gebhart/patrepeval huggingface dataset:
MetaboAnalyst 3.0—making metabolomics more meaningful (2015)

MetaboAnalyst (www.metaboanalyst.ca) is a web server designed to permit comprehensive metabolomic data analysis, visualization and interpretation. It supports a wide range of complex statistical calculations and high quality graphical rendering functions that require significant computational resources. First introduced in 2009, MetaboAnalyst has experienced more than a 50X growth in user traffic (>50 000 jobs processed each month). In order to keep up with the rapidly increasing computational demands and a growing number of requests to support translational and systems biology applications, we performed a substantial rewrite and major feature upgrade of the server. The result is MetaboAnalyst 3.0. By completely re-implementing the MetaboAnalyst suite using the latest web framework technologies, we have been able substantially improve its performance, capacity and user interactivity. Three new modules have also been added including: (i) a module for biomarker analysis based on the calculation of receiver operating characteristic curves; (ii) a module for sample size estimation and power analysis for improved planning of metabolomics studies and (iii) a module to support integrative pathway analysis for both genes and metabolites. In addition, popular features found in existing modules have been significantly enhanced by upgrading the graphical output, expanding the compound libraries and by adding support for more diverse organisms.
Regulation of the Adenomatous Polyposis Coli Gene by the miR-135 Family in Colorectal Cancer (2008)

Inactivation of the adenomatous polyposis coli (APC) gene is a major initiating event in colorectal tumorigenesis. Most of the mutations in APC generate premature stop codons leading to truncated proteins that have lost beta-catenin binding sites. APC-free beta-catenin stimulates the Wnt signaling pathway, leading to active transcription of target genes. In the current study, we describe a novel mechanism for APC regulation. We show that miR-135a&b target the 3' untranslated region of APC, suppress its expression, and induce downstream Wnt pathway activity. Interestingly, we find a considerable up-regulation of miR-135a&b in colorectal adenomas and carcinomas, which significantly correlated with low APC mRNA levels. This genetic interaction is also preserved in full-blown cancer cell lines expressing miR-135a&b, regardless of the mutational status of APC. Thus, our results uncover a miRNA-mediated mechanism for the control of APC expression and Wnt pathway activity, and suggest its contribution to colorectal cancer pathogenesis.
Second-level buffer cache management (2004)

Buffer caches are commonly used in servers to reduce the number of slow disk accesses or network messages. These buffer caches form a multilevel buffer cache hierarchy. In such a hierarchy, second-level buffer caches have different access patterns from first-level buffer caches because accesses to a second-level are actually misses from a first-level. Therefore, commonly used cache management algorithms such as the least recently used (LRU) replacement algorithm that work well for single-level buffer caches may not work well for second-level. We investigate multiple approaches to effectively manage second-level buffer caches. In particular, we report our research results in 1) second-level buffer cache access pattern characterization, 2) a new local algorithm called multi-queue (MQ) that performs better than nine tested alternative algorithms for second-level buffer caches, 3) a set of global algorithms that manage a multilevel buffer cache hierarchy globally and significantly improve second-level buffer cache hit ratios over corresponding local algorithms, and 4) implementation and evaluation of these algorithms in a real storage system connected with commercial database servers (Microsoft SQL server and Oracle) running industrial-strength online transaction processing benchmarks.
A transgenic zebrafish model of neutrophilic inflammation (2006)

We have established an in vivo model for genetic analysis of the inflammatory response by generating a transgenic zebrafish line that expresses GFP under the neutrophil-specific myeloperoxidase promoter. We show that inflammation is induced after transection of the tail of zebrafish larvae and that this inflammation subsequently resolves over a similar time course to mammalian systems. Quantitative data can be generated from this model by counting of fluorescent cells or by digital image analysis. In addition, we show that the resolution of experimentally induced inflammation can be inhibited by the addition of a pancaspase inhibitor, zVD.fmk, demonstrating that experimental manipulation of the resolution of inflammation is possible in this model.
RACK1, a New ADAM12 Interacting Protein (2008)

