gebhart/patrepeval huggingface dataset:
Thrombin Induces Proteinase-activated Receptor-1 Gene Expression in Endothelial Cells via Activation of Gi-linked Ras/Mitogen-activated Protein Kinase Pathway (1999)

We addressed the mechanisms of restoration of cell surface proteinase-activated receptor-1 (PAR-1) by investigating thrombin-activated signaling pathways involved in PAR-1 re-expression in endothelial cells. Exposure of endothelial cells transfected with PAR-1 promoter-luciferase reporter construct to either thrombin or PAR-1 activating peptide increased the steady-state PAR-1 mRNA and reporter activity, respectively. Pretreatment of reporter-transfected endothelial cells with pertussis toxin or co-expression of a minigene encoding 11-amino acid sequence of COOH-terminal Galphai prevented the thrombin-induced increase in reporter activity. Pertussis toxin treatment also prevented thrombin-induced MAPK phosphorylation, indicating a role of Galphai in activating the downstream MAPK pathway. Expression of constitutively active Galphai2 mutant or Gbeta1gamma2 subunits increased reporter activity 3-4-fold in the absence of thrombin stimulation. Co-expression of dominant negative mutants of either Ras or MEK1 with the reporter construct inhibited the thrombin-induced PAR-1 expression, whereas constitutively active forms of either Ras or MEK1 activated PAR-1 expression in the absence of thrombin stimulation. Expression of dominant negative Src kinase or inhibitors of phosphoinositide 3-kinase also prevented the MAPK activation and PAR-1 expression. We conclude that thrombin-induced activation of PAR-1 mediates PAR-1 expression by signaling through Gi1/2 coupled to Src and phosphoinositide 3-kinase, and thereby activating the downstream Ras/MAPK cascade.
Detection of Driver Drowsiness Using Wavelet Analysis of Heart Rate Variability and a Support Vector Machine Classifier (2013)

Driving while fatigued is just as dangerous as drunk driving and may result in car accidents. Heart rate variability (HRV) analysis has been studied recently for the detection of driver drowsiness. However, the detection reliability has been lower than anticipated, because the HRV signals of drivers were always regarded as stationary signals. The wavelet transform method is a method for analyzing non-stationary signals. The aim of this study is to classify alert and drowsy driving events using the wavelet transform of HRV signals over short time periods and to compare the classification performance of this method with the conventional method that uses fast Fourier transform (FFT)-based features. Based on the standard shortest duration for FFT-based short-term HRV evaluation, the wavelet decomposition is performed on 2-min HRV samples, as well as 1-min and 3-min samples for reference purposes. A receiver operation curve (ROC) analysis and a support vector machine (SVM) classifier are used for feature selection and classification, respectively. The ROC analysis results show that the wavelet-based method performs better than the FFT-based method regardless of the duration of the HRV sample that is used. Finally, based on the real-time requirements for driver drowsiness detection, the SVM classifier is trained using eighty FFT and wavelet-based features that are extracted from 1-min HRV signals from four subjects. The averaged leave-one-out (LOO) classification performance using wavelet-based feature is 95% accuracy, 95% sensitivity, and 95% specificity. This is better than the FFT-based results that have 68.8% accuracy, 62.5% sensitivity, and 75% specificity. In addition, the proposed hardware platform is inexpensive and easy-to-use.
Pancreatic cancer: Are "liquid biopsies" ready for prime-time? (2016)

Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells (CTCs) have been investigated as a potential "liquid biopsy" in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms. Circulating tumour DNA (ctDNA) has also been detected in pancreas cancer with a sensitivity ranging from 26%-100% in studies across different platforms and using different genetic markers. However, there is no clear consensus on which platform is the most effective for detection, nor which genetic markers are the most useful to use. Potential roles of liquid biopsies include diagnosis, screening, guiding therapies and prognosis. The presence of CTCs or ctDNA has been shown to be of prognostic value both at diagnosis and after treatment in patients with pancreatic cancer. However, more prospective studies are required before this promising technology is ready for adoption into routine clinical practice.
Stability of Order in Solvent-Annealed Block Copolymer Thin Films (2003)

