gebhart/patrepeval huggingface dataset:
Production and activation of recombinant hK2 with propeptide mutations resulting in high expression levels (1999)

Human glandular kallikrein 2 (hK2) is a serine protease expressed mainly by the prostate gland with 80% identity in primary structure to prostate specific antigen (PSA). hK2 has proven to be a useful marker of prostate cancer which can be used in combination with PSA to better discriminate between prostate cancer and benign prostate hyperplasia. The studies on hK2 have been hampered by its very low phyciological levels (6 microgram.mL-1), its close similarity to PSA, and the low expression levels obtained using recombinant procedures to produce hK2 (0.7 mg.L-1). We have now generated propeptide mutations of hK2 which can be used to isolate stable, inactive prohK2 mutants. Compared with wild-type hK2, expression of the propeptide hK2 mutants increases the expression levels up to 15-40-fold giving 10-30 mg hK2.L-1. These results indicate that the low expression levels of wild-type hK2 are related to the activation or autoactivation of the wild-type enzyme and the instability of the active protease in cell culture and possibly also in tissue. The purified mutant hK2 may be activated by either enterokinase or factor Xa to generate an enzyme for use in functional studies with the characteristics of the original wild-type protein. Further, the stable inactive mutant hK2 protein may be used for immunizations to generate novel monoclonal antibodies, used as standard material for clinical assays or in crystallization studies where large quantities of protein are required.
Modeling of Arrhythmogenic Right Ventricular Cardiomyopathy With Human Induced Pluripotent Stem Cells (2013)

Background— Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disorder resulting from desmosomal protein mutations. ARVC is characterized pathologically by fibrofatty infiltration and clinically by arrhythmias and sudden cardiac death. We aimed to establish a patient-/disease-specific human induced pluripotent stem cell (hiPSC) model of ARVC. Methods and Results— Dermal fibroblasts were obtained from 2 patients with ARVC with plakophilin-2 ( PKP2 ) mutations, reprogrammed to generate hiPSCs, coaxed to differentiate into cardiomyocytes (CMs), and then compared with healthy control hiPSC-derived CMs (hiPSC-CMs). Real-time polymerase chain reaction showed a significant decrease in the expression of PKP2 in the ARVC-hiPSC-CMs. Immunostainings revealed reduced densities of PKP2, the associated desmosomal protein plakoglobin, and the gap-junction protein connexin-43. Electrophysiological assessment demonstrated prolonged field potential rise time in the ARVC-hiPSC-CMs. Transmission electron microscopy identified widened and distorted desmosomes in the ARVC-hiPSC-CMs. Clusters of lipid droplets were identified in the ARVC-CMs that displayed the more severe desmosomal pathology. This finding was associated with upregulation of the proadipogenic transcription factor peroxisome proliferator-activated receptor-γ. Exposure of the cells to apidogenic stimuli augmented desmosomal distortion and lipid accumulation. The latter phenomenon was prevented by application of a specific inhibitor of glycogen synthase kinase 3β (6-bromoindirubin-3'-oxime). Conclusions— This study highlights the unique potential of the hiPSC technology for modeling inherited cardiac disorders in general and ARVC specifically. The hiPSC-CMs were demonstrated to recapitulate the ARVC phenotype in the dish, provide mechanistic insights into early disease pathogenesis, and provide a unique platform for drug discovery and testing in this disorder.
Micelle/Monomer Control over the Membrane-Disrupting Properties of an Amphiphilic Antibiotic (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMicelle/Monomer Control over the Membrane-Disrupting Properties of an Amphiphilic AntibioticKeiji Yamashita, Vaclav Janout, Edward Bernard, Donald Armstrong, and Steven L. RegenCite this: J. Am. Chem. Soc. 1995, 117, 23, 6249–6253Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/ja00128a011https://doi.org/10.1021/ja00128a011research-articleACS PublicationsRequest reuse permissionsArticle Views401Altmetric-Citations41LEARN 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
DIC Complicating APL Successfully Treated With Recombinant Thrombomodulin Alfa (2016)

An 8-year-old boy developed anorexia, fatigue, and fever. Laboratory examination revealed a high white blood cell (WBC) count of 145×10/μL with 97.5% abnormal promyelocytic cells that contained Auer bodies. Faggot cells were seen. He was diagnosed with acute promyelocytic leukemia. Later, a chromosome analysis showed 46,XY,t(15;17)(q22;q12). Promyelocytic Leukemia-retinoic acid receptor α-fused gene and chimeric mRNA were confirmed by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, respectively. He was complicated with disseminated intravascular coagulation (DIC) and his fibrin and fibrinogen degradation product at the onset was 37.6 μg/mL. Human recombinant thrombomodulin (rTM) was started for DIC. After dexamethasone was administered at a dose of 8 mg/m to prevent all-trans retinoic acid syndrome on day 1, all-trans retinoic acid was started at a dose of 45 mg/m on day 4. Cytarabine (100 mg/m/d) and daunorubicin (45 mg/m/d) were started on day 9. The WBC count gradually increased to 270×10/μL on day 8, and then decreased beginning on day 9. DIC improved after the initiation of chemotherapy and only minor petechia was noted. DIC did not become worse even after rTM was stopped on day 8. The risk of DIC and bleeding is high in the early stage of treatment for acute promyelocytic leukemia, especially in patients with a high WBC count. In our patient, rTM may have prevented fatal DIC and made it possible to safely administer induction chemotherapy.
Quantitation of Transcription and Clonal Selection of Single Living Cells with β-Lactamase as Reporter (1998)

Gene expression was visualized in single living mammalian cells with beta-lactamase as a reporter that hydrolyzes a substrate loaded intracellularly as a membrane-permeant ester. Each enzyme molecule changed the fluorescence of many substrate molecules from green to blue by disrupting resonance energy transfer. This wavelength shift was detectable by eye or color film in individual cells containing less than 100 beta-lactamase molecules. The robust change in emission ratio reveals quantitative heterogeneity in real-time gene expression, enables clonal selection by flow cytometry, and forms a basis for high-throughput screening of pharmaceutical candidate drugs in living mammalian cells.
Detection and monitoring of progressive degeneration of osteoarthritic cartilage by MRI (1995)

Osteoarthritis (OA) results from a failure of cells within the joint to maintain the balance between synthesis and degradation of the extracellular matrix. OA is a major cause of pain and disability in the elderly yet there is at present no effective treatment to slow down or halt progressive loss of joint function. This is partly because the condition is heterogeneous with obscure pathogenesis but also because there are no specific laboratory tests or screening procedures that provide a specific diagnosis of early OA. There is a clear need to be able to define onset of characteristic pathological changes when intervention would be timely and to monitor the natural history up to the stage of radiologically detected damage.
The adaptive transactional memory test platform (2008)

Sun has recently announced that its forthcoming multicore processor, code-named Rock, will support a form of hardware transactional memory (HTM). Our poster describes this feature, and presents the Adaptive Transactional Memory Test Platform (ATMTP)---a simulator we have developed that allows us and others to experiment with code that uses it, as well as the results of some preliminary experiments conducted using ATMTP.
Studies on Amine Oxide Rearrangements: RegioselectiveSynthesis of Pyrrolo[3,2-f ]quinolin-7-ones (1997)

A number of derivatives of the hitherto unreportedpyrrolo[3,2-f ]quinolin-7-one tricyclic system have beensynthesised from 6-nitroquinolone by successive reduction,tosylation, methylation, detosylation, prop-2-ynylation andtreatment with m -chloroperoxybenzoic acid.
The Contribution of Low Birth Weight to Infant Mortality and Childhood Morbidity (1985)

The low-birth-weight infant remains at much higher risk of mortality than the infant with normal weight at birth. In the neonatal period, when most infant deaths occur, the proportion of low-birth-weight infants, especially those with very low weight, is the major determinant of the magnitude of the mortality rates. Furthermore, differences in low-birth-weight rates account for the higher neonatal mortality rates observed in some groups, particularly those characterized by socioeconomic disadvantages. Much of the recent decline in neonatal mortality can be attributed to increased survival among low-birth-weight infants, apparently as a result of hospital-based services. The application of these services is currently considered cost-effective, although whether this will continue to be true in the future is unclear because of the increased survival of very tiny infants. Although low-birth-weight infants remain at increased risk of both postneonatal mortality and morbidity in infancy and early childhood, the risk is substantially smaller than that of neonatal death. In addition, these adverse later outcomes have not offset the gains achieved in the neonatal period. Nonetheless, the increased survival of high-risk infants raises concern about their future requirements for special medical and educational services and about the stress on their families. Despite increased access to antenatal services, only moderate declines in the proportion of low-birth-weight infants has been observed, and almost no change has occurred in the proportion of those with very low weight at birth. In addition, in many areas of the country the birth-weight-specific neonatal mortality rates are similar for groups at high and low risk of neonatal death. In view of these findings, continuation of the current decline in neonatal mortality and reduction of the mortality differentials between high- and low-risk groups require the identification and more effective implementation of strategies for the prevention of low-weight births.
Phosphoproteomics Study on the Activated PKCδ-Induced Cell Death (2013)

The proteolytic activation of protein kinase Cδ (PKCδ) generates a catalytic fragment called PKCδ-CF, which induces cell death. However, the mechanisms underlying PKCδ-CF-mediated cell death are largely unknown. On the basis of an engineering leukemic cell line with inducible expression of PKCδ-CF, here we employ SILAC-based quantitative phosphoproteomics to systematically and dynamically investigate the overall phosphorylation events during cell death triggered by PKCδ-CF expression. Totally, 3000 phosphorylation sites were analyzed. Considering the fact that early responses to PKCδ-CF expression initiate cell death, we sought to identify pathways possibly related directly with PKCδ by further analyzing the data set of phosphorylation events that occur in the initiation stage of cell death. Interacting analysis of this data set indicates that PKCδ-CF triggers complicated networks to initiate cell death, and motif analysis and biochemistry verification reveal that several kinases in the downstream of PKCδ conduct these networks. By analysis of the specific sequence motif of kinase-substrate, we also find 59 candidate substrates of PKCδ from the up-regulated phosphopeptides, of which 12 were randomly selected for in vitro kinase assay and 9 were consequently verified as substrates of PKCδ. To our greatest understanding, this study provides the most systematic analysis of phosphorylation events initiated by the cleaved activated PKCδ, which would vastly extend the profound understanding of PKCδ-directed signal pathways in cell death. The MS data have been deposited to the ProteomeXchange with identifier PXD000225.
A signature based approach to regularity extraction (1997)

Regularity extraction is an important step in the design flow of datapath-dominated circuits. This paper outlines a new method that automatically extracts regular structures from the netlist. The method is general enough to handle two types of designs: designs with structured cluster information for a portion of the datapath components that are identified at the HDL level; and designs with no such structured cluster information. The method analyzes the circuit connectivity and uses signature based approaches to recognize regularity.
Antitumor Activity of GSK1904529A, a Small-molecule Inhibitor of the Insulin-like Growth Factor-I Receptor Tyrosine Kinase (2009)

GSK1904529A is a promising candidate for therapeutic use in IGF-IR-dependent tumors.
Aptamers and aptazymes: accelerating small molecule drug discovery. (2002)

Synthetic nucleic acid ligands, known as aptamers, are versatile tools that can greatly enhance the efficiency of modern drug development. Exhibiting binding characteristics comparable to or even better than monoclonal antibodies, these ligands can be used as detection probes, highly efficient inhibitors of protein function or specific competitors in high-throughput screening (HTS) assays. Thus, aptamer technology can be exploited to address the growing demand for multi-parallel analysis of proteomes, functional prioritization of potential drug targets and accelerated small molecule lead identification. The unique advantages of this technology are the rapid automated generation of sophisticated ligands against almost any target molecule and the convenient structural or chemical modification of the nucleic acid probes. Depending on the strategy, an RNA aptamer can be expressed transgenically to investigate and inactivate an endogenous protein in an animal model, or it can be designed to function as a highly sensitive nucleic acid biosensor. More recently, the technology has been extended to directly link functional target validation with HTS, accelerating the process of drug discovery.
Optimization and use of flow injection vapour generation inductively coupled plasma mass spectrometry for the determination of arsenic, antimony and mercury in water and sea-water at ultratrace levels (1993)

