gebhart/patrepeval huggingface dataset:
Binding of Human Immunodeficiency Virus Type 1 to CD4 and CXCR4 Receptors Differentially Regulates Expression of Inflammatory Genes and Activates the MEK/ERK Signaling Pathway (1998)

We have previously shown that binding of human immunodeficiency virus type 1 (HIV-1) virions to CD4 receptors stimulates association of Lck with Raf-1 and results in the activation of Raf-1 kinase in a Ras-independent manner. In the present study, we demonstrate that HIV-1 envelope glycoproteins of both T-cell-tropic and macrophagetropic strains rapidly activate the ERK/mitogen-activated protein (MAP) kinase pathway and the binding of nuclear transcription factors (AP-1, NF-kappaB, and C/EBP) and stimulate expression of cytokine and chemokine genes. The activation of this signaling pathway requires functional CD4 receptors and is independent of binding to CXCR4. Binding of the natural ligand stromal cell-derived factor 1 (SDF-1) to CXCR4, which inhibits entry of T-cell-tropic HIV-1, activates also the ERK/MAP kinase pathway. However, SDF-1 did not affect the CD4-mediated expression of cytokine and chemokine genes. These results provide firm molecular evidence that binding of HIV-1 envelope glycoproteins to CD4 receptor initiates a signaling pathway(s) independent of the binding to the chemokine receptor that leads to the aberrant expression of inflammatory genes and may contribute significantly to HIV-1 replication as well as to deregulation of the immune system.
Rapid Identification of Phosphopeptide Ligands for SH2 Domains (1996)

A method for the identification of high-affinity ligands to SH2 domains by fluorescence-activated bead sorting (FABS) was established. Recombinant SH2 domains, expressed as glutathione S-transferase (GST) fusion proteins, were incubated with a phosphotyrosine (Y*)-containing peptide library. 6.4 x 10(5) individual peptides of nine amino acids in length (EPX6Y*X19X7X19X7X6) were each displayed on beads. Phosphopeptide interaction of a given SH2 domain was monitored by binding of fluorescein isothiocyanate-labeled antibodies directed against GST. High-fluorescence beads were isolated by flow cytometric sorting. Subsequent pool sequencing of the selected beads revealed a distinct pattern of phosphotyrosine-containing motifs for each individual SH2 domain: the SH2 domain of the adapter protein Grb2 predominantly selected beads with the sequence Y*ENDP, whereas the C-terminal SH2 domain of the tyrosine kinase Syk selected Y*EELD, each motif representing the most frequently found residues C-terminal to the phosphotyrosine. For deconvolution studies, soluble phosphopeptides comprising variations of the Grb2 motifs were resynthesized and analyzed by surface plasmon resonance.
Serotonin, Impulsivity, and Alcohol Use Disorders in the Older Adolescent: A Psychobiological Study (2000)

Background: Alcohol use disorders (AUDs) among adolescents are associated with a high prevalence of conduct disorder (CD), much as type II alcoholism in adults is associated with impulsive-aggressive behavior and antisocial personality traits. Adults with impulsive personality disorders and AUD demonstrate diminished central serotonergic responsiveness to serotonergic agonists. Dysregulation of central serotonergic function may contribute to a vulnerability to impulsive-aggressive behavior, CD, and AUD. We studied older adolescents, both male and female, to examine the relationships between sex, dispositional impulsivity, aggressivity, CD, and responsiveness to serotonergic challenge with d,l fenfluramine (FEN) early in the development of AUD. Methods: Thirty-six adolescents between the ages of 16 and 21 years were assessed for DSM-IV AUD and other Axis I disorders by using the Psychoactive Substance Use Disorders section of the Structured Clinical Interview for DSM III-R, the Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version, and CD interviews. Impulsivity and aggressivity were assessed by the Barratt Impulsiveness Scale, Lifetime History of Aggression, Buss-Durkee Hostility Inventory, Eysenck Impulsiveness Questionnaire, Youth Self Report, and Multidimensional Personality Questionnaires. FEN was administered as 0.8 mg/kg to a maximum of 60 mg, and blood was sampled at fixed intervals for prolactin, cortisol, fenfluramine, and norfenfluramine levels. Results: Eighteen adolescents (12 male, 6 female) with AUD scored significantly higher on all measures of impulsivity and aggressivity compared with 18 healthy controls (12 male, 6 female). There were no significant differences between groups in peak prolactin or cortisol responses (minus baseline), or area-under-the-curve determinations (AUC); however, 9 subjects with AUD and comorbid CD had significantly elevated cortisol AUC levels compared with subjects with AUD and no CD or with normal controls. In the total sample, cortisol AUC was associated positively with measures of aggression. Conclusions: Adolescents with early-onset AUD are characterized by impulsivity and aggressivity compared with healthy peers but do not demonstrate the diminished prolactin or cortisol responses to FEN characteristic of adult alcoholics with impulsive-aggression.
Comparative analysis of gene sets in the gene ontology space under the multiple hypothesis testing framework (2004)