One way to produce high order in a block copolymer thin film is by solution casting a thin film and slowly evaporating the solvent in a sealed vessel. Such a solvent-annealing process is a versatile method to produce a highly ordered thin film of a block copolymer. However, the ordered structure of the film degrades over time when stored under ambient conditions. Remarkably, this aging process occurs in mesoscale thin films of polystyrene−polyisoprene triblock copolymer where the monolayer of vitrified 15 nm diameter polystyrene cylinders sink in a 20 nm thick film at 22 °C. The transformation is studied by atomic force microscopy (AFM). We describe the phenomena, characterize the aging process, and propose a semiquantitative model to explain the observations. The residual solvent effects are important but not the primary driving force for the aging process. The study may lead to effective avenue to improve order and make the morphology robust and possibly the solvent-annealing process more effective.
Empirical force fields for biological macromolecules: Overview and issues (2004)

Empirical force field-based studies of biological macromolecules are becoming a common tool for investigating their structure-activity relationships at an atomic level of detail. Such studies facilitate interpretation of experimental data and allow for information not readily accessible to experimental methods to be obtained. A large part of the success of empirical force field-based methods is the quality of the force fields combined with the algorithmic advances that allow for more accurate reproduction of experimental observables. Presented is an overview of the issues associated with the development and application of empirical force fields to biomolecular systems. This is followed by a summary of the force fields commonly applied to the different classes of biomolecules; proteins, nucleic acids, lipids, and carbohydrates. In addition, issues associated with computational studies on "heterogeneous" biomolecular systems and the transferability of force fields to a wide range of organic molecules of pharmacological interest are discussed.
The interaction between Buddhist and Shinto traditions at Suwa Shrine (2003)

Suwa Shrine consists of two main sites, the Upper Shrine (kamisha) and the Lower Shrine (shimosha) by Lake Suwa in central Japan. During the medieval and early modern periods, it was not a “Shinto” shrine because Buddhist symbols, institutions and practices were signiﬁcant parts of this renowned religious center. Its early history is obscure, but it is probable, considering the date of the shrine-temples ( jing¨ji) in the principal shrines (ichi no miya) of other provinces, that the Jing¨ji of Suwa Shrine was also founded during the Nara period.1 Under the patronage of the powerful Suwa (also called Miwa or Kanasashi) clan, the descendants of the Kuni no Miyatsuko of Shinano province, these Buddhist temples developed interdependently with the shrines of kami, and formed a sizable religious complex by the middle of the Kamakura period. With their doctrinal and cultural resources, the Buddhist institutions contributed to the spread of the cult of Suwa Daimyøjin and the prosperity of the complex. At its peak during the medieval period, there were more than thirty sub-temples (in, bø) in the Lower Shrine complex alone. Though the number decreased during the Edo period, the shrinetemples continued to play indispensable roles, such as the observance of special Buddhist rites for the kami. The Buddhist parts of the combination, however, were singled out and destroyed at the beginning of the Meiji period during the so-called “separation of kami and buddhas” (shinbutsu bunri), and this destruction was so radical that the pre-modern history of the Suwa Shrine has been almost completely forgotten today. This chapter traces the history of Buddhist and Shinto interactions at this renowned shrine, focusing on the Upper Shrine during the late Edo and early Meiji periods. Our survey of shinbutsu bunri in the ﬁrst year of Meiji will show that SuwaShrine was fundamentally transformed by the “dissociation” imposed by the central government.
Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice. (1987)

