gebhart/patrepeval huggingface dataset:
Some central effects of kynurenic acid, 7-chlorokynurenic acid and 5,7- dichloro-kynurenic acid, glycine site antagonists. (1995)

Strychnine-insensitive glycine site is one of a few binding sites of NMDA receptor complex. The aim of these study was to find out whether compounds regarded as glycine antagonists-kynurenic acid (KA), 7-chlorokynurenic acid (7-CKA), 5,7-dichlorokynurenic acid (5,7-DCKA) evoke the effects analogous to those of the NMDA receptor antagonist, CGP 37849 (or MK-801) and/or can modulate the effects of the last compounds in rats. KA (but not 7-CKA, given ip) inhibited electroshock-induced seizures and increased the anticonvulsant effect of CGP 37849. CGP 37849-induced locomotor hyperactivity was enhanced by KA, 7-CKA (icv but not ip) and 5,7-DCKA. D-Amphetamine-induced hyperactivity was inhibited by KA as well as 7-CKA. In monoamine-depleted rats 7-CKA (but not KA) increased the antiakinetic effect of clonidine; the antiakinetic effect of L-DOPA was enhanced by 7-CKA and 5,7-DCKA, but not by KA. KA and 7-CKA did not change the spiperone-induced catalepsy but they attenuated the anticataleptic effect of CGP 37849; the studied drugs did not change the anticataleptic effect of MK-801. 7-CKA given icv did not influence the spiperone-induced catalepsy as well as the anticataleptic effect of CGP 37849. In the forced swimming test KA, given once, prolonged (50 mg/kg) or did not change (200 and 300 mg/kg) the immobility time. 7-CKA did not affect the immobility time in this model. When given three times KA (200 mg/kg) and 7-CKA (20 mg/kg) reduced the immobility time; the lower doses of KA and 7-CKA prolonged or did not change the immobility time, respectively. Joint injection with imipramine and KA (or 7-CKA) induced the decrease of immobility time (vs imipramine alone or glycine antagonist alone); in the case of joint injection with citalopram + KA (or 7-CKA), the time of immobility was prolonged or not changed. In conclusion, the obtained results point to similarities between glycine antagonists (kynurenine derivatives) and CGP 37849 and to the possibility of positive cooperation between the NMDA- and glycine-sites antagonists.
Purification and Properties of Rat Liver Microsomal Stearyl Coenzyme A Desaturase (1974)

The terminal enzyme of the NADH-dependent stearyl coenzyme A desaturase system has been isolated from rat liver microsomes. This desaturase is a single polypeptide of 53,000 daltons containing 62% nonpolar amino-acid residues and one atom of non-heme iron. The purified protein forms high molecular weight aggregates that can be dispersed by detergent procedures. Desaturase activity requires NADH, stearyl coenzyme A, oxygen, lipid, and the three enzymes, cytochorme b(5) reductase (EC 1.6.2.2), cytochrome b(5), and desaturase. Cytochrome b(5) is the direct electron donor to the desaturase, which appears to utilize the iron in the oxidation-reduction sequence during desaturation of stearyl coenzyme A.
Eliminating helper phage from phage display (2006)

Phage display technology involves the display of proteins or peptides, as coat protein fusions, on the surface of a phage or phagemid particles. Using standard technology, helper phage are essential for the replication and assembly of phagemid particles, during library production and biopanning. We have eliminated the need to add helper phage by using 'bacterial packaging cell lines' that provide the same functions. These cell lines contain M13-based helper plasmids that express phage packaging proteins which assemble phagemid particles as efficiently as helper phage, but without helper phage contamination. This results in genetically pure phagemid particle preparations. Furthermore, by using constructs differing in the form of gene 3 that they contain, we have shown that the display, from a single library, can be modulated between monovalent (phagemid-like) and multivalent display (phage-like) without any further engineering. These packaging cells eliminate the use of helper phage from phagemid-based selection protocols; reducing the amount of technical preparation, facilitating automation, optimizing selections by matching display levels to diversity, and effectively using the packaged phagemid particles as means to transfer genetic information at an efficiency approaching 100%.
Tandem Radical Cyclisation Reactions for the Construction of Pseudocopsinine and Aspidosperma alkaloid models (1995)

