gebhart/patrepeval huggingface dataset:
Probability Analysis of Variational Crystallization and Its Application to gp120, The Exterior Envelope Glycoprotein of Type 1 Human Immunodeficiency Virus (HIV-1) (1999)

The extensive glycosylation and conformational mobility of gp120, the envelope glycoprotein of type 1 human immunodeficiency virus (HIV-1), pose formidable barriers for crystallization. To surmount these difficulties, we used probability analysis to determine the most effective crystallization approach and derive equations which show that a strategy, which we term variational crystallization, substantially enhances the overall probability of crystallization for gp120. Variational crystallization focuses on protein modification as opposed to crystallization screening. Multiple variants of gp120 were analyzed with an iterative cycle involving a limited set of crystallization conditions and biochemical feedback on protease sensitivity, glycosylation status, and monoclonal antibody binding. Sources of likely conformational heterogeneity such as N-linked carbohydrates, flexible or mobile N and C termini, and variable internal loops were reduced or eliminated, and ligands such as CD4 and antigen-binding fragments (Fabs) of monoclonal antibodies were used to restrict conformational mobility as well as to alter the crystallization surface. Through successive cycles of manipulation involving 18 different variants, we succeeded in growing six different types of gp120 crystals. One of these, a ternary complex composed of gp120, its receptor CD4, and the Fab of the human neutralizing monoclonal antibody 17b, diffracts to a minimum Bragg spacing of at least 2.2 A and is suitable for structural analysis.
Sex-specific effects of dual ET-1/ANG II receptor (Dear) variants in Dahl salt-sensitive/resistant hypertension rat model (2004)

Essential (polygenic) hypertension is a complex genetic disorder that remains a major risk factor for cardiovascular disease despite clinical advances, reiterating the need to elucidate molecular genetic mechanisms. Elucidation of susceptibility genes remains a challenge, however. Blood pressure (BP) regulatory pathways through angiotensin II (ANG II) and endothelin-1 (ET-1) receptor systems comprise a priori candidate susceptibility pathways. Here we report that the dual ET-1/ANG II receptor gene (Dear) is structurally and functionally distinct between Dahl salt-sensitive, hypertensive (S) and salt-resistant, normotensive (R) rats. The Dahl S S44/M74 variant is identical to the previously reported Dear cDNA with equivalent affinities for both ET-1 and ANG II, in contrast to Dahl R S44P/M74T variant, which exhibits absent ANG II binding but effective ET-1 binding. The S44P substitution localizes to the ANG II-binding domain predicted by the molecular recognition theory, providing compelling support of this theory. The Dear gene maps to rat chromosome 2 and cosegregates with BP in female F2(RxS) intercross rats with highly significant linkage (LOD 3.61) accounting for 14% of BP variance, but not in male F2(RxS) intercross rats. Altogether, the data suggest the hypothesis that modification of the critical balance between ANG II and ET-1 systems through variant Dear contributes to hypertension susceptibility in female F2(RxS) intercross rats. Further investigations are necessary to corroborate genetic linkage through congenic rat studies, to investigate putative gene interactions, and to show causality by transgenesis and/or intervention. More importantly, the data reiterate the importance of sex-specific factors in hypertension susceptibility.
Synergistic antitumor effects of a combination of interferons and retinoic acid on human tumor cells in vitro and in vivo. (1997)

