gebhart/patrepeval huggingface dataset:
Human membrane protein Tim-3 facilitates hepatitis A virus entry into target cells (2006)

In this study, a cellular surface membrane protein of immunoglobulin (Ig) superfamily (IgSF) was identified from a human dendritic cell (DC) cDNA library by large-scale random sequencing, which is identical to previously reported Tim-3 (T-cell Ig- and mucin-domain-containing molecule 3). Recent data have suggested the association of the 281-residue mouse Tim-3 molecule with Th1-related T cell responses and disease in mice. Human Tim-3 is a 301-residue type I membrane protein whose extracellular region contains a Cys-rich Ig-like domain and a mucin domain, the characteristics of Tim proteins. It shows significant homology to human hepatitis A virus (HAV) cellular receptor-1 (HuHAVcr-1)/Tim-1. Human Tim-3 mRNA was highly expressed in monocytes or monocyte-derived cells, and the expression level decreased when DC underwent maturation and activation. There is no previous report on the biological functions of human Tim-3, especially the involvement in virus infection. We demonstrated that HeLa cells, which are refractory to HAV infection, acquired a limited susceptibility to HAV infection after stably overexpressing human Tim-3 as confirmed by Western blot analysis using anti-Tim-3 antibody, but Tim-3-Fc fusion protein had no direct HAV-binding activity. The results indicated that human Tim-3 can promote HAV entry into target cells but itself may not function as a cellular receptor of HAV.
Thalidomide and Hematopoietic-Cell Transplantation for Multiple Myeloma (2006)

When incorporated into high-dose therapy for myeloma, thalidomide increased the frequency of complete responses and extended event-free survival at the expense of added adverse effects without improving overall survival. (ClinicalTrials.gov number, NCT00083551.).
A total and practical synthesis of ergot alkaloid, (.+-.)-aurantioclavine. (1985)

The first synthesis of (±)-aurantioclavine by a convenient and practical five-step synthetic method, involving a new intra-molecular cyclization of nitro-olefin, is achieved starting from 3-formylindole with a 31% overall yield without using any protective groups.
Proteomic identification of interactions between histones and plasma proteins: Implications for cytoprotection (2010)

Extracellular histones released from cells during acute inflammation contribute to organ failure and death in a mouse model of sepsis, and histones are known to exert in vitro cytotoxicity in the absence of serum. Since addition of histones to serum and plasma is known to induce protein aggregation, we reasoned that plasma proteins may afford protection from cytotoxicity. We found that MODE-K mouse small intestinal epithelial cells were protected from histone-induced toxicity in the presence of 10% FCS. Therefore, the main aim of this study was to identify histone-interacting plasma proteins that might be involved in cytoprotection. The precipitate formed following addition of calf thymus histones to human EDTA plasma was characterised by shotgun proteomics, identifying a total of 36 protein subunits, including complement components, coagulation factors, protease inhibitors and apolipoproteins. The highly sulphated glycosaminoglycan heparin inhibited histone-induced plasma protein aggregation. Moreover, histones bound to heparin agarose were capable of pulling down plasma proteins from solution, indicating their effective cross-linking properties. It was particularly notable that inter-alpha-trypsin inhibitor was prominent among the histone-precipitated proteins, since it contains a chondroitin sulphate glycan chain, and suggests a potential role for this protein in histone sequestration during acute inflammation in vivo.
Topological Analysis of the Functional Mimicry between a Peptide and a Carbohydrate Moiety (1997)

The shared surface topology of two chemically dissimilar but functionally equivalent molecular structures has been analyzed. A carbohydrate moiety (alpha-D-mannopyranoside) and a peptide molecule (DVFYPYPYASGS) bind to concanavalin A at a common binding site. The cross-reactivity of the polyclonal antibodies (pAbs) was used for understanding the topological relationship between these two independent ligands. The anti-alpha-D-mannopyranoside pAbs recognized various peptide ligands of concanavalin A, and the anti-DVFYPYPYASGS pAbs recognized the carbohydrate ligands, providing direct evidence of molecular mimicry. On the basis of differential binding of various rationally designed peptide analogs to the anti-alpha-D-mannopyranoside pAbs, it was possible to identify different peptide residues critical for the mimicry. The comparison of circular dichroism profiles of the designed analogs suggests that the carbohydrate mimicking conformation of the peptide ligand incorporates a polyproline type II structural fold. The concanavalin A binding activity of these analogs was found to have a direct correlation with the topological relationship between peptide and carbohydrate ligands.
Expression, processing, and assembly of foot-and-mouth disease virus capsid structures in heterologous systems: induction of a neutralizing antibody response in guinea pigs (1991)

