gebhart/patrepeval huggingface dataset:
CD40 stimulation sensitizes CLL cells to lysosomal cell death induction by type II anti-CD20 mAb GA101 (2011)

Sensitivity of chronic lymphocytic leukemia (CLL) cells to anti-CD20 mAbs is low and, therefore, the efficacy of monotherapy with current anti-CD20 mAbs is limited. At present, it is not known whether sensitivity of CLL cells to CD20 mAbs is modulated by microenvironmental stimuli. We have shown previously that in vitro CD40 stimulation of peripheral blood-derived CLL cells results in resistance to cytotoxic drugs. In the present study, we show that, in contrast, CD40 stimulation sensitizes CLL cells to the recently described novel type II anti-CD20 mAb GA101. Cell death occurred without cross-linking of GA101 and involved a lysosome-dependent mechanism. Combining GA101 with various cytotoxic drugs resulted in additive cell death, not only in CD40-stimulated CLL cells, but also in p53-dysfunctional CLL cells. Our findings indicate that GA101 has efficacy against chemoresistant CLL, and provide a rationale for combining cytotoxic drugs with anti-CD20 mAbs.
Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases (1996)

Selective concentration and anchoring of ionotropic receptors at the synapse is essential for neuronal signaling. Little is known about the molecules that mediate receptor clustering in the CNS. With use of the yeast two-hybrid system to screen a rat brain cDNA library and by in vitro binding assays, we have identified an interaction between NMDA receptor subunits 2A and 2B (NR2A and NR2B) and three distinct members of the PSD-95/SAP90 family of membrane-associated putative guanylate kinases. The interaction is mediated by binding of the C terminus of the NMDA receptor subunits to the first two PDZ (also known as GLGF or DHR) domains of PSD-95/SAP90, an abundant synaptic protein associated with the membrane cytoskeleton. PSD-95 is also known to bind and cluster Shaker-type voltage-gated K+ channels. Similarities between the C-termini of NR2 subunits and K+ channels suggest a common C-terminal binding motif for PDZ domains. These data suggest that PDZ domains can function as modules for protein-protein interactions. Members of the PSD-95 family might serve to anchor NMDA receptors to the submembrane cytoskeleton and aid in the assembly of signal transduction complexes at postsynaptic sites.
Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis (2004)

T-cell infiltration into human cancer tissues can be a manifestation of host immune responses to cancer cells. The present study was undertaken to explore the clinicopathological significance of intraepithelial CD8(+) T cells using 371 consecutively sampled human colorectal carcinomas. By univariate analysis, we noted that the survival curves by intraepithelial CD8(+) T cells became separated only after 1 to 2 years postoperation. Multivariate analyses revealed that the beneficial effect of this factor becomes significant only after a longer (more than 2 year), but not after a shorter (less than 2 year) follow-up period. Furthermore, the number of intraepithelial CD8(+) T cells was significantly higher in patients alive for more than 5 years than in patients who either died of cancer after a curative operation or patients who underwent a noncurative operation. Patients' cancer-specific death long after a curative operation is thought to be caused by the growth of micrometastases in other organs or near the primary sites. The effects of intraepithelial CD8(+) T cells, therefore, may be mediated by suppression of micrometastasis, rather than suppression of growth in the primary tumour. In conclusion, our data support a hypothesis on the presence of systemic immunosurveillance against micrometastasis of cancer cells.
Deep contextual language understanding in spoken dialogue systems (2015)

We describe a unified multi-turn multi-task spoken language understanding (SLU) solution capable of handling multiple context sensitive classification (intent determination) and sequence labeling (slot filling) tasks simultaneously. The proposed architecture is based on recurrent convolutional neural networks (RCNN) with shared feature layers and globally normalized sequence modeling components. The temporal dependencies within and across different tasks are encoded succinctly as recurrent connections. The dialog system responses beyond SLU component are also exploited as effective external features. We show with extensive experiments on a number of datasets that the proposed joint learning framework generates state-of-the-art results for both classification and tagging, and the contextual modeling based on recurrent and external features significantly improves the context sensitivity of SLU models.
Protein Structure Encodes the Ligand Binding Specificity in Pheromone Binding Proteins (1995)