Solid tumors are relatively resistant to growth inhibition by IFNs. To enhance sensitivity, we assessed combinations of IFNs with all-trans-retinoic acid (RA). Antiproliferative studies in vitro suggested that the growth of three human breast carcinomas (MCF-7, MDA-MB-231, and MDA-MB-468), an ovarian carcinoma (NIH-OVCAR-3), and a malignant melanoma (SK-MEL-1) was inhibited to a greater degree by combination treatment with human IFN-beta and RA compared to single agents. Some of these cell lines were resistant to 10-100 IU/ml human IFN-alpha2b or IFN-beta or to 0.1-1.0 microM RA. Growth was inhibited significantly by combinations of IFNs and RA in all cell lines tested, and in some cases, cytotoxicity was observed. Sequential treatment of MCF-7 cells with RA followed by IFN-beta was more effective at inhibiting growth than treatment with IFN-beta followed by RA, suggesting that RA modulated the anticellular response of IFN-beta rather than the converse. In nude mice, the growth of MCF-7 and NIH-OVCAR-3 tumors was suppressed completely when combination treatment was started 2 days after tumor inoculation. Established, 6-week-old NIH-OVCAR-3 tumors underwent regression when treated with the combination of IFN-beta and RA but not with single-agent therapy. Together with our recent studies that demonstrated enhancement of IFN-stimulated gene expression by RA pretreatment in IFN-resistant cells, these data suggest that combination treatment with RA and IFNs may increase IFN-stimulated gene expression in IFN-resistant tumors, leading to augmented antitumor effects.
IL-10 inhibits macrophage activation and proliferation by distinct signaling mechanisms: evidence for Stat3-dependent and -independent pathways (1998)

Interleukin-10 (IL-10) limits inflammatory responses by inhibiting macrophage activation. In macrophages, IL-10 activates Stat1 and Stat3. We characterized IL-10 responses of the J774 mouse macrophage cell line, and of J774 cells expressing wild-type hIL-10R, mutant hIL-10R lacking two membrane-distal tyrosines involved in recruitment of Stat3 (hIL-10R-TyrFF), a truncated Stat3 (DeltaStat3) which acts as a dominant negative, or an inducibly active Stat3-gyraseB chimera (Stat3-GyrB). A neutralizing anti-mIL-10R monoclonal antibody was generated to block the function of endogenous mIL-10R. IL-10 inhibited proliferation of J774 cells and of normal bone marrow-derived macrophages, but not J774 cells expressing hIL-10RTyrFF. Dimerization of Stat3-GyrB by coumermycin mimicked the effect of IL-10, and expression of DeltaStat3 blocked the anti-proliferative activity of IL-10. For macrophage de-activation responses, hIL10R-TyrFF could not mediate inhibition of lipopolysaccharide-induced TNFalpha, IL-1beta or CD86 expression, while DeltaStat3 did not interfere detectably with these IL-10 responses. Thus signals mediating both anti-proliferative and macrophage de-activation responses to IL-10 require the two membrane-distal tyrosines of IL-10R, but Stat3 appears to function only in the anti-proliferative response.
Mobilization of plasmid pHSV106 from Escherichia coli HB101 in a laboratory-scale waste treatment facility (1987)

The mobilization of plasmid pHSV106 from Escherichia coli HB101, in a laboratory model waste treatment facility, by both laboratory and indigenous wastewater strains of E. coli was monitored by transfer of antibiotic resistance characteristics and by detection of pHSV106 DNA sequences in recipient cells. The mobilization was demonstrated to occur under several different treatment conditions, such as different media composition, microbial concentrations, and waste flow rates. The herpes simplex virus thymidine kinase gene was used as a hybridization marker to confirm the occurrence of the transfer. The use of the HB101 (recA mutant) host cell implies that recA functions are unnecessary for the gene transfer.
Tyrosine Derivatives Isolated from Streptomyces sp. IFM 10937 in a Screening Program for TRAIL-Resistance-Overcoming Activity (2008)

Exploration of actinomycetes for isolation of natural products for abrogating TRAIL resistance led to the isolation of two new tyrosine derivatives (1 and 2) along with novobiocin (3). The structures of 1 and 2 were determined by spectroscopic methods, while the absolute configuration was determined by analyzing CD spectra and by a modified Marfey's method. Compounds 1 (150 μM) and 3 (37.5 and 75 μM) in combination with TRAIL showed synergistic activity in sensitizing TRAIL-resistant human gastric adenocarcinoma cells.
CREB-binding Protein Activates Transcription through Multiple Domains (1996)

