gebhart/patrepeval huggingface dataset:
Characterization of the first-in-class T-cell-engaging bispecific single-chain antibody for targeted immunotherapy of solid tumors expressing the oncofetal protein claudin 6 (2015)

The fetal tight junction molecule claudin 6 (CLDN6) is virtually absent from any normal tissue, whereas it is aberrantly and frequently expressed in various cancers of high medical need. We engineered 6PHU3, a T-cell-engaging bispecific single chain molecule (bi-(scFv)<sub>2</sub>) with anti-CD3/anti-CLDN6 specificities, and characterized its pharmacodynamic properties. Our data show that upon engagement by 6PHU3, T cells strongly upregulate cytotoxicity and activation markers, proliferate and acquire an effector phenotype. 6PHU3 exerts potent killing of cancer cells <i>in vitro</i> with EC<sub>50</sub> values in the pg/mL range. Subcutaneous xenograft tumors in NSG mice engrafted with human PBMCs are eradicated by 6PHU3 treatment and survival of mice is significantly prolonged. Tumors of 6PHU3-treated mice are strongly infiltrated with activated CD4<sup>+</sup>, CD8<sup>+</sup> T cells and T<sub>EM</sub> type cells but not T<sub>regs</sub> and display a general activation of a mostly inflammatory phenotype. These effects are only observed upon bispecific but not monospecific engagement of 6PHU3. Together with the exceptionally cancer cell selective expression of the oncofetal tumor marker CLDN6, this provides a safeguard with regard to toxicity. In summary, our data shows that the concept of T-cell redirection combined with that of highly selective targeting of CLDN6-positive solid tumors is effective. Thus, exploring 6PHU3 for clinical therapy is warranted.
Image probability distribution based on generalized gamma function (2005)

In this letter, we propose results of distribution tests that indicate that for many natural images, the statistics of the discrete cosine transform (DCT) coefficients are best approximated by a generalized gamma function (G/spl Gamma/F), which includes the conventional Gaussian, Laplacian, and gamma probability density functions. The major parameter of the G/spl Gamma/F is estimated according to the maximum likelihood (ML) principle. Experimental results on a number of /spl chi//sup 2/ tests indicate that the G/spl Gamma/F can be used effectively for modeling the DCT coefficients compared to the conventional Laplacian and generalized Gaussian function (GGF).
Mixed anxiety depression. For and against. (1993)

The subject of mixed anxiety depression has been the topic of a somewhat confused discussion. At one point, it was held that anxiety and depression were both manifestations of an underlying affective disorder, but systematic work by Martin Roth and others clearly demonstrated that anxiety disorders could be separated from depressive disorders via a multivariate scale. Interestingly, spontaneous panic attacks were among the highest loading items on this scale. Nonetheless, it was plain that many patients were simultaneously anxious and depressed. Interest then grew in understanding the evolution of these syndromes over time. In general, anxiety syndromes antecede depressive syndromes, although there are many exceptions. For instance, some people only develop panic attacks when in the midst of a depressive episode. To attempt to understand these complexities, detailed family studies have been attempted with often contradictory results. We shall present family study data indicating that patients with comorbid panic disorder and depression have different familial patterns from those with panic disorder alone. In addition, a practical question is whether there exist patients, primarily in private settings, who present with symptoms of anxiety and depression but do not meet full criteria for any of the currently defined syndromes. Such patients are often referred to as subsyndromal or subthreshold patients. Epidemiological data indicates that such patients exist and that their symptomatology is associated with social and functional impairment. Recently the DSM IV field trial has specifically addressed this issue by clinical investigations of primary care and psychiatric facilities. These results will be reported.
Identification, sequencing, and expression of Mycobacterium leprae superoxide dismutase, a major antigen (1990)

The gene encoding a major 28-kilodalton antigen of Mycobacterium leprae has now been sequenced and identified as the enzyme superoxide dismutase (SOD) on the basis of the high degree of homology with known SOD sequences. The deduced amino acid sequence shows 67% homology with a human manganese-utilizing SOD and 55% homology with the Escherichia coli manganese-utilizing enzyme. The gene is not expressed from its own promoter in E. coli but is expressed from its own promoter in Mycobacterium smegmatis. The amino acid sequences of epitopes recognized by monoclonal antibodies against the 28-kilodalton antigen have been determined.
Role of the Distal Half of the c-Mpl Intracellular Domain in Control of Platelet Production by Thrombopoietin In Vivo (2000)

The cytokine thrombopoietin (TPO) controls the formation of megakaryocytes and platelets from hematopoietic stem cells. TPO exerts its effect through activation of the c-Mpl receptor and of multiple downstream signal transduction pathways. While the membrane-proximal half of the cytoplasmic domain appears to be required for the activation of signaling molecules that drive proliferation, the distal half and activation of the mitogen-activated protein kinase pathway have been implicated in mediating megakaryocyte maturation in vitro. To investigate the contribution of these two regions of c-Mpl and the signaling pathways they direct in mediating the function of TPO in vivo, we used a knock-in (KI) approach to delete the carboxy-terminal 60 amino acids of the c-Mpl receptor intracellular domain. Mice lacking the C-terminal 60 amino acids of c-Mpl (Delta60 mice) have normal platelet and megakaryocyte counts compared to wild-type mice. Furthermore, platelets in the KI mice are functionally normal, indicating that activation of signaling pathways connected to the C-terminal half of the receptor is not required for megakaryocyte differentiation or platelet production. However, Delta60 mice have an impaired response to exogenous TPO stimulation and display slower recovery from myelosuppressive treatment, suggesting that combinatorial signaling by both ends of the receptor intracellular domain is necessary for an appropriate acute response to TPO.
A Safe, Economical Method for the Preparation of β-Oxo Esters (1993)

A high yield, economical method for preparation of ß-oxo esters has been developed involving the reaction of acid chlorides with potassium ethyl malonate using a magnesium chloride-triethylamine base system in either acetonitrile or ethyl acetate solvents. The method is suitable for the preparation of high purity ß-oxo esters in the laboratory and also in large scale production.
A simplified method of CT assisted localization and biopsy of intracranial lesions. (1979)

A simplified technique available to most neurosurgeons is described for using computerized tomography (CT) to localize and/or biopsy intracranial lesions. Illustrative cases are presented.
Inductively coupled plasma mass spectrometry for trace element analysis in the clinical laboratory. (1995)

Inductively coupled plasma mass spectrometry (ICP-MS) is a relatively new technique for trace element analysis. The basic operating principles of ICP-MS are described and our experience with this technique in a clinical setting is discussed for the analysis of serum, whole blood, and urine. Advantages to ICP-MS include the favorable detection limits (0.01 to 0.1 micrograms/L for many elements), simple specimen preparation, high throughput (about 40 specimens per hour), and the ability to measure more than one element simultaneously. A major disadvantage is the high capital cost of the instrumentation. Heavier elements, such as lead, are well-suited for ICP-MS analysis, whereas lighter elements are prone to more interferences. Lighter elements which are not amenable to assay by ICP-MS include chromium and iron. The ability to measure isotopes is a major advantage for mass spectrometry methods and has the potential to expand the usefulness of trace element analysis.
PREDICTION OF APPLE FIRMNESS FROM MASS LOSS AND SHRINKAGE (2004)

ABSTRACT Prediction of firmness from mass loss and shrinkage was investigated in apples (Malus x domestica Borkh.) under regular atmosphere (RA) storage conditions. Apples (‘Delicious’ and ‘Fuji’) were repeatedly weighed to determine mass loss. Shrinkage was measured with a strain gauge sensor. ‘Delicious’ apples lost firmness (73 to 58 N) while ‘Fuji’ apples maintained firmness at 69 N over 57 days in storage. Apples lost mass at a constant rate with ‘Delicious’ losing mass slower (0.6 % per month) than ‘Fuji’ (1.1% per month). ‘Delicious’ apple shrank less (0.28 mm) than the ‘Fuji’ (0.70 mm) over 57 days. The relationship between firmness and mass loss, or shrinkage was dependent on apple cultivar. Firmness was significantly and linearly related to mass loss and to shrinkage in ‘Delicious’ apples. It is possible to predict firmness of ‘Delicious’ apples under RA storage conditions by tracking mass loss or shrinkage.
Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: a double blind, randomized, multicenter, placebo controlled trial. (1999)

Controlled release oxycodone q12h and immediate release oxycodone-APAP qid, added to NSAID, were superior to placebo for reducing OA pain and improving quality of sleep. The active treatments provided comparable pain control and sleep quality. Controlled release oxycodone was associated with a lower incidence of some side effects.
Production of extracellular acidic lipase by Rhizopus arrhizus as a function of culture conditions. (1994)

Thermophilic strain of Rhizopus arrhizus accumulates an acidic lipase in culture fluid when grown in a medium containing ground nut oil, milk powder and inorganic salts. Addition of 2.0% ground nut oil yielded the highest productivity of enzyme. Soyabean meal and arabinose were found to be the best nitrogen and carbon sources for enzyme production respectively. Addition of metal ions such as MnCl2, SnCl2 and CaCl2 increased the enzyme productivity by 4 fold. The enzyme productivity in the fermenter was much higher (310 U/ml) than in shake-flask (180 U/ml). Crude lipase preparation showed pH and temperature activity optima at 3.5 and 45 degrees C respectively. The enzyme is thermostable and highly active in hydrolysing triglycerides and failed to hydrolyse-methyl esters of caprylate and palmitate.
The Major Attenuating Mutations of the Respiratory Syncytial Virus Vaccine Candidate cpts 530/1009 Specify Temperature-Sensitive Defects in Transcription and Replication and a Non-Temperature-Sensitive Alteration in mRNA Termination (1999)

The live-attenuated respiratory syncytial virus vaccine candidate cpts530/1009 was previously shown to contain two separate amino acid changes in the L protein, mutations 530 and 1009 (Phe-521-->Leu and Met-1169-->Val, respectively, according to the amino acid sequence of the L protein). Each mutation independently specifies temperature-sensitive (ts) and attenuation phenotypes. In this study, we examined the effects of these mutations on transcription and RNA replication, using complete infectious recombinant virus as well as a plasmid-based minireplicon system, the latter under conditions in which effects on replication and transcription are uncoupled. In comparison with recombinant wild-type virus, the 530 and 1009 viruses were partially restricted at 37 degrees C for RNA replication, mRNA synthesis, and virus growth. The 1009 virus was partially restricted for RNA synthesis and virus growth even at 32 degrees C, which suggested that the 1009 mutation has a non-ts component in addition to the ts component. Interestingly, the synthesis of polycistronic readthrough mRNAs was elevated 1.6- to 3.8-fold for the 1009 virus, and this defect was non-ts. Studies with the minigenome system showed that the 530 and 1009 mutations each directly affect both replication and transcription, that the effect on replication was marginally greater than on transcription for the 530 mutation, and that the increase in readthrough mRNA associated with the 1009 mutation also was observed with the minigenome system.
Comprehensive phenotypic analysis for identification of genes affecting growth under ethanol stress inSaccharomyces cerevisiae (2008)

We quantified the growth behavior of all available single gene deletion strains of budding yeast under ethanol stress. Genome-wide analyses enabled the extraction of the genes and determination of the functional categories required for growth under this condition. Statistical analyses revealed that the growth of 446 deletion strains under stress induced by 8% ethanol was defective. We classified these deleted genes into known functional categories, and found that many were important for growth under ethanol stress including several categories that have not been characterized, such as peroxisome. We also performed genome-wide screening under osmotic stress and identified 329 osmotic-sensitive strains. We excluded these strains from the 446 ethanol-sensitive strains to extract the genes whose deletion caused sensitivity to ethanol-specific (359 genes), osmotic-specific (242 genes), and both stresses (87 genes). We also extracted the functional categories that are specifically important for growth under ethanol stress. The genes and functional categories identified in the analysis might provide clues to improving ethanol stress tolerance among yeast cells.
Embryonic stem cell differentiation and the analysis of mammalian development (2002)

Molecular and cellular analysis of early mammalian development is compromised by the experimental inaccessibility of the embryo. Pluripotent embryonic stem (ES) cells are derived from and retain many properties of the pluripotent founder population of the embryo, the inner cell mass. Experimental manipulation of these cells and their environment in vitro provides an opportunity for the development of differentiation systems which can be used for analysis of the molecular and cellular basis of embryogenesis. In this review we discuss strengths and weaknesses of the available ES cell differentiation methodologies and their relationship to events in vivo. Exploitation of these systems is providing novel insight into embryonic processes as diverse as cell lineage establishment, cell progression during differentiation, patterning, morphogenesis and the molecular basis for cell properties in the early mammalian embryo.
Is 3D chip technology the next growth engine for performance improvement? (2008)

