gebhart/patrepeval huggingface dataset:
Antiepileptic drug discovery: lessons from the past and future challenges (2005)

Historically, most antiepileptic drugs (AEDs) have been discovered either by serendipity, or the screening of compounds using acute seizure models. However, an increasing understanding of the molecular mechanisms underlying epileptogenesis has led to more rational approaches to drug discovery, which have focused on either enhancing inhibitory gamma-amino butyric acid (GABA)-ergic, or antagonizing excitatory glutamatergic, neurotransmission. Unfortunately, AEDs generated using such strategies have poor efficacy and safety profiles, as they interfere with normal cell processes, while ignoring the complex underlying pathophysiology of epilepsy. Recently, however, the use of new epilepsy models has led to the discovery of levetiracetam, an AED with a truly unique mechanism of action, devoid of anticonvulsant activity in normal animals, but with potent seizure suppression in genetic and kindled chronic epilepsy models, and an unusually high safety margin. The recent identification of brivaracetam and seletracetam, which optimize this unique mechanism of action, may further improve the medical management of epilepsy. The experience with levetiracetam, brivaracetam and seletracetam reveals that new experimental epilepsy models can detect AEDs possessing a unique mechanism of action and thereby target the future challenge of providing clinicians novel additions to the current armamentarium of AEDs.
Identifying Gut Microbe–Host Phenotype Relationships Using Combinatorial Communities in Gnotobiotic Mice (2014)

Identifying a scalable, unbiased method for discovering which members of the human gut microbiota influence specific physiologic, metabolic, and immunologic phenotypes remains a challenge. We describe a method in which a clonally arrayed collection of cultured, sequenced bacteria was generated from one of several human fecal microbiota samples found to transmit a particular phenotype to recipient germ-free mice. Ninety-four bacterial consortia of diverse size, randomly drawn from the culture collection, were introduced into germ-free animals. We identified an unanticipated range of bacterial strains that promoted accumulation of colonic regulatory T cells (T(regs)) and expansion of Nrp1(lo/-) peripheral T(regs), as well as strains that modulated mouse adiposity and cecal metabolite concentrations, using feature selection algorithms and follow-up monocolonizations. This combinatorial approach enables a systems-level understanding of microbial contributions to human biology.
Chromatid contamination can impair the purity of flow‐sorted metaphase chromosomes (1993)

We describe a phenomenon where a second flow karyotype is superimposed on the normal metaphase flow karyotype of human lymphoblastoid chromosomes. The events of this second flow karyotype contain half the DNA content of corresponding events in the normal flow karyotype and, when sorted, show the morphology of single chromatids. DNA amplified by degenerate oligonucleotide-primed PCR of 300 chromatids sorted from a single peak and hybridized onto normal metaphase spreads painted the entire length of the corresponding chromosome type. In retrospect, we could observe this phenomenon at a low level in 37% of randomly selected, previously analyzed flow karyotypes and in several published flow karyotypes from other laboratories. Experimentally, chromatid frequency was shown to vary with the colcemid blocking conditions as well as with the cell line used. At the extreme, we obtained a 4:10 ratio of chromatids to metaphase chromosomes, whereas this could be reduced tenfold by altering the colcemid blocking conditions in the same cell line. The presence of chromatids in chromosome preparations has important implications for the purity of isolated fractions used for generating libraries and in PCR analysis.
Atomic spectrometry update. Clinical and biological materials, foods and beverages (2003)

