gebhart/patrepeval huggingface dataset:
SH3 domains: complexity in moderation (2001)

The SH3 domain is perhaps the best-characterized member of the growing family of protein-interaction modules. By binding with moderate affinity and selectivity to proline-rich ligands, these domains play critical roles in a wide variety of biological processes ranging from regulation of enzymes by intramolecular interactions, increasing the local concentration or altering the subcellular localization of components of signaling pathways, and mediating the assembly of large multiprotein complexes. SH3 domains and their binding sites have cropped up in many hundreds of proteins in species from yeast to man, which suggests that they provide the cell with an especially handy and adaptable means of bringing proteins together. The wealth of genetic, biochemical and structural information available provides an intimate and detailed portrait of the domain, serving as a framework for understanding other modular protein-interaction domains. Processes regulated by SH3 domains also raise important questions about the nature of specificity and the overall logic governing networks of protein interactions.
A Distinct Group of Hepacivirus/Pestivirus-Like Internal Ribosomal Entry Sites in Members of Diverse Picornavirus Genera: Evidence for Modular Exchange of Functional Noncoding RNA Elements by Recombination (2007)

The 5' untranslated regions (UTRs) of the RNA genomes of Flaviviridae of the Hepacivirus and Pestivirus genera contain internal ribosomal entry sites (IRESs) that are unrelated to the two principal classes of IRESs of Picornaviridae. The mechanism of translation initiation on hepacivirus/pestivirus (HP) IRESs, which involves factor-independent binding to ribosomal 40S subunits, also differs fundamentally from initiation on these picornavirus IRESs. Ribosomal binding to HP IRESs requires conserved sequences that form a pseudoknot and the adjacent IIId and IIIe domains; analogous elements do not occur in the two principal groups of picornavirus IRESs. Here, comparative sequence analysis was used to identify a subset of picornaviruses from multiple genera that contain 5' UTR sequences with significant similarities to HP IRESs. They are avian encephalomyelitis virus, duck hepatitis virus 1, duck picornavirus, porcine teschovirus, porcine enterovirus 8, Seneca Valley virus, and simian picornavirus. Their 5' UTRs are predicted to form several structures, in some of which the peripheral elements differ from the corresponding HP IRES elements but in which the core pseudoknot, domain IIId, and domain IIIe elements are all closely related. These findings suggest that HP-like IRESs have been exchanged between unrelated virus families by recombination and support the hypothesis that RNA viruses consist of modular coding and noncoding elements that can exchange and evolve independently.
Increased numbers of interleukin-15-expressing cells in active ulcerative colitis. (1996)

UC patients with moderate and severe disease activity have increased percentage of IL-15 expressing PBMC, which might be induced by in vivo cell activation and can lead to elevation of released IL-15 in serum. Increased IL-15 expression after in vitro LPS stimulation of control PBMC suggests a nonspecific production of this cytokine during the immunoinflammatory response.
The presence of a defective LEU2 gene on 2 mu DNA recombinant plasmids of Saccharomyces cerevisiae is responsible for curing and high copy number (1983)

The copy number of 2 mu DNA-derived plasmids in CIR+ Saccharomyces cerevisiae transformants is determined by its selective marker and is usually much lower than that of the endogenous plasmid. Only plasmids containing the leu2 allele of pJDB219, designated as leu2-d, under selective conditions displayed a higher copy number than did endogenous 2 mu DNA and by displacement generated cured cells. Spontaneous loss of 2 mu DNA occurred with a frequency of about 0.02% per generation. Curing plasmids, like pMP78, have copy numbers of 35; noncuring plasmids, like pDB248 or YEp6, have copy numbers of 4 to 8. The 2 mu DNA copy number in strains AH22 and YNN27 were determined to be 40 and 100, respectively. The high copy number of leu2-d-containing plasmids can be explained by its weak expression of less than 5% that of the wild-type LEU2 gene. The leu2-d allele has a deletion of the 5'-end sequence starting from 29 base pairs before the ATG initiation codon, but surprisingly, its expression is still regulated. On YRp7, which contains the chromosomal autonomic replication sequence ARS1, the defective leu2-d allele could not complement a leu2 host strain. This suggests a more stringent control of replication of ARS1-containing plasmids than of 2 mu-containing plasmids.
CNS complications of cocaine abuse: prevalence, pathophysiology, and neuroradiology. (1992)

