is accomplished by searching to find the location that explains the largest fractional signal energy using a dipole model. Expressions for the probability of a false positive decision and probability of correct detection are derived and used to evaluate the effect of variability in the dipole on performance and to address the effects of model mismatch and location errors. Simulated and measured data experiments are presented to illustrate the performance of both detection and localization methods. The results indicate that models which account for variance outperform the constant orientation and magnitude model even when the number of observations is relatively small and the signal of interest contains a very modest variance component.
Genetic and biological analyses of a herpes simplex virus intertypic recombinant reduced specifically for neurovirulence (1987)

RS6 is a herpes simplex virus intertypic recombinant derived from type 1 strain 17 syn+ and type 2 strain HG52. With a 50% lethal dose of about 10(5) PFU after intracerebral inoculation of mice, RS6 was approximately 100,000 times less neurovirulent than either of its wild-type parental viruses were. When compared with strains 17 syn+ and HG52, RS6 replicated intermediately in primary mouse embryo fibroblasts in vitro at 38.5 degrees C (mouse temperature) and to wild-type peak titers in mouse feet in vivo. In contrast, following intracranial inoculation of mice, RS6 replicated significantly less well than did either of its parental viruses in brains. The genetic defect(s) responsible for the reduced neurovirulence of RS6 was stable after in vitro and in vivo serial passage, was not manifested as temperature-sensitive plaquing in vitro, and did not affect thymidine kinase expression. These data indicate that RS6 has a genetic defect(s) specifically affecting its ability to replicate in the mouse brain. Using marker rescue technologies, we increased the neurovirulence of RS6 and localized one genetic determinant(s) involved with the reduced neurovirulence of this agent to 0.72 to 0.87 map units (and, tentatively, to 0.79 to 0.83 map units) of the herpes simplex virus genome. When coupled with the work suggesting that thymidine kinase expression is essential for efficient replication in nerve tissues and earlier reports from this laboratory and others, the results presented in this study indicate that more than one herpes simplex virus gene is involved with neurovirulence.
Noncontact Atomic Force Microscopy. To What Extent Can We Observe Semiconductor Surfaces Using NC-AFM? (2002)

In this review article, we clarified what we can image on semiconductor surfaces using noncontact atomic force microscopy (NC-AFM): 1. We can image covalent bonding force on Si(111)7×7 surface. 2. We can discriminate Si adatoms from Sb adatoms on Si(111)5√3×5√3-Sb surface with a Si tip and a Sb adsorbed tip. 3. We can image tilted dangling bond on Si(100)2×1 surface. 4. We can image individual hydrogen atom on Si(100)2×1:H monohydride surface. 5. We can measure atomic strain around missing dimer. 6. We can image a potential map on Si(111)√3×√3-Ag surface by measuring NC-AFM image as a function of tip-sample distance. 7. We can selectively control atomic force by placing an adequate atom on the tip apex. 8. We can pull up lower Si atoms constituting buckled Si dimer by increasing attractive force between tip and sample surface.
Kinetics for Hybridization of Peptide Nucleic Acids (PNA) with DNA and RNA Studied with the BIAcore Technique (1997)

The binding of a mixed-sequence pentadecamer PNA (peptide nucleic acid) containing all four nucleobases to the fully complementary as well as various singly mismatched RNA and DNA oligonucleotides has been systematically investigated using thermal denaturation and BIAcore surface-interaction techniques. The rate constants for association (k(a)) and dissociation (k(d)) of the duplex formation as well as the thermal stability (melting temperature, T(m)) of the duplexes have been determined. Upon binding to PNA tethered via a biotin-linker to streptavidin at the dextran/gold surface, DNA and RNA sequences containing single mismatches at various positions in the center resulted in increased dissociation and decreased association rate constants. T(m) values for PNA x RNA duplexes are on average 4 degrees C higher than for PNA x DNA duplexes and follow quantitatively the same variation with mismatches as do the PNA x DNA duplexes. Also a faster k(a) and a slower k(d) are found for PNA x RNA duplexes compared to the PNA x DNA duplexes. An overall fair correlation between T(m), k(a), and k(d) is found for a series of PNA x DNA and PNA x RNA duplexes although the determination of k(a) seemed to be prone to artifacts of the method and was not considered capable of providing absolute values representing the association rate constant in bulk solution.
Functional profiling of a human cytomegalovirus genome (2003)