This ASU reviews publications that appeared in the twelve months up to the end of October 2002. The writers found there to be an interesting collection of publications and enjoyed the opportunity to review current analytical activity for clinical and biological materials, foods and beverages. It was noted that Chinese-based scientists are responsible for much of the innovations that we have reported in this Update. This year has seen tremendous growth in the employment of permanent chemical modifiers for electrothermal atomisers. Rhodium was introduced for the measurement of selenium, just a couple of years ago, and now it is looking as if it may displace palladium as the modifier of choice for this and many other determinations. The writers were impressed by an unusual device that produced a dry ‘aerosol’, allowing the transfer of solid powdered material into a quartz tube mounted above a flame burner head. As the sample had to be reduced in size to a very fine powder it is unlikely that the technique will gain widespread popularity but the idea in principle appears very clever. Similarly, the use of ICP-mass spectrometry as a measurement technique for immunoassay, while novel, does not appear to be very practical when an assay can involve several hundred measurements. A number of intriguing papers were noted. We were impressed by the subjects who participated in studies of dermal penetration of nickel compounds—these individuals had sticky tape placed on the skin, which was then pulled off together with underlying cells; this procedure was then repeated up to 20 times. We pondered over a method that involved formation of SeH2, which was oxidised to Se0 and trapped on a hot gold wire. After a trapping period of up to 5 min the Se0 was released for hydride formation and measurement. The English expression “takes the biscuit” came to mind as we puzzled with an even more remarkable report of the measurement of iron and manganese in biscuits by a cold vapour technique! After which, the revelation that camels’ milk is an ideal nutrient caused barely a second thought.
Temperature Effects on the Molecular Properties of Liquid Lignin Recovered from Kraft Black Liquor (2015)

The effect of temperature on the molecular properties of a “liquid-lignin” phase recovered from Kraft black liquor via CO2 acidification at elevated temperatures was investigated. For softwood black liquors, up to a 4-fold increase in the molecular weight (mol wt) of the recovered liquid-lignin phase was observed as the acidification temperature was increased from 100 to 150 °C. Thus, experiments were carried out in which the CO2-acidification steps of preheating, acidification, and phase separation were decoupled from each other in order to elucidate the mechanisms for the observed changes in molecular weight. Results indicate that some lignin cleavage and a corresponding decrease in molecular weight occur during the black-liquor preheating step. However, a significant net increase in molecular weight occurs after the lignin has phase-separated from the black liquor in the form of a new, denser liquid phase, pointing to condensation reactions as the most likely cause. Minimal changes in lignin aromatic content were observed in the new liquid-lignin phase. Because elevated-temperature, CO2 acidification can be carried out continuously via the SLRP process, adjusting residence times in the black liquor–liquid lignin phase separator would be an effective method for controlling the molecular weight of the recovered lignin for a given product application.
The Convergence of Synthetic Organic and Polymer Chemistries (2005)

Several recent conceptual advances, which take advantage of the design criteria and practical techniques of molecular-level control in organic chemistry, allow preparation of well-defined polymers and nanostructured materials. Two trends are clear: the realization that synthesis of complex macromolecules poses major challenges and opportunities and the expectation that such materials will exhibit distinctive properties and functions. Polymer synthesis methods now being developed will yield well-defined synthetic macromolecules that are capable of mimicking many of the features of proteins (for example, three-dimensional folded structure) and other natural materials. These macromolecules have far-reaching potential for the study of molecular-level behavior at interfaces, in thin films, and in solution, while also enabling the development of encapsulation, drug-delivery, and nanoscale-patterning technologies.
Solvents for Solid-Phase Peptide Synthesis (2003)

Effective solvation of the peptide resin is perhaps the most crucial condition for efficient chain assembly during solid-phase peptide synthesis (SPPS) (). 1H-, 2H-, 13C-, and 19F-nuclear magnetic resonance (NMR) experiments have shown that, under proper solvation conditions, the linear polystyrene chains of copoly(styrene-l%-divinylbenzene)resin (PS) are nearly as accessible to reagents as if free in solution (2–6). When PS is well solvated, diffusion of reagents is not ratelimiting (7–9). PS swelling tests are thus recommended strongly prior to synthesis (). The swelling capability of peptidyl-PS increases with increasing peptide length owing to a net decrease in free energy from solvation of the linear peptide chains (). Under proper solvent conditions, there was no decrease in synthetic efficiency of the model peptide (Leu-Ala-Gly-Val)n up to a length of 60 amino acids ().
Catalytic Enantioselective Decarboxylative Protonation (2006)

