gebhart/patrepeval huggingface dataset:
Extending the Aerolysin Family: From Bacteria to Vertebrates (2011)

A number of bacterial virulence factors have been observed to adopt structures similar to that of aerolysin, the principal toxin of Aeromonas species. However, a comprehensive description of architecture and structure of the aerolysin-like superfamily has not been determined. In this study, we define a more compact aerolysin-like domain -or aerolysin foldand show that this domain is far more widely spread than anticipated since it can be found throughout kingdoms. The aerolysin-fold could be found in very diverse domain and functional contexts, although a toxic function could often be assigned. Due to this diversity, the borders of the superfamily could not be set on a sequence level. As a border-defining member, we therefore chose pXO2-60 -a protein from the pathogenic pXO2 plasmid of Bacillus anthracis. This fascinating protein, which harbors a unique ubiquitin-like fold domain at the C-terminus of the aerolysin-domain, nicely illustrates the diversity of the superfamily. Its putative role in the virulence of B. anthracis and its three dimensional model are discussed.
Hypoxia-Inducible Factor 1α Induces Fibrosis and Insulin Resistance in White Adipose Tissue (2009)

Adipose tissue can undergo rapid expansion during times of excess caloric intake. Like a rapidly expanding tumor mass, obese adipose tissue becomes hypoxic due to the inability of the vasculature to keep pace with tissue growth. Consequently, during the early stages of obesity, hypoxic conditions cause an increase in the level of hypoxia-inducible factor 1alpha (HIF1alpha) expression. Using a transgenic model of overexpression of a constitutively active form of HIF1alpha, we determined that HIF1alpha fails to induce the expected proangiogenic response. In contrast, we observed that HIF1alpha initiates adipose tissue fibrosis, with an associated increase in local inflammation. "Trichrome- and picrosirius red-positive streaks," enriched in fibrillar collagens, are a hallmark of adipose tissue suffering from the early stages of hypoxia-induced fibrosis. Lysyl oxidase (LOX) is a transcriptional target of HIF1alpha and acts by cross-linking collagen I and III to form the fibrillar collagen fibers. Inhibition of LOX activity by beta-aminoproprionitrile treatment results in a significant improvement in several metabolic parameters and further reduces local adipose tissue inflammation. Collectively, our observations are consistent with a model in which adipose tissue hypoxia serves as an early upstream initiator for adipose tissue dysfunction by inducing a local state of fibrosis.
Nonlinear denoising filter for images with interactive evolutionary computing considering the subjective assessment (2008)

A new type of digital filter for removing random noise in images is proposed using interactive evolutionary computing. This filter is realized as combination of several nonlinear digital filters, such as an epsiv-filter and a conditional median filter. Interactive evolutionary computing is adopted in order to optimize the parameters in the nonlinear filters, considering the subjective assessment by human. Combination of nonlinear filters is usually a powerful tool for noise reduction of images, but such a filter system contains multiple filter parameters which are difficult to be optimized. Interactive evolutionary computing is effective for the total optimization of these filter parameters. Moreover, human taste and subjective sense are highly considered in the filter performance. As an example of this type of filter, a cascade of two epsiv-filters and a conditional median filter is presented for reducing random noise, and its computer simulations are shown to verify its high performance.
The TRPS1 transcription factor: androgenic regulation in prostate cancer and high expression in breast cancer (2004)

