gebhart/patrepeval huggingface dataset:
ENDOTHELIAL STRUCTURAL INTEGRITY IS MAINTAINED DURING ENDOTOXIC SHOCK IN AN INTERLEUKIN-1 TYPE 1 RECEPTOR KNOCKOUT MOUSE (1997)

The derangement of arterial endothelial cell morphology is a good indicator of a severe shock state. Because interleukin (IL)-1 has been implicated in this process, we examined the structural integrity of aortic endothelial cells in conjunction with serum IL-6 concentrations and nitric oxide levels, which are known to increase during endotoxemia in animals genetically devoid of the type 1 IL-1 receptor. Endotoxin (10 mg/kg Escherichia coli, injected intraperitoneally) (LD100) or saline vehicle was administered to adult male C57BL/129J wild-type control mice and C57BL/129J knockout mice possessing a homozygous deletion of the type 1 IL-1 receptor. The integrity of the aortic endothelium was determined by comparisons of ultrastructure. Mice injected with sterile vehicle showed normal endothelial ultrastructure with intact membranes. Wild-type and knockout control animals receiving saline vehicle showed a complete aortic endothelium (29.11 +/- .27 and 30.85 +/- .21 intact endothelial cells per millimeter of internal elastic lamina (IEL), respectively, p = N.S.). Endotoxin-treated wild-type animals showed extensive endothelial damage with most sections showing only denuded IEL on the luminal surface (1.83 +/- .38 cells/mm IEL, p < .001 vs. control). Knockout animals treated with endotoxin showed complete maintenance of endothelial structural integrity (34.08 +/- .57 cells/mm IEL, p < .001 vs. endotoxin-treated wild type) with ultrastructural morphology appearing identical to those given saline vehicle. Also, no apparent correlation was observed between serum IL-6 concentrations or serum nitric oxide levels and aortic endothelial damage. The maintenance of endothelial integrity in animals devoid of the IL-1 receptor confirms earlier observations of endothelial cell protection with IL-1 receptor antagonism and suggests that IL-1 contributes significantly to sepsis-induced endothelial damage.
MICROBIAL ELICITORS AND THEIR RECEPTORS IN PLANTS (1996)

Elicitors are molecules that stimulate any of a number of defense responses in plants. Research over the past decade has focused on the mechanisms by which plant cells perceive and transduce these biological signals to activate defense responses. Of particular interest has been the identification of specific elicitor-binding proteins that might function as physiological receptors in the signal transduction cascade. The existence of specific high-affinity binding sites has been demonstrated for oligosaccharide, glycopeptide, and peptide elicitors, and candidate elicitor-binding proteins have been identified for several of them. The properties of these binding sites/proteins are consistent with those expected of physiologically important receptors, although experimental verification of the role of these binding proteins as receptors has not yet been obtained. The purification and characterization of specific elicitor-binding proteins is essential for a detailed understanding of the molecular basis for the signal exchange between plant hosts and microbial pathogens that leads to activation of host defenses.
The Interaction of Fibulin-1 with Fibrinogen (1995)

The fibulins are an emerging family of extracellular matrix and blood proteins presently having two members designated fibulin-1 and -2. Fibulin-1 is the predominant fibulin in blood, present at a concentration of 30-40 micrograms/ml (approximately 1000-fold higher than fibulin-2). During the course of isolating fibulin-1 from plasma by immunoaffinity chromatography, a 340-kDa polypeptide was consistently found to co-purify. This protein was identified as fibrinogen (Fg) based on its electrophoretic behavior and reactivity with Fg monoclonal antibodies. Radioiodinated fibulin-1 was shown to bind to Fg transferred onto nitrocellulose filters after SDS-polyacrylamide gel electrophoresis. In enzyme-linked immunosorbent assay, fibulin-1 bound to Fg (and fibrin) adsorbed onto microtiter well plastic, and conversely, Fg bound to fibulin-1-coated wells. The binding of Fg to fibulin-1 was also observed in surface plasmon resonance assays, and a dissociation constant (Kd) of 2.9 +/- 1.6 microM was derived. In addition, fluorescence anisotropy experiments demonstrated that the interaction was also able to occur in fluid phase, which suggests that complexes of fibulin-1 and Fg could exist in the blood. To localize the portion of Fg that is responsible for interacting with fibulin-1, proteolytic fragments of Fg were evaluated for their ability to promote fibulin-1 binding. Fragments containing the carboxyl-terminal region of the Bbeta chain (residues 216-468) were able to bind to fibulin-1. In addition, it was found that fibulin-1 was able to incorporate into fibrin clots formed in vitro and was immunologically detected within newly formed fibrin-containing thrombi associated with human atherectomy specimens. The interaction between fibulin-1 and Fg highlights potential new roles for fibulin-1 in hemostasis as well as thrombosis.
Alzheimer's Disease is Incurable but Preventable (2010)