We report a highly enantioselective, general catalytic system for the facile synthesis of tertiary stereocenters by protonation adjacent to cyclic ketones. The method relies on catalytic decarboxylative protonation of readily accessible racemic quaternary beta-ketoesters. A range of substituted cycloalkanone compounds can be accessed through this process with high levels of enantioselectivity.
Regulation of cell proliferation and differentiation by interferons (1985)

Research Article| March 01 1985 Regulation of cell proliferation and differentiation by interferons M J Clemens; M J Clemens Search for other works by this author on: This Site PubMed Google Scholar M A McNurlan M A McNurlan Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1985) 226 (2): 345–360. https://doi.org/10.1042/bj2260345 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation M J Clemens, M A McNurlan; Regulation of cell proliferation and differentiation by interferons. Biochem J 1 March 1985; 226 (2): 345–360. doi: https://doi.org/10.1042/bj2260345 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1985 London: The Biochemical Society1985 Article PDF first page preview Close Modal You do not currently have access to this content.
Studies of performance of antiscatter grids in digital radiography: Effect on signal‐to‐noise ratio (1990)

We developed a theoretical model which describes the improvement of signal-to-noise ratio (SNR) by a grid in digital radiography. The model takes into account the effects of spatial variations in the scatter-to-primary ratio and in the large-area contrast over an image with structured background on quantum noise, and the effects of noise in the imaging system such as electronic noise and digitization noise. Based on the theoretical model, we analyzed the effects of these factors on the SNR when a grid is employed. We performed experimental measurements to evaluate the improvement in the SNR by a grid when quantum noise is the dominant noise source. It was found that the measured SNR improvement factor due to quantum noise agreed closely with that determined from the measured transmission values of a grid, as predicted from our theoretical model. In order to evaluate the relative performance of grids with various geometric design parameters for digital radiographic systems, we employed Monte Carlo calculations and determined the transmission values of a number of grids under various scatter conditions. The calculated SNR improvement factor, due to quantum noise, correlated well with the measured improvement of the SNR by the grids. Our model predicts that the SNR improvement factor depends strongly on the local contrast ratio and also on the scatter-to-primary ratio. The SNR improvement factor is higher in the underpenetrated regions than in the well-penetrated regions of an image.
Self-organizing molecular photonic structures based on functionalized synthetic nucleic acid (DNA) polymers (1991)

Work has been carried out with the objective of imparting the electronic/photonic property of extended Forster energy transfer into organized structures formed by the programmed self-assembly of synthetic nucleic acid units (fluorescent oligonucleotides and polynucleotides). Forster energy transfer is a non-radiative process by which a fluorescent donor molecule excited at one wavelength is able to transfer its absorbed photonic energy efficiently to a fluorescent acceptor molecule, in close proximity, which then re-emits it at a second wavelength. An extended energy transfer system, with multiple donor molecules, could be considered a molecular photonic antenna or amplifier structure. Relatively efficient extended Forster energy transfer was observed in initial experiments involving multiple fluorescent donor and acceptor oligonucleotides. These results provide a clear demonstration of totally synthetic molecules, with highly specific programmable self-assembling properties, organizing into molecular structures with useful electronic/photonic properties.
Identification of the Major Oxidatively Damaged Proteins inEscherichia coli Cells Exposed to Oxidative Stress (1998)