The United States is facing an epidemic of cocaine use by adolescents and young adults from all socioeconomic backgrounds. Epidemiologic data suggest that the use of the drug continues to increase on a year-by-year basis. This is a serious public health problem because cocaine is highly addictive and is associated with a variety of serious complications. In the CNS, these include stroke, intracerebral hemorrhage, vascular spasm, and possibly vasculitis. Seizures and sudden death have been reported. Cocaine use during pregnancy may be associated with fetal hypoxia, intracerebral hemorrhage, and possibly congenital malformations in the neonate. Many of these complications have been recognized only in the last 5-10 years. For example, ischemic changes in the brains of chronic cocaine abusers have been reported only recently. Because even further increases in cocaine use are predicted by drug enforcement officials, it is expected that radiologists will encounter its complications more frequently in the future. Therefore, radiologists should become familiar with the radiologic manifestations of the drug's effects. This article describes the drug's pathophysiology and complications and discusses the evolving role of imaging procedures.
An hierarchical approach to clock routing in high performance systems (1994)

In this paper, we present an hierarchical clock routing scheme, which minimizes the longest source to sink path, and obtains a path balanced clock tree with minimal total wirelength. Our scheme takes into consideration, the hierarchical design of a circuit. Our approach is applicable to large VLSI circuits and MCM's. The algorithm has been implemented and experimental results are encouraging.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins. (1994)

CRK protein, together with GRB2/ASH and Nck proteins, belongs to the adaptor-type Src homology (SH)2-containing molecules, which transduce signals from tyrosine kinases. Here another guanine nucleotide-releasing protein (GNRP), C3G, has been identified as a CRK SH3-binding protein. The nucleotide sequence of a 4.1-kb C3G cDNA contains a 3.2-kb open reading frame encoding a 121-kDa protein, and antibodies against C3G have been shown to detect a protein of 130-140 kDa. The carboxyl terminus of C3G has a peptide sequence homologous to GNRPs for Ras, and the expression of this carboxyl terminus region suppresses the loss of CDC25 function in the yeast Saccharomyces cerevisiae. The C3G protein expressed in Escherichia coli binds to CRK and GRB2/ASH proteins. Mutational analysis of C3G assigns the SH3 binding region to a 50-amino acid region containing a proline-rich sequence. The mRNAs of both the C3G and CRK proteins are expressed ubiquitously in human adult and fetal tissues. The results of these studies suggest that the complex of CRK and C3G, or GRB2/ASH and C3G, may transduce the signals from tyrosine kinases to Ras in a number of different tissues.
Overcharge Protection for Rechargeable Lithium Polymer Electrolyte Batteries (1996)

Overcharge protection for rechargeable lithium polymer electrolyte cells by addition of redox shuttle additives to the polymer electrolyte was examined. Shuttle onset potentials and effective diffusion coefficients were determined for 12 redox shuttle species in polyethylene oxide‐based electrolytes at 85°C. The four most promising additives were tested in cells under normal and severe overcharging conditions. In addition to tricyanobenzene and tetracyanoquinodimethane, two anionic redox shuttle additives, salts of 1,2,4‐triazole and imidazole, demonstrated effectiveness in extending cycle life and good compatibility with cell components.
Regulation of dimorphism in Saccharomyces cerevisiae: involvement of the novel protein kinase homolog Elm1p and protein phosphatase 2A. (1993)