TRPS1 mRNA is more highly expressed in androgen-dependent lymph node carcinoma of prostate-fast growing colony (LNCaP-FGC) compared with androgen-independent lymph node carcinoma of prostate-lymph node original (LNCaP-LNO) prostate cancer cell lines. Furthermore, TRPS1 mRNA expression is down-regulated by androgens in LNCaP-FGC cells, a process mediated by the androgen receptor (AR). Here, we present TRPS1 protein expression in human prostate cancer material derived from a panel of six androgen-dependent and eight androgen-independent human prostate cancer xenografts. TRPS1 protein is expressed in all androgen-dependent xenografts, which also express AR and prostate-specific antigen (PSA). Androgen withdrawal by castration resulted in an increase in TRPS1 protein in two androgen-dependent xenografts, indicating relieved repression by action of AR. TRPS1 protein is expressed in four androgen-independent xenografts and is low or absent in the other four androgen-independent xenografts. Androgen withdrawal by castration demonstrates that TRPS1 protein levels remain the same in 1 androgen-independent xenograft, most likely due to the lack of AR expression. These data show that TRPS1 protein expression is regulated by androgens via the AR in human prostate cancer xenografts. Analysis of TRPS1 mRNA expression in normal and tumour tissue of the prostate and 18 other human tissues, showed that TRPS1 had the highest mRNA expression levels in normal and tumour tissues of breast. In addition, high TRPS1 mRNA and protein expression levels were observed in four out of five human breast cancer cell lines. In conclusion, TRPS1 protein expression is down-regulated by androgens in human prostate cancer, and analysis of TRPS1 mRNA expression levels in several human tissues showed that the highest levels were observed in normal and tumour breast tissue.
Structure and function of animal fatty acid synthase (2004)

Fatty acid synthase (FAS; EC 2.3.1.85) of animal tissues is a complex multifunctional enzyme consisting of two identical monomers. The FAS monomer (approximately 270 kDa) contains six catalytic activities and from the N-terminus the order is beta-ketoacyl synthase (KS), acetyl/malonyl transacylase (AT/MT), beta-hydroxyacyl dehydratase (DH), enoyl reductase (ER), beta-ketoacyl reductase (KR), acyl carrier protein (ACP), and thioesterase (TE). Although the FAS monomer contains all the activities needed for palmitate synthesis, only the dimer form of the synthase is functional. Both the biochemical analyses and the small-angle neutron-scattering analysis determined that in the dimer form of the enzyme the monomers are arranged in a head-to-tail manner generating two centers for palmitate synthesis. Further, these analyses also suggested that the component activities of the monomer are organized in three domains. Domain I contains KS, AT/MT, and DH, domain II contains ER, KR, and ACP, and domain III contains TE. Approximately one fourth of the monomer protein located between domains I and II contains no catalytic activities and is called the interdomain/core region. This region plays an important role in the dimer formation. Electron cryomicrographic analyses of FAS revealed a quaternary structure at approximately 19 A resolution, containing two monomers (180 x 130 x 75 A) that are separated by about 19 A, and arranged in an antiparallel fashion, which is consistent with biochemical and neutron-scattering data. The monomers are connected at the middle by a hinge generating two clefts that may be the two active centers of fatty acid synthesis. Normal mode analysis predicted that the intersubunit hinge region and the intrasubunit hinge located between domains II and III are highly flexible. Analysis of FAS particle images by using a simultaneous multiple model single particle refinement method confirmed that FAS structure exists in various conformational states. Attempts to get higher resolution of the structure are under way.
Effects of Gaseous Anesthetics Nitrous Oxide and Xenon on Ligand-gated Ion Channels (2000)

Nitrous oxide and xenon displayed a similar spectrum of receptor actions, but this spectrum is distinct from that of isoflurane or ethanol. These results suggest that NMDA receptors and nACh receptors composed of beta2 subunits are likely targets for nitrous oxide and xenon.
On-column sample concentration using field amplification in CZE (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOn-Column Sample Concentration Using Field Amplification in CZERing-Ling Chien and Dean S. BurgiCite this: Anal. Chem. 1992, 64, 8, 489A–496APublication Date (Print):April 15, 1992Publication History Published online31 May 2012Published inissue 15 April 1992https://pubs.acs.org/doi/10.1021/ac00032a721https://doi.org/10.1021/ac00032a721research-articleACS PublicationsRequest reuse permissionsArticle Views335Altmetric-Citations278LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Factors affecting the priming efficiency of short contiguous oligonucleotide strings in the primer walking strategy of DNA sequencing (1996)