The Gene Ontology (GO) resource can be used as a powerful tool to uncover the properties shared among, and specific to, a list of genes produced by high-throughput functional genomics studies, such as microarray studies. In the comparative analysis of several gene lists, researchers maybe interested in knowing which GO terms are enriched in one list of genes but relatively depleted in another. Statistical tests such as Fisher's exact test or Chi-square test can be performed to search for such GO terms. However, because multiple GO terms are tested simultaneously, individual p-values from individual tests do not serve as good indicators for picking GO terms. Furthermore, these multiple tests are highly correlated, usual multiple testing procedures that work under an independence assumption are not applicable. In this paper we introduce a procedure, based on False Discovery Rate (FDR), to treat this correlated multiple testing problem. This procedure calculates a moderately conserved estimator of q-value for every GO term. We identify the GO terms with q-values that satisfy a desired level as the significant GO terms. This procedure has been implemented into the GoSurfer software. GoSurfer is a windows based graphical data mining tool. It is freely available at http://www.gosurfer.org.
The Ups and Downs of EAE (1993)

Experimental allergic encephalomyelitis (EAE) is considered the animal disease model for multiple sclerosis (MS) in humans. However, EAE is an acute disease whereas MS is a chronic disease. The on-off nature in both diseases of autoimmune reactivity suggests a regulatory response by the host, a response which can effect the autoreactive T cell by modulating-up or modulating-down. This review discusses various aspects of this regulation, seen after administration of autoantigen, of antibody directed at the T cell receptor (TcR), and of fragments of the TcR itself.
Molekulare gemischtvalente Platin-Iod-Amin-Komplexe: Das dreikernige Pt3I8(NHEt2)2 mit kantenverknüpften planaren und oktaedrischen Baugruppen (1998)

PtI2 · NHEt2 wurde durch Umsetzung von K2PtCl4 mit KI und NEt2H in wäßriger Lösung erhalten. Die Kristallstruktur der monoklinen Verbindung (a = 20,558(4) Å; b = 7,254(1) Å; c = 13,790(3) Å; β = 100,47(3)°; Raumgruppe C2/c) wird aufgebaut aus zweikernigen Komplexen [{Pt(NHEt2)I}2(μ-I)2]. Bei der Oxidation der Platin(II)-Verbindung mit I2 in CH2Cl2 entstanden Gemische, die den gemischtvalenten Komplex Pt3I8(NHEt2)2 und den zweikernigen Platin(IV)-Komplex [{Pt(NHEt2)I3}2(μ-I)2] enthielten. Die monokline Kristallstruktur von Pt3I8(NHEt2)2 (a = 20,278(4) Å; b = 10,627(2) Å, c =14,232(3) Å; β = 115,66(3)° Raumgruppe C2/c) besteht aus dreikernigen Molekülen, bei denen zwei planare Baugruppen PtII(NEt2H)I3 mit einem zentralen PtIVI6-Oktaeder über I-Kanten verbunden sind. Mixed Valence Molecular Platinum Iodide Amin Complexes: The Trinuclear Pt3I8(NHEt2)2 with Edgeshared Planar and Octahedral Building Groups PtI2 · NHEt2 was prepared by reaction of K2PtCl4 with KI and NEt2H in aqueous solution. The crystal structure of the monoclinic compound (a = 20.558(4) Å; b = 7.254(1) Å; c = 13.790(3) Å; β = 100.47(3)°; space group C2/c) consists of binuclear molecules of [{Pt(NH(Et)2)I}2(μ-I)2]. On oxidation of this Pt(II) compound by I2 in CH2Cl2 mixtures of the trinuclear mixed-valence compound Pt3I8(NHEt2)2 and of the binuclear PtIV complex [{Pt(NHEt2)I3}2(μ-I)2] were obtained. The monoclinic crystal structure of Pt3I8(NHEt2)2 (a = 20.278(4) Å; b = 10.627(2) Å, c = 14.232(3) Å; β = 115.66(3)° space group C2/c) is built up by trimeric units of two planar PtIII3(NHEt2) groups sharing edges with a central PtIVI6-octhedron.
Contribution of newly synthesized cholesterol to rat plasma and bile determined by mass isotopomer distribution analysis: bile-salt flux promotes secretion of newly synthesized cholesterol into bile (1998)