The Saccharomyces cerevisiae genes ELM1, ELM2, and ELM3 were identified on the basis of the phenotype of constitutive cell elongation. Mutations in any of these genes cause a dimorphic transition to a pseudohyphal growth state characterized by formation of expanded, branched chains of elongated cells. Furthermore, elm1, elm2, and elm3 mutations cause cells to grow invasively under the surface of agar medium. S. cerevisiae is known to be a dimorphic organism that grows either as a unicellular yeast or as filamentous cells termed pseudohyphae; although the yeast-like form usually prevails, pseudohyphal growth may occur during conditions of nitrogen starvation. The morphologic and physiological properties caused by elm1, elm2, and elm3 mutations closely mimic pseudohyphal growth occurring in conditions of nitrogen starvation. Therefore, we propose that absence of ELM1, ELM2, or ELM3 function causes constitutive execution of the pseudohyphal differentiation pathway that occurs normally in conditions of nitrogen starvation. Supporting this hypothesis, heterozygosity at the ELM2 or ELM3 locus significantly stimulated the ability to form pseudohyphae in response to nitrogen starvation. ELM1 was isolated and shown to code for a novel protein kinase homolog. Gene dosage experiments also showed that pseudohyphal differentiation in response to nitrogen starvation is dependent on the product of CDC55, a putative B regulatory subunit of protein phosphatase 2A, and a synthetic phenotype was observed in elm1 cdc55 double mutants. Thus, protein phosphorylation is likely to regulate differentiation into the pseudohyphal state.
Treatment of Myeloproliferative Disorders With Hydroxyurea: Effects on Red Blood Cell Geometry and Deformability (1998)

Hydroxyurea (HU) is used in suppressing the bone marrow and producing fetal-like red blood cells (RBCs). These RBCs are large in size and may theoretically disturb the microcirculation. In five patients with myeloproliferative disorders (MPD), the RBC geometry and deformability were analyzed before and after 6 to 8 months of HU treatment. In untreated MPD, the RBC geometry and filterability was normal. After HU, the RBC membrane area increased 24% and the cell volume increased 39% (P &lt; .005). This change resulted in a 12% increase in the minimum cylindrical diameter (MCD). From a static bending model of initial deformation, the RBC diametrical cross-section had a significantly increased section modulus. However, this increase in profile stiffness was compensated for by its larger projected cell area and, thus, pressure load on the RBC corpuscle. The resulting resistance to initial deformation therefore remained unchanged after HU. These findings were tested experimentally; with 3-μm filter membranes, HU treatment caused a significant increase in flow resistance (P &lt; .02), in accordance with MCD. However, with 5-μm pores, no difference was seen, again in consonance with the theoretical findings of initial deformation. Because most capillaries are larger than 3 μm, we suggest that HU is acceptable from a perspective of cellular microrheology.
The role of vitamin D3 in the proliferation of a human colon cancer cell line in vitro. (1987)

LoVo, a cultured colon cancer cell line, is shown to possess a receptor for 1,25-dihydroxy vitamin D3 (1 alpha,25(OH)2D3) with a low capacity (28 fmol/mg protein) and high affinity (Kd: 1.9 x 10(-21)0M). When these cells were grown in monolayer culture in a chemically defined serum-free medium, a significant inhibition of proliferation was seen in the presence of 10 nM to 1 microM of 1 alpha,25(OH)2D3 (p less than 0.005. Furthermore, 1 alpha,25(OH)2D3 delayed early attachment of cells. After 8 days of treatment, aggregated cuboidal cells showed a marked change to an apparently spindle like morphology. The 1 alpha,25(OH)2D3 growth-inhibitory effect was modulated by verapamil (1 microM), a calcium channel blocker, hydrocortisone (1 microM), and moxestrol (1 mM), an estrogen analogue, and 2% charcoal-treated fetal bovine serum. This study represents the first demonstration of 1 alpha,25(OH)2D3 modulation of growth of human colon cells.
Mitigating Adversarial Effects Through Randomization (2017)

Convolutional neural networks have demonstrated high accuracy on various tasks in recent years. However, they are extremely vulnerable to adversarial examples. For example, imperceptible perturbations added to clean images can cause convolutional neural networks to fail. In this paper, we propose to utilize randomization at inference time to mitigate adversarial effects. Specifically, we use two randomization operations: random resizing, which resizes the input images to a random size, and random padding, which pads zeros around the input images in a random manner. Extensive experiments demonstrate that the proposed randomization method is very effective at defending against both single-step and iterative attacks. Our method provides the following advantages: 1) no additional training or fine-tuning, 2) very few additional computations, 3) compatible with other adversarial defense methods. By combining the proposed randomization method with an adversarially trained model, it achieves a normalized score of 0.924 (ranked No.2 among 107 defense teams) in the NIPS 2017 adversarial examples defense challenge, which is far better than using adversarial training alone with a normalized score of 0.773 (ranked No.56). The code is public available at https://github.com/cihangxie/NIPS2017_adv_challenge_defense.
Admixture Mapping Identifies a Quantitative Trait Locus Associated with FEV1/FVC in the COPDGene Study (2014)

