gebhart/patrepeval huggingface dataset:
Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility (2009)

The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate--and structurally plastic--layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.
Determination of Three Isoforms of the Receptor Activator of Nuclear Factor-κΒ Ligand and Their Differential Expression in Bone and Thymus* (2001)

The receptor activator of nuclear factor (NF)-kappaB ligand [RANKL; also known as tumor necrosis factor-related activation-induced cytokine, osteoprotegerin ligand, and osteoclast differentiation factor] is known to bind with the receptor activator of NF-kappaB (RANK) and act not only as a key factor for osteoclastogenesis but also as a regulator of lymphocyte development. In this study, we found two additional isoforms of RANKL. RANKL 2 has a shorter intracellular domain than the original RANKL (RANKL 1), and RANKL 3 lacks a transmembrane domain and was thought to act as a soluble form. In the bone marrow stromal cell line ST2 and preosteoblastic cell line MC3T3-E1, all three RANKL isoforms were detected, but the expression of RANKL 2 was preferentially suppressed by treatment with 1alpha,25-dihydroxyvitamin D(3) and dexamethasone. In young adult thymus, CD4(-)CD8(-) double-negative cells were positive for all three isoforms, CD4(+)CD8(+) double-positive cells were positive for RANKL 1 and RANKL 3 but negative for RANKL 2, and CD4(+)CD8(-) and CD4(-)CD8(+) single-positive cells were positive for all three isoforms. Immunofluorescence analyses of NIH3T3 cells transfected with each RANKL isoform indicated that the three RANKL isoforms were translated, and RANKL 2 protein predominantly stayed in the endoplasmic reticulum and Golgi networks. These results indicate that there are three kinds of RANKL-RANK pathways. The presence of multiple RANKL-RANK pathways suggests a more complicated RANKL-RANK system for osteoclastogenesis or T cell differentiation than previously thought.
Bayesian Network Approach for Gas Path Fault Diagnosis (2004)

A method for solving the gas path analysis problem of jet engine diagnostics based on a probabilistic approach is presented. The method is materialized through the use of a Bayesian Belief Network (BBN). Building a BBN for gas turbine performance fault diagnosis requires information of a stochastic nature expressing the probability of whether a series of events occurred or not. This information can be extracted by a deterministic model and does not depend on hard to find flight data of different faulty operations of the engine. The diagnostic problem and the overall diagnostic procedure are first described. A detailed description of the way the diagnostic procedure is set-up, with focus on building the BBN from an engine performance model, follows. The case of a turbofan engine is used to evaluate the effectiveness of the method. Several simulated and benchmark fault case scenarios have been considered for this reason. The examined cases demonstrate that the proposed BBN-based diagnostic method composes a powerful tool. This work also shows that building a diagnostic tool, based on information provided by an engine performance model, is feasible and can be efficient as well.
Enzymic Assay of 10−7 to 10−14 Moles of Sucrose in Plant Tissues (1977)

Procedures are described for measuring sucrose in plant extracts or freeze-dried tissue in the range between 10(-7) and 10(-14) moles. The method is based on the destruction of pre-existing glucose and fructose, followed by the hydrolysis of sucrose and reduction of NADP(+) by a series of coupled enzymic reactions. Depending on the sensitivity required, the NADPH is determined directly with a spectrophotometer or a fluorometer, or is amplified as much as 30,000 times before fluorometric assay. The procedures suggested for the macro level are simpler than current methods, and those suggested for microanalysis are several orders of magnitude more sensitive.With this technique, single palisade parenchyma cells and single spongy parenchyma cells of Vicia faba leaflets were each found to contain about 2.2 pmoles of sucrose.
Site-Controlled Deposition of Microsized Particles Using an Electrostatic Assembly (2002)

A new technique for the arrangement of microsized particles with site-controlled deposition has been demonstrated. Positively charged dots are drawn with a focused Ga+ ion beam. Monodisperse particles are selectively attracted to the electric field of the dots in a one-to-one relationship. Thus two-dimensional arrays of deposited spheres can be formed with controlled spacing (see Figure).
Outcome of Cord-Blood Transplantation From Related and Unrelated Donors (1998)

Gluckman, Eliane; Rocha, Vanderson; Boyer-Chammard, Agnes; Locatelli, Franco; Arcese, William; Pasquini, Ricardo; Ortega, Juan; Souillet, Gerard; Ferreira, Euripedes; Laporte, Jean-Philippe; Fernandez, Manual; Chastang, Claude Author Information
Assessment of the risk of reoffending by Indigenous male violent and sexual offenders (2004)