We use modified oligonucleotides with enhanced strength of complementary DNA binding for primer walking DNA sequencing with strings of short contiguous oligonucleotides as primers. Such an approach allows us to reduce the probability of primer failures due to unstable binding of oligos with templates. In this paper the factors affecting the priming efficiency of segmented primers (strings composed of several short oligonucleotides contiguously juxtaposed on the template) used for DNA sequencing were investigated. Modified oligonucleotides were used to discriminate the effects caused by intrinsic properties of the oligonucleotides and by template features. It was shown that the most crucial factor is the stability of the duplex formed by the template with the 3'-outermost oligonucleotide of a string. The data were obtained with a model M13 template and in the process of sequencing the region flanking a long terminal repeat of human endogenous retrovirus HERVK mapped on chromosome 19. The sequencing was done by primer walking with strings of contiguous modified hexanucleotides. The effects revealed should be taken into consideration when choosing oligonucleotide units of segmented primers and for construction of minimised libraries composed of short unit oligonucleotides.
All EGF(ErbB) receptors have preformed homo- and heterodimeric structures in living cells (2008)

The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, also known as ErbB or HER, plays crucial roles in the development of multicellular organisms. Mutations and over-expression of the ErbB receptors have been implicated in a variety of human cancers. It is widely thought that the ErbB receptors are located in the plasma membrane, and that ligand binding to the monomeric form of the receptors induces its dimeric form for activation. However, it still remains controversial whether prior to ligand binding the receptors exist as monomers or dimers on the cell surface. Using bimolecular fluorescence complementation (BiFC) assays in the present study, we demonstrate that in the absence of bound ligand, all the ErbB family members have preformed, yet inactive, homo- and heterodimers on the cell surface, except for ErbB3 homodimers and heterodimers with cleavable ErbB4, which exist primarily in the nucleus. BiFC assays of the dimerization have also suggested that the ligand-independent dimerization of the ErbB receptors occurs in the endoplasmic reticulum (ER) before newly synthesized receptor molecules reach the cell surface. Based on BiFC and mammalian two-hybrid assays, it is apparent that the intracellular domains of the receptors are responsible for the spontaneous dimer formation. These provide new insights into an understanding of transmembrane signal transduction mediated by the ErbB family members, and are relevant to the development of anti-cancer drugs.
Congenital Tremor in Pigs Farrowed from Sows Given Hog Cholera Virus During Pregnancy (1981)

At different stages of gestation, 3 groups of pregnant sows were inoculated with a strain of hog cholera virus (HCV). After the infection, clinical signs of hog cholera were not observed in the sows. Pigs from the sows infected on day 22 or 43 of gestation showed varying degrees of muscular tremor, ataxia, splayleg, and suckling inability. Of the pigs with tremor, 83% had cerebellar hypoplasia. Surviving pigs demonstrated persistent viral infection and continued to shed HCV, but did not have antibodies to HCV. Sows infected at 72 days of gestation farrowed numerous mummified and stillborn pigs. Signs of tremor were not seen in any pigs from these sows.
Endonuclease V cleaves at inosines in RNA (2013)

Endonuclease V orthologues are highly conserved proteins found in all kingdoms of life. While the prokaryotic enzymes are DNA repair proteins for removal of deaminated adenosine (inosine) from the genome, no clear role for the eukaryotic counterparts has hitherto been described. Here we report that human endonuclease V (ENDOV) and also Escherichia coli endonuclease V are highly active ribonucleases specific for inosine in RNA. Inosines are normal residues in certain RNAs introduced by specific deaminases. Adenosine-to-inosine editing is essential for proper function of these transcripts and defects are linked to various human disease. Here we show that human ENDOV cleaves an RNA substrate containing inosine in a position corresponding to a biologically important site for deamination in the Gabra-3 transcript of the GABA(A) neurotransmitter. Further, human ENDOV specifically incises transfer RNAs with inosine in the wobble position. This previously unknown RNA incision activity may suggest a role for endonuclease V in normal RNA metabolism.
Genetic Impact on the Risk of Intramammary Infection Following Staphylococcus aureus Challenge (1994)