ADAM12 belongs to a disintegrin-like and metalloproteinase-containing protein family that possesses multidomain structures composed of a pro-domain, a metalloprotease, disintegrin-like, cysteine-rich, epidermal growth factor-like, and transmembrane domains, and a cytoplasmic tail. Overexpression of several ADAMs has been reported in human cancer, and we recently described the involvement of ADAM12 in liver injury (Le Pabic, H., Bonnier, D., Wewer, U. M., Coutand, A., Musso, O., Baffet, G., Clement, B., and Theret, N. (2003) Hepatology 37, 1056-1066). In this study, we used a yeast two-hybrid screening of a cDNA library from human hepatocellular carcinoma to analyze binding partners of ADAM12. We identify RACK1, a receptor for activated protein kinase C (PKC), as a new ADAM12 interacting protein. RACK1 is up-regulated in patients with hepatocellular carcinoma and is highly expressed by activated hepatic stellate cells. We demonstrate the involvement of RACK1 in mediating the PKC-dependent translocation of ADAM12 to membranes of activated hepatic stellate cells. In particular, treatment of cells with phorbol esters enhances ADAM12 immunostaining in the membrane fractions and the co-immunoprecipitation of ternary complexes containing RACK1, ADAM12, and PKC. By using RNA interference, we demonstrate that inhibition of RACK1 expression diminishes the phorbol 12-myristate 13-acetate-dependent translocation of ADAM12 to membranes of hepatic stellate cells. Finally, hepatic stellate cells cultured on coated type I collagen induces relocalization of ADAM12 in the membrane, suggesting that this major matrix component in liver cancer and fibrogenesis might stimulate ADAM12 translocation to the cell membrane where its shedding activity takes place.
Spatio-temporal coding for wireless communications (2002)

A compact model is derived for the multiple-input multiple output (MIMO), dispersive, spatially selective wireless communication channel. The multivariate information capacity behavior is then analyzed for various input and output antenna configurations. For high SNR conditions, the MIMO channel can exhibit a capacity slope in bits per dB of power increase that is proportional to the minimum of the number multipath components, the number of input antennas, or the number of output antennas. The discrete matrix multitone (DMMT) is proposed as an asymptotically optimal, practical spatio-temporal coding structure. Experimental examples that support the theoretical results are presented.
Regulation of Insulin Gene Transcription by ERK1 and ERK2 in Pancreatic β Cells (2003)

We show that the mitogen-activated protein kinases ERK1/2 are components of the mechanism by which glucose stimulates insulin gene expression. ERK1/2 activity is required for glucose-dependent transcription from both the full-length rat insulin I promoter and the glucose-sensitive isolated E2A3/4 promoter element in intact islets and beta cell lines. Dominant negative ERK2 and MEK inhibitors suppress glucose stimulation of the rat insulin I promoter and the E2A3/4 element. Overexpression of ERK2 is sufficient to stimulate transcription from the E2A3/4 element. The glucose-induced response is dependent upon ERK1/2 phosphorylation of a subset of transcription factors that include Beta2 (also known as NeuroD1) and PDX-1. Phosphorylation increases their functional activity and results in a cumulative transactivation of the promoter. Thus, ERK1/2 act at multiple points to transduce a glucose signal to insulin gene transcription.
Acute otitis media: influence of the PCV-7 vaccine on changes in the disease and its management. (2005)

Studies have shown that most cases of acute otitis media (AOM) are of viral or "no bacteria isolated" origin. In these cases, watchful waiting may be appropriate. This publication addresses presumed bacterial causes of AOM for which antibiotic use may be efficacious.
A DNA Probe of Ruthenium Bipyridine Complex Using Photocatalytic Activity (1989)

Abstract A method is presented for labelling DNA and for detection of the complimentary sequence using photocatalytic activity of tris(2,2′-bipyridine)ruthenium(II). A hybridization experiment with a model system has shown that plasmid DNA of ca. 0. 6 μg can well be detected by a dye-forming reaction in photocatalytical redox cycles.
A New Large-DNA-Fragment Delivery System Based on Integrase Activity from an Integrative and Conjugative Element (2013)

