gebhart/patrepeval huggingface dataset:
Dissecting the catalytic mechanism of protein-tyrosinephosphatases. (1994)

Protein-tyrosine phosphatases (PTPases) contain an evolutionarily conserved segment of 250 amino acids referred to as the PTPase catalytic domain. The recombinant PTPase domain from Yersinia enterocolitica enhances the rate of hydrolysis of p-nitrophenyl phosphate, a phosphate monoester, by approximately 10(11) over the non-enzyme-catalyzed rate by water. Specific amino acid residues responsible for the catalytic rate acceleration have been examined by site-directed mutagenesis. Our results suggest that Asp-356 (D356) and Glu-290 (E290) are the general acid and the general base catalysts responsible for Yersinia PTPase-catalyzed phosphate ester hydrolysis. The PTPase with both E290Q and D356N mutations shows no pH dependence for catalysis but displays a rate enhancement of 2.6 x 10(6), compared to the noncatalyzed hydrolysis of p-nitrophenyl phosphate by water. This rate enhancement probably occurs via transition-state stabilization. Our results suggest that all PTP-ases use a common mechanism that depends upon formation of a thiol-phosphate intermediate and general acid-general base catalysis.
The Product of the Saccharomyces cerevisiae Cell Cycle Gene DBF2 Has Homology with Protein Kinases and Is Periodically Expressed in the Cell Cycle (1990)

Several Saccharomyces cerevisiae dbf mutants defective in DNA synthesis have been described previously. In this paper, one of them, dbf2, is characterized in detail. The DBF2 gene has been cloned and mapped, and its nucleotide sequence has been determined. This process has identified an open reading frame capable of encoding a protein of molecular weight 64,883 (561 amino acids). The deduced amino acid sequence contains all 11 conserved domains found in various protein kinases. DBF2 was periodically expressed in the cell cycle at a time that clearly differed from the time of expression of either the histone H2A or DNA polymerase I gene. Its first function was completed very near to initiation of DNA synthesis. However, DNA synthesis in the mutant was only delayed at 37 degrees C, and the cells blocked in nuclear division. Consistent with this finding, the execution point occurred about 1 h after DNA synthesis, and the nuclear morphology of the mutant at the restrictive temperature was that of cells blocked in late nuclear division. DBF2 is therefore likely to encode a protein kinase that may function in initiation of DNA synthesis and also in late nuclear division.
Selective plane illumination microscopy techniques in developmental biology (2009)

Selective plane illumination microscopy (SPIM) and other fluorescence microscopy techniques in which a focused sheet of light serves to illuminate the sample have become increasingly popular in developmental studies. Fluorescence light-sheet microscopy bridges the gap in image quality between fluorescence stereomicroscopy and high-resolution imaging of fixed tissue sections. In addition, high depth penetration, low bleaching and high acquisition speeds make light-sheet microscopy ideally suited for extended time-lapse experiments in live embryos. This review compares the benefits and challenges of light-sheet microscopy with established fluorescence microscopy techniques such as confocal microscopy and discusses the different implementations and applications of this easily adaptable technology.
Provision of Guaranteed QoS with Hybrid Automatic Repeat Request in Interleave Division Multiple Access Systems (2006)

Provision of guaranteed quality of service (QoS) in wireless communication has always been a demanding task. QoS can be ensured by the mechanism of repeat request, however real time systems can tolerate only a finite delay. In this paper we investigate the problem of provision of guaranteed QoS by hybrid automatic repeat request (HARQ) schemes, based on soft outputs of a channel decoder. Focus is on adaptive interleave-division multiple access (IDMA) transmission. Such a system is able to provide virtually arbitrary bit error rates (BER). The proposed HARQ schemes use the reliability information provided by the channel decoder to decide whether a packet satisfies the quality of service (QoS) requirements. QoS can be specified in terms of a minimum required throughput/data rate or a minimum required BER. Effect of truncation of repeat requests on the bit error rate and packet throughput is investigated. An adaptation scheme based upon the bit error rate in the accepted packets is proposed and the effect of the adaptation on the effective throughput is demonstrated
Multidimensional Protein Separations in a Plastic Microfluidic Network (2003)

The field of microfabrication of bioanalytical devices has grown significantly over the last decade from academic research to several commercially available systems. The performances of the microfluidic systems in terms of reproducibility, resolution, sensitivity, and speed can be achieved by applying these technologies to complex biological samples. A commonly used capillary fitting is employed for housing miniaturized membrane chromatography for performing reversed-phase peptide separations. Separation performance of cytochrome C digest in miniaturized membrane chromatography is compared with the results obtained from μ-LC and capillary LC. The use of miniaturized membrane chromatography allows significant reduction in sample consumption together with enhanced detection sensitivity. In order to further reduce sample consumption and dead volume, an isoelectric focusing separation and dynamic sample introduction are demonstrated in a microfluidic microchannel. The dynamic sample introduction in plastic microfluidic devices can be directly controlled by various electrokinetic conditions, including the injection time and the applied electric field strength. It enhances sample loading and therefore the concentrations of focused analytes by approximately 10-100 fold in comparison with conventional isoelectric focusing. An integrated 2-D protein separation system provides significant resolving power for complex protein mixtures. Non-native IEF is chosen for the first separation dimension and gel electrophoresis for the second dimension. Once the focusing is complete, the focusing proteins at IEF microchannel are simultaneously transferred using an electrokinetic method from the first dimensional microchannel into an array of the second dimensional microchannels for achieving parallel size-depended separation on each sampled fraction. Although this simple study involves a limited number of second dimensional microchannels, the ability for a microfluidic platform to perform parallel 2-D separations of complex protein samples has been successfully demonstrated. This study investigates that microfabricated systems have the potential to automate and combine high throughput multidimensional protein separations in a microfluidic network. It is crucial to combine various microfluidic components, which enable all required proteome technologies in an integrated platform for a true lab-on-a-chip.
Ranking algorithms for named-entity extraction (2001)

This paper describes algorithms which rerank the top N hypotheses from a maximum-entropy tagger, the application being the recovery of named-entity boundaries in a corpus of web data. The first approach uses a boosting algorithm for ranking problems. The second approach uses the voted perceptron algorithm. Both algorithms give comparable, significant improvements over the maximum-entropy baseline. The voted perceptron algorithm can be considerably more efficient to train, at some cost in computation on test examples.
Human Dendritic Cells Transfected with RNA Encoding Prostate-Specific Antigen Stimulate Prostate-Specific CTL Responses In Vitro (2000)

Although immunological tolerance to self Ags represents an important mechanism to prevent normal tissue injury, there is growing evidence that tolerance to tumor Ags, which often represent normal peripherally expressed proteins, is not absolute and can be effectively reverted. Prostate-specific Ag (PSA) is a self Ag expressed by both normal and malignant prostatic epithelium, and therefore offers a unique opportunity to examine the ability of self Ags to serve as specific CTL targets. In this study, we investigated the efficacy of autologous dendritic cells (DC) transfected with mRNA encoding PSA to stimulate CTL against PSA Ags in vitro. Ag in form of RNA carries the advantage to encode multiple epitopes for many HLA alleles, thus permitting induction of CTL responses among many cancer patients independent of their HLA repertoire. In this study, we show that PSA mRNA-transfected DC were capable of stimulating primary CTL responses against PSA Ags in vitro. The PSA-specific CTL did not cross-react with kallikrein Ags, a protein, which shares significant homology with PSA, suggesting that harmful autoimmune toxicity may not represent a significant problem with this approach. PSA RNA-transfected DC generated from male or female healthy volunteers or from cancer patients were equally effective in stimulating PSA-specific CTL in vitro, implying that neither natural tolerance to PSA Ags nor tumor-mediated T cell anergy may represent major barriers for CTL generation against the self Ag PSA. This study provides a preclinical rationale for using PSA RNA-transfected DC in active or adoptive immunization protocols.
Dynamics of three-dimensional replication patterns during the s-phase, analysed by double labelling of dna and confocal microscopy (1992)

The temporal and spatial progression of DNA replication in interphase nuclei of eukaryotic cells has been investigated. Application of a recently developed technique for the immunofluorescence double staining of cell nuclei labelled first with iododeoxyuridine (IdUrd) and subsequently with chlorodeoxyuridine (CldUrd) allows the visualization of two replication patterns in the same nucleus originating from two different periods of the S-phase. We have analysed changes in the three-dimensional replication patterns during the S-phase. To record dual colour three-dimensional images of doubly stained nuclei, a confocal microscope is used. This CSLM is equipped with a specific laser/filter combination to collect both fluorescence signals (FITC and Texas Red) in a single scan, thus precluding pixel shift between the images. A method for the quantitative evaluation of the degree of overlap between DNA regions replicated in two different periods of the S-phase is applied. The results confirm the generally accepted theory that DNA is replicated coordinately in a specific temporal order during the S-phase. The replication time of a DNA domain (i.e. the time between initiation and termination of DNA replication within a domain) at the very beginning of the S-phase was known to be one hour (Nakamura et al., 1986). Our observations show that in the rest of the S-phase, the replication time of a DNA region is also about one hour. We conclude that replicon clusters located in the same region are replicated in the same relatively short period of time. After this period there is no unreplicated DNA left in this region.
Recent Advances in Isocyanate Chemistry (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRecent Advances in Isocyanate ChemistryShoichiro. OzakiCite this: Chem. Rev. 1972, 72, 5, 457–496Publication Date (Print):October 1, 1972Publication History Published online1 May 2002Published inissue 1 October 1972https://pubs.acs.org/doi/10.1021/cr60279a002https://doi.org/10.1021/cr60279a002research-articleACS PublicationsRequest reuse permissionsArticle Views5063Altmetric-Citations372LEARN 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
New Directions in the Assessment of Gastric Function: Clinical Applications of Physiologic Measurements (2006)

A variety of methods exist to assess gastric motor and sensory function. Specific techniques allow for the measurement of emptying, contractility, accommodation and sensation. Several of these techniques are suitable for in-office use rather than in a hospital or gastroenterology laboratory. While gastric function tests continue to proliferate and become more clinically accessible, their relevance to specific digestive symptoms or syndromes remains poorly studied. Additionally, the ability of gastric function testing to guide therapy or predict responses to interventions also remains poorly studied. Gastric function testing should be employed cautiously in clinical practice with an awareness that test results represent observations rather than diagnosis.
Lack of Hypoxic Response in Uterine Leiomyomas despite Severe Tissue Hypoxia (2008)

Hypoxia is now established as a key factor influencing the pathophysiology of malignant growth. Among other effects, hypoxia modulates the expression of a multitude of genes through the induction of hypoxia-inducible transcription factors. This differential gene expression favors angiogenesis, cell survival, an invasive/metastatic phenotype, and resistance to anticancer therapies. Because benign tumors do not exhibit these traits, one might expect these entities to be neither hypoxic nor to induce the genetic hypoxia response program. To test this hypothesis, an investigation of the oxygenation status of 17 leiomyomas and 1 leiomyosarcoma of the uterus using polarographic needle electrodes (Eppendorf pO(2) sensor) and the expression of hypoxia-related markers in biopsy specimens of the same tumors was carried out. Marker expression in eight additional archival leiomyosarcomas was also assessed. Leiomyoma tissue was generally found to be severely hypoxic, with median oxygen (O(2)) partial pressure values ranging from 1 to 5 mm Hg. In contrast, none of the hypoxia-related markers hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, glucose transporter-1, or carbonic anhydrase IX were expressed in any leiomyoma. Larger intercapillary distances were correlated with a poorer oxygenation status. Conversely, the expression of hypoxia-related markers was abundant in the leiomyosarcomas and they also exhibited a high-turnover phenotype (significantly increased proliferation and apoptosis). Uterine leiomyoma might therefore represent a state of oxygen-limited proliferation. Malignancy in the same organ system is associated with growth and metabolism beyond tissue-inherent limitations leading to the induction of hypoxia-related markers, thereby contributing to a self-perpetuating aggressive phenotype.
RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea (2006)

The trace element selenium is found in proteins as selenocysteine (Sec), the 21st amino acid to participate in ribosome-mediated translation. The substrate for ribosomal protein synthesis is selenocysteinyl-tRNA(Sec). Its biosynthesis from seryl-tRNA(Sec) has been established for bacteria, but the mechanism of conversion from Ser-tRNA(Sec) remained unresolved for archaea and eukarya. Here, we provide evidence for a different route present in these domains of life that requires the tRNA(Sec)-dependent conversion of O-phosphoserine (Sep) to Sec. In this two-step pathway, O-phosphoseryl-tRNA(Sec) kinase (PSTK) converts Ser-tRNA(Sec) to Sep-tRNA(Sec). This misacylated tRNA is the obligatory precursor for a Sep-tRNA:Sec-tRNA synthase (SepSecS); this protein was previously annotated as SLA/LP. The human and archaeal SepSecS genes complement in vivo an Escherichia coli Sec synthase (SelA) deletion strain. Furthermore, purified recombinant SepSecS converts Sep-tRNA(Sec) into Sec-tRNA(Sec) in vitro in the presence of sodium selenite and purified recombinant E. coli selenophosphate synthetase (SelD). Phylogenetic arguments suggest that Sec decoding was present in the last universal common ancestor. SepSecS and PSTK coevolved with the archaeal and eukaryotic lineages, but the history of PSTK is marked by several horizontal gene transfer events, including transfer to non-Sec-decoding Cyanobacteria and fungi.
IgG2 Antibodies against a Clinical Grade Plasmodium falciparum CSP Vaccine Antigen Associate with Protection against Transgenic Sporozoite Challenge in Mice (2014)