This study evaluated relationships among intramammary challenge with Staphylococcus aureus, SCC, and susceptibility to infection and determined the genetic contribution to susceptibility of infection with special emphasis on bovine lymphocyte antigens. Intramammary challenge with S. aureus Newbould 305 was used as a model for natural infection. A total of 124 cows were challenged in all quarters with 600 cfu of S. aureus Newbould 305 in 2 ml of PBS solution. Quarter milk samples for bacteriology and SCC were taken at three times both before and after challenge. Lymphocytes were separated from whole blood and tested with a standard microlymphocytotoxicity test to determine the presence of bovine lymphocyte antigens class I alleles. One hundred and thirteen cows were negative for S. aureus at challenge, and 11 cows exhibited positive S. aureus counts in one or more quarters at challenge. Fifty-three percent of quarters from the 124 cows challenged became infected after challenge. Nineteen cows had no quarters infected; 19 cows, one; 26 cows, two; 25 cows, three; and 24 cows had four quarters infected after challenge. Average SCC before challenge was 181,000 and after challenge was 758,600. The SCC prior to challenge of cows that resisted infection were higher than prior SCC of cows that became infected (282,000 and 91,000, respectively). The reverse was true after challenge. Presence of the bovine lymphocyte antigens class I allele CA42, instead of EU28 (based on gene substitution), increased susceptibility to S. aureus infection. Heritability estimates of S. aureus susceptibility after experimental challenge were low and unstable.
Project LEARN — Light Exchangeable, Add/Drop Ring Network (1997)

WDM networking based on wavelength add/drop multiplexing and/or wavelength routing offers the following benefits: (1) reduced processing load and latency in intermediate nodes by handling through-traffic optically; (2) significant terminal equipment savings as only a sub-set of wavelengths are terminated and/or generated at each node; and (3) optical transparency that allows a variety of traffic formats and rates to be transmitted over the network without modification to node equipment.
Kevin: A Visualiser Pupil. (2000)

l. Introduction The role that mental images play in human thought processes and in the construction of mathematical knowledge has been the object of study, throughout time, by different people: philosophers, poets, speakers, religious teachers and psychologists (Kosslyn, 1983; Sommer, 1978). Over the last twenty years or so a number of researchers in mathematical education have dedicated some of their efforts
Portable performance of data parallel languages (1997)

A portable program executes on different platforms and yields consistent performance. With the focus on portability, this paper presents an in-depth study of the performance of three NAS benchmarks (EP, MG, FT) compiled with three commercial HPF compilers (APR, PGI, IBM) on the IBM SP2. Each benchmark is evaluated in two versions: using DO loops and using F90 constructs and/or HPF's Forall statement. Base-line comparison is provided by versions of the benchmarks written in Fortran/MPI and ZPL, a data parallel language developed at the University of Washington.While some F90/Forall programs achieve scalable performance with some compilers, the results indicate a considerable portability problem in HPF programs. Two sources for the problem are identified. First, Fortran's semantics require extensive analysis and optimization to arrive at a parallel program; therefore relying on the compiler's capability alone leads to unpredictable performance. Second, the wide differences in the parallelization strategies used by each compiler may require an HPF program to be customized for the particular compiler. While improving compiler optimizations may help to reduce some performance variations, the results suggest that the foremost criteria for portability is a concise performance model that the compiler must adhere to and that the users can rely on.
The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands (2005)