Plasmids containing the foot-and-mouth disease virus structural protein precursor (P1) and 3C protease genes or the P1 gene alone were expressed in Escherichia coli. A recombinant baculovirus containing the P1 gene was also generated and expressed in Spodoptera frugiperda cells. Expression of the P1 and 3C genes in E. coli resulted in efficient synthesis and processing of the structural protein precursor and assembly into 70S empty capsids. This material reacted with neutralizing monoclonal antibodies which recognize only conformational epitopes and elicited a significant neutralizing antibody response in vaccinated guinea pigs. Expression of the P1 gene in E. coli resulted in synthesis of an insoluble product, whereas in insect cells infected with the recombinant baculovirus a soluble product was synthesized. Both soluble and insoluble P1 reacted with a 12S-specific monoclonal antibody, but only soluble P1 elicited a neutralizing antibody response in guinea pigs.
CALGB 50401: A randomized trial of lenalidomide alone versus lenalidomide plus rituximab in patients with recurrent follicular lymphoma. (2012)

8000 Background: Lenalidomide (L) and rituximab (R) are active as single agents in follicular (FL) and other B-cell lymphomas, although combination strategies have not been previously assessed in a randomized fashion. Methods: CALGB 50401 is a randomized phase II study, initially designed to evaluate 3 regimens: R alone (375 mg/m2 weekly x 4), L alone (15 mg cycle 1, then escalated to 20 mg cycles 2-12, administered days 1-21 q 28 days x 12 cycles) or the combination of L+ R (other 2 arms combined). The R alone arm was discontinued due to slow accrual with 3 enrolled subjects. Eligibility included recurrent FL, prior therapy with rituximab alone or in combination, and TTP of ≥ 6 months from last rituximab dose. Prophylactic ASA or LMW heparin was recommended for patients at high risk for thrombosis. Results: Of 94 pts registered to L or LR, 89 (45 L and 44 LR) received at least one dose and had adequate data for analysis. Baseline characteristics include median age 63 (range 34-85) and 60% with intermediate- or high-risk FLIPI. Grade 3-4 adverse events (AE) were most commonly neutropenia (16% L,19% LR), fatigue (9% L, 14% LR) and thrombosis (16% - 7 pts L, 4% - 2 pts LR, p=0.158), and overall were seen in 49% (L) and 52% (LR) with 9% grade 4 in each arm. The full regimen was completed in 33% (L) and 59% (LR) of patients, with the difference due to more progressions or non-responders in the L group. In both arms about 19% of subjects discontinued therapy early due to AEs and dose intensity was over 80%. Objective response rates are L - 49% (13% CR) and LR - 75% (32% CR). With a median follow-up of 1.5 years (range 0.1- 3.6 years), median EFS is 1.2 years (L) and 2.0 years (LR), p=0.0063, log-rank test. Conclusions: Lenalidomide + rituximab is more active than lenalidomide alone in patients with recurrent FL with similar toxicity. A trend toward lower thrombosis risk with LR may relate to greater anti-tumor efficacy. The LR regimen warrants further study in FL including as a backbone for addition of novel agents in relapsed and frontline settings.
Surfactants in epitaxial growth (1989)

We have investigated the role of surface-active species (surfactants) in heteroepitaxial growth. In general, the growth mode is determined by the balance between surface, interface, and film free energies. Thus, if A wets B, B will not wet A. Any attempt at growing an A/B/A heterostructure must overcome this fundamental obstacle. We propose the use of a segregating surfactant to reduce the surface free energies of A and B and suppress island formation, as demonstrated in the growth of Si/Ge/Si(001) with a monolayer of As. Control of growth by amnipulation of surface energetics provides a new avenue to achieve high-quality man-made microstructures against thermodynamic odds.
Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice (2010)