Human cytomegalovirus (HCMV), a ubiquitous herpesvirus, causes a lifelong subclinical infection in healthy adults but leads to significant morbidity and mortality in neonates and immunocompromised individuals. Its ability to grow in different cell types is responsible for HCMV-associated diseases, including mental retardation and retinitis, and vascular disorders. To globally assess viral gene function for replication in cells, we determined the genomic sequence of a bacterial artificial chromosome (BAC)-based clone of HCMV Towne strain and used this information to delete each of its 162 unique ORFs and generate a collection of viral mutants. The growth of these mutants in different cultured cells was examined to systematically investigate the necessity of each ORF for replication. Our results showed that 45 ORFs are essential for viral replication in fibroblasts and 117 are nonessential. Some genes were found to be required for viral replication in retinal pigment epithelial cells and microvascular endothelial cells, but not in fibroblasts, indicating their role as tropism factors. Interestingly, several viral mutants grew 10- to 500-fold better than the parental strain in different cell types, suggesting that the deleted ORFs encode replication temperance or repressing functions. Thus, HCMV encodes supportive and suppressive growth regulators for optimizing its replication in human fibroblasts, epithelial, and endothelial cells. Suppression of viral replication by virus-encoded temperance factors represents a novel mechanism for regulating the growth of an animal virus, and may contribute to HCMV's optimal infection of different tissues and successful proliferation among the human population.
Fourier transform infrared spectroscopic study on the Ca2+‐bound coordination structures of synthetic peptide analogues of the calcium‐binding site III of troponin C (2006)

The coordination structures of Ca(2+) ion bound to synthetic peptide analogues of the calcium-binding site III of rabbit skeletal muscle troponin C (TnC) were investigated by Fourier transform infrared (FTIR) spectroscopy. The region of the COO(-) antisymmetric stretching vibration provides information about the coordination modes of a COO(-) group to a metal ion. The 34-residue peptide corresponding to the EF hand motif (helix-loop-helix) showed a band at 1552 cm(-1) in the Ca(2+)-loaded state, indicating that the side-chain COO(-) group of Glu at the 12th position serves as a ligand for Ca(2+) in the bidentate coordination mode. On the other hand, the 13-residue peptide (Ac-DRDADGYIDAEEL-NH(2)) containing the Ca(2+)-binding site III (DRDADGYIDAEE) did not show such spectral patterns in the Ca(2+)-loaded state, meaning that shorter synthetic peptide corresponding to the site III has less or no affinity for Ca(2+). It was found that the 17-residue peptide (Ac-DRDADGYIDAEELAEIF-NH(2)) is the minimum peptide necessary for the interaction of side-chain COO(-)of Glu at the 12th position with Ca(2+) in the bidentate coordination mode. We discuss the relationship between the amino acid length of synthetic peptide analogues and the formation of Ca(2+)-bound coordination structure.
Selective Chemical Labeling of Proteins with Small Fluorescent Molecules Based on Metal-Chelation Methodology (2008)

Site-specific chemical labeling utilizing small fluorescent molecules is apowerful and attractive technique for in vivo and in vitro analysis of cellular proteins,which can circumvent some problems in genetic encoding labeling by large fluorescentproteins. In particular, affinity labeling based on metal-chelation, advantageous due to thehigh selectivity/simplicity and the small tag-size, is promising, as well as enzymaticcovalent labeling, thereby a variety of novel methods have been studied in recent years.This review describes the advances in chemical labeling of proteins, especially highlightingthe metal-chelation methodology.
The covalent eukaryotic topoisomerase I-DNA intermediate catalyzes pH-dependent hydrolysis and alcoholysis (1994)