Modern corrections practice requires an assessment of the risk of reoffending on at least two levels. First, risk assessments are necessary to decide which offenders should be targeted for rehabilitation. Second, risk assessment is necessary to deal with the increasing demand by the public and politicians that offenders who are at a high risk of reoffending, especially violent and sexual offending, should not be released prematurely. This paper reports on a risk assessment tool that has been developed specifically for Indigenous offenders. The study was based on analysis of the file data of adult male Western Australian Indigenous offenders who had since 1987 been identified as requiring either a violent or sexual offender program. Separate risk prediction instruments were developed to assess the risk of reoffending by both violent offenders and sexual offenders. A three factor predictor model, developed for sexual offenders, was found to be highly accurate. However the research has also found that further work is required on developing tools for the various sub-groups of violent (family violence versus other violence) and sexual (violent versus non-violent) offenders.
Nonrandom Dimerization of Murine Leukemia Virus Genomic RNAs (2004)

Retroviral genomes consist of two unspliced RNAs linked noncovalently in a dimer. Although these two RNAs are generally identical, two different RNAs can be copackaged when virions are produced by coinfected cells. It has been assumed, but not tested, that copackaging results from random RNA associations in the cytoplasm to yield encapsidated RNA homodimers and heterodimers in Hardy-Weinberg proportions. Here, virion RNA homo- and heterodimerization were examined for Moloney murine leukemia virus (MLV) using nondenaturing Northern blotting and a novel RNA dimer capture assay. The results demonstrated that coexpressed MLV RNAs preferentially self-associated, even when RNAs were identical in known packaging and dimerization sequences or when they differed overall by less than 0.1%. In contrast, HIV-1 RNAs formed homo- and heterodimers in random proportions. We speculate that these species-specific differences in RNA dimer partner selection may at least partially explain the higher frequency of genetic recombination observed for human immunodeficiency virus type 1 than for MLV.
Expression of transforming acidic coiled‐coil containing protein 3 is a novel independent prognostic marker in non‐small cell lung cancer (2006)

Transforming acidic coiled-coil containing protein 3 (TACC3) is known to be involved in the control of normal cell growth and differentiation and in mechanisms of unregulated growth leading to tumorigenesis. The aim of the present paper was to determine the rate of TACC3 expression in a non-small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters. A total of 163 NSCLC were analyzed immunohistochemically using a polyclonal TACC3 antibody and monoclonal p53 and Ki-67 antibodies on NSCLC tissue microarrays. A high level of TACC3 expression was observed in 14.8% of cases, preferentially squamous cell carcinomas. Patients whose tumors had a high TACC3 expression had a significantly shorter median survival time. In the Cox regression-based multivariate analysis, TACC3 expression proved to be an independent prognostic parameter (P = 0.031). TACC3 expression was correlated with p53 expression, and patient whose tumors highly expressed TACC3 and p53 had a significantly poorer prognosis than patients whose tumors had low-level expression for both immunostainings (P = 0.006). It is suggested that increase in TACC3 may impart a proliferative advantage to NSCLC and contribute to tumor progression, and that TACC3 expression is a strong prognostic indicator of clinical outcome in NSCLC.
Recurrent Arterial Thrombosis Linked to Autoimmune Antibodies Enhancing von Willebrand Factor Binding to Platelets and Inducing FcγRII Receptor-Mediated Platelet Activation (1998)

A patient with a history of recurrent late fetal loss associated with multiple placental infarcts and cerebrovascular ischemia at the age of 36, followed a year later by a myocardial infarction, was referred for further investigation. Coronary angiography was normal. Antinuclear factor, lupus anticoagulant, anticardiolipin antibodies, and other thrombophilia parameters were negative, but there was moderate hyperthyroidism with positive thyroid peroxidase antibodies. Platelet numbers and von Willebrand factor (vWF) were normal. Her platelets showed spontaneous aggregation that disappeared with aspirin intake. However, aggregation still was induced by low levels of ristocetin (0.3 to 0.5 mg/mL). The low-dose ristocetin aggregation in patient platelet-rich plasma (PRP) was completely blocked by neutralizing antiglycoprotein Ib (GPIb) and anti-vWF antibodies. The monoclonal anti-Fc gamma RII receptor antibody IV.3 inhibited partly, which suggests that PRP aggregation by low-dose ristocetin was elicited by vWF-immunoglobulin (Ig) complexes. Upon addition to washed human platelets, with vWF (10 micrograms/mL), purified patient Igs dose-dependently enhanced ristocetin (0.15 mg/mL)-induced aggregation between 0 and 500 micrograms/mL, an effect that disappeared again above 1 mg/mL. Aggregation was dependent on the vWF concentration and was blocked by IV.3 or neutralizing anti-GPIb or anti-vWF antibodies. The spontaneous aggregation of normal platelets resuspended in patient plasma could be inhibited totally by IV.3 and partially by neutralizing anti-GPIb or anti-vWF antibodies. Perfusion with normal anticoagulated blood, enriched with 10% of control or patient plasma, over surfaces coated with vWF showed increased platelet adhesion and activation in the presence of patient antibodies. Treatment of the patient with the antithyroid drug thiamazol and temporary corticosteroids, aspirin, and ticlopidine did not correct the platelet hypersensitivity to ristocetin. These observations suggest that some autoantibodies to vWF may both enhance vWF binding to platelets and cause platelet activation through binding to the Fc gamma RII receptor, and thereby may be responsible for a new form of antibody-mediated thrombosis.
Transcriptional organization of the Clostridium acetobutylicum genome (2004)

