gebhart/patrepeval huggingface dataset:
Susceptibility of Fanconi's anemia lymphoblasts to DNA-cross-linking and alkylating agents. (1982)

In order to develop the usefulness of Fanconi's anemia (FA) lymphoblast lines for biochemical and genetic studies, we have determined their sensitivity to a variety of DNA-damaging chemicals. We have adapted a growth inhibiton protocol in which the sensitivity of a cell line is characterized by the drug concentration yielding a 50% inhibiton of growth (EC50). The DNA-cross-linking agents, mitomycin C, nitrogen mustard, melphalan, 1,3-butadiene diepoxide, cis-diaminedichloroplatinum(II), and cyclophosphamide, were all more toxic to four FA cell lines than to five normal lines. Three lines, HSC 72 (FA), 99 (FA) and 230 (FA), had EC50s that were 10 to 20 times lower than that of controls while the fourth line, HSC 62 (FA), had an intermediate EC50. Three nitrosourea compounds were also more toxic to FA cells than to controls. However, 2 normal cell lines (HSC 92 and 93) had nitrosourea EC50s 4 to 7 times lower than the other nine controls and overlapped the sensitivity of the intermediate [HSC 62 (FA)] cell line. The same 2 normal cell lines were also more sensitive than 12 other controls, including FA heterozygotes, xeroderma pigmentosum, and ataxia telangiectasis, to the monofunctional alkylating agents, ethyl methane sulfonate, methyl methane sulfonate, and N-methyl-N'-nitro-N-nitrosoguanidine. Heterogeneity was also found with FA lines. Two FA cell lines (HSC 72 and 230) had EC50s lower than all control lines while one FA line (HSC 99) had an EC50 similar to that of the resistant normal lines. FA and normal cells had nearly the same sensitivity to 4-nitroquinoline-1-oxide and bleomycin. These results demonstrate that FA lymphoblast lines are more sensitive than normal cell lines to all DNA-cross-linking agents examined. These cell lines should therefore be useful for the analysis of DNA cross-link repair and the biochemical defect in FA. We have also found an unexpected sensitivity of some FA and normal lines to monofunctional alkylating agents.
Phenotype and Genotype of Advanced Premalignant Head and Neck Lesions After Chemopreventive Therapy (1998)

Our data suggest that clinical and histologic assessments of the response to chemopreventive agents may be insufficient to determine their efficacy and that critical genetic alterations could be used as independent biomarkers to augment the ability to evaluate the efficacy of such agents.
A beta-galactosidase hybrid protein targeted to nuclei as a marker for developmental studies. (1987)

The Escherichia coli lacZ gene has been used as an indicator gene for the study of cell lineage in vivo. To adapt this marker for gene expression studies, a sequence encoding a modified beta-galactosidase and including the simian virus 40 large tumor nuclear location signal (nls-beta-Gal) has been introduced into vectors. In differentiated cells, multipotential cells, and embryos, the constructs led to the expression of an enzymatically active protein. Its location was examined by its beta-galactosidase activity or by using antibodies and electron microscopy. The results show that the nls-beta-Gal protein remains mainly located at the nuclear periphery (probably at the nuclear pores) but does not reach the nucleoplasm. It suggests that an interaction with the nuclear membrane is necessary but not sufficient for protein uptake into the nucleus. In multipotential cells, the expression of nuclear location signal LacZ (nls-LacZ) interferes neither with cell growth nor with differentiation. Using various lacZ constructs, the transcriptional activity of embryos was studied. At the two-cell stage, the promoters of the Rous sarcoma virus, simian virus 40, and the beta-actin gene are functional but the Moloney murine leukemia virus long terminal repeat is not. Thus, transcriptional specificity must already be present at the stage of activation of the embryonic genome.
Partial Reduction of Human FOXP3+ CD4 T Cells In Vivo After CD25-directed Recombinant Immunotoxin Administration (2008)