Eukaryotic topoisomerase I catalysis was characterized by the use of a DNA substrate system, which allows uncoupling of cleavage and ligation half-reactions. Covalent topoisomerase I-DNA intermediates formed by cleavage without concomitant ligation were able to catalyze hydrolysis of the 3'-phosphotyrosyl bond in the pH range 7.5-10, with a broad pH optimum between pH 8.5 and 9.5. In comparison, the DNA cleavage and ligation activity of topoisomerase I were found to be independent of pH in the pH range 7-10 and strongly impaired at higher pH values. Moreover, different polyhydric alcohol compounds were found to function as nucleophiles at pH 9 to facilitate the release of topoisomerase I. The hydrolysis and alcoholysis activities of topoisomerase I were specific for the 3'-phosphotyrosyl bond and blocked by enzyme denaturation or proteolysis. Taken together the data suggest that site-specific hydrolysis or alcoholysis mediated by topoisomerase I-DNA complexes reflects the ability of the enzyme to direct the activation of the 3'-phosphotyrosyl bond or the incoming nucleophile. Analysis of enzyme-directed coupling of non-DNA nucleophiles to the cleaved DNA strand may provide a useful tool for elucidation of the biochemical mechanism of type I DNA topoisomerases.
Effect of Pupillary Dilation on Corneal Optical Aberrations After Photorefractive Keratectomy (1998)

Quantitative characterization of irregular astigmatism with the measurement of aberration structures following corneal surgery and the correlation of these data with visual performance in clinical trials provide the basis for understanding patient complaints and for improving surgical approaches. Our analysis shows that, whereas induced aberrations are minimal for simulated day-time vision (3-mm pupil), the increase in aberrations measured for simulated night vision (7-mm pupil) supports the use of large treatment zones to reduce visual disturbances such as glare and halos.
An introduction to QUEST (1997)

This paper describes QUEST, a true 3D discrete event simulation package that is designed for simulating manufacturing processes. QUEST is used as a tool in ensuring cost-effective process design, identifying and understanding process problems and in evaluating proposals for changes to processes.
Differentiation of endothelium (1995)

Vascular endothelial cells cover the entire inner surface of blood vessels in the body. They play an important role in tissue homeostasis, fibrinolysis and coagulation, blood-tissue exchange, vasotonus regulation, the vascularization of normal and neoplastic tissues, and blood cell activation and migration during physiological and pathological processes. It is therefore important to define the basic determinants of the endothelial phenotype and its modulation in response to different signals. Signal recognition, transduction, and processing are likely to be complex events dependent on the status of the target endothelial cell in a given organ or tissue. This status is a consequence of inductive and permissive interactions of a pluripotent cell with soluble and insoluble signaling molecules of the environment during embryonic and postnatal development. This review will focus on the biological mechanisms involved in the differentiation of endothelial cells from the mesoderm and their subsequent functional heterogeneity in different organs and tissues under physiological as well as pathological conditions.
Negative Regulation of Ros Receptor Tyrosine Kinase Signaling (2001)

Male "viable motheaten" (me(v)) mice, with a naturally occurring mutation in the gene of the SH2 domain protein tyrosine phosphatase SHP-1, are sterile. Known defects in sperm maturation in these mice correlate with an impaired differentiation of the epididymis, which has similarities to the phenotype of mice with a targeted inactivation of the Ros receptor tyrosine kinase. Ros and SHP-1 are coexpressed in epididymal epithelium, and elevated phosphorylation of Ros in the epididymis of me(v) mice suggests that Ros signaling is under control of SHP-1 in vivo. Phosphorylated Ros strongly and directly associates with SHP-1 in yeast two-hybrid, glutathione S-transferase pull-down, and coimmunoprecipitation experiments. Strong binding of SHP-1 to Ros is selective compared to six other receptor tyrosine kinases. The interaction is mediated by the SHP-1 NH(2)-terminal SH2 domain and Ros phosphotyrosine 2267. Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling.
PROVENGE (Sipuleucel-T) in Prostate Cancer: The First FDA-Approved Therapeutic Cancer Vaccine (2011)

Sipuleucel-T (PROVENGE; Dendreon) is the first therapeutic cancer vaccine to be approved by the U.S. Food and Drug Administration. In men who have metastatic castration-resistant prostate cancer with no or minimal symptoms, sipuleucel-T prolongs median survival by 4.1 months compared with results in those treated with placebo. At 3 years, the proportion of patients in the vaccine group who were alive was 50% higher than that in the control group (31.7% versus 21.7%, respectively). Sipuleucel-T, which is designed to elicit an immune response to prostatic acid phosphatase, uses the patient's own immune system to recognize and combat his cancer. Currently, no other agents are available that offer a survival benefit for this population of asymptomatic patients who have not been treated with chemotherapy, except for docetaxel (whose inherent toxicities often lead patients and physicians to delay administration until symptoms develop). Straightforward strategies to increase the efficacy of sipuleucel-T are likely to provide even greater benefit. The preclinical and clinical development of sipuleucel-T is reviewed, and approaches to enhance efficacy are considered herein.
Neck motion in the high school football player (1979)