In the present study we have analyzed protein oxidation on Escherichia coli when these cells were submitted to different stress conditions such as hydrogen peroxide, superoxide-generating compounds, and iron overloading. Carbonyl groups on oxidized cell proteins were examined by Western blot immunoassay. When anaerobically grown E. coli cells were exposed to hydrogen peroxide stress, alcohol dehydrogenase E, elongation factor G, the heat shock protein DNA K, oligopeptide-binding protein A, enolase, and the outer membrane protein A were identified as the major protein targets. A similar immunostained band pattern was found when cells were shifted from anaerobic to aerobic conditions in the presence of different concentrations of iron; it is relevant to note that oxidation of outer membrane protein C, not observed in peroxide stress conditions, was clearly detected as the concentration of iron was increased in the culture media. The hydrogen peroxide stress performed under aerobic conditions affected the beta-subunit of F0F1-ATPase; the rest of the oxidized protein pattern was very similar to that found for anaerobic conditions, with the exception of alcohol dehydrogenase E, a protein not synthesized aerobically. Cells submitted to superoxide stress using menadione showed a more specific pattern in which elongation factor G and the beta-subunit of F0F1-ATPase were affected significantly. When paraquat was used, although the degree of oxidative damage was lower, the same two modified proteins were detected, and DNA K was also clearly damaged. Cell viability was affected to different extents depending on the type of stress exerted. The results described in this paper provide data about the in vivo effects of oxidative stress on protein oxidation and give insights into understanding how such modifications can affect cellular functions.
Use of gene fusions and protein-protein interaction in the isolation of a biologically active regulatory protein: the replication initiator protein of plasmid R6K. (1983)

The initiation of DNA replication of plasmid R6K is triggered by a 35-kilodalton initiator protein. The initiator protein had been elusive because of its lability and the lack of a convenient assay procedure to aid its purification. Using recombinant DNA techniques, we have fused the cistron of the initiator near its COOH-terminal end, in the correct reading frame, to the lacZ cistron of Escherichia coli at the ninth codon from the NH2 terminus. The fused cistron yielded a protein that was not only stable in vivo but also had dual activities: initiation of DNA replication in vivo and in vitro and hydrolysis of beta-galactoside. Using an affinity column that is specific for beta-galactosidase, we have demonstrated the rapid purification of the hybrid protein to near homogeneity. Exploiting the polymeric structure of the initiator, we have also isolated the nonfused form of the initiator protein, associated through subunit interaction with the beta-galactosidase-fused protein, which permits its purification by affinity chromatography. NH2-terminal amino acid sequence analysis of the heteropolymer has not only shown that the fused and nonfused initiators have the same sequence but also confirmed the protein sequence of the initiator as predicted from its nucleotide sequence. The techniques described here should be generally useful for the isolation of other proteins that are difficult to purify by conventional procedures.
Restricted use of fetal VH3 immunoglobulin genes by unselected B cells in the adult. Predominance of 56p1-like VH genes in common variable immunodeficiency. (1992)

The large VH3 family of human immunoglobulin genes is commonly used throughout B cell ontogeny. However, B cells of the fetus and certain autoantibody-producing clones are restricted to a recurrent subset of VH3 genes, and VH3 B cells are deficient in certain immunodeficiency diseases. In this study, we have sequenced a set of rearranged VH3 genes generated by genomic polymerase chain reaction (PCR) from normal adults and those with common variable immunodeficiency (CVI). In both groups, all cones were readily identifiable with the fetal VH3 subset, and were further distinguished by limited DH motifs and exclusive use of JH4. In CVI, the residual population of VH3 B cells were notable for predominant use of 56p1-like VH genes. All clones displayed sequence divergence (including somatic mutation) with evidence of strong selection against complementarity-determining region (CDR) coding change. A survey of other V gene families indicates that human V gene diversity may be restricted in general by germline mechanisms. These findings suggest that the expressed antibody repertoire in the human adult may be much smaller than anticipated, and selected by processes in part distinct from the paradigm of maximal antigen-binding diversity.
Purple Medicine: The Case for a Joint Medical Command (2007)