Gastric acid secretion is activated by two distinct pathways: a neuronal pathway via the vagus nerve and release of acetylcholine and an endocrine pathway involving gastrin and histamine. Recently, we demonstrated that activation of H(+)-K(+)-ATPase activity in parietal cells in freshly isolated rat gastric glands is modulated by the calcium-sensing receptor (CaSR). Here, we investigated if the CaSR is functionally expressed in freshly isolated gastric glands from human patients undergoing surgery and if the CaSR is influencing histamine-induced activation of H(+)-K(+)-ATPase activity. In tissue samples obtained from patients, immunohistochemistry demonstrated the expression in parietal cells of both subunits of gastric H(+)-K(+)-ATPase and the CaSR. Functional experiments using the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein and measurement of intracellular pH changes allowed us to estimate the activity of H(+)-K(+)-ATPase in single freshly isolated human gastric glands. Under control conditions, H(+)-K(+)-ATPase activity was stimulated by histamine (100 microM) and inhibited by omeprazole (100 microM). Reduction of the extracellular divalent cation concentration (0 Mg(2+), 100 microM Ca(2+)) inactivated the CaSR and reduced histamine-induced activation of H(+)-K(+)-ATPase activity. In contrast, activation of the CaSR with the trivalent cation Gd(3+) caused activation of omeprazole-sensitive H(+)-K(+)-ATPase activity even in the absence of histamine and under conditions of low extracellular divalent cations. This stimulation was not due to release of histamine from neighbouring enterochromaffin-like cells as the stimulation persisted in the presence of the H(2) receptor antagonist cimetidine (100 microM). Furthermore, intracellular calcium measurements with fura-2 and fluo-4 showed that activation of the CaSR by Gd(3+) led to a sustained increase in intracellular Ca(2+) even under conditions of low extracellular divalent cations. These experiments demonstrate the presence of a functional CaSR in the human stomach and show that this receptor may modulate the activity of acid-secreting H(+)-K(+)-ATPase in parietal cells. Furthermore, our results show the viability of freshly isolated human gastric glands and may allow the use of this preparation for experiments investigating the physiological regulation and properties of human gastric glands in vitro.
Understanding the rates of certain enzyme-catalyzed reactions: Proton abstraction from carbon acids, acyl transfer reactions, and displacement reactions of phosphodiesters (1993)

The structural factors responsible for the rapid rates (kcats) of enzyme-catalyzed reactions are not well understood. In this paper, we outline an analysis that we believe can provide a quantitative understanding of the kcats of three types of reactions: abstraction of the alpha-protons from carbon acids, acyl-transfer reactions, and displacement reactions of phosphodiesters. We propose that these reactions proceed via the formation of intermediates in which negative charge develops on the carbonyl or phosphoryl oxygens. Our analysis is based on Marcus formalism that separates the activation energy barrier for conversion of bound substrate to the intermediate, delta G++, into contributions from a thermodynamic barrier, delta G zero, and an intrinsic kinetic barrier, delta G++int. We propose that one (or more) general acid catalyst positioned adjacent to the carbonyl or phosphoryl oxygens of the substrate is primarily responsible for reducing both delta G zero and delta G++int from the values that characterize nonenzymatic reactions. The proton donors (1) stabilize the intermediates via the formation of short, strong hydrogen bonds (the pKas of the protonated intermediates and the general acid catalysts are matched), thereby reducing delta G zero, and (2) stabilize the transition states for formation of the intermediates by negating the developing charge on the oxygens without the requirement for significant structural reorganization, thereby reducing delta G++int. The possible reductions in delta G zero and delta G++int are sufficient to understand the rapid kcats of these reactions.
Synthesis and biological evaluation of amphotericin B derivatives (2010)

Covering: 1955 to 2009
Continuous incisional infusion of local anesthetic in pediatric patients following open heart surgery (2009)

A continuous incisional infusion of LA reduced postoperative analgesic requirement and sedative use in pediatric patients undergoing a median sternotomy incision. Dosed at a maximum rate of 0.4 mg x kg(-1) x h(-1), a continuous incisional infusion of LA is effective and safe for up to 72 h, with plasma levels of local anesthetic well below the toxic threshold.
If you can teach it, you can measure it (2005)

This article describes how the author measured three different variables in her classes: 1) computer anxiety, 2) systems analysis and design skills, and 3) attitude toward ethical issues. In the first case she chose two validated tools from many choices on the topic; in the second case she developed her own tool from a template in an assessment book; in the third case she selected questions from a validated tool and also developed her own. In each case the results of the measuring tool were consistent with what she predicted.