gebhart/patrepeval huggingface dataset:
Nicotine and brain disorders. (2000)

During the last decade, brain nicotinic acetylcholine receptors were extensively characterized from electrophysiological and pharmacological points of view. These receptors play important roles in memory and cognition and participate in the pathogenesis of several brain disorders (Parkinson's and Alzheimer's diseases, Tourette's syndrome, schizophrenia, depression, attention deficit disorder). In the same diseases, clinical studies showed that nicotine had beneficial effects, both as therapeutic and prophylactic agent. This review presents recent data concerning the structure and properties of neuronal nicotinic receptors, their involvement in the pathogenesis of various brain disorders and the beneficial effects of nicotine as therapeutic agent.
Dynamic data integration using Web services (2004)

We address the problem of large-scale data integration, where the data sources are unknown at design time, are from autonomous organisations, and may evolve. Experiments are described involving a demonstrator system in the field of health services data integration within the UK. Current Web services technology has been used extensively and largely successfully in these distributed prototype systems. The work shows that Web services provide a good infrastructure layer, but integration demands a higher level "broker" architectural layer; the paper identifies eight specific requirements for such an architecture that have emerged from the experiments, derived from an analysis of shortcomings which are collectively due to the static nature of the initial prototype. The way in which these are being met in the current version in order to achieve a more dynamic integration is described.
Antimicrobial properties of phenolic compounds from berries (2001)

These properties can be utilized in functional food development and in food preservative purposes.
Effect of threading dislocations on the Bragg peakwidths of GaN, AlGaN, and AlN heterolayers (2005)

We develop a reciprocal-space model that describes the (hkl) dependence of the broadened Bragg peakwidths produced by x-ray diffraction from a dislocated epilayer. We compare the model to experiments and find that it accurately describes the peakwidths of 16 different Bragg reflections in the [010] zone of both GaN and AlN heterolayers. Using lattice-distortion parameters determined by fitting the model to selected reflections, we estimate threading-dislocation densities for seven different GaN and AlGaN samples and find improved agreement with transmission electron microscopy measurements.
Seismic velocities from surface measurements (1955)

Abstract The purpose of this paper is to discuss field and interpretive techniques which permit, in favorable cases, the quite accurate determination of seismic interval velocities prior to drilling. A simple but accurate formula is developed for the quick calculation of interval velocities from "average velocities" determined by the known x 2 -T 2 technique. To secure accuracy a careful study of multiple reflections is necessary, and this is discussed. Although the principal objective in determining velocities is to allow an accurate structural interpretation to be made from seismic reflection data, an important secondary objective is to get some lithological information. This is obtained through a correlation of velocities with rock type and depth.
Rescue of a segmented negative-strand RNA virus entirely from cloned complementary DNAs (1996)

We provide the first report, to our knowledge, of a helper-independent system for rescuing a segmented, negative-strand RNA genome virus entirely from cloned cDNAs. Plasmids were constructed containing full-length cDNA copies of the three Bunyamwera bunyavirus RNA genome segments flanked by bacteriophage T7 promoter and hepatitis delta virus ribozyme sequences. When cells expressing both bacteriophage T7 RNA polymerase and recombinant Bunyamwera bunyavirus proteins were transfected with these plasmids, full-length antigenome RNAs were transcribed intracellularly, and these in turn were replicated and packaged into infectious bunyavirus particles. The resulting progeny virus contained specific genetic tags characteristic of the parental cDNA clones. Reassortant viruses containing two genome segments of Bunyamwera bunyavirus and one segment of Maguari bunyavirus were also produced following transfection of appropriate plasmids. This accomplishment will allow the full application of recombinant DNA technology to manipulate the bunyavirus genome.
Introduction to Polymer Chemistry (2010)

As the first polymer book to receive the CHOICE Outstanding Academic Title distinction (2007), Introduction to Polymer Chemistry provided undergraduate students with a much-needed, well-rounded presentation of the principles and applications of natural, synthetic, inorganic, and organic polymers. With an emphasis on the environment and green chemis
Real-Time Monitoring of IntracellularStaphylococcus aureusReplication (2004)

