gebhart/patrepeval huggingface dataset:
Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil. (1988)

Verapamil, a phenylalkylamine calcium channel blocker, has been shown to reverse multidrug resistance in tumor cells, possibly by increasing drug retention through interaction with an outward drug transporter of the resistant cells. In this study two photoactive radioactive analogs of verapamil, N-(p-azido[3,5-3H]benzoyl)aminomethyl verapamil and N-(p-azido[3-125I]salicyl)aminomethyl verapamil, were synthesized and used to identify the possible biochemical target(s) for verapamil in multidrug-resistant DC-3F/VCRd-5L Chinese hamster lung cells selected for resistance to vincristine. The results show that a specifically labeled 150- to 180-kDa membrane protein in resistant cells was immunoprecipitated with a monoclonal antibody specific for P-glycoprotein. Phenylalkylamine binding specificity was established by competitive blocking of specific photolabeling with the nonradioactive photoactive analogs as well as with verapamil. Photoaffinity labeling was also inhibited by 50 microM concentrations of the calcium channel blockers nimodipine, nifedipine, nicardipine, azidopine, bepridil, and diltiazem and partially by prenylamine. Bay K8644, a calcium channel agonist, also inhibited P-glycoprotein photolabeling. Moreover, P-glycoprotein labeling was inhibited in a dose-dependent manner by vinblastine with half-maximal inhibition at 0.2 microM compared to that by verapamil at 8 microM. Photolabeling was also partially inhibited by two of the drugs to which these cells are cross-resistant, doxorubicin and actinomycin D, at 100 microM, but not by colchicine. These data provide direct evidence that P-glycoprotein has broad drug recognition capacity and that it serves as a molecular target for calcium channel blocker action in reversing multidrug resistance.
Interleukin 1 stimulates human endothelial cells to produce granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor. (1987)

Endothelial cells are a potent source of hematopoietic growth factors when stimulated by soluble products of monocytes. Interleukin 1 (IL 1) is released by activated monocytes and is a mediator of the inflammatory response. We determined whether purified recombinant human IL 1 could stimulate cultured human umbilical vein endothelial cells to release hematopoietic growth factors. As little as 1 U/ml of IL 1 stimulated growth factor production by the endothelial cells, and increasing amounts of IL 1 enhanced growth factor production in a dose-dependent manner. Growth factor production increased within 2 to 4 hr and remained elevated for more than 48 hr. To investigate the molecular basis for these findings, oligonucleotide probes for granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and multi-CSF were hybridized to poly(A)-containing RNA prepared from unstimulated and IL 1-stimulated endothelial cells. Significant levels of GM-CSF and G-CSF, but not M-CSF or multi-CSF, mRNA were detected in the IL 1-stimulated endothelial cells. Biological assays performed on the IL 1-stimulated endothelial cell-conditioned medium confirmed the presence of both GM- and G-CSF. These results demonstrate that human recombinant IL 1 can stimulate endothelial cells to release GM-CSF and G-CSF, and provide a mechanism by which IL 1 could modulate both granulocyte production and function during the course of an inflammatory response.
Low-level boron doping and light-induced effects in amorphous silicon pin solar cells (1982)

Amorphous silicon solar cells with the structure pin/ITO produced in our laboratory show an AM1 efficiency of up to 7.4 % on 6 mm/sup 2/. The impact of doping the i-layer slightly with boron on the cell performance was studied together with its possible influence on the cell stability. Cells exposed to continuous AM1 illumination (up to 2000 hours) show a degradation of the efficiency. Differences in the biasvoltage during the deposition lead to significant differences in the stability whereas the influence of boron doping was not so prominent. The ..mu../tau/-products for electrons and holes were shown to degrade differently through light-soaking for different doping-level. A further investigation was made by evaluating the frequency dependence of the capacitance via a new p-i-n junction model to obtain the density of states and the drift field in the i-layer for doping and light-soaking.
The design of an atmospheric pressure ionization/time-of-flight mass spectrometer using a beam deflection method (1992)

A novel time-of-flight (TOF) mass spectrometer configuration has been designed which can be interfaced to a continuous ion beam source produced by atmospheric pressure ionization. The TOF device uses a beam deflection method to sweep the ion beam past a slit placed near the ionization source in order to generate a start pulse for TOF detection. The beam sweep technique is modeled by computer simulation and optimized for the various experimental parameters. Nonvolatile samples are injected into the TOF device using liquid injection into a glow discharge atmospheric pressure ionization source in helium. A resolution of at least 519 at m/z 311 is obtained, which is limited by the experimental parameters available in our experiment. The mass resolution is computer modeled and it is shown that as the mass increases, the experimental constraints become less important, and the resolution will increase. It is predicted that using the correct experimental conditions and with the addition of an ion reflector that resolution of well over 1000 should be obtained.
Structure of sangivamycin (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of sangivamycinKoppaka V. RaoCite this: J. Med. Chem. 1968, 11, 5, 939–941Publication Date (Print):September 1, 1968Publication History Published online1 May 2002Published inissue 1 September 1968https://pubs.acs.org/doi/10.1021/jm00311a005https://doi.org/10.1021/jm00311a005research-articleACS PublicationsRequest reuse permissionsArticle Views198Altmetric-Citations39LEARN 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
Training deep neural nets to aggregate crowdsourced responses (2016)

We propose a new method for aggregating crowdsourced responses, based on a deep neural network. Once trained, the aggregator network gets as input the responses of multiple participants to the same set of questions, and outputs its prediction for the correct response to each question. We empirically evaluate our approach on a dataset of responses to a standard IQ questionnaire, and show it outperforms existing state-of-the-art methods.
Clinical and psychological outcomes of patient education in rheumatoid arthritis (2005)

Patients offered education gained knowledge and reported personal benefit, but only improved in self-efficacy for pain and only for a short time. RA patients drawn from hospital outpatient clinics and allocated to an educational intervention may not gain changes in health status as measured by the instruments employed in this study.
Applied plant biotechnology (1999)

Biotechnology - multibillion dollar industry genetic modification of plant carbohydrate metabolism modification of fatty acid metabolism in plants manipulation of sequiterpene pathways in plants transgenic plants for the production of human therapeutics application of recombinant DNA to floriculture technology for the control of insect pests of plants molecular techniques for the identification of plants transgenic sugarbeet - progress and development molecular biology and genetic analysis of Novartis seed's event 176 bt-corn biosafety concerns in plant biotechnology ecological impacts of transgenic crops biotechnology and plant breeding.
Theoretical study of the influence of a metal enclosure on the parameters of a plasma column sustained by a travelling electromagnetic surface wave (1991)

In this paper, we have studied the influence of a metal enclosure on the electromagnetic wave characteristics and on the structure of a plasma column sustained by the wave itself. The present work is an extension of a theoretical model of a plasma column produced by a traveling azimuthally-symmetric electromagnetic surface wave (Zhelyazkov, I. and Benova, E., J. Appl. Phys. 66, 1641 (1989)). The axial profiles of the dimensionless electron number density, wave power, wave number, and wave electric field components have been obtained as a function of an additional parameter η - R1/R taking into account the presence of a metal enclosure near the discharge tube (R being the plasma column radius, R1 the metal tube radius). These results are applied to particular experimental setups.
Differential Substrate Specificity and Kinetic Behavior of Escherichia coli YfdW and Oxalobacter formigenes Formyl Coenzyme A Transferase (2008)

The yfdXWUVE operon appears to encode proteins that enhance the ability of Escherichia coli MG1655 to survive under acidic conditions. Although the molecular mechanisms underlying this phenotypic behavior remain to be elucidated, findings from structural genomic studies have shown that the structure of YfdW, the protein encoded by the yfdW gene, is homologous to that of the enzyme that mediates oxalate catabolism in the obligate anaerobe Oxalobacter formigenes, O. formigenes formyl coenzyme A transferase (FRC). We now report the first detailed examination of the steady-state kinetic behavior and substrate specificity of recombinant, wild-type YfdW. Our studies confirm that YfdW is a formyl coenzyme A (formyl-CoA) transferase, and YfdW appears to be more stringent than the corresponding enzyme (FRC) in Oxalobacter in employing formyl-CoA and oxalate as substrates. We also report the effects of replacing Trp-48 in the FRC active site with the glutamine residue that occupies an equivalent position in the E. coli protein. The results of these experiments show that Trp-48 precludes oxalate binding to a site that mediates substrate inhibition for YfdW. In addition, the replacement of Trp-48 by Gln-48 yields an FRC variant for which oxalate-dependent substrate inhibition is modified to resemble that seen for YfdW. Our findings illustrate the utility of structural homology in assigning enzyme function and raise the question of whether oxalate catabolism takes place in E. coli upon the up-regulation of the yfdXWUVE operon under acidic conditions.
Asymmetric Homoaldol Reaction by Enantioselective Lithiation of a Prochiral 2‐Butenyl Carbamate (1989)

A second-order asymmetric conversion of the configurationally labile racemic lithium complex 2 initially formed from 1 enables the recovery of crystalline (R)-2.sparteine. This, and the transmetalation of (R)-2.sparteine (as solid) to the configurationally stable titanium derivative are decisive for the title reaction. (R)-2 is not only of interest as chiral homoenolate, but also as antiselective propanal enolate equivalent that adds with good reagent-controlled stereoselectivity; an example is the reaction leading to 3.
Theory of light sail acceleration by intense lasers:an overview (2014)

A short overview of the theory of acceleration of thin foils driven by the radiation pressure of superintense lasers is presented. A simple criterion for radiation pressure dominance at intensities around 5×1020W cm-2is given, and the possibility for fast energy gain in the relativistic regime is discussed.
Scrambling adversarial errors using few random bits, optimal information reconciliation, and better private codes (2007)

Communicating over a noisy channel is typically much easier when errors are drawn from a fixed, known distribution than when they are chosen adversarially. This paper looks at how one can use schemes designed for random errors in an adversarial context, at the cost of few additional random bits and without relying on unproven computational assumptions.The basic approach is to permute the positions of a bit string using a permutation drawn from a t-wise independent family, where t = o(n). This leads to several new results:• We show that concatenated codes can correct errors up to the Shannon capacity even when the errors are only slightly random --- it is sufficient that they be t-wise independently distributed, for t roughly ω(log n).• We construct computationally efficient information reconciliation protocols correcting pn adversarial binary Hamming errors with optimal communication complexity and entropy loss n(h(p) + o(1)) bits, where n is the length of the strings and h() is the binary entropy function.Information reconciliation protocols allow cooperating parties to correct errors in a shared string. They are important tools in two applications: first, for dealing with noisy secrets in cryptography; second, for synchronizing remote copies of large files. Entropy loss measures how much information is leaked to an eavesdropper listening in on the protocol.• We improve the randomness complexity (key length) of efficiently decodable capacity-approaching private codes from Θ(n log n) to n + o(n).We also present a simplified proof of an existential result on private codes due to Langberg (FOCS '04).
Childhood Maltreatment Predicts Unfavorable Course of Illness and Treatment Outcome in Depression: A Meta-Analysis (2011)

Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression.
Definition of a GC-rich motif as regulatory sequence of the human IL-3 gene: coordinate regulation of the IL-3 gene by CLE2/GC box of the GM-CSF gene in T cellactivation (1991)

The human IL-3 gene, located on chromosome 5, contains several cis-acting DNA sequences, i.e. CLE (conserved lymphokine element) and a GC-rich region, similar to the GM-CSF gene. To investigate the role of these elements, the 5' flanking region of the IL-3 gene was attached to a bacterial chloramphenicol acetyltransferase (CAT) gene. The fusion plasmids were analyzed by an in vitro transcription system using Jurkat cell nuclear extract prepared from cells stimulated with phorbol-12-myristate-13-acetate and calcium ionophore (PMA/A23187), introduced into Jurkat cells, expressed transiently, and stimulated by co-transfection of human T cell leukemia virus type I (HTLV-I) encoded transactivator, p40tax. The GC-rich region enhanced TATA-dependent transcription in the in vitro transcription system and also strongly responded to p40tax stimulation in the in vivo cotransfection assay. Using this GC-rich region as a probe, we identified a constitutive DNA-protein complex, alpha, whose binding specificity correlates with transcription activity. However, this element is not sufficient for the expression of the IL-3 gene in response to T cell activation signals (PMA/A23187) and no sequence was found within the IL-3 gene which mediates the response to PMA/A23187. The enhancer sequence which responds to T cell activation signals may be located outside the IL-3 gene and may be shared by other lymphokines, possibly by GM-CSF. We propose that the GM-CSF enhancer (CLE2/GC box) which mediates the response to T cell activation signals may stimulate the expression of the IL-3 gene.
Human Sperm Tail Proteome Suggests New Endogenous Metabolic Pathways (2012)

Proteomic studies are contributing greatly to our understanding of the sperm cell, and more detailed descriptions are expected to clarify additional cellular and molecular sperm attributes. The aim of this study was to characterize the subcellular proteome of the human sperm tail and, hopefully, identify less concentrated proteins (not found in whole cell proteome studies). Specifically, we were interested in characterizing the sperm metabolic proteome and gaining new insights into the sperm metabolism issue. Sperm were isolated from normozoospermic semen samples and depleted of any contaminating leukocytes. Tail fractions were obtained by means of sonication followed by sucrose-gradient ultracentrifugation, and their purity was confirmed via various techniques. Liquid chromatography and tandem mass spectrometry of isolated sperm tail peptides resulted in the identification of 1049 proteins, more than half of which had not been previously described in human sperm. The categorization of proteins according to their function revealed two main groups: proteins related to metabolism and energy production (26%), and proteins related to sperm tail structure and motility (11%). Interestingly, a great proportion of the metabolic proteome (24%) comprised enzymes involved in lipid metabolism, including enzymes for mitochondrial beta-oxidation. Unexpectedly, we also identified various peroxisomal proteins, some of which are known to be involved in the oxidation of very long chain fatty acids. Analysis of our data using Reactome suggests that both mitochondrial and peroxisomal pathways might indeed be active in sperm, and that the use of fatty acids as fuel might be more preponderant than previously thought. In addition, incubation of sperm with the fatty acid oxidation inhibitor etomoxir resulted in a significant decrease in sperm motility. Contradicting a common concept in the literature, we suggest that the male gamete might have the capacity to obtain energy from endogenous pools, and thus to adapt to putative exogenous fluctuations.
Practical Lessons from Predicting Clicks on Ads at Facebook (2014)