The ligand specificities and binding affinities of three recombinant pheromone binding proteins (PBPs) of two saturniid moths (genus Antheraea) were determined by using a novel binding assay in conjunction with two tritium-labeled constituents of the pheromone blend, [3H]-6E,11Z-hexadecadienyl acetate and [3H]-4E,9Z-tetradecadienyl acetate. The new binding assay, in which nonspecific adsorption to a plastic vessel is suppressed by presaturation of the surface with a 1-alkanol, allows measurement of dissociation constants (KD) for lipophilic ligands for their carrier proteins. The three PBPs showed KD values for [3H]-6E,11Z-16:Ac and [3H]-4E,9Z-14:Ac between 0.6 and 30 microM, as determined by Scatchard analysis. Importantly, two PBPs (Aper-1 and Aper-2) from one species showed opposite binding specificities for these two ligands. Aper-1, like Apol-3, showed 15-fold higher affinity for 6E,11Z-16:Ac than for 4E,9Z-14:Ac, while Aper-2 showed a 3.5-fold preference for binding the shorter chain compound. In addition, for the Apol-3 PBP, displacement of [3H]-6E,11Z-16:Ac binding by other pheromone components or analogs showed a clear trend in relative binding affinity: 6E,11Z-16:Ac > 4E,9Z-14:Ac > 6E,11Z-16:Al approximately 16:Ac > 6E,11Z-16:OH > 4E,9Z-14:OH. These data clearly demonstrate a > 1000-fold range of binding affinities among these very similar structures and unambiguously demonstrate the specificity of the PBP-pheromone interaction. Moreover, this assay offers the potential for determining ligand specificities for odorant binding proteins and other proteins in the vertebrate lipocalin superfamily.
Pharmacokinetic interaction between endogenous cortisol and exogenous corticosteroids. (1995)

A problem in the evaluation of pharmacokinetic interactions between prednisolone and cortisol is that both steroids bind to cortisol binding globulin (CBG) and albumin. The binding of both steroids to CBG is saturable in the therapeutic concentration range. General drug binding equations were applied to two drugs and two binding sites and two implicit cubic equations were derived. These equations cannot be solved algebraically. However, the free concentration can be calculated using spreadsheet programs on a personal computer. A spreadsheet for these equations was developed using EXCEL 5.0 and its SOLVER option. Free concentrations of prednisolone and cortisol were determined as a function of total concentrations of both ligands. The simulations show that the protein binding of cortisol remains relatively constant in the physiological range but changes when exogenous corticosteroid is present. However, the degree of protein binding of exogenous corticosteroids that bind to CBG depends on the cortisol concentration which competes for binding sites. At the same time, the exogenous corticosteroid suppresses the release of endogenous cortisol. The presented approach is able to take all of these pharmacokinetic and pharmacodynamic interactions into account leading to a more accurate estimation of active free corticosteroid concentrations.
Role of Wood anomalies in optical properties of thin metallic films with a bidimensional array of subwavelength holes (2003)

Recents works dealt with the optical transmission on arrays of subwavelength holes in a metallic layer deposited on a dielectric substrate. Making the system as realistic as possible, we perform simulations to enlighten the experimental data. This paper proposes an investigation of the optical properties related to the transmission of such devices. Numerical simulations give theoretical results in good agreement with experiment, and we observe that the transmission and reflection behavior correspond to Fano's profile correlated with resonant response of the eigen modes coupled with nonhomogeneous diffraction orders. We thus conclude that the transmission properties observed could conceivably be explained as resulting from resonant Wood's anomalies.
Conservatism of Ecological Niches in Evolutionary Time (1999)

Theory predicts low niche differentiation between species over evolutionary time scales, but little empirical evidence is available. Reciprocal geographic predictions based on ecological niche models of sister taxon pairs of birds, mammals, and butterflies in southern Mexico indicate niche conservatism over several million years of independent evolution (between putative sister taxon pairs) but little conservatism at the level of families. Niche conservatism over such time scales indicates that speciation takes place in geographic, not ecological, dimensions and that ecological differences evolve later.
Handbook of thermodynamic diagrams (1996)

Thermodynamic property data are important in many engineering applications in the chemical processing and petroleum refining industries. The Handbook of Thermodynamic Diagrams series presents volume and enthalpy diagrams (graphs) for the major organic chemicals and hydrocarbons, as well as the major inorganic compounds and elements. The graphs, arranged by carbon number and chemical formula, cover a wide range of pressures and temperatures to enable engineers to determine quickly values at various points. This volume covers inorganic compounds and elements.
Flow를 이용한 소비자 구매의도에 관한 연구 (2003)