A high-throughput system to rapidly assess the intracellular replication of Staphylococcus aureus has been developed utilizing S. aureus transformed with a dual gfp-luxABCDE reporter operon under the control of a growth-dependent promoter. Replication of tagged bacteria internalized into bovine mammary epithelial cells (MAC-T) could be measured by monitoring fluorescence and bioluminescence from the reporter operon following removal of extracellular bacteria from the plates. Bacterial replication inside cells was confirmed by a novel ex vivo time-lapse confocal microscopic method. This assay of bacterial replication was used to evaluate the efficacy of antibiotics which are commonly used to treat staphylococcal infections. Not all antibiotics tested were able to prevent intracellular replication of S. aureus and some were ineffective at preventing replication of intracellular bacteria at concentrations above the MIC determined for bacteria in broth culture. Comparison of the fluorescence and bioluminescence signals from the bacteria enabled effects on protein synthesis and metabolism to be discriminated and gave information on the entry of compounds into the eukaryotic cell, even if bacterial replication was not prevented. Elevated resistance of S. aureus to antibiotics inside host cells increases the likelihood of selecting S. aureus strains which are resistant to commonly used antimicrobial agents within the intracellular niche. The approach presented directly assesses intracellular efficacy of antibiotics and provides an evidence-based approach to antibiotic selection for prescribing physicians and medical microbiologists.
The ileal brake--inhibition of jejunal motility after ileal fat perfusion in man. (1984)

The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents.
Reduction in Functional Antibody Activity Against Streptococcus pneumoniae in Vaccinated Elderly Individuals Highly Correlates with Decreased IgG Antibody Avidity (1999)

The pneumococcal polysaccharide vaccine is recommended as a means of preventing invasive disease in the elderly. We compared responses to the 23-valent polysaccharide vaccine in 46 previously unvaccinated, healthy, institutionalized elderly persons (mean age, 85.5 years) with those in 12 healthy younger adults (mean age, 37 years) by measuring prevaccination and postvaccination serum IgG antibody concentrations (by ELISA), functional antibody activity (by opsonophagocytosis), IgG antibody avidity, and passive protection in mice. Postvaccination IgG antibody concentrations for two serotypes (6B and 19F) of the five studied (4, 6B, 14, 19F, and 23F) were significantly lower in elderly than in younger adults; however, opsonophagocytic activity was significantly reduced for all serotypes in the elderly. Sera with reduced opsonophagocytic activity (titer, <64) correlated with low IgG antibody avidity and protected mice poorly against pneumococcal challenge. In elderly persons receiving polysaccharide vaccination, there was a significant reduction in the functionality of postvaccination antibodies, and this appeared to increase with advanced age.
Genetic Evidence for Single-Strand Lesions Initiating Nbs1-Dependent Homologous Recombination in Diversification of Ig V in Chicken B Lymphocytes (2009)

Homologous recombination (HR) is initiated by DNA double-strand breaks (DSB). However, it remains unclear whether single-strand lesions also initiate HR in genomic DNA. Chicken B lymphocytes diversify their Immunoglobulin (Ig) V genes through HR (Ig gene conversion) and non-templated hypermutation. Both types of Ig V diversification are initiated by AID-dependent abasic-site formation. Abasic sites stall replication, resulting in the formation of single-stranded gaps. These gaps can be filled by error-prone DNA polymerases, resulting in hypermutation. However, it is unclear whether these single-strand gaps can also initiate Ig gene conversion without being first converted to DSBs. The Mre11-Rad50-Nbs1 (MRN) complex, which produces 3' single-strand overhangs, promotes the initiation of DSB-induced HR in yeast. We show that a DT40 line expressing only a truncated form of Nbs1 (Nbs1(p70)) exhibits defective HR-dependent DSB repair, and a significant reduction in the rate--though not the fidelity--of Ig gene conversion. Interestingly, this defective gene conversion was restored to wild type levels by overproduction of Escherichia coli SbcB, a 3' to 5' single-strand-specific exonuclease, without affecting DSB repair. Conversely, overexpression of chicken Exo1 increased the efficiency of DSB-induced gene-targeting more than 10-fold, with no effect on Ig gene conversion. These results suggest that Ig gene conversion may be initiated by single-strand gaps rather than by DSBs, and, like SbcB, the MRN complex in DT40 may convert AID-induced lesions into single-strand gaps suitable for triggering HR. In summary, Ig gene conversion and hypermutation may share a common substrate-single-stranded gaps. Genetic analysis of the two types of Ig V diversification in DT40 provides a unique opportunity to gain insight into the molecular mechanisms underlying the filling of gaps that arise as a consequence of replication blocks at abasic sites, by HR and error-prone polymerases.
Principles and Practice of Nuclear Medicine (1995)

Principles and Practice of Nuclear Medicine contains information provided by 40 contributors.
Characterization of Size-Fractionated cDNA Libraries Generated by the in vitro Recombination-Assisted Method (2002)