During the past few decades, numerous plasmid vectors have been developed for cloning, gene expression analysis, and genetic engineering. Cloning procedures typically rely on PCR amplification, DNA fragment restriction digestion, recovery, and ligation, but increasingly, procedures are being developed to assemble large synthetic DNAs. In this study, we developed a new gene delivery system using the integrase activity of an integrative and conjugative element (ICE). The advantage of the integrase-based delivery is that it can stably introduce a large DNA fragment (at least 75 kb) into one or more specific sites (the gene for glycine-accepting tRNA) on a target chromosome. Integrase recombination activity in Escherichia coli is kept low by using a synthetic hybrid promoter, which, however, is unleashed in the final target host, forcing the integration of the construct. Upon integration, the system is again silenced. Two variants with different genetic features were produced, one in the form of a cloning vector in E. coli and the other as a mini-transposable element by which large DNA constructs assembled in E. coli can be tagged with the integrase gene. We confirmed that the system could successfully introduce cosmid and bacterial artificial chromosome (BAC) DNAs from E. coli into the chromosome of Pseudomonas putida in a site-specific manner. The integrase delivery system works in concert with existing vector systems and could thus be a powerful tool for synthetic constructions of new metabolic pathways in a variety of host bacteria.
Using vector interfaces to deliver millions of IOPS from a networked key-value storage server (2012)

The performance of non-volatile memories (NVM) has grown by a factor of 100 during the last several years: Flash devices today are capable of over 1 million I/Os per second. Unfortunately, this incredible growth has put strain on software storage systems looking to extract their full potential.
Identifying survival associated morphological features of triple negative breast cancer using multiple datasets (2013)

Using TCGA data, we identified 48 pairs of significantly correlated morphological features and gene clusters; four morphological features were able to separate the local cohort with significantly different survival outcomes. Gene clusters correlated with these four morphological features further proved to be effective in predicting patient survival using multiple public gene expression datasets. These results suggest the efficacy of our workflow and demonstrate that integrative analysis holds promise for discovering biomarkers of complex diseases.
Probing the Ubiquinol-Binding Site in Cytochromebdby Site-Directed Mutagenesis (2006)

To probe the structure of the quinol oxidation site in loop VI/VII of the Escherichia coli cytochrome bd, we substituted three conserved residues (Gln249, Lys252, and Glu257) in the N-terminal region and three glutamates (Glu278, Glu279, and Glu280) in the first internal repeat. We found that substitutions of Glu257 by Ala or Gln, and Glu279 and Glu280 by Gln, severely reduced the oxidase activity and the expression level of cytochrome bd. In contrast, Lys252 mutations reduced only the oxidase activity. Blue shifts in the 440 and 630 nm peaks of the reduced Lys252 mutants and in the 561 nm peak of the reduced Glu257 mutants indicate the proximity of Lys252 to the heme b(595)-d binuclear center and Glu257 to heme b(558), respectively. Perturbations of reduced heme b(558) upon binding of aurachin D support structural changes in the quinol-binding site of the mutants. Substitutions of Lys252 and Glu257 caused large changes in kinetic parameters for the ubiquinol-1 oxidation. These results indicate that Lys252 and Glu257 in the N-terminal region of the Q-loop are involved in the quinol oxidation by bd-type terminal oxidase.
Against which human papillomavirus types shall we vaccinate and screen? the international perspective (2004)

At least 15 types of HPV have been associated with cervical cancer, but current HPV vaccines confer only type-specific immunity. To determine geographic variations in the HPV type distribution in cervical cancer, we carried out a pooled analysis of data from an international survey of HPV types in cervical cancer and from a multicenter case-control study, both co-coordinated by the IARC. Study cases were 3,607 women with incident, histologically confirmed cervical cancer recruited in 25 countries. HPV DNA detection and typing in cervical cells or biopsies were centrally done using PCR assays. Estimates of the potential number of cases prevented by HPV type-specific vaccines and changes in the validity of different HPV screening cocktails were calculated. HPV DNA was detected in 96% of specimens, and 30 different types were detected. The 15 most common types were, in descending order of frequency, 16, 18, 45, 31, 33, 52, 58, 35, 59, 56, 39, 51, 73, 68 and 66. Higher than average proportions of type 16 were found in northern Africa, of type 18 in south Asia, of type 45 in sub-Saharan Africa and of type 31 in Central/South America. A vaccine including types 16 and 18 could potentially prevent 71% of cervical cancers worldwide, but its impact with regard to the percentage of cases potentially prevented would be higher in Asia and Europe/North America. In contrast, a vaccine containing the 7 most common HPV types would prevent about 87% of cervical cancers worldwide, with little regional variation. The impact of modifying the number of types in the screening cocktail tests would be small and probably irrelevant for screening programs.
High-Performance Field-Effect Transistors Based on Langmuir−Blodgett Films of Cyclo[8]pyrrole (2005)