요 약 본 연구는 Hoffman and Novak (1996) 을 중심으로 마케팅 분야에서 연구되기 시작하는 flow 개념을 인터. 넷 환경에서 소비자들의 구매의도 관련변수를 중심으로 하여 지각된 위험 관여도와 서비스품질에 어떠,; 한 영흥k올 미치며 더 나아가 구매의도에 미치는 영향력을 파악하고자 연구툴 진행하였다. 본 연구의 구체적인 목적은 첫째, 선행연구를 기초로 전자상거래에서 flow 개념율 이해하기 위해 기존 i i 의 flow 관련 연구툴 살펴보고, 숙련도와 도전감으로 분류한다. 둘째, flow개념미 지각위험, 관여도 더 나 flow 아가 구매의도와의 상호관계룰 정립하여 이를 모형화하고 검증한다. 즉, flow의 구성 요인인 숙련도, 도전 i; 감에 있어서 지각된 품질, 지각된 위험과 관여도와의 영향관계훌륭 파악하고 구매의도와의 영향관계를 알 ii 아보고자한다. 따라서 본 연구에서는 인터넷 환경에서 소비자의 구매행동을 파악하고 특히 어떤 요인들이 소비자들의 flow 구매의도룰 결정짓는지를 알아보기 위하여 최근에 연구되고 있는 flow개념이라는 이론적 톨에 바탕을 두 !j 어 소비자 구매의도 결정요인들을 분석하고자 한다. 연구 결과 숙련도와 도전감이 높율수록 관여도와 지 ij 각된 품질은 증가하고 숙련도는 도전감보다 지각된 위험에 부의 영흥t올 미치며, 지각된 품질은 관여도와 : i 구매의도에, 지각된 위험은 구매의도에, 관여도는 구매의도에 유의한 영흥k율 미치는 것으로 나타났다. Abstract In order for electronic commerce to be successful, it must have a theoretical framework that considers the characteristics of the internet user who are consumers in the cyber space and impacts their purchase intentions. We were able to obtain participation of 350 people from across the country using 316 responses(34 responses removed), we derived statistics by means of SPSS/PC version 10.0 and AMOS 4.0 statistics package. We found that, the higher the degree of skill and the sense of challenge, the level of involvement and perceived service quality increased. And the degree of skill has a negative influence on awareness of perceived risk than the sense of challenge. Perceived service quality, perceived risk and involvement has a influence on purchase intentions. 주제어: 전자상거래Flow지각된 위험관여도숙련도도전감Key Words: electronic commerceflowperceived riskinvolvementskillchallenge
Infectious Agents as Causes of Non-Hodgkin Lymphoma (2007)

Abstract Among exposures presently viewed as possible etiologic factors in non-Hodgkin lymphoma (NHL), infections are close to being regarded as established causes. Infectious agents causing NHL can be classified, according to mechanism, into three broad groups. First, some viruses can directly transform lymphocytes. Lymphocyte-transforming viruses include Epstein Barr virus (linked to Burkitt's lymphoma, NHLs in immunosuppressed individuals, and extranodal natural killer/T-cell NHL), human herpesvirus 8 (primary effusion lymphoma), and human T lymphotropic virus type I (adult T-cell leukemia/lymphoma). Second, human immunodeficiency virus is unique in causing profound depletion of CD4+ T lymphocytes, leading to acquired immunodeficiency syndrome and an associated high risk for some NHL subtypes. Third, recent evidence suggests that some infections increase NHL risk through chronic immune stimulation. These infections include hepatitis C virus as well as certain bacteria that cause chronic site-specific inflammation and seem to increase risk for localized mucosa-associated lymphoid tissue NHLs. Establishing that an infectious agent causes NHL depends on showing that the agent is present in persons with NHL as well as laboratory experiments elucidating the mechanisms involved. Only epidemiologic studies can provide evidence that infection is actually a risk factor by showing that infection is more frequent in NHL cases than in controls. Given the range of mechanisms by which infections could plausibly cause NHL and our growing molecular understanding of this malignancy, this field of research deserves continued attention. (Cancer Epidemiol Biomarkers Prev 2007;16(3):401–4)
Fluorescence-activated cell sorted rat islet cells and studies of the insulin secretory process (1996)