The semiconductor industry is reaching a fascinating confluence in several evolutionary trends that will likely lead to a number of revolutionary changes in how computer systems are designed, implemented, scaled, and used. Since Moore's Law, which has driven the evolution in systems for the last several decades, is imminently approaching real and severe limitations, the ability to create three-dimensional (3D) device stacks appears promising as a way to continue to integrate more devices into a “chip.” While on the one hand, this nascent ability to make “3D technology” can be interpreted as merely an extension of Moore's Law, on the other hand, the fact that systems can now be integrated across multiple planes poses some novel opportunities, as well as serious challenges and questions. In this paper, we explore these various challenges and opportunities and discuss structures and systems that are likely to be facilitated by 3D technology. We also describe the ways in which these systems are likely to change. Since 3D technology offers some different value propositions, we expect that some of the most important ways in which 3D technology will likely impact our approach to future systems design, implementation, and usage are not yet obvious to most system designers, and we outline several of them.
A performance comparison of three supercomputers (1991)

The performance of two second-generation supercomputers, the NEC SX-3 and the Fujitsu VP2600, is analyzed using the Standard Los Alamos Benchmark Set, the Mendez Fluid Dynamics Codes, and some highly vectorizable production-type codes from Los Alamos. For comparison, data are also given for a single processor of the CRAY Y-MP8/264.
Vision assisted robotic tele-training (2006)

This paper presents a self-calibrated vision system for human-guided robot task-learning. The system assists robot operators in training industrial robots quickly, safely, and accurately. The system can be used in various industrial environments and requires no predetermined model of the working space. The system self-calibrates to compute the initial sensor locations and orientations. Next, the user demonstrates the tool path that is to be followed by the robot arm using a 6 DOF training medium. Finally, the system optimizes the sensor locations so that, at those locations, the sensors can provide to the operator the sufficient images for the operator to observe and perform further remote training of the robot as required.
Autoimmunity against a Tissue Kallikrein in IQI/Jic Mice (2004)

We have recently characterized IQI/Jic mice as a model for Sjogren's syndrome (SS), a chronic autoimmune disease in humans. In SS, local lymphocytic infiltrations into salivary and lacrimal glands frequently develop to the involvement of systemic exocrine and nonexocrine organs, and the mechanism for progression of this disease remains obscure. Herein, we report identification of an autoantigen shared by various target organs in IQI/Jic mice. Polypeptides identified based on immunorecognition by autoantibodies in sera from IQI/Jic mice affected with autoimmune disease (>12 weeks of age) were tissue kallikrein (Klk)-1 and -13 and were cross-reactive to the autoantibodies. Interestingly, Klk-13, but not Klk-1, caused a proliferative response of splenic T cells from IQI/Jic mice from the age of 4 weeks onward. In addition, remarkably enhanced expression of Klk-13 was observed in the salivary glands of the mice in accordance with the development of inflammatory lesions. These results indicate that Klk-13 acts as an autoantigen and may increase T cells responsive to organs commonly expressing Klk-13, playing a pivotal role in the etiology of progression of disease in IQI/Jic mice. Our findings provide insights into the contributions of autoantigens shared by multiple organs in the progress of SS from an organ-specific to a systemic disorder.
TRANSPLANTATION OF THE BONE MARROW MICROENVIRONMENT LEADS TO HEMATOPOIETIC CHIMERISM WITHOUT CYTOREDUCTIVE CONDITIONING1 (2000)

Transplantation of bone marrow in the form of a bone graft may facilitate the production of hematopoietic chimerism and lead to long-term donor-specific hyporesponsiveness in the absence of a cytoreductive conditioning regimen.
Epoxy resin cured by bisphenol A based benzoxazine (1998)