We here modified a previously reported method for the construction of cDNA libraries by employing an in vitro recombination reaction to make it more suitable for comprehensive cDNA analysis. For the evaluation of the modified method, sets of size-selected cDNA libraries of four different mouse tissues and human brain were constructed and characterized. Clustering analysis of the 3' end sequence data of the mouse cDNA libraries indicated that each of the size-fractionated libraries was complex enough for comprehensive cDNA analysis and that the occurrence rates of unidentified cDNAs varied considerably depending on their size and on the tissue source. In addition, the end sequence data of human brain cDNAs thus generated showed that this method decreased the occurrence rates of chimeric clones by more than fivefold compared to conventional ligation-assisted methods when the cDNAs were larger than 5 kb. To further evaluate this method, we entirely sequenced 13 human unidentified cDNAs, named KIAA1990-KIAA2002, and characterized them in terms of the predicted protein sequences and their expression profiles. Taking all these results together, we here conclude that this new method for the construction of size-fractionated cDNA libraries makes it possible to analyze cDNAs efficiently and comprehensively.
Highly Specific Gene Silencing by Artificial MicroRNAs in Arabidopsis (2006)

Plant microRNAs (miRNAs) affect only a small number of targets with high sequence complementarity, while animal miRNAs usually have hundreds of targets with limited complementarity. We used artificial miRNAs (amiRNAs) to determine whether the narrow action spectrum of natural plant miRNAs reflects only intrinsic properties of the plant miRNA machinery or whether it is also due to past selection against natural miRNAs with broader specificity. amiRNAs were designed to target individual genes or groups of endogenous genes. Like natural miRNAs, they had varying numbers of target mismatches. Previously determined parameters of target selection for natural miRNAs could accurately predict direct targets of amiRNAs. The specificity of amiRNAs, as deduced from genome-wide expression profiling, was as high as that of natural plant miRNAs, supporting the notion that extensive base pairing with targets is required for plant miRNA function. amiRNAs make an effective tool for specific gene silencing in plants, especially when several related, but not identical, target genes need to be downregulated. We demonstrate that amiRNAs are also active when expressed under tissue-specific or inducible promoters, with limited nonautonomous effects. The design principles for amiRNAs have been generalized and integrated into a Web-based tool (http://wmd.weigelworld.org).
Identification of a Caulobacter crescentus operon encoding hrcA, involved in negatively regulating heat-inducible transcription, and the chaperone gene grpE (1996)

In response to elevated temperature, both prokaryotic and eukaryotic cells increase expression of a small family of chaperones. The regulatory network that functions to control the transcription of the heat shock genes in bacteria includes unique structural motifs in the promoter region of these genes and the expression of alternate sigma factors. One of the conserved structural motifs, the inverted repeat CIRCE element, is found in the 5' region of many heat shock operons, including the Caulobacter crescentus groESL operon. We report the identification of another C. crescentus heat shock operon containing two genes, hrcA (hrc for heat shock regulation at CIRCE elements) and a grpE homolog. Disruption of the hrcA gene, homologs of which are also found upstream of grpE in other bacteria, increased transcription of the groESL operon, and this effect was dependent on the presence of an intact CIRCE element. This suggests a role for HrcA in negative regulation of heat shock gene expression. We identified a major promoter transcribing both hrcA and grpE and a minor promoter located within the hrcA coding sequence just upstream of grpE. Both promoters were heat shock inducible, with maximal expression 10 to 20 min after heat shock. Both promoters were also expressed constitutively throughout the cell cycle under physiological conditions. C. crescentus GrpE, shown to be essential for viability at low and high temperatures, complemented an Escherichia coli delta grpE strain in spite of significant differences in the N- and C-terminal regions of these two proteins, demonstrating functional conservation of this important stress protein.
Transforming Acidic Coiled Coil 1 Promotes Transformation and Mammary Tumorigenesis (2005)