Vapour generation flow injection inductively coupled plasma mass spectrometry (FI-ICP-MS) was used for the determination of As, Sb and Hg in four international water reference materials (National Research Council of Canada). A commercially available FI device was easily connected to the ICP-MS system. Flow injection parameters such as sample volume, purge gas flow rate and concentration of reductant were investigated and optimized (univariate) as were different sample pre-reduction techniques. The precision and accuracy of the results obtained show the applicability of this method to the determination of vapour-forming elements at ultratrace levels in environmental samples. Detection limits are in the range 0.5–7 ng l–1 for Bi, Sb, 82Se, Te, Hg and As (with pre-reduction).
Towards Liver-Directed Gene Therapy for Crigler-Najjar Syndrome (2009)

Crigler-Najjar (CN) syndrome is a recessive inherited disorder caused by deficiency of uridine diphospho-glucuronosyl transferase 1A1. This hepatic enzyme catalyzes the glucuronidation of bilirubin, an essential step in excretion into bile of this neurotoxic compound. As a result, CN patients suffer from severe unconjugated hyperbilirubinemia and are at risk of bilirubin encephalopathy. Over the last decades ex vivo and in vivo gene therapy using viral and non-viral vectors has been used to correct hyperbilirubinemia in the relevant animal model for CN syndrome, the Gunn rat. Several of these approaches did result in long-term correction of serum bilirubin levels in this animal model. However, none have been translated into a clinical trial. In this review we will recapitulate the strategies used and discuss their suitability for clinical application in the near future. We will also address specific safety measures in the gene therapy protocol needed to prevent adverse effects such as bilirubin toxicity. Since CN seems an ideal model for other monogenetic inherited metabolic liver disorders, development of liver-directed gene-therapy has relevance beyond this rare disease.
Purification, Partial Characterization and Substrate Specificity of a Squalene Cyclase fromBacillus acidocaldarius (1986)

From the thermophilic Bacillus acidocaldarius, a membrane bound cyclase catalysing the formation of 22(29)-hopene (diploptene) and 22-hopanol (diplopterol) from squalene was enriched 670-fold to a purity of 95% as judged by gel chromatography. The specific activity of the purified enzyme in the presence of Triton X-100 is 0.22 mumol product formation per min and mg protein at 54 degrees C. The molecular mass is 150 kDa and that of the subunits 80 kDa as determined by FPLC gel chromatography and sodium dodecyl sulfate gel electrophoresis, respectively. Not only squalene but also E,E-homofarnesol, homogeraniol and homofarnesyl (1,5,9-trimethyl-4,8-decadienyl) ether are substrates. The ether bond of the latter substrate is split by the enzyme. The products of the aforementioned three additional substrates are ambroxan (dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]-furan), octahydro-4,4,7a-trimethylbenzofuran and ambroxan together with 1,5,9-trimethyl-4,8-decadienol. The cyclization rates of these substrates compared to squalene are 3%, 0.05% and 0.3%, respectively. The half-life of the enzyme activity is 80 h at 45 degrees C and 18 h at 54 degrees C.
Photoablation of Polymer Materials (2010)

This chapter contains sections titled: Introduction Classification of polymers used for laser ablation Laser sources Commercially available polymers Doped polymers Designed polymers Comparison of designed and commercially available polymers References
Safety and immunogenicity of a recombinant outer surface protein A Lyme vaccine. (1994)

Two or three doses of OspA Lyme vaccine are safe and immunogenic in adults.
Clostridium perfringens Enterotoxin Utilizes Two Structurally Related Membrane Proteins as Functional Receptors in Vivo (1997)