The activated human Ha-ras oncogene was subjected to the control of the promoter region of the murine whey acidic protein (Wap) gene, which is expressed in mammary epithelial cells in response to lactogenic hormones. The Wap-ras gene was stably introduced into the mouse germ line of five transgenic mice (one male and four females). Wap-ras expression was observed in the mammary glands of lactating females in two lines derived from female founders. The tissue-directed and hormone-dependent Wap expression was conferred on the Ha-ras oncogene. The signals governing Wap expression are located within 2.5 kilobases of 5' flanking sequence. The other two lines derived from female founders did not express the chimeric gene. In the line derived from the male founder, the Wap-ras gene is integrated into the Y chromosome. Expression was found in the salivary gland of male animals only. After a long latency, Wap-ras-expressing mice developed tumors. The tumors arose in tissues expressing Wap-ras--i.e., mammary or salivary glands. Compared to the corresponding nonmalignant tissues, Wap-ras expression was enhanced in the tumors.
SCALPS: Smart card for limited payment systems (1996)

Secure money-transfer cards continue to find acceptance in commerce. Currently, three main types of these cards coexist: magnetic stripe, mass memory, and smart. We describe another approach: merging the processor and coprocessor on a small chip dedicated to public-key cryptography. We added parts needed to obtain a low-cost smart card compatible with the ISO 7816-3 standard. By developing the processor for specific applications, we drastically reduced the complexity without affecting the chip's usefulness. To prove the feasibility of such a chip, we built one for use in a payment application with prepaid tokens.
PD-L1 Expression in Triple-Negative Breast Cancer (2014)

Early-phase trials targeting the T-cell inhibitory molecule programmed cell death ligand 1 (PD-L1) have shown clinical efficacy in cancer. This study was undertaken to determine whether PD-L1 is overexpressed in triple-negative breast cancer (TNBC) and to investigate the loss of PTEN as a mechanism of PD-L1 regulation. The Cancer Genome Atlas (TCGA) RNA sequencing data showed significantly greater expression of the PD-L1 gene in TNBC (n = 120) compared with non-TNBC (n = 716; P < 0.001). Breast tumor tissue microarrays were evaluated for PD-L1 expression, which was present in 19% (20 of 105) of TNBC specimens. PD-L1(+) tumors had greater CD8(+) T-cell infiltrate than PD-L1(-) tumors (688 cells/mm vs. 263 cells/mm; P < 0.0001). To determine the effect of PTEN loss on PD-L1 expression, stable cell lines were generated using PTEN short hairpin RNA (shRNA). PTEN knockdown led to significantly higher cell-surface PD-L1 expression and PD-L1 transcripts, suggesting transcriptional regulation. Moreover, phosphoinositide 3-kinase (PI3K) pathway inhibition using the AKT inhibitor MK-2206 or rapamycin resulted in decreased PD-L1 expression, further linking PTEN and PI3K signaling to PD-L1 regulation. Coculture experiments were performed to determine the functional effect of altered PD-L1 expression. Increased PD-L1 cell surface expression by tumor cells induced by PTEN loss led to decreased T-cell proliferation and increased apoptosis. PD-L1 is expressed in 20% of TNBCs, suggesting PD-L1 as a therapeutic target in TNBCs. Because PTEN loss is one mechanism regulating PD-L1 expression, agents targeting the PI3K pathway may increase the antitumor adaptive immune responses.
The C-terminal repressor region of herpes simplex virus type 1 ICP27 is required for the redistribution of small nuclear ribonucleoprotein particles and splicing factor SC35; however, these alterations are not sufficient to inhibit host cell splicing (1995)