The dramatic rising incidence and costs of Alzheimer's disease (AD) require that research efforts and funding be primarily directed on either finding a cure or applying preventive measures to curb this disorder. A cure for AD appears unlikely when significant cognitive loss has occurred because the neuronal networks that controlled the perturbed cognitive abilities are either dead or irreversibly damaged and replacing them, even if it were technically possible, would not reconstruct the intellectual identity of the host. Prevention of risk factors to sporadic AD is a more realistic stratagem and treatment, when indicated, ideally should begin in cognitively intact individuals as part of a mass screening effort. Prevention of modifiable risk factors to AD is cost-effective because it reduces hospice or hospital stay, repeated doctor visits, and long-term care. Presently, neurocognitive and neuroimaging tests are used with partial success in identifying persons at higher risk of AD but these tests can not pinpoint either a cause or a specific intervention that could attenuate disease progress. We previously proposed that carotid artery ultrasound +echocardiography together with ankle-brachail index (CAUSE+ABI) as mass screening tests in asymptomatic persons could detect not only cardio-cerebrovascular risk factors to AD, but also identify an indicated intervention. CAUSE+ABI are simple to perform, cost-effective, non-invasive, and reasonably accurate for the intended purpose. Additionally, detection of cardio-cerebrovasacular abnormalities long before expression of cognitive deterioration allows higher success rate with earlier treatment. Evidence-based medicine is recommended for optimizing clinical decision-making in evaluating AD risk factors and their treatment.
Primary Structure and Anticandidal Activity of the Major Histatin from Parotid Secretion of the Subhuman Primate, Macaca fascicularis (1990)

A major macaque histatin (M-histatin 1) from the parotid secretion of the subhuman primate, Macaca fascicularis, was isolated by gel filtration on Bio-Gel P-2 and purified to homogeneity by reversed-phase high-performance liquid chromatography on a TSK-ODS C18 column. The complete amino acid sequence of M-histatin 1, determined by automated Edman degradation, is: (formula; see text) M-histatin 1 contains 38 amino acid residues, a phosphoserine at residue 2, has a molecular weight of 4881.8, a calculated pI of 8.5, and histidine forms 26.3% of the mass. The hydropathicity plot of M-histatin 1 predicts that the molecule is entirely hydrophilic, and Chou-Fasman secondary prediction indicates that the polypeptide is devoid of alpha-helix and beta-sheet conformation in aqueous solutions but contains a series of beta turns. M-histatin 1 includes a six-amino-acid insert (residue 10-15) not present in human histatins and, with the introduction of gaps to maximize homology, it displays 89% and 91% sequence similarity with human histatins 1 and 3, respectively. M-histatin 1 exhibited fungicidal and fungistatic effects against the dimorphic pathogen, Candida albicans, in three separate bioassays. Its anticandidal effects were comparable with or greater than those of human histatins 1, 3, and 5. M-histatins 2, 3, and 4 were not sequenced directly because insufficient materials were available, but the amino acid composition of M-histatin 3 was nearly identical to that of the N-terminal 20 amino acid residues of M-histatin 1.(ABSTRACT TRUNCATED AT 250 WORDS)
IN SILICO DESIGN, SYNTHESIS AND PHARMACOLOGICAL SCREENING OF NOVEL MONO AND DI- BROMO QUINAZOLINONE DERIVATIVES AS NMDA RECEPTOR ANTAGONISTS FOR ANTICONVULSANT ACTIVITY (2013)