CREB-binding protein (CBP) functions as a coactivator molecule for a number of transcription factors including CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. Although binding sites for these factors within CBP have been identified, the regions of CBP responsible for transcriptional activation are unknown. In this report, we show that the N-terminal half of CBP is sufficient for activation of CREB-mediated transcription and that this region contains a strong transcriptional activation domain (TAD). Both deletion of this TAD or sequestering of factors that the TAD binds using a squelching assay were found to greatly decrease the ability of CBP to activate CREB-mediated transcription. In vivo studies by others have shown that p300/CBP associates with TBP; using an in vitro approach, we show the N-terminal TAD binds TBP. We also examined the ability of the C terminus of CBP to activate transcription using GAL-CBP chimeras. With this approach, we identified two C-terminal TADs located adjacent to the c-Fos binding site. In previous studies, cAMP-dependent protein kinase A (PKA) increased the transcriptional activity of a GAL full-length CBP chimera in F9 cells, and of the C terminus in PC-12 cells. Here, we demonstrate that PKA also increased the ability of the N-terminal TADs of CBP to activate transcription in PC-12 but not F9 or COS-7 cells, suggesting that this PKA-responsiveness is cell type-specific.
Spreads, Depths, and the Impact of Earnings Information: An Intraday Analysis (1993)

Journal Article Spreads, Depths, and the Impact of Earnings Information: An Intraday Analysis Get access Charles M. C. Lee, Charles M. C. Lee University of Michigan Address correspondence to Charles M. C. Lee, Department of Accounting, School of Business Administration, The University of Michigan, Ann Arbor, MI 48109–1234. Search for other works by this author on: Oxford Academic Google Scholar Belinda Mucklow, Belinda Mucklow University of Wisconsin Search for other works by this author on: Oxford Academic Google Scholar Mark J. Ready Mark J. Ready University of Wisconsin Search for other works by this author on: Oxford Academic Google Scholar The Review of Financial Studies, Volume 6, Issue 2, April 1993, Pages 345–374, https://doi.org/10.1093/rfs/6.2.345 Published: 02 April 2015
The Atrial Natriuretic Peptide Receptor (NPR-A/GC-A) Is Dephosphorylated by Distinct Microcystin-sensitive and Magnesium-dependent Protein Phosphatases (2002)

Natriuretic peptide receptor (NPR)-A is the primary signaling receptor for atrial natriuretic peptide and brain natriuretic peptide. Ligand binding to NPR-A rapidly activates its guanylyl cyclase domain, but its rate of cGMP synthesis declines with time. This waning of activity is called homologous desensitization and is mediated in part by receptor dephosphorylation. Here, we characterize two distinct NPR-A phosphatase activities. The serine/threonine protein phosphatase inhibitor, microcystin, inhibited the desensitization of NPR-A in membrane guanylyl cyclase assays in the absence of magnesium. EDTA also inhibited the desensitization, whereas MgCl(2) stimulated the desensitization. Because the effects of microcystin and EDTA were additive, and microcystin did not block the magnesium-dependent desensitization, the targets for these agents appear to be distinct. Incubation of membranes at 37 degrees C stimulated the dephosphorylation of NPR-A, and microcystin blocked the temperature-dependent dephosphorylation. The addition of MgCl(2) or MnCl(2), but not CaCl(2), further stimulated the dephosphorylation of NPR-A, and microcystin failed to inhibit this process. The desensitization required changes in the phosphorylation state of NPR-A because the guanylyl cyclase activity of a receptor variant containing glutamate substitutions at all six phosphorylation sites was unaffected by MgCl(2), EDTA, or microcystin. Together, these data indicate that NPR-A is regulated by two distinct phosphatases, possibly including a member of the protein phosphatase 2C family. Finally, we observed that the desensitization of NPR-A in membranes from mouse kidneys and NIH3T3 cells was increased by prior exposure to atrial natriuretic peptide, suggesting that hormone binding enhances receptor dephosphorylation.
Encyclopedia of virology (1999)

The Encyclopedia of Virology covers biological, molecular, and medical topics concerning viruses in animals, plants, bacteria, and insects. More general articles focus on the effects of viruses on the immune system, the role of viruses in disease, oncology, gene therapy, and evolution, plus a wide range of related topics.
Widespread natural variation in murine natural killer T‐cell number and function (2008)