To quantify the contribution of newly synthesized cholesterol to total plasma and biliary cholesterol under physiological conditions, unrestrained rats were infused intravenously with [1-13C]acetate (0. 6mmol/h per kg) from 12:00 to 24:00 h, and fractional and absolute cholesterol-synthesis rates were determined by mass isotopomer distribution analysis (MIDA). As bile diversion leads to changes in cholesterol metabolism, rats were equipped with permanent catheters in the bile duct and duodenum, allowing sampling of small amounts of bile from an intact enterohepatic circulation. For comparison, rats with chronic bile diversion were also studied. Fractional synthesis of plasma cholesterol was 10.8+/-1.7% (mean+/-S.D.) after 12 h in rats with intact circulation. Fractional synthesis of biliary cholesterol was significantly higher than that of plasma cholesterol, i.e. 16.5+/-2.0% (P<0.05) after 12 h. In contrast, no differences between fractional synthesis of cholesterol in plasma and bile were found in bile-diverted animals (31.8+/-2.1 and 33.1+/-3.3% respectively after 12 h). The calculated absolute rate of cholesterol biosynthesis increased from 53+/-10 to 221+/-19 micromol/day per kg after bile diversion. A comparison of MIDA results with those obtained from balance studies indicated that MIDA does not assess total body synthesis in rats, presumably because of incomplete equilibration of newly synthesized molecules with cholesterol in the plasma compartment. These studies demonstrate that the contribution of newly synthesized cholesterol to biliary cholesterol is higher than to plasma cholesterol under physiological conditions, probably reflecting bile-salt-induced secretion of newly formed cholesterol by the periportal hepatocytes.
Integration of adeno-associated virus vectors in CD34+ human hematopoietic progenitor cells after transduction (1996)

Gene transfer vectors based on adeno-associated virus (AAV) appear promising because of their high transduction frequencies regardless of cell cycle status and ability to integrate into chromosomal DNA. We tested AAV-mediated gene transfer into a panel of human bone marrow or umbilical cord-derived CD34+ hematopoietic progenitor cells, using vectors encoding several transgenes under the control of viral and cellular promoters. Gene transfer was evaluated by (1) chromosomal integration of vector sequences and (2) analysis of transgene expression. Southern hybridization and fluorescence in situ hybridization analysis of transduced CD34 genomic DNA showed the presence of integrated vector sequences in chromosomal DNA in a portion of transduced cells and showed that integrated vector sequences were replicated along with cellular DNA during mitosis. Transgene expression in transduced CD34 cells in suspension cultures and in myeloid colonies differentiating in vitro from transduced CD34 cells approximated that predicted by the multiplicity of transduction. This was true in CD34 cells from different donors, regardless of the transgene or selective pressure. Comparisons of CD34 cell transduction either before or after cytokine stimulation showed similar gene transfer frequencies. Our findings suggest that AAV transduction of CD34+ hematopoietic progenitor cells is efficient, can lead to stable integration in a population of transduced cells, and may therefore provide the basis for safe and efficient ex vivo gene therapy of the hematopoietic system.
Query Size Estimation using Systematic Sampling. (1996)

In this paper, we propose a new approach to the estimation of query size for select and join operations. The technique, which we have called &amp;quot;systematic sampling&amp;quot;, is a novel variant of the sampling approach, which sorts the relation before sampling, and which maintains a summary relation to improve run-time performance. We compare the method to a number of existing methods to tackle the problem of query size estimation, and demonstrate, with extensive experimental results, that it performs better than existing approaches over a wide range of data sets.
Comparison between 5,10,15,20-Tetraaryl- and 5,15-Diarylporphyrins as Photosensitizers:  Synthesis, Photodynamic Activity, and Quantitative Structure−Activity Relationship Modeling (2006)