The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive T(H1)/T(H2) response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans.
Finite element modelling of three‐phase flow in deforming saturated oil reservoirs (1993)

Abstract A numerical simulation is presented for three‐dimensional three‐phase fluid flow in a deforming saturated oil reservoir. The mathematical formulation describes a fully coupled governing equation systen which consists of the equilibrium and continuity equations for three immiscible fluids flowing in a porous medium. An elastoplastic soil model, based on a Mohr–Coulomb yield surface, is used. The finite element method is applied to obtain simultaneous solutions to the governing equations where displacement and fluid pressures are the primary unknowns. The final discretized equations are solved by a direct solver using fully implicit procedures. The developed model is used to investigate the problems of three‐phase fluid flow in a deforming saturated oil reservoir.
Clinical decision making for caries management in children. (2003)

The aim of this review of clinical decision making for caries management in children is to integrate current knowledge in the field of cariology into clinically usable concepts and procedures. Current evidence regarding the carious process and caries risk assessment allows the practitioner to go beyond traditional surgical management of dental caries. Therapy should focus on patient-specific approaches that include disease monitoring and preventive therapies supplemented when necessary by restorative care. The type and intensity of these therapies should be determined utilizing clinical data as well as knowledge of the caries process for that child. Changes in the management of dental caries will require health organizations and dental schools to educate students, practitioners, and patients in evidence- and risk-based care.
Membrane‐bound IgM obstructs B cell development in transgenic mice (1989)

Rearranged immunoglobulin genes encoding either the secreted (microsecond) or membrane (micron) form of IgM were introduced into the mouse germ line. We report here the phenotypic analysis of lymphocyte populations in these mice (T microsecond and T micron). In T microsecond mice the transgenic mu chain is present in serum antibodies. The frequencies of B cells in the various B cell compartments of T microsecond mice are normal or slightly reduced compared to littermates. In T micron mice, however, B cell (but not T cell) development is severely affected. Spleens of 8-week-old T micron mice contain about 3%-8% B cells, increasing to approximately 20% at the age of 8 months. These cells express endogenous IgM. B cells expressing only transgenic micron chains are not detectable. In the bone marrow B cells are almost completely depleted. A B cell population characterized by reduced levels of IgD on the cell surface is enriched in the spleen and present at almost normal levels in the peritoneum of T micron mice.
Direct Comparison of Antigen Production and Induction of Apoptosis by Canarypox Virus- and Modified Vaccinia Virus Ankara-Human Immunodeficiency Virus Vaccine Vectors (2007)

Recombinant poxvirus vectors are undergoing intensive evaluation as vaccine candidates for a variety of infectious pathogens. Avipoxviruses, such as canarypox virus, are replication deficient in mammalian cells by virtue of a poorly understood species-specific restriction. Highly attenuated vaccinia virus strains such as modified vaccinia virus Ankara (MVA) are similarly unable to complete replication in most mammalian cells but have an abortive-late phenotype, in that the block to replication occurs post-virus-specific DNA replication. In this study, an identical expression cassette for human immunodeficiency virus gag, pro, and env coding sequences was placed in canarypox virus and MVA vector backbones in order to directly compare vector-borne expression and to analyze differences in vector-host cell interactions. Antigen production by recombinant MVA was shown to be greater than that from recombinant canarypox virus in the mammalian cell lines and in the primary human cells tested. This observation was primarily due to a longer duration of antigen production in recombinant MVA-infected cells. Apoptosis induction was found to be more profound with the empty canarypox virus vector than with MVA. Remarkably, however, the inclusion of a gag/pro/env expression cassette altered the kinetics of apoptosis induction in recombinant MVA-infected cells to levels equal to those found in canarypox virus-infected cells. Antigen production by MVA was noted to be greater in human dendritic cells and resulted in enhanced T-cell stimulation in an in vitro antigen presentation assay. These results reveal differences in poxvirus vector-host cell interactions that should be relevant to their use as immunization vehicles.