Natural killer T (NKT) cells comprise a novel T-lymphocyte subset that can influence a wide variety of immune responses through their ability to secrete large amounts of a variety of cytokines. Although variation in NKT-cell number and function has been extensively studied in autoimmune disease-prone mice, in which it has been linked to disease susceptibility, relatively little is known of the natural variation of NKT-cell number and function among normal inbred mouse strains. Here, we demonstrate strain-dependent variation in the susceptibility of C57BL/6J and BALB/cJ mice to NKT-mediated airway hyperreactivity, which correlated with significant increases in serum interleukin-4 (IL-4) and IL-13 elicited by the synthetic glycosphingolipid alpha-galactosylceramide. Examination of NKT-cell function revealed a significantly greater frequency of cytokine-producing NKT cells in C57BL/6J versus BALB/cJ mice as well as significant differences in the kinetics of NKT-cell cytokine production. Extension of this analysis to a panel of inbred mouse strains indicated that variability in NKT-cell cytokine production was widespread. Similarly, an examination of NKT-cell frequency revealed a significantly greater number of liver NKT cells in the C57BL/6J mice versus BALB/cJ mouse livers. Again, examination of a panel of inbred mouse strains revealed that liver NKT-cell numbers were quite variable, spanning over a 100-fold range. Taken together, these results demonstrate the presence of widespread natural variation in NKT-cell number and function among common inbred mouse strains, which may have implications for the examination of the influence of NKT cells in immune responses and disease pathogenesis among different genetic backgrounds.
Biosynthesis of Metal Sites (2003)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiosynthesis of Metal SitesJason Kuchar and Robert P. HausingerView Author Information Departments of Biochemistry & Molecular Biology and Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan 48824-4320 Cite this: Chem. Rev. 2004, 104, 2, 509–526Publication Date (Web):December 16, 2003Publication History Received27 March 2003Published online16 December 2003Published inissue 1 February 2004https://pubs.acs.org/doi/10.1021/cr020613phttps://doi.org/10.1021/cr020613presearch-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views1866Altmetric-Citations109LEARN 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:Cluster chemistry,Ions,Ligands,Metals,Peptides and proteins Get e-Alerts
Learning from Noisy Labels with Distillation (2017)

The ability of learning from noisy labels is very useful in many visual recognition tasks, as a vast amount of data with noisy labels are relatively easy to obtain. Traditionally, label noise has been treated as statistical outliers, and techniques such as importance re-weighting and bootstrapping have been proposed to alleviate the problem. According to our observation, the real-world noisy labels exhibit multimode characteristics as the true labels, rather than behaving like independent random outliers. In this work, we propose a unified distillation framework to use “side” information, including a small clean dataset and label relations in knowledge graph, to “hedge the risk” of learning from noisy labels. Unlike the traditional approaches evaluated based on simulated label noises, we propose a suite of new benchmark datasets, in Sports, Species and Artifacts domains, to evaluate the task of learning from noisy labels in the practical setting. The empirical study demonstrates the effectiveness of our proposed method in all the domains.
The nucleocapsid of the lipid-containing double-stranded RNA bacteriophage phi 6 contains a protein skeleton consisting of a single polypeptide species (1987)

The nucleocapsid of the enveloped double-stranded RNA bacteriophage phi 6 was isolated by extraction with the nonionic detergent Triton X-114 and subjected to disruption analysis with chelating and protein-denaturing agents. The subnucleocapsid particles were separated in rate-zonal sucrose gradients, and their ultrastructure and protein composition were analyzed. The role of divalent cations in the nucleocapsid structure was studied by using a precipitation assay of the isolated nucleocapsid proteins. The phi 6 nucleocapsid had a cagelike skeleton consisting of a single polypeptide species (P1). Two other proteins (P2 and P4) were associated with the P1 cage. These three early proteins were previously known to be involved in the RNA synthesis machinery of the virus. The stability of the nucleocapsid surface lattice consisting of protein P8 was dependent on Ca2+ ions.
An Algorithm for Detecting and Resolving Store-and-Forward Deadlocks in Packet-Switched Networks (1987)