The synthesis of a panel of seven nonsymmetric 5,10,15,20-tetraarylporphyrins, 13 symmetric and nonsymmetric 5,15-diarylporphyrins, and one 5,15-diarylchlorin is described. In vitro photodynamic activities on HCT116 human colon adenocarcinoma cells were evaluated by standard cytotoxicity assays. A predictive quantitative structure-activity relationship (QSAR) regression model, based on theoretical holistic molecular descriptors, of a series of 34 tetrapyrrolic photosensitizers (PSs), including the 24 compounds synthesized in this work, was developed to describe the relationship between structural features and photodynamic activity. The present study demonstrates that structural features significantly influence the photodynamic activity of tetrapyrrolic derivatives: diaryl compounds were more active with respect to the tetraarylporphyrins, and among the diaryl derivatives, hydroxy-substituted compounds were more effective than the corresponding methoxy-substituted ones. Furthermore, three monoarylporphyrins, isolated as byproducts during diarylporphyrin synthesis, were considered for both photodynamic and QSAR studies; surprisingly they were found to be particularly active photosensitizers.
SUMOylation of the Human Cytomegalovirus 72-Kilodalton IE1 Protein Facilitates Expression of the 86-Kilodalton IE2 Protein and Promotes Viral Replication (2004)

The 72-kDa immediate-early 1 protein (IE1-72kDa) of human cytomegalovirus has been previously shown to be posttranslationally modified by covalent conjugation to the ubiquitin-related protein SUMO-1. Using an infectious bacterial artificial chromosome clone of human cytomegalovirus, we constructed a mutant virus (BADpmIE1-K450R) that is deficient for SUMOylation of IE1-72 kDa due to a single amino acid exchange in the SUMO-1 attachment site. Compared to wild-type virus, this mutant grew more slowly and generated a reduced yield in infected human fibroblasts, indicating that SUMO modification is required for the full activity of IE1-72 kDa. The lack of SUMOylation did not affect the intranuclear localization of IE1-72 kDa, including its ability to target to and disrupt PML bodies and to bind to mitotic chromatin. Likewise, SUMOylation-deficient IE1-72 kDa activated several viral promoters as efficiently as the wild-type protein. However, the failure to modify IE1-72 kDa resulted in substantially reduced levels of the IE2 transcript and its 86-kDa protein (IE2-86 kDa). These observations suggest that SUMO modification of IE1-72 kDa contributes to efficient HCMV replication by promoting the accumulation of IE2-86 kDa.
Churchmanship and Personality among Clergymen in the Church in Wales: Are Anglo-Catholic Priests More Feminine? (2012)

Abstract The aim of the present study is to develop and test a new measure of Anglo-Catholic orientation capable of assessing the extent of the continuing influence of the Anglican-Catholic movement among Anglican clergy and useful for testing theories regarding the association between Anglo-Catholic orientation and personality. Data provided by a sample of 232 clergymen serving in the Church in Wales support the internal consistency reliability of the 21-item Francis-Littler Anglo-Catholic Orientation Scale, and, in terms of the Eysenckian dimensional model of personality, demonstrate that Anglo-Catholic orientation is associated with higher levels of psychological femininity as assessed by the neuroticism scale, but not as assessed by the psychoticism scale.
Impaired integrin-mediated signal transduction, altered cytoskeletal structure and reduced motility in Hck/Fgr deficient macrophages (1999)

ABSTRACT Integrin-mediated adhesion of monocytes and macrophages initiates a signal transduction pathway that leads to actin cytoskeletal reorganization, cell migration and immunologic activation. This signaling pathway is critically dependent on tyrosine kinases. To investigate the role of the Src-family of tyrosine kinases in integrin signal transduction, we have examined the adhesive properties of macrophages isolated from hck-/-fgr-/- double knockout mice which lack two of the three predominant Src-family kinases expressed in myeloid cells. Previous examination of polymorphonuclear leukocytes from these animals indicated that these kinases were critical in initiating the actin cytoskeletal rearrangements that lead to respiratory burst and granule secretion following integrin ligation. Double mutant peritoneal exudate macrophages demonstrated markedly reduced tyrosine phosphorylation responses compared to wild-type cells following plating on fibronectin, collagen or vitronectin-coated surfaces. Tyrosine phosphorylation of several actin-associated proteins (cortactin, paxillin, and tensin), as well as the Syk and Pyk2 tyrosine kinases, were all significantly reduced in double mutant cells. The subcellular localization of focal-adhesion associated proteins was also dramatically altered in mutant macrophages cultured on fibronectin-coated surfaces. In wild-type cells, filamentous actin, paxillin, and talin were concentrated along leading edges of the plasma membrane, suggesting that these proteins contribute to cellular polarization during migration in culture. Double mutant cells failed to show the polarized subcellular localization of these proteins. Likewise, double mutant macrophages failed to form normal filopodia under standard culture conditions. Together, these signaling and cytoskeletal defects may contribute to the reduced motility observed in in vitro assays. These data provide biochemical and morphological evidence that the Src-family kinases Hck and Fgr are required for normal integrin-mediated signal transduction in murine macrophages.
Pulsed field ablation of the cavotricuspid isthmus using a multispline-electrode pulsed field ablation catheter (2021)