Studies of individual cell types in the islets of Langerhans are complicated by the cells' functional coupling by gap junctions and paracrine interaction. Access to purified alpha and beta cells is therefore desirable. We present a simplified and optimized method for fluorescence-activated cell sorting of endocrine pancreatic rat islets. For dispersion of the islets, dispase was superior to trypsin, as the number of vital single cells was higher (1.1 +/- 0.1 x 10(3) vs 0.6 +/- 0.1 x 10(3)/islet, P < 0.05). The purity of the sorted cells was 96.7 +/- 1.2% for the non-beta cells and 97.8 +/- 0.6% for the beta cells (numbers in percentages of endocrine cells). In culture, isolated beta cells, non-beta cells and mixtures of beta and non-beta cells formed aggregates, but not at low temperature (4 degrees C) and not in medium with low serum content (2%). Finally, in pure beta cell aggregates, glucose stimulated changes in cytoplasmic free Ca2+ concentration although both glucose- and arginine-induced insulin secretion was much reduced. We conclude that alpha cells are necessary for insulin secretion but not for glucose sensing.
Sphingosine-1-phosphate modulates spiral modiolar artery tone: A potential role in vascular-based inner ear pathologies? (2006)

We conclude that all key signalling pathway constituents are present at the mRNA level for S1P to act as an endogenous regulator of SMA tone. S1P stimulates potent, RhoA/Rho kinase-dependent SMA vasoconstriction and Ca2+ sensitization. The high sensitivity to S1P suggests that SMA vasoconstriction is likely to occur under pathological conditions that increase intramural S1P concentrations (i.e., inflammation). From a clinical perspective, the present study identifies new potential therapeutic targets for the treatment of vascular-based, "stroke-like" inner ear pathologies: the enzymes responsible for S1P bioavailability and the S1P receptors.
Monoclonal Antibodies: Interspecies Scaling With Minimal Preclinical Information (2011)

Interspecies scaling for predicting human pharmacokinetics with information from multiple animal species is an established approach for small-molecule drugs. However, in general, the strategy is not a viable approach for therapeutic monoclonal antibodies, since relevant preclinical information is often limited due to highly specific biological activity and unique disposition mechanisms of these biologic agents. Existing data from a limited database indicates that applying minimal but relevant preclinical information and an appropriate approach; for example, fixed-exponent, provides a pragmatic and reasonably accurate prediction of human pharmacokinetics. This article briefly reviews the factors that affect the disposition of monoclonal antibodies and reiterates the importance of biological similarities between animal species and humans when selecting preclinical information for interspecies scaling. The article outlines the rationalization for utilizing the one-species with fixed-exponent approach, with discussions focused on the assumptions in allometry and monoclonal antibodies disposition mechanisms, and provides specific considerations related to practically applying such an approach.
Military Applications of Speech Understanding Systems (1974)

Abstract : The report identifies applications of speech understanding systems (SUS) in military man/computer systems which appear to provide operational benefits over current man/computer interfaces or which could lead to entirely new operational capabilities. It also provides an overview of the nontechnical factors in the military environment which are likely to affect the introduction of SUS capabilities in military systems. Among these factors are various political, manpower, and fiscal trends.
96-Plex Molecular Barcoding for the Illumina Genome Analyzer (2011)

Next-generation sequencing technologies have a massive throughput, which dramatically reduces the cost of sequencing per gigabase, compared to standard Sanger sequencing. To make the most efficient use of this throughput when sequencing small regions or genomes, we developed a barcoding method, which allows multiplexing of 96 or more samples per lane. The method employs 8 bp tags, incorporated into each sequencing library during the library preparation enrichment polymerase chain reaction (PCR), pooling bar-coded libraries in equimolar ratios based on quantitative PCR, and sequencing using the three-read Illumina method.
Fibrin containing gels induce angiogenesis. Implications for tumor stroma generation and wound healing. (1987)