Transforming acidic coiled coil 1 (TACC1) is a putative oncogene located within a breast cancer amplicon found on human chromosome 8p11. Although TACC1 has been reported to transform fibroblasts, it is also down-regulated in a subset of mammary tumors treated with anthracyclin. Here, we show that ectopic TACC1 overexpression can cooperate with Ras to induce focus formation in murine fibroblast cultures and prevent death caused by overexpression of Pten or a dominant-negative form of protein kinase B (PKB)/Akt. In transgenic mice carrying TACC1 under the control of the mouse mammary tumor virus promoter, TACC1 expression reduced apoptosis during mammary gland involution, increased the penetrance of mammary tumors in a pten+/- background, and decreased the average age of mammary tumor onset in a mouse model based on a phosphatidylinositol 3'-kinase (PI3K)-decoupled mutant of polyoma middle T. Elevated levels of both phospho-PKB and phospho-extracellular signal-regulated kinase were found in mammary tissue containing the TACC1 transgene. Thus, TACC1 positively regulates the Ras and PI3K pathways, promotes Ras-mediated transformation, and prevents apoptosis induced by PI3K pathway inhibition. TACC1 also cooperates with tumorigenic mutations in the PI3K pathway and thereby plays an oncogenic role in tumor formation in the murine mammary gland.
The Alternative Splicing Gallery (ASG): bridging the gap between genome and transcriptome (2004)

Alternative splicing essentially increases the diversity of the transcriptome and has important implications for physiology, development and the genesis of diseases. Conventionally, alternative splicing is investigated in a case-by-case fashion, but this becomes cumbersome and error prone if genes show a huge abundance of different splice variants. We use a different approach and integrate all transcripts derived from a gene into a single splicing graph. Each transcript corresponds to a path in the graph, and alternative splicing is displayed by bifurcations. This representation preserves the relationships between different splicing variants and allows us to investigate systematically all possible putative transcripts. We built a database of splicing graphs for human genes, using transcript information from various major sources (Ensembl, RefSeq, STACK, TIGR and UniGene). A Web interface allows users to display the splicing graphs, to interactively assemble transcripts and to access their sequences as well as neighboring genomic regions. We also provide for each gene an exhaustive pre-computed catalog of putative transcripts--in total more than 1.2 million sequences. We found that approximately 65% of the investigated genes show evidence for alternative splicing, and in 5% of the cases, a single gene might produce over 100 transcripts.
The Bacterial Chromosome (2008)

Bacteria represent the vast majority of biological diversity found on Earth. In this review, we focus on selected aspects of their genetic material, those providing insight into structural, functional, dynamic, and evolutionary aspects of their genomes. Bacterial chromosomes are far more dynamic than previously realized, and dozens of mechanisms giving rise to genomic plasticity are now understood. Maturation of the genomics era has provided the tools for unraveling the interwoven details of DNA structure/function relationships that provide a basis for organismal diversity. Some of the most throughly understood processes that underlie the dynamics of genomic structure and function in prokaryotes are examined.
Synthesis and antiallergic activities of 1,3-oxazolo[4,5-h]quinolines (1985)

A series of new 1,3-oxazolo[4,5-h]quinolines has been prepared. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (PCA). After several modifications of the original lead, the most potent compound of the series was determined to be 5-chloro-1,3-oxazolo[4,5-h]quinoline-2-carboxylic acid methyl ester (4a). It has an IC50 of 0.3 microM in the RMC assay and an ED50 (intraperitoneal) of 0.1 mg/kg in the PCA test, which is 10 times and 60 times more potent than disodium cromoglycate (DSCG), respectively. Of greater importance, it is orally active (ED50 = 0.5 mg/kg) as an inhibitor of the PCA test.
Evaluation of the Prodesse Hexaplex Multiplex PCR Assay for Direct Detection of Seven Respiratory Viruses in Clinical Specimens (2001)

We evaluated the Hexaplex assay (Prodesse, Waukesha, WI) for the detection of 7 respiratory viruses (influenza A and B, parainfluenza 1-3, and respiratory syncytial virus [RSV] A and B). The Hexaplex assay was performed on 300 respiratory samples during the 1999-2000 respiratory virus season. Results of this assay were compared with shell vial cell culture and/or direct fluorescent antibody stain. The overall sensitivity and specificity of the assay were 96.6% and 94.1%, respectively. The respective sensitivity and specificity of the Hexaplex assay for detection of specific virus groups were as follows: influenza A, 98.6% and 97.8%; influenza B, 100% and 100%; and for parainfluenza viruses (1-3), 100% and 99.1%. The assay did not perform as well with patients infected with RSV: sensitivity and specificity were 91.0% and 98.6%, respectively. There are 2 major drawbacks to this assay: it is technically demanding (3-4 hours hands-on time), and it is expensive ($80-$90 direct cost). Nevertheless, because of the excellent sensitivity and specificity, the Hexaplex assay may be valuable in the diagnosis of respiratory viral infections in immunocompromised patients.
PD-1 Blockade in Chronically HIV-1-Infected Humanized Mice Suppresses Viral Loads (2013)

An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012), with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV) loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus) humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8(+) T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8(+) T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus.