gebhart/patrepeval huggingface dataset:
Triggering of CD40 Antigen Inhibits Fludarabine-Induced Apoptosis in B Chronic Lymphocytic Leukemia Cells (1998)

We analyzed the effect of CD40 triggering on the fludarabine-induced apoptosis of B chronic lymphocytic leukemia (B-CLL) cells. Peripheral blood samples obtained from 15 patients were incubated with fludarabine in the absence or the presence of the anti-CD40 monoclonal antibody (MoAb) G28-5. In 12 patients a significant proportion of apoptotic cells, ranging from 22% to 38% (mean +/- SE: 28.5 +/- 1.6), were detected after 3 days of culture. In 9 of these samples, the addition of G28-5 reduced apoptosis by at least 30.1% and by 57.1% +/- 7.8% on average (P = .0077). Because the CD40 antigen activates NF-kappaB/Rel transcription factors in B cells, and NF-kappaB/Rel complexes can inhibit cell apoptosis, we investigated whether the antiapoptotic effect of G28-5, in our system, could be related to modulation of NF-kappaB/Rel activity. As expected, B-CLL cells displayed significant levels of nuclear NF-kappaB/Rel activity; p50, RelA, and c-Rel components of the NF-kappaB/Rel protein family were identified in these complexes. After exposure to fludarabine, NF-kappaB/Rel complexes were decreased in the nuclei. The addition of G28-5 upregulated the NF-kappaB/Rel levels. To determine the involvement of NF-kappaB/Rel activity in the G28-5-mediated inhibition of apoptosis, we blocked the transcription factor with a decoy oligonucleotide, corresponding to the NF-kappaB/Rel consensus sequence. Cells incubated with the anti-CD40 MoAb in the presence of the decoy oligonucleotide but not a control oligonucleotide displayed a complete impairment of the G28-5 antiapoptotic effect, indicating that NF-kappaB/Rel activity was required for the inhibition of apoptosis. These results suggest that CD40 triggering in vivo could counteract the apoptotic effect of fludarabine on B-CLL cells and that its neutralization, or the use of NF-kappaB/Rel inhibitors, could improve the therapeutic effect of fludarabine.
A Study on the Luminous Environment Investigation of Subway Stations In SEOUL -Comparison with the Artificial Lighting Design and Daylighting Design- (2004)

최근 다양한 용도로 활용되고 있는 지하철 역사는 새로운 거주공간으로 주목되고 있다. 그러나 지하철 역사는 지하공간으로 인한 폐쇄성 및 사용자의 심리적 거부감을 완화시키기 위해 자연광의 유입이 필요하다. 본 연구는 자연광이 도입된 지하철 역사와 인공조명으로 계획된 역사를 대상으로 조명환경 실태 및 실내 시환경을 평가하였다. 이를 위해, 먼저 선정된 지하철 역사의 현장측정을 자연광의 영향이 적은 담천공에서 실시하였다. 또한, 사용자를 대상으로 주간에 설문조사를 실시하여 실내 시환경에 대한 조명인식을 평가하였다. 연구결과, 지하철 역사의 시환경에 대한 자연광의 영향 및 출입구 부분에 완화조명이 필요한 것으로 분석되었다. 본 연구결과는 앞으로 보다 효과적인 지하철 역사 조명계획을 위한 기초 활용될 수 있으리라 기대된다.
Neural Acceleration for General-Purpose Approximate Programs (2012)

This paper describes a learning-based approach to the acceleration of approximate programs. We describe the \emph{Parrot transformation}, a program transformation that selects and trains a neural network to mimic a region of imperative code. After the learning phase, the compiler replaces the original code with an invocation of a low-power accelerator called a \emph{neural processing unit} (NPU). The NPU is tightly coupled to the processor pipeline to accelerate small code regions. Since neural networks produce inherently approximate results, we define a programming model that allows programmers to identify approximable code regions -- code that can produce imprecise but acceptable results. Offloading approximable code regions to NPUs is faster and more energy efficient than executing the original code. For a set of diverse applications, NPU acceleration provides whole-application speedup of 2.3× and energy savings of 3.0× on average with quality loss of at most 9.6%.
Isoelectric focusing patterns of urinary kallikrein in Dahl salt-hypertension susceptible and resistant rats. (1984)