We report the in silico prioritization, synthesis and pharmacological evaluation of some prioritized mono and di –bromo quinazolines as NMDA receptor antagonists for anticonvulsant activity. AUTODOCK 1.5.4. software was used to dock mol files of the molecules from the mono bromo (SKMBD 1-3) and di-bromo series (SKDBD 1-2). Docking score for these molecules was analyzed. In silico prioritization was further performed with the help of Biological activity score (BAS), LogP prediction (pLogP) and ADME predictions obtained from pass server, mol inspiration and PreADMET software respectively. Molecule having acceptable docking score, BAS as compared with Memantine and complying with ADME predictions were prioritized. LogP values for anticonvulsant activity being +2.00, molecules complying with this criteria were prioritized. Molecules were synthesized and characterized by TLC, FT-IR and 1H-NMR. Further these prioritized molecules were evaluated by antagonism of NMDA induced convulsions for anticonvulsant activity in mice. Pharmacological screening rendered LD 50 of all drugs same at a dose of 2000 mg/kg from AOT studies and it was observed that as dose increases time of prolongation of convulsion and percentage of inhibition also increases while percentage of death decreases. Prioritized molecules (SKMBD 1-3 & SKDBD 1-2) shown to have comparable results of BAS activity, Log p values and ADME properties with that of standard Memantine which is anticonvulsant agent.
Catalytic Asymmetric Synthesis of α-Amino Acids (2007)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCatalytic Asymmetric Synthesis of α-Amino AcidsCarmen Nájera and José M. SansanoView Author Information Departamento de Química Orgánica, Facultad de Ciencias, and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante, Apdo. 99, 03080-Alicante, Spain Cite this: Chem. Rev. 2007, 107, 11, 4584–4671Publication Date (Web):October 4, 2007Publication History Received29 November 2006Published online4 October 2007Published inissue 1 November 2007https://pubs.acs.org/doi/10.1021/cr050580ohttps://doi.org/10.1021/cr050580oresearch-articleACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views13954Altmetric-Citations699LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Catalysts,Ligands,Organic compounds,Reaction products,Stereoselectivity Get e-Alerts
DBA/1 mice expressing the human TNF-alpha transgene develop a severe, erosive arthritis: characterization of the cytokine cascade and cellular composition (1997)

Arthritis spontaneously develops in mice expressing a human TNF-alpha transgene modified with the 3' untranslated region of beta-globin. We have backcrossed these mice onto the arthritis-susceptible DBA/1 background and found an acceleration of the onset of arthritis with successive generations of interbreeding. Bioactive TNF-alpha in primary synovial membrane cell cultures was significantly higher in the DBA/1 transgenic mice than in transgenic mice on the original background. Elevated levels of human TNF-alpha were accompanied by increases in synovial cell expression of murine IL-1beta and IL-6, but murine granulocyte-macrophage CSF, IFN-gamma, and IL-4 could not be detected. Interestingly, the anti-inflammatory cytokine IL-10 could be detected, but levels were not modulated by expression of the transgene. Analysis of the synovial membrane cell composition revealed that >50% of synovial cells were CD45-negative cells, presumably fibroblasts and endothelial cells, and the majority of CD45-expressing cells were neutrophils. Peritoneal macrophages and lymphocytes from the spleen, bone marrow, and lymph nodes required LPS stimulation to produce human TNF-alpha, indicating that, when activated, cells of these lineages were capable of expressing the transgene; however, few were found in synovial tissues. In contrast, fibroblasts derived from synovial tissue spontaneously released human TNF-alpha, and using immunohistochemical techniques, this cytokine was localized to fibroblast-like cells and chondrocytes. We propose that arthritis in DBA/1 human TNF-alpha transgenic mice is driven in part through the spontaneous expression of transgene by connective tissue cells, and there is little evidence of the participation of lymphocytes in this model.
255 CBGA electrical performance comparison through package electrical characterization and system simulations (2002)

The electrical performance of 255 CBGA packages from three suppliers are compared. This is done through the extraction of signal, power, and ground parasitic parameters such as resistance (R), self-inductance (L), mutual-inductance (M), and capacitance (C), and through SPICE system simulations. The results indicate that, although the three CBGAs' electrical performances were different, they all performed satisfactorily at 100 MHz bus-frequency, for a 2.0 ns through 0.5 ns rise/fall time. A similar behavior in electrical performance was observed at other frequencies.
Bioactivated herbicides (1990)