Bisphenol A based benzoxazine was prepared from bisphenol A, formaline, and aniline. This benzoxazine was used as a hardener of the epoxy resin. Curing behavior of the epoxy resin and the properties of the cured resin were investigated. Consequently, curing reaction proceeded without a curing accelerator. The molding compound showed good thermal stability under 150°C, which corresponded to the temperature in the cylinder of injection molding. Above 150°C, the curing reaction proceeded rapidly. The cured epoxy resin showed good heat resistance, water resistance, electrical insulation, and mechanical properties compared with the epoxy resin cured by the bisphenol A type novolac. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 68: 1903–1910, 1998
Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism (2014)

Lipid oxidation leads to endothelial dysfunction, inflammation, and foam cell formation during atherogenesis. Glucose also contributes to lipid oxidation and promotes pathologic changes in membrane structural organization, including the development of cholesterol crystalline domains. In this study, we tested the comparative effects of eicosapentaenoic acid (EPA), an omega-3 fatty acid indicated for the treatment of very high triglyceride (TG) levels, and other TG-lowering agents (fenofibrate, niacin, and gemfibrozil) on lipid oxidation in human low-density lipoprotein (LDL) as well as membrane lipid vesicles prepared in the presence of glucose (200 mg/dL). We also examined the antioxidant effects of EPA in combination with atorvastatin o-hydroxy (active) metabolite (ATM). Glucose-induced changes in membrane structural organization were measured using small angle x-ray scattering approaches and correlated with changes in lipid hydroperoxide (LOOH) levels. EPA was found to inhibit LDL oxidation in a dose-dependent manner (1.0-10.0 µM) and was distinguished from the other TG-lowering agents, which had no significant effect as compared to vehicle treatment alone. Similar effects were observed in membrane lipid vesicles exposed to hyperglycemic conditions. The antioxidant activity of EPA, as observed in glucose-treated vesicles, was significantly enhanced in combination with ATM. Glucose treatment produced highly-ordered, membrane-restricted, cholesterol crystalline domains, which correlated with increased LOOH levels. Of the agents tested in this study, only EPA inhibited glucose-induced cholesterol domain formation. These data demonstrate that EPA, at pharmacologic levels, inhibits hyperglycemia-induced changes in membrane lipid structural organization through a potent antioxidant mechanism associated with its distinct, physicochemical interactions with the membrane bilayer.
Sequence of the gene for a NAD(P)-dependent formaldehyde dehydrogenase (class III alcohol dehydrogenase) from a marine methanotroph Methylobacter marinus A45 (1994)

A fragment of Methylobacter marinus A45 DNA has been cloned and sequenced, and an open reading frame has been identified that could code for a 46-kDa polypeptide. Comparison of the deduced amino acid sequence of the polypeptide against the protein data bank has revealed strong similarity with a number of alcohol dehydrogenases, with highest similarity towards class III alcohol dehydrogenases, which recently have been shown to be identical to glutathione-dependent formaldehyde dehydrogenases. We were unable to measure appreciable levels of NAD(P)-dependent formaldehyde dehydrogenases or alcohol dehydrogenase activities using aldehydes or primary or secondary alcohols in cell-free extracts from batch cultures of M. marinus A45. However, formaldehyde dehydrogenases activity was detected on zymograms. Our data suggest that, although NAD(P)-linked formaldehyde dehydrogenase or alcohol dehydrogenase activities are undetectable in cell-free extracts of most methylotrophs employing the ribulose monophosphate pathway for formaldehyde assimilation and dissimilation, the gene encoding formaldehyde dehydrogenase is present in M. marinus A45 and may be present in more of these organisms as well.
Self-Transfer and Genetic Recombination Mediated by P, the Sex Factor of Vibrio cholerae (1972)

Vibrio cholerae cells, infected with the sex factor P, produce discrete, plaque-like clearings when plated on lawns of P(-) cells. We investigated the nature of these clearings and conclude that they are probably sites of active mating. We developed a quantitative assay for P(+) cells and used it to study the kinetics of sex factor spread in broth cultures. Both established and newly infected donor populations were efficient sex factor donors, indicating that P is not self-repressed. We also investigated the kinetics of recombinant formation in broth matings. In 1-hr matings, we routinely found recombination frequencies of 10(-6) per donor cell. Kinetic studies of recombinant formation showed that the markers tested all appeared at early times. Thus P, the V. cholerae sex factor, seems to resemble F in its transfer properties.