A very simple and potentially valuable synthetic approach to indole alkaloids is described which utilises a 3+2 nitrone cycloaddition1 followed by a tandem radical cyclisation2.
Clinical trial: evaluation of gastric acid suppression with three doses of immediate‐release esomeprazole in the fixed‐dose combination of PN 400 (naproxen/esomeprazole magnesium) compared with naproxen 500 mg and enteric‐coated esomeprazole 20 mg: a randomized, open‐label, Phase I study in healthy volunteers (2010)

PN 400 containing 20 mg esomeprazole was the lowest dose to achieve gastric acid suppression comparable to EC esomeprazole 20 mg and was selected for further evaluation.
Characterization of a new minor lymphocyte stimulatory system. I. Cluster of self antigens recognized by "I-E-reactive" V beta s, V beta 5, V beta 11, and V beta 12 T cell receptors for antigen (1991)

In the mouse, two sets of V beta gene products have been shown to be associated with T cell recognition of endogenous self Ag. One of these is the set of V beta associated with T cell reactivities to stimulatory Mls gene products, Mlsa (V beta 6, V beta 8.1, V beta 9) or Mlsc (V beta 3); another is the set of V beta, such as V beta 5, V beta 11, V beta 12, or V beta 17a, which were originally found to be related to I-E recognition. Although the Mls system has been well characterized, little is known about the nature of the ligands for the second set of V beta. In this work, we describe the evidence that the natural ligand or ligands of V beta 5, V beta 11, and V beta 12 may be novel Mls determinants that are recognized by naive T cells at a high precursor frequency and function as the ligand for clonal deletion of self-reactive T cells by negative selection. However, surprisingly, unlike the conventional Mls system, in which all V beta associated with Mlsa recognition or Mlsc recognition are uniformly deleted in those animals expressing the relevant Mls type, expression of these three V beta segregates independently among strains. Based on these observations, the nature of T cell recognition for this new Mls gene product(s) is discussed.
Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling. (2002)

The formation of cranial bone requires the differentiation of osteoblasts from undifferentiated mesenchymal cells. The balance between osteoblast recruitment, proliferation, differentiation and apoptosis in sutures between cranial bones is essential for calvarial bone formation. The mechanisms that control human osteoblasts during normal calvarial bone formation and premature suture ossification (craniosynostosis) begin to be understood. Our studies of the human calvaria osteoblast phenotype and calvarial bone formation showed that premature fusion of the sutures in non-syndromic and syndromic (Apert syndrome) craniosynostoses results from precocious osteoblast differentiation. We showed that Fibroblast Growth Factor-2 (FGF-2), FGF receptor-2 (FGFR-2) and Bone Morphogenetic Protein-2 (BMP-2), three essential factors involved in skeletal development, regulate the proliferation, differentiation and apoptosis in human calvaria osteoblasts. Mechanisms that induce the differentiated osteoblast phenotype have also been identified in human calvaria osteoblasts. We demonstrated the implication of molecules (N-cadherin, Il-1) and signaling pathways (src, PKC) by which these local factors modulate human calvaria osteoblast differentiation and apoptosis. The identification of these essential signaling molecules provides new insights into the pathways controlling the differentiated osteoblast phenotype, and leads to a more comprehensive view in the mechanisms that control normal and premature cranial ossification in humans.
Suppression of RNA Interference by Adenovirus Virus-Associated RNA (2005)

We show that human adenovirus inhibits RNA interference (RNAi) at late times of infection by suppressing the activity of two key enzyme systems involved, Dicer and RNA-induced silencing complex (RISC). To define the mechanisms by which adenovirus blocks RNAi, we used a panel of mutant adenoviruses defective in virus-associated (VA) RNA expression. The results show that the virus-associated RNAs, VA RNAI and VA RNAII, function as suppressors of RNAi by interfering with the activity of Dicer. The VA RNAs bind Dicer and function as competitive substrates squelching Dicer. Further, we show that VA RNAI and VA RNAII are processed by Dicer, both in vitro and during a lytic infection, and that the resulting short interfering RNAs (siRNAs) are incorporated into active RISC. Dicer cleaves the terminal stem of both VA RNAI and VA RNAII. However, whereas both strands of the VA RNAI-specific siRNA are incorporated into RISC, the 3' strand of the VA RNAII-specific siRNA is selectively incorporated during a lytic infection. In summary, our work shows that adenovirus suppresses RNAi during a lytic infection and gives insight into the mechanisms of RNAi suppression by VA RNA.
Opening black boxes (2008)