Most herbicides on entering the target plant undergo some metabolic transformation. This generally results in a loss of biological activity but there are a few instances where the parent molecule becomes activated in the plant.
T Cell-Independent Rescue of B Lymphocytes from Peripheral Immune Tolerance (2000)

Autoimmunity arises when immune tolerance to specific self-antigens is broken. The mechanisms leading to such a failure remain poorly understood. One hypothesis proposes that infectious agents or antigens can break B or T lymphocyte self-tolerance by expressing epitopes that mimic self. Using a transgenic immunoglobulin model, we show that challenge with self-mimicking foreign antigen rescues B cells from peripheral tolerance independent of T cell help, resulting in the accumulation of self-reactive cells in the lymph nodes and secretion of immunoglobulins that bind to a liver-expressed self-antigen. Therefore, our studies reveal a potentially important mechanism by which B lymphocytes can escape self-tolerance.
Floor holder detection and end of speaker turn prediction in meetings (2010)

We propose a novel fully automatic framework to detect which meeting participant is currently holding the conversational floor and when the current speaker turn is going to finish. Two sets of experiments were conducted on a large collection of multiparty conversations: the AMI meeting corpus. Unsupervised speaker turn detection was performed by post-processing the speaker diarization and the speech activity detection outputs. A supervised end-of-speaker-turn prediction framework, based on Dynamic Bayesian Networks and automatically extracted multimodal features (related to prosody, overlapping speech, and visual motion), was also investigated. These novel approaches resulted in good floor holder detection rates (13:2% Floor Error Rate), attaining state of the art end-of-speaker-turn prediction performances.
Hepatitis Delta Antigen Requires a Minimum Length of the Hepatitis Delta Virus Unbranched Rod RNA Structure for Binding (2009)

Hepatitis delta virus (HDV) is a subviral pathogen that increases the severity of liver disease caused by hepatitis B virus. Both the small circular RNA genome and its complement, the antigenome, form a characteristic unbranched rod structure in which approximately 70% of the nucleotides are base paired. These RNAs are associated with the sole virally encoded protein, hepatitis delta antigen (HDAg), in infected cells; however, the nature of the ribonucleoprotein complexes (RNPs) is not well understood. Previous analyses of binding in vitro using native, bacterially expressed HDAg have been hampered by a lack of specificity for HDV RNA. Here, we show that removal of the C-terminal 35 amino acids of HDAg yields a native, bacterially expressed protein, HDAg-160, that specifically binds HDV unbranched rod RNA with high affinity. In an electrophoretic mobility shift assay, this protein produced a discrete, micrococcal nuclease-resistant complex with an approximately 400-nucleotide (nt) segment of HDV unbranched rod RNA. Binding occurred with several segments of HDV RNA, although with various affinities and efficiencies. Analysis of the effects of deleting segments of the unbranched rod indicated that binding did not require one or two specific binding sites within these RNA segments. Rather, a minimum-length HDV RNA unbranched rod approximately 311 nt was essential for RNP formation. The results are consistent with a model in which HDAg binds HDV unbranched rod RNA as multimers of fixed size rather than as individual subunits.
RNAi in mouse oocytes and early embryos (2002)