Prokaryotic genes are frequently organized in multicistronic operons (or transcriptional units, TUs), and usually the regulatory motifs for the whole TU are located upstream of the first TU gene. Although the number of sequenced genomes has increased dramatically, experimental information on TU organization is extremely limited. Even for organisms as extensively studied as Escherichia coli and Bacillus subtilis, TU annotation is far from complete. It therefore becomes imperative to rely on computational approaches to complement experimental information. Here we present a TU map for the obligate anaerobe Clostridium acetobutylicum ATCC 824. This map is largely based on the distance between pairs of consecutive genes but enhanced and refined by predictions of several types of promoters (sigmaA, sigmaE and sigmaF/G) and rho-independent terminator structures. Based on the set of known C.acetobutylicum TUs, the presented TU map offers an 88% prediction accuracy.
Error correction and symmetrization in quantum computers (1996)

Errors in quantum computers are of two kinds: sudden perturbations to isolated qubits, and slow random drifts of all the qubits. The latter may be reduced, but not eliminated, by means of symmetrization, namely by using many replicas of the computer, and forcing their joint quantum state to be completely symmetric. On the other hand, isolated errors can be corrected by quantum codewords that represent a logical qubit in a redundant way, by several physical qubits. If one of the physical qubits is perturbed, for example if it gets entangled with an unknown environment, there still is enough information encoded in the other physical qubits to restore the logical qubit, and disentangle it from the environment. The recovery procedure may consist of unitary operations, without the need of actually identifying the error.
The Responses of Rat Trigeminal Ganglion Neurons to Capsaicin and Two Nonpungent Vanilloid Receptor Agonists, Olvanil and Glyceryl Nonamide (1997)

Capsaicin, the pungent ingredient in hot pepper, activates and subsequently desensitizes a subset of polymodal nociceptors. Because its initial application to skin produces pain, nonpungent analogs such as olvanil and glyceryl nonivamide (GLNVA) were synthesized to enhance its clinical use. To explore how these nonpungent analogs differ from capsaicin, whole-cell patch-clamp recordings were performed on cultured rat trigeminal ganglion neurons. In neurons held at -60 mV, capsaicin, olvanil, and GLNVA were found to activate one or two kinetically distinct inward currents. Two inward currents were also activated when extracellular Ca2+ was replaced with Ba2+ and also when intracellular chloride was replaced by aspartate. The reversal potentials of the rapidly and slowly activating currents were 15.3 +/- 6 and -4.0 +/- 2.5 mV, respectively. These data provide strong evidence for subtypes of vanilloid receptors. One difference among these agonists is that, on average, the activation kinetics of the currents evoked by 1 microM olvanil and 30 microM GLNVA are considerably slower than those evoked by 1 microM capsaicin. Measurements of the peak current, Ip, versus agonist concentration were fit to the Hill equation to yield values of the half maximal concentrations (K1/2), and the Hill coefficients (n). For capsaicin, olvanil, and GLNVA, K1/2 = 0.68, 0.59, and 27.0 microM and n = 1.38, 1.32, and 1.24, respectively. We propose that olvanil and GLNVA are nonpungent because they activate different subtypes of receptors and/or because of their activation kinetics (compared with capsaicin) are, on average, slower than the rate they inhibit action potentials from polymodal nociceptors.
Molecular characterization of a supratypic cross-reactive idiotype associated with IgM autoantibodies (1991)