Dahl salt-sensitive (S) rats which are susceptible to hypertension have lower urinary kallikrein excretion than salt-resistant (R) rats which are not susceptible. Some physicochemical characteristics of partially purified urinary kallikrein were compared between the S and R strains. The isoelectric focusing pattern of S kallikrein was shifted so that a higher proportion of enzyme was present in isoelectric forms that had higher pI values compared to the pattern for R kallikrein. This strain difference was unique to urinary kallikrein; it was not seen in kallikrein extracted from salivary glands. The isoelectric focusing pattern for R urinary kallikrein could be converted to an S-type pattern by treatment with neuraminidase, which suggests that the differing isoelectric focusing patterns arose from differences in the sialic acid content of the kallikrein. The S kallikrein was slightly more heat-labile than R kallikrein, which was also compatible with the lower sialic acid content of the S enzyme. Tests involving the active site of the enzyme (Km values, pH curves, and heat of activation) were identical for the S and R strains. It was concluded that the structural differences observed in urinary kallikrein between S and R strains were compatible with strain-specific posttranslational processing of the enzyme.
Acylation of Naturally Occurring and Synthetic 1-Deoxysphinganines by Ceramide Synthase (1998)

Fumonisin B1 (FB1) is the predominant member of a family of mycotoxins produced by Fusarium moniliforme (Sheldon) and related fungi. Certain foods also contain the aminopentol backbone (AP1) that is formed upon base hydrolysis of the ester-linked tricarballylic acids of FB1. Both FB1 and, to a lesser extent, AP1 inhibit ceramide synthase due to structural similarities between fumonisins (as 1-deoxy-analogs of sphinganine) and sphingoid bases. To explore these structure-function relationships further, erythro- and threo-2-amino, 3-hydroxy- (and 3, 5-dihydroxy-) octadecanes were prepared by highly stereoselective syntheses. All of these analogs inhibit the acylation of sphingoid bases by ceramide synthase, and are themselves acylated with Vmax/Km of 40-125 for the erythro-isomers (compared with approximately 250 for D-erythro-sphinganine) and 4-6 for the threo-isomers. Ceramide synthase also acylates AP1 (but not FB1, under the conditions tested) to N-palmitoyl-AP1 (PAP1) with a Vmax/Km of approximately 1. The toxicity of PAP1 was evaluated using HT29 cells, a human colonic cell line. PAP1 was at least 10 times more toxic than FB1 or AP1 and caused sphinganine accumulation as an inhibitor of ceramide synthase. These studies demonstrate that: the 1-hydroxyl group is not required for sphingoid bases to be acylated; both erythro- and threo-isomers are acylated with the highest apparent Vmax/Km for the erythro-analogs; and AP1 is acylated to PAP1, a new category of ceramide synthase inhibitor as well as a toxic metabolite that may play a role in the diseases caused by fumonisins.
Bioanalytical Applications of Accelerator Mass Spectrometry for Pharmaceutical Research (2000)

Accelerator mass spectrometry (AMS) is a mass spectrometric method for quantifying isotopes. It has had great impact in the geosciences and is now being applied in the biomedical fields. AMS measures radioisotopes such as 14C, 3H, 41Ca, and 36Cl, and others, with attomole sensitivity and high precision. Its use is allowing absorption, distribution, metabolism and elimination studies, as well as detailed pharmacokinetics, to be carried out directly in humans with very low chemical or radiological hazard. It is used in combination with standard separation methodologies, such as chromatography, in identification of metabolites and molecular targets for both toxicants and pharmacologic agents. AMS allows the use of very low specific activity chemicals (< 1 mCi/mmol), creating opportunities to use compounds not available in a high specific activity form, such as those that must be biosynthesized, produced in combinatorial libraries, or made through inefficient synthesis. AMS is allowing studies to be carried out with agents having low bioavailability, low systemic distributions, or high toxicity where administered doses must be kept low (<1 microg/kg). It may have uses in tests for idiosyncratic metabolism, drug interaction, or individual susceptibility, among others. The ability to use very low chemical doses, low radiological doses, small samples and conduct multiple dose studies may help move drug candidates into humans faster and safer than before. The uses of AMS are growing and its potential for drug development is only now beginning to be realized.
Stability of the Listeria monocytogenes ActA protein in mammalian cells is regulated by the N-end rule pathway (1999)