Double-strand RNA (dsRNA) induced specific mRNA degradation, also known as RNA interference (RNAi), is a recently recognized phenomenon conserved among eukaryotic species. This work summarizes the results of RNAi studies in mouse oocytes and early embryos, which focused on two aspects of RNAi in mouse oocytes and early embryos: its biology and its experimental use in silencing genes of interest. This work was the first to demonstrate and characterize RNAi in mammalian cells. The analysis of the biology of RNAi further (1) identified and characterized the mouse Dicer homolog, a protein involved in the initial step of RNAi; (2) suggested that the mammalian RNAi pathway, unlike those of Caenorhabditis, Arabidopsis , and Neurospora, most likely lacks RNA-dependent RNA polymerase suggesting that not all components of RNAi are universally conserved; and (3) implicated a possible role of RNAi in silencing of transposable elements during mouse preimplantation development. It was observed that the increase in Dicer activity correlates with zygotic genome activation (ZGA). It is hypothesized that ZGA provides a window of opportunity for expression of parasitic sequences. It was found that transcription of the transposable elements L1, IAP, and MuERV-L is initiated during ZGA, and that inhibition of Dicer correlates with increased mRNA levels of IAP and MuERV-L, supporting the hypothesis that RNAi is involved in repression of parasitic sequences during early mouse development. Studies examining RNAi as an approach (1) demonstrated that RNAi is a very suitable approach to study genes in mouse oocytes and early embryos; (2) generated protocols for RNAi induced by microinjection of dsRNA or plasmid expressing dsRNA; and (3) resulted in the first successful transgenic RNAi experiment in the mouse, which has demonstrated that the expression of dsRNA from a transgene leads to specific degradation of the cognate transcript and silencing of the cognate gene. Taken together, this work represents an extensive analysis of RNAi in mouse oocytes and early embryos that is a firm foundation for further RNAi studies.
Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells (2006)

We propose that the conserved N-terminus of BCL11A defines a superfamily of C2HC zinc-finger transcription factors involved in hematopoietic malignancies.
Drag reduction in fish-like locomotion (1999)

We present experimental force and power measurements demonstrating that the power required to propel an actively swimming, streamlined, fish-like body is significantly smaller than the power needed to tow the body straight and rigid at the same speed U . The data have been obtained through accurate force and motion measurements on a laboratory fish-like robotic mechanism, 1.2 m long, covered with a flexible skin and equipped with a tail fin, at Reynolds numbers up to 10 6 , with turbulence stimulation. The lateral motion of the body is in the form of a travelling wave with wavelength λ and varying amplitude along the length, smoothly increasing from the front to the tail end. A parametric investigation shows sensitivity of drag reduction to the non-dimensional frequency (Strouhal number), amplitude of body oscillation and wavelength λ, and angle of attack and phase angle of the tail fin. A necessary condition for drag reduction is that the phase speed of the body wave be greater than the forward speed U . Power estimates using an inviscid numerical scheme compare favourably with the experimental data. The method employs a boundary-integral method for arbitrary flexible body geometry and motions, while the wake shed from the fish-like form is modelled by an evolving desingularized dipole sheet.
A Homozygous Microdeletion in Helix 7 of the Luteinizing Hormone Receptor Associated with Familial Testicular and Ovarian Resistance Is Due to Both Decreased Cell Surface Expression and Impaired Effector Activation by the Cell Surface Receptor (1998)

In this report, the genomic DNA was examined from two siblings with gonadal LH resistance. A 46,XY pseudohermaphrodite presented with female external genitalia and his 46,XX sister exhibited menstrual irregularities (oligoamenorrhea) and infertility. Exons 1-11 of the LH receptor (LHR) gene were amplified by the PCR using different sets of intronic primers and were directly sequenced. Sequencing revealed that both individuals carried a deletion of nucleotides 1822-1827, resulting in the deletion of Leu-608 and Val-609 within the seventh transmembrane helix. This mutation was introduced into a recombinant human (h) LHR cDNA. Transfections of 293 cells with hLHR(wt) vs. hLHR(deltaL608,V609) revealed that very little of the mutant receptor was expressed at the cell surface. This was due to both a decrease in the total amount of receptor expressed as well as to an increased intracellular retention of the mutant receptor. In spite of the decreased cell surface expression of the mutant, sufficient amounts were present to allow for assessment of its functions. Equilibrium binding assays showed that the cell surface hLHR(deltaL608,V609) binds hCG with an affinity comparable to that of the wild-type receptor. However, the cells expressing the hLHR(deltaL608,V609) exhibit only a 1.5- to 2.4-fold stimulation of cAMP production in response to hCG. In contrast, cells expressing comparably low levels of hLHR(wt) responded to hCG with 11- to 30-fold increases of cAMP levels. Therefore, the testicular and ovarian unresponsiveness to LH in these patients appears to be due to a mutation of the hLHR gene in which Leu-608 and Val-609 are deleted. As a consequence, the majority of the mutant receptor is retained intracellularly. The small percentage of mutant receptor that is expressed at the cell surface binds hormone normally but is unable to activate Gs.