Neoplastic B cells from patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphomas (SLL) frequently express surface Ig reactive with the mouse mAb, Lc1. Raised against a human monoclonal IgM with rheumatoid factor activity, Lc1 detects a major cross-reactive Id (CRI) present on the H chain of many monoclonal IgM autoantibodies. In contrast to other major autoantibody-CRI investigated to date, we note that the Lc1-CRI is expressed by subpopulation of cells in the germinal centers, as well as in the mantle zones, of secondary human B cell follicles. To examine the molecular basis for Lc1 expression, we used the polymerase chain reaction to isolate the functionally rearranged Ig VH genes of monoclonal Lc1-reactive B cell populations from six unrelated patients with CLL or SLL. Although the neoplastic B cells from most patients with CLL or SLL express the CD5 surface differentiation Ag, the lymphoma cells from one patient with SLL were CD5-negative. We find that the Lc1-reactive cells from each cell population have Ig rearrangements involving a VH gene of the VH4 subgroup. However, the VH4 genes rearranged in different Lc1-reactive tumor populations may originate from at least two disparate germ-line VH4 genes. Also, in contrast to the CD5-positive tumor populations, we find evidence for intraclonal diversity in the functionally rearranged VH4 genes of the CD5-negative SLL. Collectively, this study discerns a degeneracy in the VH4 genes that can encode the Lc1 CRI, indicating the term "supratypic cross-reactive idiotype" may best describe the specificity of the Lc1 mAb. Also, this study suggests that expression of CD5 may delineate categories of B cell SLL that differ in their relative rates of constitutive Ig V gene somatic mutation.
Effect of bedding changes and room ventilation rates on blood and brain ammonia levels in normal rats and rats with portacaval shunts. (1984)

Normal rats and rats with portacaval shunts were exposed to low concentrations of atmospheric ammonia generated from decomposing urine and feces. The ammonia concentration in the atmosphere was varied by altering the effective ventilation rate, animal density in the enclosure, and bedding change frequency. Atmospheric ammonia concentrations in the animal holding areas varied inversely with the frequency of bedding change and the rate of air exchange. Significant differences were found between normal and shunted animals in blood ammonia and alkaline phosphatase; brain ammonia, glutamate, and glutamine; and body weight. However, these alterations were the same regardless of the atmospheric ammonia concentration; there were no differences within the control group or shunted group housed in the different conditions. The findings suggest that in the range of ammonia concentrations in this study (0 to 9 ppm), ammonia taken in through the respiratory tract is not accumulated in the body to any significant extent.
V(D)J recombination and allelic exclusion of a TCR β-chain minilocus occurs in the absence of a functional promoter (1995)

Transcriptional activation of rearranging Ag receptor gene segments has been hypothesized to regulate their accessibility to V(D)J recombination. We analyzed the role of a functional promoter in the rearrangement of the murine TCR beta-chain locus using two transgenic minilocus constructs. These miniloci each contain an unrearranged V beta 8.3 gene. One has a wild-type V beta 8.3 gene, but the other has a V beta 8.3 gene with a promoter mutation that was previously shown to abrogate transcription in tissue culture. FACS analysis of thymus and lymph node cells from transgenic mouse lines showed that only the lines with the wild-type V beta 8.3 gene promoter express an 8.3 TCR beta-chain. Consistent with the protein expression data, V beta 8.3 gene transcripts were found only in the transgenic lines with the wild-type promoter. Using a quantitative PCR-based assay, it was shown that both types of transgenic lines recombine the V beta 8.3 gene at similar levels. Rearrangement of the transgenes was normal with respect to thymic development and junctional reading frame. Interestingly, both types of miniloci also underwent allelic exclusion in that recombination was blocked by the expression of a rearranged TCR beta-chain transgene. We conclude that a functional V beta gene promoter is not necessary for proper V(D)J recombination to occur.
The Intracellular Receptor and Signal Transducers and Activators of Transcription Factor Superfamilies: Novel Targets for Small-Molecule Drug Discovery (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Intracellular Receptor and Signal Transducers and Activators of Transcription Factor Superfamilies: Novel Targets for Small-Molecule Drug DiscoveryJonathan Rosen, Adrienne Day, Todd K. Jones, E. Tracy Turner Jones, Alex M. Nadzan, and Robert B. SteinCite this: J. Med. Chem. 1995, 38, 25, 4855–4874Publication Date (Print):December 1, 1995Publication History Published online1 May 2002Published inissue 1 December 1995https://pubs.acs.org/doi/10.1021/jm00025a001https://doi.org/10.1021/jm00025a001research-articleACS PublicationsRequest reuse permissionsArticle Views400Altmetric-Citations72LEARN 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