The regulation of tolerance to self-proteins and the suppression of T-cell responses have in part been attributed to the activity of CD25+CD4+ T regulatory (Treg) cells. Further, Treg cells can inhibit the antitumor effectiveness of adoptive immunotherapy and active immunization approaches in preclinical models. In an effort to selectively eliminate Treg cells from human peripheral blood mononuclear cell to potentially bolster antitumor responses, we have evaluated the Treg-cell depleting capacity of the CD25-directed immunotoxin, RFT5-SMPT-dgA. In preclinical studies, incubation of human peripheral blood mononuclear cell with RFT5-SMPT-dgA mediated a partial reduction in the levels of CD25+, Foxp3-expressing CD4+ T cells in vitro. Administration of RFT5-SMPT-dgA to 6 patients with metastatic melanoma induced a transient but robust reduction in the number of CD25high CD4 T cells in vivo (a 97.5% mean reduction at nadir; from 69.4 +/- 12.4 cells/miroL to 1.7 +/- 0.3 cells/microL). The reduction in FOXP3+ CD4 T-cell number was less comprehensive (a 71.3% mean reduction at nadir; from 66.6 +/- 16.5 cells/microL to 14.2 +/- 3.9 cells/tL). This resulted in the selective persistence of a stable number of CD25(low/neg) FOXP3+ CD4+ T cells in vivo. No objective antitumor responses were seen in any patient. Our results indicate that the CD25-directed, RFT5-SMPT-dgA immunotoxin can mediate a transient, partial reduction in Treg-cell frequency and number in vitro and in vivo and suggest that comprehensive eradication of human Treg cells in vivo may require the ability to target and eliminate FOXP3+ CD4+ T cells expressing both high and low levels of CD25.
Reduced Retinoic Acid-Sensitivities of Nuclear Receptor Corepressor Binding to PML- and PLZF-RARα Underlie Molecular Pathogenesis and Treatment of Acute Promyelocytic Leukemia (1998)

Typical acute promyelocytic leukemia (APL) is associated with expression of the PML-RARalpha fusion protein and responsiveness to treatment with all-trans retinoic acid (ATRA). A rare, but recurrent, APL has been described that does not respond to ATRA treatment and is associated with a variant chromosomal translocation and expression of the PLZF-RARalpha fusion protein. Both PML- and PLZF-RARalpha possess identical RAR sequences and inhibit ATRA-induced gene transcription as well as cell differentiation. We now show that the above-mentioned oncogenic fusion proteins interact with the nuclear receptor corepressor N-CoR and, in comparison with the wild-type RARalpha protein, their interactions display reduced sensitivities to ATRA. Although pharmacologic concentration of ATRA could still induce dissociation of N-CoR from PML-RARalpha, it had a very little effect on its association with the PLZF-RARalpha fusion protein. This ATRA-insensitive interaction between N-CoR and PLZF-RARalpha was mediated by the N-terminal PLZF moiety of the chimera. It appears that N-CoR/histone deacetylase corepressor complex interacts directly in an ATRA-insensitive manner with the BTB/POZ-domain of the wild-type PLZF protein and is required, at least in part, for its function as a transcriptional repressor. As the above-noted results predict, histone deacetylase inhibitors antagonize oncogenic activities of the PML-RARalpha fusion protein and partially relieve transcriptional repression by PLZF as well as inhibitory effect of PLZF-RARalpha on ATRA response. Taken together, our results demonstrate involvement of nuclear receptor corepressor/histone deacetylase complex in the molecular pathogenesis of APL and provide an explanation for differential sensitivities of PML- and PLZF-RARalpha-associated leukemias to ATRA.
Performance evaluation of high-power wide band-gap semiconductor rectifiers (1999)

Applicability of GaN in unipolar and bipolar devices for high-power electronic applications is evaluated with respect to similar devices based on other materials. Specific resistance is used as a measure of unipolar performance. In order to evaluate bipolar performance, 700 and 6000 V p-i-n diodes based on Si, 6H-SiC, and GaN are compared with respect to forward conduction and reverse recovery performance at room temperature and high-temperature conditions. It is shown that GaN is advantageous not only for high voltage unipolar applications, but also for bipolar applications. An empirical closed-form expression is presented to predict the avalanche breakdown voltage of wide band-gap semiconductors. Formulation of the expression is based on an approximation of the impact ionization coefficient in terms of seventh power of the electric field.
Functionally distinct agretopic and epitopic sites. Analysis of the dominant T cell determinant of moth and pigeon cytochromes <i>c</i> with the use of synthetic peptide antigens. (1987)

The dominant T cell determinant on moth and pigeon cytochromes c in B10.A (E beta k:E alpha k) mice is located in the C-terminal portion of the protein, contained within residues 93-103 or 93-104. Thirty-seven antigen analogs, containing single amino acid substitutions at positions 98, 99, 101, 102, 103, and 104, were synthesized. The effects of the substitutions on in vitro antigenicity and in vivo immunogenicity were determined. Functional assays with T cell clones identified residues 99, 101, 102, and 103 as critical, based on their effect on antigenic potency. Peptides containing substitutions at residues 99, 101, and 102 were capable of eliciting unique clones upon immunization of B10.A mice. This was consistent with the identification of these residues as part of the epitope, the site on the antigen that interacts with the T cell receptor. Immunization with peptides substituted at residue 103, however, failed to elicit clones with unique specificity for the immunogen. When these peptides were tested for their ability to stimulate the T cell clones with antigen-presenting cells from B10.A(5R) mice expressing the E beta b:E alpha k Ia molecule, a consistent change in the relative antigenic potency was observed with 50% of the peptides. The effect of the Ia molecule on the antigenic potency ruled out the possibility that residue 103 nonspecifically affected antigen uptake or processing and identified residue 103 as part of the agretope, the site that interacts with the Ia molecule. The locations of the agretope and the epitope on this antigenic determinant appear to be fixed, even in the presence of large numbers of amino acid substitutions. However, some substitutions were found to affect both the agretope and the epitope, placing limits on the functional independence of the two sites. The results are discussed in terms of the trimolecular complex model of T cell activation and the implications of these data for antigen-Ia molecule interactions.
Monte Carlo Statistical Methods (2000)

Douc pointed out typos and mistakes in the French version, but should not be held responsible for those remaining!Part of Chapter 8 has a lot of common with a "reviewww" written by Christian Robert with Chantal Guihenneuc-Jouyaux and Kerrie Mengersen for the Valencia Bayesian meeting (and the Internet!).The input of the French working group "MC Cube," whose focus is on convergence diagnostics, can also be felt in several places of this book.Wally Gilks and David Spiegelhalter granted us permission to use their graph (Figure 2.3.1) and examples as Problems 7.44-7.55,for which we are grateful.Agostino Nobile kindly provided the data on which Figures 7.3.2and 7.3.2are based.Finally, Arnoldo Frigessi (from Roma) made the daring move of teaching (in English) from the French version in Olso, Norway
Costs of carbon dioxide removal by underground storage (2001)

A methodology and calculation tool is developed to estimate costs of CO{sub 2} removal projects in the Netherlands. For three types of emission sources and four types of storage locations, the costs of CO{sub 2} removal scenarios, i.e. total costs for recovery, compression, transport and storage for concrete projects, are determined. The recovery options considered are separation of CO{sub 2} from flue gases of a natural gas fired combined cycle power plant from the flue gases of an oil refinery furnace combined with a combined heat and power unit, and the recovery of nearly pure CO{sub 2} streams from ammonia and hydrogen production. Storage options considered are onshore and offshore aquifers, empty natural gas fields and empty oil fields. In general, costs of CO{sub 2} removal are dominated by recovery costs although transport and compression costs are substantial. 6 refs., 2 figs., 7 tabs.
Sodium hyaluronate eye drops in the treatment of dry eye disease: an open label, uncontrolled, multi-centre trial. (2014)

Sodium hyaluronate has a beneficial effect on the conjunctival epithelium in a well-defined and homogeneous population of patients with dry eye and can be considered useful for the treatment of dry eye.
Synthesis of Chiral 3-Substituted Phthalides by a Sequential Organocatalytic Enantioselective Aldol-Lactonization Reaction. Three-Step Synthesis of (<i>S</i>)-(−)-3-Butylphthalide (2009)

The development of efficient methods for the facile construction of important molecular frameworks is an important goal in organic synthesis. Chiral 3-substituted phthalides are widely distributed in a large collection of natural products with broad, potent, and potentially path-pointing biological activities. In this investigation, we have uncovered an unprecedented organocatalytic asymmetric aldol-lactonization reaction of 2-formylbenzoic esters with ketones/aldehydes for convenient construction of the enantioenriched "privileged" scaffold. As a result of the sensitive nature of substrate structures of an organocatalytic enantioselective aldol reaction, after extensive optimization of reaction conditions, catalyst L-prolinamide alcohol IV is identified as the best promoter. Interestingly, it is found that in this reaction, addition of an acid additive PhCO(2)H can significantly enhance reaction efficiency with use of only as low as 2.5 mol % IV for the process. Moreover, due to the sensitivity of reaction conditions toward a sequential aldol-lactonization process without affecting enantioselectivity and racemization, it is essential to remove the catalyst for the subsequent facile lactonization reaction in the presence of K(2)CO(3). The aldol-lactonization processes serve as a powerful approach to the preparation of synthetically and biologically important 3-substituted phthalides with a high level of enantioselectivities. A 3-step catalytic asymmetric synthesis of the natural product of 3-butylphthalide is reported.
Accuracy and Dynamics of Multi-Stage Load Balancing for Multipath Internet Routing (2007)

Flow-based load balancing algorithms for multipath Internet routing are often used for traffic engineering. However, the target load distribution and the load balanced result agree only on average, and there is a significant inaccuracy over time due to stochastic effects. Dynamic load balancing reduces this inaccuracy by relocating flows to other paths in regular time intervals. This causes packet reordering. Therefore, the flow reassignment rate should be kept low. In this paper we consider load balancing in networks. It differs from load balancing at a single node by the fact that several load balancing steps may be performed at consecutive nodes in series. This affects the flow reassignment rate and the load balancing accuracy due to interdependencies and polarization effects. We quantify the impact by simulation results, explain the observed phenomena, and give recommendations for load balancing in practice.
Properties and Roles of the Three Subclasses of Histamine Receptors in Brain (1986)

In brain, histamine (HA) is the transmitter of a neuronal system resembling other monoaminergic systems. It is also present in mast cells from which it may control vascular and inflammatory processes. Its various actions are mediated not only by the two well known H1- and H2-receptor subclasses but also by the recently discovered H3-receptors, with distinct localization and pharmacology. H1-receptors mediate a series of biochemical responses which have several features in common: they require intact cells to be observed and largely depend upon the availability of Ca2+. H1-receptor-mediated responses include glycogenolysis, stimulation of cyclic GMP formation, potentiation of cyclic AMP formation. Recent studies indicate that H1-receptors are linked with phosphatidylinositol breakdown and generation of two intracellular signals which both contribute to the final response (e.g. in the cyclic AMP generation). H2-receptors seem to be directly linked with an adenylate cyclase and their stimulation results in enhanced electrophysiologically recorded responses to excitatory agents. Finally whereas H1- and H2-receptors appear to be postsynaptically located, a novel subclass (H3) of HA receptors was recently revealed with a presynaptic localization. H3-receptors are autoreceptors mediating inhibition of HA release from and biosynthesis in histaminergic nerve terminals in the CNS. The physiological and pharmacological implications of three distinct receptor subclasses for HA will be discussed.
Glyphosate-Tolerant Corn:  The Composition and Feeding Value of Grain from Glyphosate-Tolerant Corn Is Equivalent to That of Conventional Corn (<i>Zea </i><i>mays</i> L.) (2000)

Glyphosate-tolerant (Roundup Ready) corn line GA21 has been developed by genetic modification to tolerate glyphosate, the active ingredient in Roundup herbicide. The purpose of this study was to evaluate the compositional and nutritional safety of corn line GA21 compared to that of conventional corn. Compositional analyses were conducted to measure proximate, fiber, amino acid, fatty acid, and mineral contents of grain and proximate, fiber, and mineral contents of forage collected from 16 field sites over two growing seasons. The nutritional safety of corn line GA21 was evaluated in a poultry feeding study conducted with 2-day old, rapidly growing broiler chickens, at a dietary concentration of 50-60% w/w. Compositional analysis results showed that, except for a few minor differences that are unlikely to be of biological significance, the grain and forage of GA21 corn were comparable in their composition to that of the control corn line and to conventional corn. Results from the poultry feeding study showed that there were no differences in growth, feed efficiency, adjusted feed efficiency, and fat pad weights between chickens fed with GA21 grain or with parental control grain. These data taken together demonstrate that Roundup Ready corn is as safe and nutritious as conventional corn for food and feed use.
High-throughput beamforming receiver for millimeter wave mobile communication (2013)