Herpes simplex virus type 1 infection results in a reorganization of antigens associated with the small nuclear ribonucleoprotein particles (snRNPs), resulting in the formation of prominent clusters near the nuclear periphery. In this study, we show that the immediate-early protein ICP27, which is involved in the impairment of host cell splicing and in the changes in the distribution of snRNPs, is also required for reassorting the SR domain splicing factor SC35. Other viral processes, such as adsorption and penetration, shutoff of host protein synthesis, early and late gene expression, and DNA replication, do not appear to play a role in changing the staining pattern of splicing antigens. Furthermore, the C-terminal repressor region of ICP27, which is required for the inhibitory effects on splicing, also is involved in redistributing the snRNPs and SC35. During infection or transfection with five different repressor mutants, the speckled staining pattern characteristic of uninfected cells was seen and the level of a spliced target mRNA was not reduced. Infections in the presence of activator mutants showed a redistributed snRNP pattern and a decreased accumulation of spliced target mRNA. Moreover, two arginine-rich regions in the N-terminal half of ICP27 were not required for the redistribution of snRNPs or SC35. Substitution of these regions with a lysine-rich sequence from simian virus 40 large-T antigen resulted in a redistribution of splicing antigens. Unexpectedly, a repressor mutant with a ts phenotype showed a redistributed staining pattern like that seen with wild-type infected cells. During infections with this ts mutant, splicing was not inhibited, as shown in this and previous studies, confirming its repressor phenotype. Furthermore, both the mutant and the wild-type protein colocalized with snRNPs. Therefore, the redistribution of snRNPs and SC35 correlates with ICP27-mediated impairment of host cell splicing, but these alterations are not sufficient to fully inhibit splicing. This indicates that active splicing complexes are still present even after dramatic changes in the organization of the snRNPs.
Isolation of Two Acetyl Esterases from Extracts of Bacillus subtilis (1973)

Acrylamide gel electrophoresis of crude cellular extracts of Bacillus subtilis revealed the presence of two acetyl esterases. Esterase A, the slower migrating enzyme, was found to be present in both vegetative and sporulating cells, whereas esterase B activity was more abundant after exponential growth ceased. Both esterases were present in the supernatant fraction of lysed spheroplasts and in a disrupted spore preparation. Of four pleiotropic asporogenous mutants tested, three exhibited decreased esterase B activity. Esterases A and B were partially purified by differential precipitation and co-chromatographed on diethylaminoethyl (DEAE)-cellulose (pH 7.5) and DEAE-Sephadex (pH 8.5). By employing gel filtration chromatography, the two esterases were separated, and molecular weights of 160,000 and 51,000 were estimated for esterases A and B, respectively. Esterase A was further purified to electrophoretic homogeneity by differential heating and preparative starch block electrophoresis. Sodium dodecyl sulfate-acrylamide gel electrophoresis of purified esterase A yielded a single protein band with a molecular weight of 31,000. The pI values of esterases A and B were determined to be 6.4 and 5.4, respectively.
Characterization of genotype-specific epitopes of the HN protein of mumps virus. (1997)

The SBL-1 strain of mumps virus, grouping with genotype A on the basis of the small hydrophobic protein gene sequence, was grown in the presence of three different monoclonal antibodies. The monoclonal antibodies were directed against the haemagglutinin-neuraminidase (HN) protein and they inhibited haemagglutinating activity and infectivity of the virus. The HN genes of the nine neutralization-escape virus mutants were sequenced and the predicted amino acid sequences were compared with that of the parental virus. Amino acid substitutions were found at positions 269, 352 and 354, respectively, of the 582 amino acid long protein. The three monoclonal antibodies did not react with 35 virus strains isolated in Stockholm during the years 1970 to 1985. Thirteen and four of the strains were found to belong to the D and C genotypes, respectively. A type-specific neutralization antibody response was also found in sera of rabbits hyperimmunized with purified virions of genotype A and D. The genotype-specific difference in neutralizing activity in mice and rabbits was not corroborated by an overall difference in the amino acid sequence of the HN protein of the different genotypes. Further studies are needed to explore the efficacy of mumps virus vaccines for protection against homologous and heterologous genotypes of mumps virus.
What All Social Workers Should Know About MDMA (Ecstasy) (2004)