Virtual-machine images are currently distributed as disk-image files, which are files that mirror the content of disks. This format is convenient for the virtual machine monitors that execute these images. However, it is not well-suited for administering images because storing images as disk-image files forces administrators to maintain the software on images with the same tools that they use to maintain the software on machines. Already, these tools cannot cope with physical server sprawl; in the future, because images can be snapshotted and cloned easily, enterprises that migrate from machines to images will need tools that scale to cope with the larger problem of virtual-machine image sprawl.To address this problem, this paper proposes the Mirage image format (MIF), a new storage format that exposes the rich semantic information currently buried in disk-image files. Disk-image files contain a mapping from file name to file content (and file metadata). MIF decouples this mapping into a manifest that maps file names to content descriptors (and file metadata) and a store that holds the content. Each image has its own manifest and a store may contain content for many images. As with disk-image files, images in MIF fully encapsulate application state including all software dependences. In addition, conversion between MIF and traditional disk-image formats is easy.This paper shows, through examples, that MIF makes some typical software management tasks--inventory control, customized deployment, and image update--faster and easier. The general technique is to operate on manifests instead of on content whenever possible. These tasks can be performed without starting images and, because manifests are simpler and orders of magnitude smaller than disk-image files, without accessing large amounts of data.
Weighted least squares training of support vector classifiers leading to compact and adaptive schemes (2001)

An iterative block training method for support vector classifiers (SVCs) based on weighted least squares (WLS) optimization is presented. The algorithm, which minimizes structural risk in the primal space, is applicable to both linear and nonlinear machines. In some nonlinear cases, it is necessary to previously find a projection of data onto an intermediate-dimensional space by means of either principal component analysis or clustering techniques. The proposed approach yields very compact machines, the complexity reduction with respect to the SVC solution is especially notable in problems with highly overlapped classes. Furthermore, the formulation in terms of WLS minimization makes the development of adaptive SVCs straightforward, opening up new fields of application for this type of model, mainly online processing of large amounts of (static/stationary) data, as well as online update in nonstationary scenarios (adaptive solutions). The performance of this new type of algorithm is analyzed by means of several simulations.
BIOCHEMICAL STUDIES ON INOSITOL (1957)

Apart from its incorporation into various lipides, the metabolic fate of inositol in the mammalian organism is still unknown.The observation of 'Stetten and Stetten (1) that deuterium from administered labeled inositol could be recovered in the urinary glucose of phlorizinized rats showed that inositol is metabolized in the rat.This was confirmed and extended by Posternak et al. ( 2).During our studies of the biosynthesis of myo-inositol' by mammalian and microbial systems (3-5), it was observed that homogenates from various rat tissues catalyze a rapid utilization of inositol with simultaneous formation of reducing substances.With use of an enzyme preparation from rat, kidney, we have studied this reaction in detail and have shown that inositol is converted to glucuronic acid.The present paper deals with the identification and isolation of glucuronic acid as the cleavage product resulting from the action of the kidney enzyme system on inositol.The crystalline glucuronic acid was found to be optically inactive, indicating that it, is the racemic form.EXPERIMENTAL
A simpler sort of antibody. (1994)

The monoclonal antibody NEMO is directed against a molecule expressed by human cells of the melanocytic lineage. Although obtained by conventional immunization and fusion procedures, NEMO consists solely of kappa light chain. SDS/PAGE analysis indicates that the kappa chains are present as both monomers and dimers. When these two forms were separated by gel filtration, only the monomeric form bound antigen. As kappa light chains from the myeloma MOPC-41 and the hybridoma MORK do not bind to the melanocytic cells, we conclude that the binding specificity of NEMO resides in the variable region.
"Where did we go wrong?" An examination of students treatment of experimental error in engineering mechanics laboratories (2008)