African Americans are admixed with genetic contributions from European and African ancestral populations. Admixture mapping leverages this information to map genes influencing differential disease risk across populations. We performed admixture and association mapping in 3,300 African American current or former smokers from the COPDGene Study. We analyzed estimated local ancestry and SNP genotype information to identify regions associated with FEV1 /FVC, the ratio of forced expiratory volume in one second to forced vital capacity, measured by spirometry performed after bronchodilator administration. Global African ancestry inversely associated with FEV1 /FVC (P = 0.035). Genome-wide admixture analysis, controlling for age, gender, body mass index, current smoking status, pack-years smoked, and four principal components summarizing the genetic background of African Americans in the COPDGene Study, identified a region on chromosome 12q14.1 associated with FEV1 /FVC (P = 2.1 × 10(-6) ) when regressed on local ancestry. Allelic association in this region of chromosome 12 identified an intronic variant in FAM19A2 (rs348644) as associated with FEV1 /FVC (P = 1.76 × 10(-6) ). By combining admixture and association mapping, a marker on chromosome 12q14.1 was identified as being associated with reduced FEV1 /FVC ratio among African Americans in the COPDGene Study.
Slug-Test Analysis in Double-Porosity Reservoirs (1988)

Summary The pressure response of a double-porosity reservoir to a slug test in a fully penetrating well with wellbore storage and skin is presented. Pseudosteady-state matrix flow and transient matrix flow with and without matrix skin are considered. Three kinds of type curves are discussed: early-time log-log, intermediate-time semilog, and late-time log-log. Pressure distribution around the active well and the prospects of interference slug testing are considered. The early-time response of the slug test depends on the presence of wellbore skin; hence, two kinds of early-time type curves are presented. When the active well has wellbore skin, the early-time correlating parameter is the product of the skin and the dimensionless storage, resulting in a new log-log type curve. When wellbore skin is not present, the early-time response is proportional to the square root of time with dimensionless storage as the correlating parameter. The intermediate-time semilog type curves are applicable when wellbore skin is not present, or CDe2S&amp;gt;104. The double-porosity effects are significant in the late-time log-log format, but the flat portion of the pressure response occurs at dimensionless pressures less than 0.01. The radius of investigation of the slug test in a double-porosity system is also examined with and without wellbore skin at the active well. Interference responses and pressure profiles are presented. Although the presence of wellbore skin reduces the magnitude of the dimensionless pressure responses at observation wells, the detectable radius of investigation does not significantly depend on wellbore skin. Interference slug testing in a double-porosity system requires high-precision pressure-recording tools in the observation wells because the double-porosity effects occur at small dimensionless pressures. Transient matrix flow without matrix skin reduces the double-porosity effects and limits the use of type curves for determining λ and ω. The slug-test double-porosity effects in a reservoir with transient matrix flow with fracture skin and pseudosteady-state matrix flow are similar.
Activation of polysaccharides with 2-iminothiolane and its uses (1980)

2-Iminothiolane, a cyclic thioimidate, is known to react readily with amino groups of proteins to give amidinated derivatives containing reactive sulfhydryl groups. In this report it will be shown that 2-iminothiolane also reacts with hydroxyl and sulfhydryl groups. Such a reaction with hydroxyl groups can be used to introduce sulfhydryl groups into polysaccharides. When this reaction is carried out in the presence of 4,4'-dithiodipyridine, polysaccharides containing 4-dithiopyridyl groups can be prepared. These activated polysaccharides couple easily via intermolecular disulfide bond formation with proteins containing thiol or 4-dithiopyridyl groups. The resulting polysaccharide--protein conjugates have good stability, and they are useful reagents for different biochemical applications such as the purification of proteins containing thiol groups and affinity chromatography.
Costimulation of T-cell activation and virus production by B7 antigen on activated CD4+ T cells from human immunodeficiency virus type 1-infected donors. (1993)