Human and mouse cDNAs showing homology to the Clostridium perfringens enterotoxin (CPE) receptor gene (CPE-R) from Vero cells (DDBJ/EMBL/GenBankTM accession no. D88492) (Katahira, J., Inoue, N., Horiguchi, Y., Matsuda, M., and Sugimoto, N. (1997) J. Cell Biol. 136, 1239-1247) were cloned. They were classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal apoptosis protein (RVP1; accession no. M74067) homologues, based on the similarities of primary amino acid sequences. L929 cells that were originally insensitive to CPE became sensitive to CPE on their transfection with cDNAs encoding either the CPE receptor or RVP1 homologues, indicating that these gene products are not only structurally similar but also functionally active as receptors for CPE. By binding assay, the human RVP1 homologue showed differences in affinity and capacity of binding from those of the human CPE receptor. Northern blot analysis showed that mouse homologues of the CPE receptor and RVP1 are expressed abundantly in mouse small intestine. The expression of CPE-R mRNA in the small intestine was restricted to cryptic enterocytes, indicating that the CPE receptor is expressed in intestinal epithelial cells. These results are consistent with reports that CPE binds to the small intestinal cells via two different kinds of receptors. High levels of expression of CPE-R and/or RVP1 mRNA were also detected in other organs, including the lungs, liver, and kidneys, but only low levels were expressed in heart and skeletal muscles. These results indicate that CPE uses structurally related cellular proteins as functional receptors in vivo and that organs that have not so far been recognized as CPE-sensitive have the potential to be targets of CPE.
Hybrid ARQ scheme employing TCM andpacket combining (1998)

A new hybrid automatic repeat request scheme employing packet combining based on the Viterbi decoder is presented. It is shown that the proposed form of combining, together with a rearrangement of the signal constellation, can outperform similar forms of packet combining such as average diversity combining.
London 2012 Olympic Games – Basketball Arena shell (2012)

This article describes how the building shell element of the 12 000-seat temporary demountable Basketball Arena for the London 2012 games was designed and built.
Immunostimulatory Effects of Low-Dose Cyclophosphamide Are Controlled by Inducible Nitric Oxide Synthase (2005)

Cyclophosphamide is a widely used chemotherapeutic drug that was recently applied as either an antiangiogenic/antivasculogenic or an immunostimulatory agent in combination with cancer immunotherapies. It has been previously shown that cyclophosphamide augments the efficacy of antitumor immune responses by depleting CD4+ CD25+ T regulatory cells and increasing both T-lymphocyte proliferation and T memory cells. Furthermore, cyclophosphamide was shown to mediate killing of circulating endothelial progenitors. However, the molecular basis for these observations has not yet been elucidated. We show here that the cyclophosphamide-mediated inhibition of inducible nitric oxide synthase is directly linked to its immunostimulatory but not to its antivasculogenic effects. Moreover, combined application of cyclophosphamide with a novel, oral DNA vaccine targeting platelet-derived growth factor B (PDGF-B), overexpressed by proliferating endothelial cells in the tumor vasculature, not only completely inhibited the growth of different tumor types but also led to tumor rejections in mice. These findings provide a new rationale at the molecular level for the combination of chemotherapy and immunotherapy in cancer treatment.
A new scalar planewave model for high NA lithography simulations (2002)

A high NA photolithography simulator has been developed based on the angular spectrum analysis of planewaves. Spatial partial coherence is modelled using Van Cittert-Zernike theorem, which allows the extended source in a stepper to be divided into a number of point sources. Fast Fourier transform is applied to the coherent imaging by the point sources, leading to an efficient computation of the intensities in the image space. Special attention is devoted to source discretization to avoid the intensity fluctuations and improve the speed performance. The simulator can be used to calculate the aerial images of full circuit cells in a time scale proportional to NlogN. For resist profile calculations, a new approximation method has been developed for modelling photoresist bleaching during a high NA stepper exposure. The simulator has been applied to simulation-based global proximity correction and design rule generation for IC manufacturing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>