Receptor tyrosine kinases are involved in multiple cellular processes, and drugs that inhibit their action are used in the clinic to treat several types of cancer. However, the value of receptor tyrosine kinase inhibitors (RTKIs) for treating infectious disease has yet to be explored. Here, we have shown in mice that administration of the broad-spectrum RTKI sunitinib maleate (Sm) blocked the vascular remodeling and progressive splenomegaly associated with experimental visceral leishmaniasis. Furthermore, Sm treatment restored the integrity of the splenic microarchitecture. Although restoration of splenic architecture was accompanied by an increase in the frequency of IFN-gamma+CD4+ T cells, Sm treatment alone was insufficient to cause a reduction in tissue parasite burden. However, preconditioning by short-term Sm treatment proved to be successful as an adjunct therapy, increasing the frequency of IFN-gamma+ and IFN-gamma+TNF+CD4+ T cells, enhancing NO production by splenic macrophages, and providing dose-sparing effects when combined with a first-line immune-dependent anti-leishmanial drug. We propose, therefore, that RTKIs may prove clinically useful as agents to restore immune competence before the administration of chemo- or immunotherapeutic drugs in the treatment of visceral leishmaniasis or other diseases involving lymphoid tissue remodeling, including cancer.
Estimating bulk density of compacted grains in storage bins and modifications of Janssen's load equations as affected by bulk density (2013)

Janssen created a classical theory based on calculus to estimate static vertical and horizontal pressures within beds of bulk corn. Even today, his equations are widely used to calculate static loadings imposed by granular materials stored in bins. Many standards such as American Concrete Institute (ACI) 313, American Society of Agricultural and Biological Engineers EP 433, German DIN 1055, Canadian Farm Building Code (CFBC), European Code (ENV 1991-4), and Australian Code AS 3774 incorporated Janssen's equations as the standards for static load calculations on bins. One of the main drawbacks of Janssen's equations is the assumption that the bulk density of the stored product remains constant throughout the entire bin. While for all practical purposes, this is true for small bins; in modern commercial-size bins, bulk density of grains substantially increases due to compressive and hoop stresses. Over pressure factors are applied to Janssen loadings to satisfy practical situations such as dynamic loads due to bin filling and emptying, but there are limited theoretical methods available that include the effects of increased bulk density on the loadings of grain transmitted to the storage structures. This article develops a mathematical equation relating the specific weight as a function of location and other variables of materials and storage. It was found that the bulk density of stored granular materials increased with the depth according to a mathematical equation relating the two variables, and applying this bulk-density function, Janssen's equations for vertical and horizontal pressures were modified as presented in this article. The validity of this specific weight function was tested by using the principles of mathematics. As expected, calculations of loads based on the modified equations were consistently higher than the Janssen loadings based on noncompacted bulk densities for all grain depths and types accounting for the effects of increased bulk densities with the bed heights.
Acid Strength of Heteropolyacids and Its Correlation with Catalytic Activity (1994)

Abstract UV spectrophotometry of a Hammett indicator revealed that the acid strength of the Keggin-type heteropolyacids having W as addenda atoms increased as the valency of the central atom increased (Co &amp;lt; B &amp;lt; Si, Ge &amp;lt; P). The catalytic activity for the decomposition of isobutyl propionate in a homogeneous system was correlated well with the acid strength.
SHADHO: Massively Scalable Hardware-Aware Distributed Hyperparameter Optimization (2018)

Computer vision is experiencing an AI renaissance, in which machine learning models are expediting important breakthroughs in academic research and commercial applications. Effectively training these models, however, is not trivial due in part to hyperparameters: user-configured values that control a model's ability to learn from data. Existing hyperparameter optimization methods are highly parallel but make no effort to balance the search across heterogeneous hardware or to prioritize searching high-impact spaces. In this paper, we introduce a framework for massively Scalable Hardware-Aware Distributed Hyperparameter Optimization (SHADHO). Our framework calculates the relative complexity of each search space and monitors performance on the learning task over all trials. These metrics are then used as heuristics to assign hyperparameters to distributed workers based on their hardware. We first demonstrate that our framework achieves double the throughput of a standard distributed hyperparameter optimization framework by optimizing SVM for MNIST using 150 distributed workers. We then conduct model search with SHADHO over the course of one week using 74 GPUs across two compute clusters to optimize U-Net for a cell segmentation task, discovering 515 models that achieve a lower validation loss than standard U-Net.
Effects of increasing doses of activated recombinant factor VII on haemostatic parameters in swine (2005)