Freedom from store-and-forward (S/F) deadlocks in a packet-switched network can be guaranteed with the use of deadlock avoidance protocols. However, these protocols put so many restrictions on the use of buffers that even under normal circumstances the buffer utilization is small. We propose instead a deadlock detection and resolution algorithm that is completely invisible under normal circumstances. As soon as certain channels in the network have trouble in accepting and transmitting packets due to the lack of buffers, the deadlock detection phase of the algorithm is invoked. When a deadlock is identified, the deadlock resolving phase of the algorithm is executed. Once the deadlock is resolved, the control is removed. The algorithm can be used in conjunction with either the complete partitioning or the sharing with maximum queue lengths output buffer allocation strategies. A proof on the correctness of the algorithm is given. Simulation results show that the network can maintain a relatively high throughput even when deadlocks are being detected and resolved. In addition, several properties of deadlocks are shown: i) deadlocks start to increase abruptly once the network operates beyond its capacity; and ii) under heavy load conditions, increasing the buffer pool size will not delay the occurrence of deadlocks.
The theory of database concurrency control (1986)

Comparison, analysis and explanation of the known techniques for concurrency control. It examines in detail various aspects of correctness for concurrent executions, including serializability, deadlocks and reliability
Intravenous Iron Optimizes the Response to Recombinant Human Erythropoietin in Cancer Patients With Chemotherapy-Related Anemia: A Multicenter, Open-Label, Randomized Trial (2004)

rHuEPO increases Hb levels and improves QOL in patients with chemotherapy-related anemia. Magnitude of Hb increase and QOL improvement is significantly greater if IV iron is added.
Single-Microphone Early and Late Reverberation Suppression in Noisy Speech (2012)

This paper presents a single-microphone approach to the enhancement of noisy reverberant speech via inverse filtering and spectral processing. An efficient algorithm is used to blindly estimate the inverse filter of the Room Impulse Response (RIR). This filter is used to attenuate the early reverberation. A simple technique to blindly determine the filter length is presented. A two-step spectral subtraction method is proposed to efficiently reduce the effects of background noise and the residual reverberation on the equalized impulse response. In general, the equalized impulse response has two detrimental effects, late impulses and pre-echoes. For the late impulses, an efficient spectral subtraction algorithm is developed which introduces only minor musical noise. Then a new algorithm is introduced which reduces the remaining pre-echo effects. The performance of this two-stage method is examined in different reverberant conditions including real environments. It is also evaluated with white Gaussian and recorded babble noise. The results obtained demonstrate that the proposed blind method is superior in terms of reducing early and late reverberation effects and noise compared to well known single-microphone techniques in the literature.
Cartilage regeneration following septal surgery in young rabbits (1984)

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Strongly Luminescent InP/ZnS Core-Shell Nanoparticles (2001)

The wide-bandgap semiconducting material, zinc sulfide, has been coated on indium phosphide nanoclusters to a 1-2-Å thickness. The resulting InP-ZnS core-shell particle (as shown in the TEM image; scale 1 cm=5 nm) exhibits bright luminescence at room temperature with quantum efficiencies as high as 23 %.
Fate map for the 32-cell stage ofXenopus laevis (1987)

A complete fate map has been produced for the 32-cell stage of Xenopus laevis. Embryos with a regular cleavage pattern were selected and individual blastomeres were injected with the lineage label fluorescein-dextran-amine (FDA). The spatial location of the clones was deduced from three-dimensional (3D) reconstructions of later stages and the volume of each tissue colonized by labelled cells in each tissue was measured. The results from 107 cases were pooled to give a fate map which shows the fate of each blastomere in terms of tissue types, the composition of each tissue by blastomere, the location of each prospective region on the embryo and the fate of each blastomere in terms of spatial localization. Morphogenetic movements up to stage 10 (early gastrula) were assessed by carrying out a number of orthotopic grafts at blastula and gastrula stages using donor embryos uniformly labelled with FDA. Although there is a regular topographic projection from the 32-cell stage this varies a little between individuals because of variability of positions of cleavage planes and because of short-range cell mixing during gastrulation. The cell mixing means that the topographic projection fails for anteroposterior segments of the dorsal axial structures and it is not possible to include short segments of notochord or neural tube or individual somites on the pregastrulation fate map.