Online advertising allows advertisers to only bid and pay for measurable user responses, such as clicks on ads. As a consequence, click prediction systems are central to most online advertising systems. With over 750 million daily active users and over 1 million active advertisers, predicting clicks on Facebook ads is a challenging machine learning task. In this paper we introduce a model which combines decision trees with logistic regression, outperforming either of these methods on its own by over 3%, an improvement with significant impact to the overall system performance. We then explore how a number of fundamental parameters impact the final prediction performance of our system. Not surprisingly, the most important thing is to have the right features: those capturing historical information about the user or ad dominate other types of features. Once we have the right features and the right model (decisions trees plus logistic regression), other factors play small roles (though even small improvements are important at scale). Picking the optimal handling for data freshness, learning rate schema and data sampling improve the model slightly, though much less than adding a high-value feature, or picking the right model to begin with.
Osmolyte Counteracts Urea-Induced Denaturation of α-Chymotrypsin (2009)

The stability of proteins is reduced by urea, which is methylamine and nonprotecting osmolyte; eventually urea destabilizes the activity and function and alters the structure of proteins, whereas the stability of proteins is raised by the osmolytes, which are not interfering with the functional activity of proteins. The deleterious effect of urea on proteins has been counteracted by methylamines (osmolytes), such as trimethylamine N-oxide (TMAO), betaine, and sarcosine. To distinctly enunciate the comparison of the counteracting effects between these methylamines on urea-induced denaturation of alpha-chymotrypsin (CT), we measured the hydrodynamic diameter (d(H)) and the thermodynamic properties (T(m), DeltaH, DeltaG(U), and DeltaC(p)) with dynamic light scattering (DLS) and differential scanning calorimeter (DSC), respectively. The present investigation compares the compatibility and counteracting hypothesis by determining the effects of methylamines and urea, as individual components and in combination at a concentration ratio of 1:2 (methylamine:urea) as well as various urea concentrations (0.5-5 M) in the presence of 1 M methylamine. The experimental results revealed that the naturally occurring osmolytes TMAO, betaine, and sarcosine strongly counteracted the urea actions on alpha-chymotrypsin. The results also indicated that TMAO counteracting the urea effects on CT was much stronger than betaine or sarcosine.
Anti-keratin antibodies in rheumatoid arthritis: frequency and correlation with other features of the disease. (1983)

Anti-keratin antibodies (AKA) were detected in 68 out of 98 patients (69%) with classical or definite rheumatoid arthritis (RA). The intensity of the AKA reaction correlated significantly with articular index (AI), grip strength (GS), erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) concentration, serum amyloid A (SAA) protein concentration, the level of antibodies against single stranded DNA (ssDNA) and the IgM rheumatoid factor (RF) titre. A significantly higher number of patients with nodules and Sjögren's syndrome were AKA positive compared with patients without extra-articular features (EAFs) and the AKA titre was significantly greater in the former group. The mechanisms underlying appearance of AKA are not known but may relate to an as yet unidentified structural alteration of keratin in this disease or may just reflect the rheumatoid autoimmune diathesis.
Functional Analysis of Ligand-Binding and Signal Transduction Domains of CD69 and CD23 C-Type Lectin Leukocyte Receptors (2000)

CD69 and CD23 are leukocyte receptors with distinctive pattern of cell expression and functional features that belong to different C-type lectin receptor subfamilies. To assess the functional equivalence of different domains of these structurally related proteins, a series of CD69/CD23 chimeras exchanging the carbohydrate recognition domain, the neck region, and the transmembrane and cytoplasmic domains were generated. Biochemical analysis revealed the importance of the neck region (Cys68) in the dimerization of CD69. Functional analysis of these chimeras in RBL-2H3 mast cells and Jurkat T cell lines showed the interchangeability of structural domains of both proteins regarding Ca2+ fluxes, serotonin release, and TNF-alpha synthesis. The type of the signal transduced mainly relied on the cytoplasmic domain and was independent of receptor oligomerization. The cytoplasmic domain of CD69 transduced a Ca2+-mediated signaling that was dependent on the extracellular uptake of Ca2+. Furthermore, a significant production of TNF-alpha was induced through the cytoplasmic domain of CD69 in RBL-2H3 cells, which was additive to that promoted via FcepsilonRI, thus suggesting a role for CD69 in the late phase of reactions mediated by mast cells. Our results provide new important data on the functional equivalence of homologous domains of these two leukocyte receptors.