ABSTRACT This article describes the history of MDMA, its relationship to other drugs, its manufacture and how it is trafficked, and the physiological reactions and health consequences associated with its use. It also presents recommendations for drug abuse prevention and treatment. Material was drawn from government publications, professional journals, and private organization Web sites. Effective strategies for decreasing MDMA use and for minimizing deleterious effects on users exist.
Modeling of two-phase microchannel heat sinks for VLSI chips (2002)

Microchannel heat sinks with forced convective boiling can satisfy the increasing heat removal requirements of VLSI chips. But little is known about two-phase boiling flow in channels with cross-sectional dimensions below 100 /spl mu/m. This work develops and experimentally verifies microchannel simulations, which relate the temperature field to the applied power and flowrate. The simulations consider silicon conduction and assume an immediate transition to homogeneous misty flow, without the bubbly and plug-flow regimes in larger channels. Pressure drop and wall temperature predictions are consistent with data for a channel with cross-sectional dimensions of 50 /spl mu/m/spl times/70 /spl mu/m. The simulations explore the performance of a novel heat sink system with an electrokinetic pump for the liquid phase, which provides 1 atm and 15 ml/min. A temperature rise below 40 K is predicted for a 200 W heat sink for a 25 mm/spl times/25 mm chip.
Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients (2001)

CD4 T-cell help is required during the generation and maintenance of effective antitumor CD8 T cell-mediated immunity. The goal of this study was to determine whether HER-2/neu-specific CD8 T-cell immunity could be elicited using HER-2/neu-derived MHC class II "helper" peptides, which contain encompassed HLA-A2-binding motifs. Nineteen HLA-A2 patients with HER-2/neu-overexpressing cancers received a vaccine preparation consisting of putative HER-2/neu helper peptides p369-384, p688-703, and p971-984. Contained within these sequences are the HLA-A2-binding motifs p369-377, p689-697, and p971-979. After vaccination, the mean peptide-specific T-cell precursor frequency to the HLA-A2 peptides increased in the majority of patients. In addition, the peptide-specific T cells were able to lyse tumors. The responses were long-lived and detectable for more than 1 year after the final vaccination in select patients. These results demonstrate that HER-2/neu MHC class II epitopes containing encompassed MHC class I epitopes are able to induce long-lasting HER-2-specific IFN-gamma-producing CD8 T cells.
Perturbed Amelogenin Secondary Structure Leads to Uncontrolled Aggregation in Amelogenesis Imperfecta Mutant Proteins (2010)

Mutations in amelogenin sequence result in defective enamel, and the diverse group of genetically altered conditions is collectively known as amelogenesis imperfecta (AI). Despite numerous studies, the detailed molecular mechanism of defective enamel formation is still unknown. In this study, we have examined the biophysical properties of a recombinant murine amelogenin (rM180) and two point mutations identified from human DNA sequences in two cases of AI (T21I and P41T). At pH 5.8 and 25 °C, wild type (WT) rM180 and mutant P41T existed as monomers, and mutant T21I formed lower order oligomers. CD, dynamic light scattering, and fluorescence studies indicated that rM180 and P41T can be classified as a premolten globule-like subclass protein at 25 °C. Thermal denaturation and refolding monitored by CD ellipticity at 224 nm indicated the presence of a strong hysteresis in mutants compared with WT. Variable temperature tryptophan fluorescence and dynamic light scattering studies showed that WT transformed to a partially folded conformation upon heating and remained stable. The partially folded conformation formed by P41T, however, readily converted into a heterogeneous population of aggregates. T21I existed in an oligomeric state at room temperature and, upon heating, rapidly formed large aggregates over a very narrow temperature range. Thermal denaturation and refolding studies indicated that the mutants are less stable and exhibit poor refolding ability compared with WT rM180. Our results suggest that alterations in self-assembly of amelogenin are a consequence of destabilization of the intrinsic disorder. Therefore, we propose that, like a number of other human diseases, AI appears to be due to the destabilization of the secondary structure as a result of amelogenin mutations.