We demonstrate the field-effect transistors (FETs) made of cyclo[8]pyrrole thin films prepared by the Langmuir-Blodgett (LB) method. The cyclo[8]pyrrole molecule possesses a 30-pi-electron system and narrower highest-occupied molecular orbital-lowest-unoccupied molecular orbital energy gap (0.63 eV), forms a stable, reproducible monolayer at the air-water interface, and transfers onto a substrate with a nearly unity transfer ratio and face-to-face configuration due to its strong pi-pi interaction. The LB films are uniform characterized by atomic force microscopy and in ordered form confirmed by X-ray diffraction. The FET exhibited high performances with one of the highest hole mobilities (0.68 cm2 V(-1) s(-1)) for thin-film transistors and a high on/off ratio, implying a promising material in the FET family.
Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells (2004)

De novo and acquired resistance to the anti-tumour drug gefitinib (ZD1839; Iressa), a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been reported. We have determined whether signalling through the IGF-I receptor (IGF-1R) pathway plays a role in the gefitinib-acquired resistance phenotype. Continuous exposure of EGFR-positive MCF-7-derived tamoxifen resistant breast cancer cells (TAM-R) to 1 microM gefitinib resulted in a sustained growth inhibition (90%) for 4 months before the surviving cells resumed proliferation. A stable gefitinib-resistant subline (TAM/TKI-R) was established after a further 2 months and this showed no detectable basal phosphorylated EGFR activity. Compared with the parental TAM-R cells, the TAM/ TKI-R cells demonstrated (a) elevated levels of activated IGF-1R, AKT and protein kinase C (PKC)delta, (b) an increased sensitivity to growth inhibition by the IGF-1R TKI AG1024 and (c) an increased migratory capacity that was reduced by AG1024 treatment. Similarly, the EGFR-positive androgen-independent human prostate cancer cell line DU145 was also continuously challenged with 1 microM gefitinib and, although substantial growth inhibition (60%) was seen initially, a gefitinib-resistant variant (DU145/TKI-R) developed after 3 months. Like their breast cancer counterparts, the DU145/TKI-R cells showed increases in the levels of components of the IGF-1R signalling pathway and an elevated sensitivity to growth inhibition by AG1024 compared with the parent DU145 cell line. Additionally, DU145/TKI-R cell migration was also decreased by this inhibitor. We have therefore concluded that in breast and prostate cancer cells acquired resistance to gefitinib is associated with increased signalling via the IGF-1R pathway, which also plays a role in the invasive capacity of the gefitinib-resistant phenotype.
Polymorphism in Pharmaceutical Solids (2018)