Fibrin deposition is a consistent early event in solid tumors and healing wounds and precedes new blood vessel ingrowth in both. We now demonstrate that fibrin gels of themselves induce an angiogenic response in the absence of tumor cells or platelets. Angiogenesis was enhanced when certain chemoattractants or mitogens were included in the fibrin gel. Newly devised, inert plastic chambers with one porous surface were filled with varying contents and were implanted in the subcutaneous space of guinea pigs. Chambers filled with cross-linked homologous fibrin or plasma induced an angiogenic response within 4 days. Vessels entered chambers through the surface pores and flared out radially; angiogenesis was quantitated by point counting. Vessels were functional and matured along a gradient that proceeded from distal (least mature) to proximal. The intensity of the angiogenic response was enhanced when zymosan activated serum, an N-formylmethionine tripeptide, or platelet-derived growth factor was included in the fibrin matrix. Prior aldehyde fixation or boiling of fibrin-filled chambers inhibited angiogenesis, as did high concentrations of hyaluronic acid. Chambers filled with type I collagen or agarose did not induce new blood vessel formation, but addition of collagen did not reduce fibrin's capacity to initiate angiogenesis. The novel assay introduced here offers several advantages that should facilitate the study of angiogenesis. These include reproducibility, low background, objective and quantitative scoring, and the capacity to evaluate native molecules in animals of several species. Taken together, our findings strongly implicate fibrin or related proteins in the pathogenesis of angiogenesis and offer a new approach for elucidating the underlying molecular mechanisms.
A hierarchy of trans-acting factors modulates translation of an activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. (1985)

The GCN4 gene encodes a positive effector of amino acid biosynthetic genes in Saccharomyces cerevisiae. Genetic analysis has suggested that GCN4 is regulated by a hierarchy of interacting positive and negative effectors in response to amino acid starvation. Results presented here for a GCN4-lacZ gene fusion support this regulatory model and suggest that the regulators of GCN4 exert their effects primarily at the level of translation of GCN4 mRNA. Both the GCN2 and GCN3 products appear to stimulate translation of GCN4 mRNA in response to amino acid starvation, because a recessive mutation in either gene blocked derepression of GCN4-lacZ fusion enzyme levels but did not reduce the fusion transcript level relative to that in wild-type cells grown in the same conditions. The GCD1 product appears to inhibit translation of GCN4 mRNA because under certain growth conditions, the gcd1-101 mutation led to derepression of the GCN4-lacZ fusion enzyme level in the absence of any increase in the fusion transcript level. In addition, the gcd1-101 mutation suppressed the low translational efficiency of GCN4-lacZ mRNA observed in gcn2- and gcn3- cells. A deletion of four small open reading frames in the 5' leader of GCN4-lacZ mRNA mimicked the effect of a gcd1 mutation and derepressed translation of the fusion transcript in the absence of either starvation conditions or the GCN2 and GCN3 products. By contrast, in a gcd1- strain, the deletion resulted in little additional increase in the translational efficiency of the fusion transcript. These results suggest that GCD1 mediates the translational repression normally exerted by the GCN4 leader sequences and that GCN2 and GCN3 antagonize these negative elements in response to amino acid starvation. The effects of the trans-acting mutations on the translation of GCN4-lacZ mRNA remained intact even when transcription of the fusion gene was placed under the control of the S. cerevisiae GAL1 transcriptional control element.
16 Mesenchymal Stem Cells of Human Adult Bone Marrow (2001)

We define stem cells broadly as those cells that give rise to progeny with more than one differentiated phenotype and that may be greatly expanded in an undifferentiated form. This differs from a “progenitor cell,” which gives rise to a single cell lineage only. Human mesenchymal stem cells (hMSCs) are isolated from bone marrow and expanded ex vivo. Flow cytometry using many different surface markers has demonstrated the expanded population to be >98% homogeneous and in defined in vitro assays these cells readily differentiate to multiple connective tissue lineages, including osteoblasts, chondrocytes, and adipocytes (Fig. 1) (Pittenger et al. 1999). In vivo implantation of these cells at orthotopic sites will also yield tissues in these lineages. Additionally, cultured hMSCs either produce, or can be induced to produce, cytokines for support of hematopoietic cells (Majumdar et al. 1998; Cheng et al. 2000). Cocultures of the MSCs with hematopoietic stem cells (HSCs) demonstrated that hMSCs or adipogenic hMSCs can support the in vitro maintenance, and even expansion, of HSCs, suggesting hMSCs serve as functional stroma (Thiede et al. 2000). In addition, conditions that produce myogenic differentiation of rat MSCs have been reported (Saito et al. 1995), and hMSCs show similar behavior but perhaps less efficiently. MSCs with similar potential have been isolated from other species as well, and those isolated from rabbits differentiated to tenocytes to produce a suitable replacement for severed tendon with excellent biomechanical stability (Young et al. 1998). The rabbit MSCs were also shown to form suitable cartilaginous grafts...