Upon infection of mammalian cells, Listeria monocytogenes lyses the phagosome and enters the cytosol, where it secretes proteins necessary for its intracellular growth cycle. Consequently, bacterial proteins exposed to the cytosol are potential targets for degradation by host cytosolic proteases. One pathway for degradation of host cytosolic proteins, the N-end rule pathway, involves recognition of the N-terminal amino acid and is mediated by the proteasome. However, very few natural N-end rule substrates have been identified. We have examined the L. monocytogenes ActA protein as a potential target for this pathway. ActA is an essential determinant of L. monocytogenes pathogenesis that is required to induce actin-based motility and cell-to-cell spread. We show that the half-life of a secreted form of ActA can be altered in the mammalian cytosol by changing the N-terminal amino acid. Moreover, the introduction of a destabilizing N-terminus into the functional, surface-bound form of ActA results in a small-plaque phenotype in L2 cells, which is partially reversible by an inhibitor of the proteasome. These results indicate that the L. monocytogenes ActA protein is a natural N-end rule substrate, and that optimal function of ActA in mediating cell-to-cell spread is dependent upon its intracellular turnover rate.
Clinical pharmacology of oral all-trans retinoic acid in patients with acute promyelocytic leukemia. (1992)

All-trans retinoic acid (RA) induces leukemic cell differentiation and complete remission in a high proportion of patients with acute promyelocytic leukemia (APL). However, remissions induced by all-trans RA tend to be brief, and relapses are associated with resistance to further treatment in vivo, although the leukemic cells appear to retain sensitivity to the cytodifferentiating effects of all-trans RA in vitro. The clinical pharmacology of all-trans RA was examined in 13 patients with APL. The drug was administered at a constant dose of 45 mg/m2/day, given as a single dose on the first day of therapy and in two divided doses thereafter. Plasma and urinary concentrations of the parent drug and metabolites were quantitated by reverse-phase high-performance liquid chromatography and, where required, by a combination of normal-phase liquid chromatography/negative chemical ionization mass spectrometry. In patients with APL, basal levels of endogenous retinol and natural retinoids were within the normal range. Peak plasma levels of all-trans RA (347 +/- 266 ng/ml, mean +/- SD) were reached 1-2 h after drug ingestion and decayed in a monoexponential fashion with a half-life of 0.8 +/- 0.1 h. The only drug metabolite detected in plasma or urine was 4-oxo-all-trans RA (present in urine as the glucuronide conjugate). This metabolite accounted for less than 10% of the circulating drug in plasma, and its cumulative urinary excretion accounted for less than 1% of the administered dose. The drug was not found in cerebrospinal fluid. Continued oral administration of all-trans RA was associated with a significant decrease in both the plasma peak levels and the area under the concentration-time curve (P = 0.01 and 0.004, respectively) when measured after 2-6 weeks of treatment. We previously reported that a decrease in plasma area under the concentration-time curve was highly correlated with clinical relapse. Observations in a subset of patients in this study suggested that, in fact, the major decrease occurred early, within the first 7 days of treatment. These changes were associated with a 10-fold increase in urinary excretion of 4-oxo-all-trans RA glucuronide, suggesting that the accelerated clearance from plasma was associated with increased drug catabolism. The rapid disappearance may explain early relapse from remissions induced by all-trans RA; clinical "resistance" to all-trans RA may either wholly or in part result from an inability to sustain effective plasma concentrations of all-trans RA during continuous treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
Transepithelial Transport of Immunoglobulins (1994)