The ability of engineers and applied scientists to undertake experimental measurements is a fundamental requirement of the profession. However, it is not simply good enough to be able to perform experiments if we are not able to interpret the results. In this study, reports prepared by mechanical engineering students were examined to determine how students dealt with the disparity between experimental measurements and theoretical results in their Engineering Mechanics laboratories. Analysis of the reports, and discussions with students in their laboratory classes, revealed a superficial understanding or regard for experimental error. This superficial treatment of experimental error is, most likely, due to a number of factors that are discussed. Some possible strategies for addressing the issue are also examined.
Anti-miRs Competitively Inhibit microRNAs in Argonaute Complexes (2014)

MicroRNAs (miRNAs), small RNA molecules that post-transcriptionally regulate mRNA expression, are crucial in diverse developmental and physiological programs and their misregulation can lead to disease. Chemically modified oligonucleotides have been developed to modulate miRNA activity for therapeutic intervention in disease settings, but their mechanism of action has not been fully elucidated. Here we show that the miRNA inhibitors (anti-miRs) physically associate with Argonaute proteins in the context of the cognate target miRNA in vitro and in vivo. The association is mediated by the seed region of the miRNA and is sensitive to the placement of chemical modifications. Furthermore, the targeted miRNAs are stable and continue to be associated with Argonaute. Our results suggest that anti-miRs specifically associate with Argonaute-bound miRNAs, preventing association with target mRNAs, which leads to subsequent stabilization and thus increased expression of the targeted mRNAs.
Improving multiple removal using least-squares dip filters and independent component analysis (2011)

ABSTRACT The suppression of multiple events is a crucial task in seismic data processing, and the adaptive subtraction of the predicted multiples is recognized as one of the main challenges for the success of the surface-related multiple elimination technique. The traditional least-squares matching approach can affect the primary events because the estimated multiples tend to adapt to the primaries under the minimum energy condition. We investigate two filtering techniques for improving the multiple removal results. In the first proposed method, we combine the advantages of the least-squares and pattern dip-based subtraction methods. Doing so, we exploit the separation of primaries and multiples in the dip domain, and then we apply the least-squares adaptive subtraction in each dip band before recomposing the data to obtain the final subtraction result. As a result of the dip decomposition, the primary-multiple interferences are reduced, allowing for a more reliable least-squares filtering. In the second method, we propose to replace the multiple subtraction step by a separation step using independent component analysis (ICA) methods. We employ the ICA method after least-squares adaptive filtering. Because of the non-Gaussian distributions of the involved signals, primaries and multiples can be separated by computing the optimal rotation between these two signals. We apply the ICA method in local 2D time-space windows to better compensate the space and time variant character of the data. Two-dimensional synthetic and field data examples demonstrate that the multiple subtraction results of both methods are indeed improved with respect to the classical least-squares method.
Characterization of a Novel Glucose-Responsive Insulin-Secreting Cell Line, BRIN-BD11, Produced by Electrofusion (1996)