This study examined dose-response relationships between activated recombinant factor VII (rFVIIa) and (1) in vivo haemostasis and (2) in vitro measures of coagulation and platelet function. Anesthetized swine were used. Ear bleeding time (BT) was measured and blood was sampled following increasing doses of rFVIIa (0, 90, 180, 360 and 720 microg/kg; n=6) or saline (n=6). BT was not altered by rFVIIa. Prothrombin time (PT) using standard or pig-specific methods was decreased by rFVIIa. Activated clotting time (ACT) was decreased by rFVIIa. Thromboelastography using collagen (COLL) or pig thromboplastin (p-ThP) as agonist demonstrated shorter reaction times, shortened time to reach maximum velocity of clot formation, and increased alpha-angle in the presence of rFVIIa. rFVIIa dosing increased maximum velocity of clot formation when p-ThP was used to initiate the reaction but not when COLL was used. rFVIIa at the highest concentration increased maximum amplitude when COLL was used to initiate the reaction. Platelet aggregation was not altered by rFVIIa. Following completion of the dose escalation phase, a severe liver injury was produced. rFVIIa altered neither blood loss nor survival time following injury but improved mean arterial pressure. A small increase in systemic thrombin-antithrombin III complex occurred after administration of rFVIIa at doses of 180 microg/kg and above. However, there was no histological evidence of intravascular coagulation after rFVIIa administration. In summary, rFVIIa activity was detectable in vitro but did not change haemostasis in normal swine.
Selective Amplification And Cloning Of Four New Members Of The G Protein-coupled Receptor Family (1989)

An approach based on the polymerase chain reaction has been devised to clone new members of the family of genes encoding guanosine triphosphate-binding protein (G protein)-coupled receptors. Degenerate primers corresponding to consensus sequences of the third and sixth transmembrane segments of available receptors were used to selectively amplify and clone members of this gene family from thyroid complementary DNA. Clones encoding three known receptors and four new putative receptors were obtained. Sequence comparisons established that the new genes belong to the G protein-coupled receptor family. Close structural similarity was observed between one of the putative receptors and the 5HT1a receptor. Two other molecules displayed common sequence characteristics, suggesting that they are members of a new subfamily of receptors with a very short nonglycosylated (extracellular) amino-terminal extension.
Increased Levels of Circulating Interleukin-8 in Patients with Large Burns (1995)

Large burns are followed by significant trauma-induced immunomodulation, and activated neutrophils can be demonstrated in the circulation of burn patients shortly after injury. Interleukin-8 (IL-8) is a recently described molecule with neutrophil activating properties and in the present study we have measured the concentration of this cytokine in plasma from 27 patients with large burns during hospitalization using an enzyme linked immunosorbent assay (ELISA). The mean patient plasma concentration of IL-8 at admission was about 60 times higher than that of healthy controls. Furthermore, patients with total body surface area burn of more than 40% had significantly higher IL-8 concentrations in plasma than patients with smaller burns. For patients without serious infectious complications, the IL-8 concentration fell gradually after injury, whereas in patients with complicating sepsis a second peak of IL-8 was demonstrated. Thus, the increased IL-8 concentrations seem to be related to burn size and to have a role in the pathophysiology of sepsis in patients with large burns. The large amounts of circulating IL-8 following thermal injury may contribute to the strong and sustained activation of neutrophils reported earlier in patients with large burns.
Treatment Guidelines for Nosocomial Pneumonia: Agreeing to Disagree (1993)

This article has no abstract.
Noninvasive measurement of forearm blood flow and oxygen consumption by near-infrared spectroscopy (1994)