In a group of 40 high school athletes (height: 166.37 to 189.57 cm, average, 174.40 cm; neck circumference: 35.56 to 41.91 cm, average, 39.12 cm), the neck motions were studied in flexion and extension, clinically, radiographically, and cineoradiographically. Flexion ranged from 34 to 84 degrees (average 72 degrees) and extension from 21 to 64 degrees (average 45 degrees) without helmet and shoulder pads. In well-fitting equipment flexion ranged from 36 to 86 degrees (average 73 degrees) and extension from 12 to 56 degrees(average 34 degrees). No correlation was determined between the size of the athlete's neck and the range of motion. The size of the athlete's neck was important in the determination of maximum stresses in the neck. The helmets impinged on the shoulder pads or interscapular region; this impingement diminished tension on the anterior portion of the cervical spine in extension. The face masks impinged on the shoulder pads in flexion of the neck; this impingement diminished stress on the posterior musculature. Proper fitting equipment, conditioning neck exercises, and changes in the rules of the game so that abuse of the head and neck is not encouraged are some of the aspects that may reduce the risk of injury to the cervical region in football players.
Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. (1993)

Binding sites of Torpedo acetylcholinesterase (EC 3.1.1.7) for quaternary ligands were investigated by x-ray crystallography and photoaffinity labeling. Crystal structures of complexes with ligands were determined at 2.8-A resolution. In a complex with edrophonium, and quaternary nitrogen of the ligand interacts with the indole of Trp-84, and its m-hydroxyl displays bifurcated hydrogen bonding to two members of the catalytic triad, Ser-200 and His-440. In a complex with tacrine, the acridine is stacked against the indole of Trp-84. The bisquaternary ligand decamethonium is oriented along the narrow gorge leading to the active site; one quaternary group is apposed to the indole of Trp-84 and the other to that of Trp-279, near the top of the gorge. The only major conformational difference between the three complexes is in the orientation of the phenyl ring of Phe-330. In the decamethonium complex it lies parallel to the surface of the gorge; in the other two complexes it is positioned to make contact with the bound ligand. This close interaction was confirmed by photoaffinity labelling by the photosensitive probe 3H-labeled p-(N,N-dimethylamino)benzenediazonium fluoroborate, which labeled, predominantly, Phe-330 within the active site. Labeling of Trp-279 was also observed. One mole of label is incorporated per mole of AcChoEase inactivated, indicating that labeling of Trp-279 and that of Phe-330 are mutually exclusive. The structural and chemical data, together, show the important role of aromatic groups as binding sites for quaternary ligands, and they provide complementary evidence assigning Trp-84 and Phe-330 to the "anionic" subsite of the active site and Trp-279 to the "peripheral" anionic site.
Hydride and Fluoride Transfer Reactions Accompanying Nucleophilic Substitution at Pentacoordinate Silicon (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydride and Fluoride Transfer Reactions Accompanying Nucleophilic Substitution at Pentacoordinate SiliconYanjian Wan and John G. VerkadeCite this: J. Am. Chem. Soc. 1995, 117, 1, 141–156Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://pubs.acs.org/doi/10.1021/ja00106a018https://doi.org/10.1021/ja00106a018research-articleACS PublicationsRequest reuse permissionsArticle Views618Altmetric-Citations18LEARN 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 (3)»Supporting Information Supporting Information Get e-Alerts
Enhanced Control of Pathogenic Simian Immunodeficiency Virus SIVmac239 Replication in Macaques Immunized with an Interleukin-12 Plasmid and a DNA Prime-Viral Vector Boost Vaccine Regimen (2011)

DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (P < 0.01). In 5 out of 6 infected RMs, strong suppression of viremia was observed, with intermittent "blips" in virus replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12 demonstrated a typical maximum of 1.5 log reduction in virus load. There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines. This vaccine strategy is relevant for existing vaccine candidates entering clinical evaluation, and this model may provide insights into control of retrovirus replication.