In this paper, we present a novel FPGA-based high-throughput beamforming MIMO receiver for millimeter wave mobile communication. With vast spectrum and small antenna element size, millimeter wave communication becomes very attractive and promising to support next generation mobile communication (5G). However, the high data rate requirement challenges both algorithm and architecture. In order to support the high data rate and to reduce the overhead of selecting the best beam pair, we propose a novel beamforming synchronization scheme more suitable for mobile communication. By further optimizing the algorithm and the architecture, we present a complete mobile receiver based on FPGA, which includes RF frontend, ADC, beamforming control, synchronization, channel estimator, soft MAP detector, and channel decoder. The design operates at 28 GHz carrier frequency with 500 MHz bandwidth. The throughput can reach 1.52 Gbps. We also performed the indoor and outdoor over-the-air transmission field tests. This work provides a platform for future millimeter wave mobile communication research.
IL-32: An Emerging Player in the Immune Response Network against Tuberculosis? (2006)

IL-32 has emerged as an important player in innate and adaptive immune responses. Kundu and Basu discuss a new study in PLoS Medicine that explored the role of IL-32 in the context of M. tuberculosis infection.
Neural network architecture for online system identification and adaptively optimized control (2002)

A neural network architecture for simultaneous system identification and adaptively optimized control is presented. Basic ingredients consisting of tapped delay lines and standard analog neurons (with backpropagation) are combined within a modular/hierarchical architecture to implement an MRAC scheme having rigorous stability and convergence properties. Control adaptation is carried out in the presence of unknown (and possibly persistent) plant disturbances and instrumentation noise and requires no built-in modeling information. The overall adaptive neural controller is composed of a system replicator network and the control adaptor network. With no prior information, the system replicator autonomously builds an internal model of the plant, effectively identifying the plant within the closed loop. Simultaneously, this internal model is used by the control adaptor to adapt the online dynamic compensation so that the closed-loop input/output characteristics match those of the ideal refractive system. The efficacy of the proposed approach is illustrated by several numerical examples involving vibration control for precision space structures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Expression of the <i>Escherichia coli pntA</i> and <i>pntB</i> Genes, Encoding Nicotinamide Nucleotide Transhydrogenase, in <i>Saccharomyces cerevisiae</i> and Its Effect on Product Formation during Anaerobic Glucose Fermentation (1999)

We studied the physiological effect of the interconversion between the NAD(H) and NADP(H) coenzyme systems in recombinant Saccharomyces cerevisiae expressing the membrane-bound transhydrogenase from Escherichia coli. Our objective was to determine if the membrane-bound transhydrogenase could work in reoxidation of NADH to NAD+ in S. cerevisiae and thereby reduce glycerol formation during anaerobic fermentation. Membranes isolated from the recombinant strains exhibited reduction of 3-acetylpyridine-NAD+ by NADPH and by NADH in the presence of NADP+, which demonstrated that an active enzyme was present. Unlike the situation in E. coli, however, most of the transhydrogenase activity was not present in the yeast plasma membrane; rather, the enzyme appeared to remain localized in the membrane of the endoplasmic reticulum. During anaerobic glucose fermentation we observed an increase in the formation of 2-oxoglutarate, glycerol, and acetic acid in a strain expressing a high level of transhydrogenase, which indicated that increased NADPH consumption and NADH production occurred. The intracellular concentrations of NADH, NAD+, NADPH, and NADP+ were measured in cells expressing transhydrogenase. The reduction of the NADPH pool indicated that the transhydrogenase transferred reducing equivalents from NADPH to NAD+.
Determination of Ideal Broth Formulations Needed to Prepare Hydrous Aluminum Oxide Microspheres via the Internal Gelation Process (2009)

A simple test-tube methodology was used to determine optimum process parameters for preparing hydrous aluminum oxide microspheres by the internal gelation process. Broth formulations of aluminum, hexamethylenetetramine, and urea were found that can be used to prepare hydrous aluminum oxide gel spheres in the temperature range of 60-90 C. A few gel-forming runs were made in which microspheres were prepared with some of these formulations in order to equate the test-tube gelation times with actual gelation times. These preparations confirmed that the test-tube methodology is reliable for determining the ideal broths.