Immunoglobulins are transported across a variety of epithelial tissues. The best studied example of this is the transport of polymeric IgA and IgM by the polymeric immunoglobulin receptor (pIgR) across many types of epithelial cells. The pIgR binds its ligand at the basolateral surface and is internalized into endosomes. Here it is sorted into vesicles that transcytose it to the apical surface. At the apical surface the pIgR is proteolytically cleaved, and the large extracellular fragment (known as secretory component) is released together with the ligand. The pIgR contains a cytoplasmic domain of 103 amino acids that contains several sorting signals. Targeting from the trans-Golgi network to the basolateral surface is determined by the membrane-proximal 17 residues of this domain. There are two endocytosis signals that contain crucial tyrosine residues. Transcytosis of the pIgR is stimulated by binding of polymeric IgA. Phosphorylation of a cytoplasmic serine promotes transcytosis of the pIgR without ligand bound. Transcytosis may be regulated by the heterotrimeric Gs protein, protein kinase C and calmodulin. IgG is transcytosed from the apical to basolateral surface in several epithelial tissues such as the placenta and the small intestine of newborn rats. The receptor for intestinal transport of IgG is structurally similar to class I MHC molecules.
Dienophilic Reactions of Aromatic Double Bonds in the Synthesis of β-Substituted Naphthalenes (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDienophilic Reactions of Aromatic Double Bonds in the Synthesis of β-Substituted NaphthalenesA. A. Danish, M. Silverman, and Y. A. TajimaCite this: J. Am. Chem. Soc. 1954, 76, 23, 6144–6150Publication Date (Print):December 1, 1954Publication History Published online1 May 2002Published inissue 1 December 1954https://pubs.acs.org/doi/10.1021/ja01652a083https://doi.org/10.1021/ja01652a083research-articleACS PublicationsRequest reuse permissionsArticle Views571Altmetric-Citations33LEARN 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
Heparanase – A Link Between Coagulation, Angiogenesis and Cancer (2012)

Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis, and angiogenesis. Recently we have demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. Heparanase was shown to up-regulate tissue factor (TF) expression and interact with tissue factor pathway inhibitor (TFPI) on the cell surface, leading to dissociation of TFPI from the cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity. More recently, we have shown that heparanase directly enhances TF activity, resulting in increased factor Xa production and activation of the coagulation system. Data indicate increased levels and possible involvement of heparanase in vascular complications in pregnancy. Taking into account the prometastatic and proangiogenic functions of heparanase, overexpression in human malignancies, and abundance in platelets and placenta, its involvement in the coagulation machinery is an intriguing novel arena for further research.
Bee venom hyaluronidase is homologous to a membrane protein of mammalian sperm. (1993)

The venom of honeybees, Apis mellifera, contains several biologically active peptides and two enzymes, one of which is a hyaluronidase. By using degenerate oligonucleotides derived from the amino-terminal sequence of this hyaluronidase reported by others, clones encoding the precursor for this enzyme could be isolated from a cDNA library prepared from venom glands of worker bees. The deduced amino acid sequence showed that bee venom hyaluronidase is a polypeptide composed of 349 amino acids containing four cysteines and three potential sites for N-glycosylation. The sequence of the precursor also indicated that the conversion of the pro-enzyme to the end product must involve cleavage of a Thr-Pro bond, a most unusual processing reaction. The mRNA encoding hyaluronidase could also be detected in testes from drones. Expression of the cloned cDNA in Escherichia coli yielded a 41-kDa polypeptide that had hyaluronidase activity. Interestingly, the hyaluronidase from bee venom glands exhibited significant homology to PH-20, a membrane protein of guinea pig sperm involved in sperm-egg adhesion. These structural data support the long-held view that hyaluronidases play a role in fertilization.
Parameter Estimation for a Generalized Gamma Distribution (1965)

It is fairly commonplace in reliability analyses to encounter data which is incompatible with the exponential, Weibull, and other familiar probability models. Such data motivates research to enlarge the group of probability distributions which are useful to the reliability analyst. In this paper, we examine a three-parameter generalization of the gamma distribution and derive parameter estimation techniques for that distribution. Those techniques, in the general case, depend upon method of moments considerations which lead to simultaneous equations for which closed form solutions are not available. Graphic solution is proposed and aids to the computations are provided. Major concepts in the paper are summarized by means of a numerical example. Details are given for the special case in which only the scale parameter is unknown. Three unbiased estimators for that parameter are derived along with their variance formulas. Minimum variance considerations are discussed by application of the Cramér-Rao Theorem.
CD4+CD8dim T lymphocytes exhibit enhanced cytokine expression, proliferation and cytotoxic activity in response to HCMV and HIV-1 antigens (2001)