Key Teaching Points•Pulsed field ablation (PFA) is a promising method for pulmonary vein isolation (PVI).•Atrial fibrillation and coexisting cavotricuspid isthmus (CTI) flutter is a common problem and PVI and CTI ablation is often performed in the same procedure.•In this case we describe the successful use of the multispline-electrode PFA catheter for PVI and supplementary ablation of the CTI in a patient with acquired atrioventricular block and cardiac resynchronization therapy-defibrillator.•High-resolution voltage and propagation maps after PFA in the CTI showed extensive low voltage on the CTI region but normal voltage in the triangle of Koch and coronary sinus and lateral to the CTI. •Pulsed field ablation (PFA) is a promising method for pulmonary vein isolation (PVI).•Atrial fibrillation and coexisting cavotricuspid isthmus (CTI) flutter is a common problem and PVI and CTI ablation is often performed in the same procedure.•In this case we describe the successful use of the multispline-electrode PFA catheter for PVI and supplementary ablation of the CTI in a patient with acquired atrioventricular block and cardiac resynchronization therapy-defibrillator.•High-resolution voltage and propagation maps after PFA in the CTI showed extensive low voltage on the CTI region but normal voltage in the triangle of Koch and coronary sinus and lateral to the CTI.
Immunity of Hamsters to West Nile and Murray Valley Viruses Following Immunization with St. Louis and Japanese B. (1956)

An available strain of Syrian hamsters was found to be highly susceptible to WN and MVE viruses by peripheral routes of inoculation. Groups of animals of this species were then immunized with JBE and SLE viruses and subsequently challenged subcutaneously with serial dilutions of WN and MVE viruses. Complete protection against these two agents was afforded by JBE immunization, and protection of a lesser degree obtained by SLE immunization. Neutralizing antibody titers of the immunized hamsters to the 2 heterologous challenge viruses paralleled their peripheral resistance in that the JBE virus immunes had higher neutralizing antibody titers to WN and MVE viruses than did the SLE virus immunes. These findings together with previously reported data support the hypothesis that cross immunity to these viruses probably occurs in man and that there might be some practical application of this concept in the field of human immunization. Further work with animals using other virus combinations is in progress.
Total Complement Inhibition (1999)

Total complement inhibition with sCR1 and sCR1+HB circuits optimizes recovery during the revascularization of ischemic myocardium.
Rituximab Using A Thrice Weekly Dosing Schedule in B-Cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Demonstrates Clinical Activity and Acceptable Toxicity (2001)

Rituximab administered thrice weekly for 4 weeks demonstrates clinical efficacy and acceptable toxicity. Initial infusion-related events seem to be cytokine mediated and resolve by the third infusion making rapid administration possible. Future combination studies of rituximab with other therapies in CLL seem warranted.
Homozygosity Mapping of Alstrom Syndrome to Chromosome 2p (1997)

Alström syndrome is a rare autosomal recessive disorder characterized by pigmentary retinal degeneration, sensorineural hearing loss, childhood obesity, non-insulin-dependent diabetes mellitus, hyperlipidemia and chronic nephropathy. Features occasionally observed include acanthosis nigricans, hypogonadism, hypothyroidism, alopecia, short stature and cardiomyopathy. We report here the results of a linkage study in a large French Acadian kindred, as a first step in identifying the molecular basis of Alström syndrome. Evidence of a founder effect made if feasible to use a homozygosity mapping strategy to identify the chromosomal location of the Alström gene. In a genome-wide screen, haplotype sharing for a region on chromosome 2 was observed in all affected individuals. Two point linkage analysis resulted in a maximum lod score of 3.84 (theta = 0.00) for marker D2S292. By testing additional markers, the disease gene was localized to a 14.9 cM region on chromosome 2p.
Red to green rainbow photoluminescence from unoxidized silicon nanocrystallites (1998)

We prepared luminescent silicon by incorporating H2O2 in the anodizing process. Under UV excitation, our samples appear reddish, orangish, yellowish to greenish as the electrolyte-air interface at the meniscus is approached. Under high current anodization, the emission becomes broad but unstable. The time characteristics of all the emission regions are in the range of 1–10 μs. The results are consistent with a significant reduction of crystallite sizes, and may be explained via novel Si–Si dimer surface states that are induced by quantum confinement.