Abstract : In response to a broad set of complex national security challenges of the twenty-first century, the Quadrennial Defense Review (QDR) report of February 2006 advised that all the organizations, processes, and practices within the Department of Defense be given a high degree of agility, flexibility, responsiveness, and ultimately effectiveness in supporting the joint war fighter and future national defense goals. In that connection, the 2006 QDR recommends that medical support be likewise aligned with emerging joint force employment concepts. Indeed, the Department of Defense, in conjunction with the chairman of the Joint Chiefs of Staff, had already been directed to develop an implementation plan for such a unified structure, the Joint Medical Command. An antecedent clause in the Department of Defense Program Budget Decision 753 of 23 December 2004 laid the conceptual groundwork. It directed that a plan for a Joint Medical Command be accomplished by the fiscal year 2008?2013 Program/ Budget Review. How can this intention be best brought to fruition? The organizational structure of the present military. The organizational structure of the present military hospital system predates World War II,when each service provided for all of its own health care. In the sixty years since the conclusion of that conflict, there have been numerous proposals for a unified medical command structure. Largely due to cost-containment pressure exercised by the executive branch, Congress,sand the services themselves, some cooperation has evolved in the delivery of peacetime health care to eligible Department of Defense beneficiaries in a framework known as the Military Health System (MHS). During this time no less than fifteen federally sponsored studies and numerous scholarly reports have examined the MHS, and the overwhelming majority has proposed the creation of a unified medical command.
Relación entre el índice biespectral y parámetros hemodinámicos durante la anestesia con sevoflurano en perros (2004)

The 10 day old fries of Tilapia mossambica Peters were irradiated with 350 R dose. Dynamics of germ cells in control and after irradiation was studied. In 10 day old fry primordial germ cells and gonial cells were observed; in 15 days--mainly gonial cells were seen; in 20 days part of gonial cells move in the early prophase of meiosis; in 25 days gonial cells and oocytes of early prophase of meiosis are seen; in 30 days oogonial cells, oocytes of early prophase of meiosis and of previtellogenesis are observed. After irradiation of 13--14 day old fries some anomalies of mitosis were observed. But mass destruction of germ cells took place during the pachytene stage in 25 day old fries. The causes of the destruction of germ cells are discussed.
σ S -Dependent Gene Expression at the Onset of Stationary Phase in Escherichia coli : Function of σ S -Dependent Genes and Identification of Their Promoter Sequences (2004)

The sigma(S) subunit of RNA polymerase, the product of the rpoS gene, controls the expression of genes responding to starvation and cellular stresses. Using gene array technology, we investigated rpoS-dependent expression at the onset of stationary phase in Escherichia coli grown in rich medium. Forty-one genes were expressed at significantly lower levels in an rpoS mutant derived from the MG1655 strain; for 10 of these, we also confirmed rpoS and stationary-phase dependence by reverse transcription-PCR. Only seven genes (dps, osmE, osmY, sodC, rpsV, wrbA, and yahO) had previously been recognized as rpoS dependent. Several newly identified rpoS-dependent genes are involved in the uptake and metabolism of amino acids, sugars, and iron. Indeed, the rpoS mutant strain shows severely impaired growth on some sugars such as fructose and N-acetylglucosamine. The rpoS gene controls the production of indole, which acts as a signal molecule in stationary-phase cells, via regulation of the tnaA-encoded tryptophanase enzyme. Genes involved in protein biosynthesis, encoding the ribosome-associated protein RpsV (sra) and the initiation factor IF-1 (infA), were also induced in an rpoS-dependent fashion. Using primer extension, we determined the promoter sequences of a selection of rpoS-regulated genes representative of different functional classes. Significant fractions of these promoters carry sequence features specific for Esigma(S) recognition of the -10 region, such as cytosines at positions -13 (70%) and -12 (30%) as well as a TG motif located upstream of the -10 region (50%), thus supporting the TGN(0-2)C(C/T)ATA(C/A)T consensus sequence recently proposed for sigma(S).
Genetic changes associated with prostate cancer in humans. (1991)

We have detected allelic loss in a majority of prostate cancers analysed. These losses have been detected on several chromosomes known to harbour tumour suppressor genes important in the development of other tumour types. Elevated rates of loss of heterozygosity on chromosome 16q and 10q suggest that tumour suppressor genes important in the pathogenesis of prostate cancer may be present on these chromosomes. Conversely, determination of the frequency of ras gene mutations in prostate cancer tissue suggests that these genetic alterations play a minor part in both the initiation and progression of this disease in humans.