Infection with the human immunodeficiency virus type 1 (HIV-1) requires T-cell activation. Recent studies have shown that interactions of the T-lymphocyte receptors CD28 and CTLA-4 with their counter receptor, B7, on antigen-presenting cells are required for optimal T-cell activation. Here we show that HIV-1 infection is associated with decreased expression of CD28 and increased expression of B7 on CD4+ T-cell lines generated from seropositive donors by alloantigen stimulation. Loss of CD28 expression was not seen on CD4+ T-cell lines from seronegative donors, but up-regulation of B7 expression was observed upon more prolonged culture. Both T-cell proliferation and interleukin 2 mRNA accumulation in HIV-1-infected cultures required costimulation with exogenous B7 because these events were blocked by CTLA4Ig, a soluble form of CTLA-4 that binds B7 with high avidity. In contrast, levels of HIV-1 RNA were not affected by CTLA4Ig, indicating that regulation of virus transcription in these cultures did not depend upon CD28-B7 engagement. Infected T cells could present alloantigen to fresh, uninfected CD4+ T cells, leading to increased proliferation and virus spread to the activated cells. Both of these events were blocked by CTLA4Ig. Thus, chronic activation of HIV-1-infected CD4+ T cells reduces expression of CD28 and increases expression of B7, thereby enabling these T cells to become antigen-presenting cells for uninfected CD4+ T cells; this might be another mechanism for HIV-1 transmission via T-cell-T-cell contact.
A novel method of activation of cross-linked agaroses with 1,1'-carbonyldiimidazole which gives a matrix for affinity chromatography devoid of additional charged groups. (1979)

1,1'-Carbonyldiimidazole, a carbonylating reagent, has been shown to be suitable for the activation of cross-linked agaroses for affinity chromatography. The activated matrix (an imidazolyl carbamate) is relatively stable to hydrolysis but smoothly reacts with N-nucleophiles such as those present in either affinity chromatography ligands or leashes, e.g. ethylenediamine or 6-aminohexanoic acid. If butylamine was attached via the 1,1'-carbonyldiimidazole method, the resulting product was devoid of charged groups and thus had the same titration curve as agarose. The suitability of this new matrix for affinity chromatography was demonstrated by the successful purification of trypsin by several different systems.
Modulating the Expression of IFN Regulatory Factor 8 Alters the Protumorigenic Behavior of CD11b+Gr-1+ Myeloid Cells (2009)

CD11b(+)Gr-1(+)-expressing cells, termed myeloid-derived suppressor cells, can mediate immunosuppression and tumor progression. However, the intrinsic molecular events that drive their protumorigenic behavior remain to be elucidated. Although CD11b(+)Gr-1(+) cells exist at low frequencies in normal mice, it also remains unresolved whether they are biologically distinct from those of tumor-bearing hosts. These objectives were investigated using CD11b(+)Gr-1(+) cells from both implantable (4T1) and autochthonous (mouse mammary tumor virus-polyomavirus middle T Ag (MMTV-PyMT)) mouse models of mammary carcinoma. Limited variation was observed in the expression of markers associated with immunoregulation between CD11b(+)Gr-1(+) cells of both tumor models, as well as with their respective controls (Cnt). Despite limited differences in phenotype, tumor-induced CD11b(+)Gr-1(+) cells were found to produce a more immunosuppressive cytokine profile than that observed by Cnt CD11b(+)Gr-1(+) cells. Furthermore, when admixed with tumor cells, CD11b(+)Gr-1(+) cells from tumor-bearing mice significantly enhanced neoplastic growth compared with counterpart cells from Cnt mice. However, the protumorigenic behavior of these tumor-induced CD11b(+)Gr-1(+) cells was significantly diminished when the expression of IFN regulatory factor 8, a key myeloid-associated transcription factor, was enhanced. The loss of this protumorigenic effect occurred independently of the host immune system and correlated with a CD11b(+)Gr-1(+) cytokine/chemokine production pattern that resembled cells from nontumor-bearing Cnt mice. Overall, our data indicate that 1) tumor-induced CD11b(+)Gr-1(+) cells from both cancer models were phenotypically similar, but biologically distinct from their nontumor-bearing counterparts and 2) modulation of IFN regulatory factor 8 levels in tumor-induced CD11b(+)Gr-1(+) cells can significantly abrogate their protumorigenic behavior, which may have important implications for cancer therapy.