CD4(+)CD8(dim) T cells represent a minor subset of the total CD3(+) T cell population in peripheral blood. Although transient and persistent expansions of these cells have been reported in both healthy and diseased individuals, the functional properties of the CD4(+)CD8(dim) population are largely unknown. In this study, we examined antigen-specific cytokine and proliferative responses of the CD4(+)CD8(dim) subset. In whole blood cultures stimulated with the viral antigens HCMV and HIV-1, a significant fraction of the CD4(+)CD8(dim) subset exhibited cytokine expression and proliferation in response to antigen activation. Typically, the CD4(+)CD8(dim) population contained two- to eightfold higher frequencies of antigen-specific cytokine producing cells than the CD4(+)CD8(-) population. Phenotypic analysis of the cytokine expressing CD4(+)CD8(dim) population indicated that these cells are memory T cells, with a high frequency of this population expressing the cytotoxic markers CD56 and perforin. Furthermore, the CD4(+)CD8(dim) cytokine responses to CMV were shown to be MHC class II dependent. Significantly, purified CD4(+)CD8(dim) T cells were found to possess higher CMV-specific cytotoxic activity than purified CD4(+)CD8(-) T cells in a standard (51)Cr-release CTL assay. Thus, CD4(+)CD8(dim) T cells appear to be MHC class II dependent, are capable of cytolytic effector activity, and are highly enriched within the CD4(+) cell populations specific for HCMV and HIV-1.
Design Optimization of Spirally Grooved Thrust Air Bearings for Polygon Mirror Laser Scanners (1993)

Polygon mirror laser scanners have been widely used in computer peripheral equipment and office automation systems, and improvement in scanning quality has been desired. In light of this, the use of self-acting air bearings has been recommended in spindle design to realize superior performance in terms of rotational speed and rotational errors. This study concerns the analysis of characteristics of spirally grooved thrust air bearings. Namely, it reports the rigidity, load capacity, power loss and critical damping factors. Employed in this study are the finite element method (FEM) and the computer simulation method in order to obtain a numerical solution to the Reynolds equation. Based on calculation results, the load characteristics and the effects of various design parameters of the bearing are discussed, and optimization principles for designing the bearing are proposed. The proposal may be summarized as follows. ( 1 ) The bearing rigidity and load capacity are closely related to the spiral groove width, depth, length in the radial direction and spiral groove pump-in angle, and the number of grooves should be as large as possible. ( 2 ) Decrease in the bearing clearance and increase in the bearing outer radius together achieve the best damping characteristics.
Gene Organization and Expression in Mesophilic Lactic Acid Bacteria (1989)

A detailed understanding of gene structure and expression in lactic acid bacteria is essential for the successful application of genetic modification techniques for both the improvement of these bacteria used in industrial dairy and food fermentations and their use as food-grade production organisms. This paper is intended to review the organization and expression of homologous and heterologous genes in the mesophilic lactic acid bacteria of the genera Lactococcus and Leuconostoc.
Modeling the Electrical Effects of Metal Dishing Due to CMP for On-Chip Interconnect Optimization (2004)

A dishing model is developed to investigate the electrical effects of metal dishing in the damascene process, based on experimental data and physical analysis. A metric for dishing, the dishing radius, has been defined. A study utilizing this model shows that the impact of dishing on performance can be mitigated at both the process and design stages. More specifically, process improvement is most effective when the dishing radius is less than 50 /spl mu/m. During design, dishing effects can be suppressed by uniformly splitting a wide line into several narrower lines; the most beneficial number of line-splitting is between two and four from both efficiency and performance considerations.
Nucleotide Sequence of an Arabidopsis thaliana Turgor-Responsive cDNA Clone Encoding TMP-A, a Transmembrane Protein Containing the Major Intrinsic Protein Motif (1993)

Plants have the capacity of responding to changes in the environment. Water stress is one of the environmental stresses to which a plant might be exposed. Upon exposure to such stress, a plant undergoes a series of physiological and biochemical changes. These changes include the closure of stomata, decrease in photosynthesis, increase in ABA (Zeevart and Creelman, 1988), and alteration in gene expression (Skriver and Mundy, 1990). Here we describe a cDNA clone encoding TMP-A from Arabidopsis thaliana. The protein encoded by it is very homologous to that encoded by the turgorresponsive 7a cDNA cloned from pea (Guerrero et al., 1990).