We applied near-infrared spectroscopy (NIRS) for the simultaneous measurement of forearm blood flow (FBF) and oxygen consumption (VO2) in the human by inducing a 50-mmHg venous occlusion. Eleven healthy subjects were studied both at rest and after hand exercise during vascular occlusion. FBF was also measured by strain-gauge plethysmography. FBF measured by NIRS was 1.9 +/- 0.8 ml.100 ml-1.min-1 at rest and 8.2 +/- 2.9 ml.100 ml-1.min-1 after hand exercise. These values showed a correlation (r = 0.94) with those obtained by the plethysmography. VO2 values were 4.6 +/- 1.3 microM O2 x 100 ml-1.min-1 at rest and 24.9 +/- 11.2 microM O2 x 100 ml-1.min-1 after hand exercise. The scatter of the FBF and VO2 values showed a good correlation between the two variables (r = 0.93). The results demonstrate that NIRS provides the particular advantage of obtaining the contemporary evaluation of blood flow and VO2, allowing correlation of these two variables by a single maneuver without discomfort for the subject.
Gene symbol assigned for linolenic acid mutant in the soybean (1987)

Backcross and F2 seed from the cross between a low (3.2 percent) and a normal (7.2 percent) linolenic acid line of soybean [Glycine max (L.) Merr.] were evaluated for fatty acid composition of their oil. Backcross and F2 ratios for levels of linolenic acid in the seed were consistent with a model for two alleles at a single locus. The gene symbols Fan Fan for high (⁠X&macr; = 7.2 percent ± 0.11), Fan fan for intermediate (⁠X&macr; = 5.2 percent ± 0.07), and fan fan for low (⁠X&macr; = 3.2 percent ± 0.13) levels of linolenic acid were assigned. Levels of linolenic acid were controlled by the genotype of the embryo rather than by the genotype of the maternal parent.
Structural Basis for Substrate-specific Acetylation of Nα-acetyltransferase Ard1 from Sulfolobus solfataricus (2015)

Nα-acetyltransferases (Nats) possess a wide range of important biological functions. Their structures can vary according to the first two residues of their substrate. However, the mechanisms of substrate recognition and catalysis of Nats are elusive. Here, we present two structure of Sulfolobus solfataricus Ard1 (SsArd1), a member of the NatA family, at 2.13 and 1.84 Å. Both structures contain coenzyme A, while the latter also contains a substrate-derived peptide. Sequential structure-based mutagenesis revealed that mutations of critical residues for CoA binding decreased the binding affinity of SsArd1 by 3 ~ 7-fold. Superimposition of SsArd1 (NatA) with human Naa50p (NatE) showed significant differences in key residues of enzymes near the first amino-acid position of the substrate peptide (Glu35 for SsArd1 and Val29 for Naa50p). Further enzyme activity assays revealed that the substrate specificity of SsArd1 could be altered from SSGTPT to MEEKVG by a range of Glu35 mutants. These studies provide not only a molecular elucidation of substrate recognition and specificity for the NatA family, but also insight into how members of the NAT family distinguish between amino acids at the substrate N-terminus from the ancient monomeric archaeal Ard1.
Hepatocyte growth factor accelerates recovery from acute ischemic renal injury in rats (1994)

Effects of hepatocyte growth factor (HGF) administration were examined in a model of acute ischemic renal injury induced by bilateral renal artery occlusion in rats. Compared with rats administered vehicle, rats administered 20 micrograms HGF subcutaneously 30 min postischemia had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion, enhanced insulin clearances measured on day 2 postocclusion, reduced mortality, and much less injury evident by examination of kidney histologies 7 days postinjury. The tubular regeneration that occurred postischemic injury was reflected by increased incorporation of 5-bromo-2'-deoxyuridine (BrdU) in cortical tubular epithelium compared with incorporation in kidneys from noninjured rats. HGF enhanced BrdU incorporation compared with vehicle, indicating enhanced mitogenesis. The weight loss that occurs postischemic injury was not ameliorated by the dose of HGF we employed. We conclude that administration of HGF postischemic injury to rats stimulates the recovery of normal kidney function and the regeneration of proximal tubular epithelium.