A novel insulin-secreting cell line (BRIN-BD11) was established after electrofusion of RINm5F cells with New England Deaconess Hospital rat pancreatic islet cells. Wells of cell fusion mixture with insulin output 5-10 times greater than parent RINm5F cells were subcultured with eventual establishment of clones, including BRIN-BD11. Morphological studies established that these cells grow as monolayers with epithelioid characteristics, maintaining stability in tissue culture for > 50 passages. Culture of these cells for 24 h at 5.6-33.3 mmol/l glucose revealed a 1.8- to 2.0-fold increase of insulin output compared with 1.4 mmol/l glucose. Dynamic insulin release was recorded in response to 16.7 mmol/l glucose, resulting in a rapid threefold insulin secretory peak followed by a sustained output slightly above basal. In acute 20-min tests, 4.2-16.7 mmol/l glucose evoked a stepwise two- to three-fold stimulation of insulin release. 3-Isobutyl-1-methylxanthine (1 mmol/l) served to increase basal and glucose-stimulated insulin release, shifting the threshold from 4.4 to 1.1 mmol/l glucose. Stimulation of insulin secretion with 16.7 mmol/l glucose was abolished by mannoheptulose or diazoxide (15 or 0.5 mmol/l). In contrast, glyceraldehyde (10 mmol/l) and 25 mmol/l K+ evoked 1.7- to 9.0-fold insulin responses. L-Alanine (10 mmol/l) evoked a twofold secretory response, which was potentiated 1.4-fold by increasing the Ca2+ concentration from 1.28 to 7.68 mmol/l. Forskolin (25 mumol/l) and phorbol 12-myristate 13-acetate (10 nmol/l) both increased insulin secretion in the presence of L-alanine (1.4- and 1.8-fold, respectively). Western blotting confirmed that BRIN-BD11 cells expressed the GLUT2 glucose transporter. This, coupled with a high glucokinase/hexokinase ratio in the cells, confirms an intact glucose sensing mechanism. High-performance liquid chromatography analysis demonstrated that insulin was the major product secreted under stimulatory conditions. Collectively, these data indicate that the BRIN-BD11 cell line represents an important stable glucose-responsive insulin-secreting beta-cell line for future studies.
Proton-dependent multidrug efflux systems (1996)

Multidrug efflux systems display the ability to transport a variety of structurally unrelated drugs from a cell and consequently are capable of conferring resistance to a diverse range of chemotherapeutic agents. This review examines multidrug efflux systems which use the proton motive force to drive drug transport. These proteins are likely to operate as multidrug/proton antiporters and have been identified in both prokaryotes and eukaryotes. Such proton-dependent multidrug efflux proteins belong to three distinct families or superfamilies of transport proteins: the major facilitator superfamily (MFS), the small multidrug resistance (SMR) family, and the resistance/ nodulation/cell division (RND) family. The MFS consists of symporters, antiporters, and uniporters with either 12 or 14 transmembrane-spanning segments (TMS), and we show that within the MFS, three separate families include various multidrug/proton antiport proteins. The SMR family consists of proteins with four TMS, and the multidrug efflux proteins within this family are the smallest known secondary transporters. The RND family consists of 12-TMS transport proteins and includes a number of multidrug efflux proteins with particularly broad substrate specificity. In gram-negative bacteria, some multidrug efflux systems require two auxiliary constituents, which might enable drug transport to occur across both membranes of the cell envelope. These auxiliary constituents belong to the membrane fusion protein and the outer membrane factor families, respectively. This review examines in detail each of the characterized proton-linked multidrug efflux systems. The molecular basis of the broad substrate specificity of these transporters is discussed. The surprisingly wide distribution of multidrug efflux systems and their multiplicity in single organisms, with Escherichia coli, for instance, possessing at least nine proton-dependent multidrug efflux systems with overlapping specificities, is examined. We also discuss whether the normal physiological role of the multidrug efflux systems is to protect the cell from toxic compounds or whether they fulfil primary functions unrelated to drug resistance and only efflux multiple drugs fortuitously or opportunistically.
Multi-Antenna Broadcast Channels with Limited Feedback and User Selection (2006)

We analyze the sum-rate performance of a multi-antenna downlink system carrying more users than transmit antennas, with partial channel knowledge at the transmitter due to finite rate feedback. In order to exploit multiuser diversity, we show that the transmitter must have, in addition to directional information, information regarding the quality of each channel. Such information should reflect both the channel magnitude and the quantization error. Expressions for the SINR distribution and the sum-rate are derived, and tradeoffs between the number of feedback bits, the number of users, and the SNR are observed. In particular, for a target performance, having more users reduces feedback load.
Antitumor Efficacy of a Combination of CMC-544 (Inotuzumab Ozogamicin), a CD22-Targeted Cytotoxic Immunoconjugate of Calicheamicin, and Rituximab against Non-Hodgkin's B-Cell Lymphoma (2006)

The demonstration of superior antitumor activity of a combination of CMC-544 and rituximab described here provides the preclinical basis for its clinical evaluation as a treatment option for B-NHL.