THERMODYNAMIC AND THEORETICAL ISSUES Theory and Principles of Polymorphic Systems, Harry G. Brittain Application of the Phase Rule to the Characterization of Polymorphic and Solvatomorphic Systems, Harry G. Brittain Computational Methodologies: Toward Crystal Structure and Polymorph Prediction, Sarah (Sally) L. Price PREPARATIVE METHODS FOR POLYMORPHS AND SOLVATOMORPHS Classical Methods of Preparation of Polymorphs and Alternative Solid Forms, Peter W. Cains Approaches to High-Throughput Physical Form Screening and Discovery, Alastair J. Florence STRUCTURAL PROPERTIES OF POLYMORPHS AND SOLVATOMORPHS Structural Aspects of Polymorphism, Harry G. Brittain, Stephen R. Byrn, and Eunhee Lee Structural Aspects of Solvatomorphic Systems, Harry G. Brittain, Kenneth R. Morris, and Stephan X. M. Boerrigter Pharmaceutical Co-crystals: A New Opportunity in Pharmaceutical Science for a Long-Known but Little-Studied Class of Compounds, Kapildev K. Arora and Michael J. Zaworotko CHARACTERIZATION METHODS FOR POLYMORPHS AND SOLVATOMORPHS Thermoanalytical and Crystallographic Methods, Sisir Bhattacharya, Harry G. Brittain, and Raj Suryanarayanan Vibrational Spectroscopy, Harry G. Brittain Solid-State Nuclear Magnetic Resonance Spectroscopy, Patrick A. Tishmack Effects of Polymorphism and Solid-State Solvation on Solubility and Dissolution Rate, Harry G. Brittain, David J. R. Grant, and Paul B. Myrdal INTERCONVERSION OF POLYMORPHS AND SOLVATOMORPHS Solid-State Phase Transformations, Harry G. Brittain Effects of Pharmaceutical Processing on the Solid Form of Drug and Excipient Materials, Peter L. D. Wildfong SPECIAL TOPICS RELATED TO POLYMORPHISM AND SOLVATOMORPHISM Structural Aspects of Molecular Dissymmetry, Harry G. Brittain Amorphous Solids, Lynne S. Taylor and Sheri L. Shamblin Index
Release of peptide YY (PYY) after resection of small bowel, colon, or pancreas in man. (1987)

To investigate the possible role of peptide YY (PYY) in the adaptive changes that accompany enterectomy, plasma levels of this peptide were measured during breakfast in patients with resected small or large intestines and in controls. In 18 patients who had undergone partial ileal resection, basal PYY concentrations were greatly elevated when compared with controls (51.4 +/- 8.7 pmol/L versus 10.3 +/- 1.0; p less than 0.001) and the postprandial response was similarly increased. In contrast, PYY concentrations were low in 16 patients who had undergone colonic resection and ileostomy (fasting 7.1 +/- 0.7 pmol/L, p less than 0.01). In eight patients who had undergone pancreatectomies, basal and postprandial PYY levels were moderately increased (23.4 +/- 3.5 pmol/L; fasting p less than 0.001). PYY does not appear to have a role in the adaptive trophic response after small intestinal resection, but it may contribute to reduction of gastric secretion and gastrointestinal transit in these patients.
Soluble B-Cell Maturation Antigen Mediates Tumor-Induced Immune Deficiency in Multiple Myeloma (2016)

Our results show that soluble BCMA sequesters circulating BAFF, thereby preventing it from performing its signaling to stimulate normal B-cell and plasma cell development, resulting in reduced polyclonal antibody levels in multiple myeloma patients. Clin Cancer Res; 22(13); 3383-97. ©2016 AACR.
Proteins specified by the short unique region of the genome of pseudorabies virus play a role in the release of virions from certain cells (1986)

Two pseudorabies virus vaccine strains (Bartha and Norden) that have a similar deletion in the short unique (Us) region of the genome have been identified previously (B. Lomniczi, M. L. Blankenship, and T. Ben-Porat, J. Virol. 49:970-979, 1984). These strains do not code for the glycoprotein gI, a glycoprotein that has been mapped on the wild type virus genome by T. C. Mettenleiter, N. Lukacs, and H. J. Rziha (J. Virol. 53:52-57, 1985) to the sequences deleted from the vaccine strain. Restoration of these deleted sequences to the Bartha strain genome restores to the virus the ability to specify the gI glycoprotein. The Bartha vaccine strain grows as well as wild-type virus in pig kidney and in rabbit kidney (RK) cells, but is not released efficiently from and forms small plaques in RK cells. The rescued Bartha 43/25a strain (which has an intact Us) is released considerably more efficiently than the Bartha vaccine strain, but less efficiently than wild-type virus from RK cells; it also forms larger plaques on RK cells than does the parental Bartha vaccine strain. The Norden vaccine strain, which has a deletion in the Us, is released better from RK cells than is the Bartha strain, but not as well as is wild-type virus. We conclude that whereas the sequences in the Us that are deleted from the Bartha and Norden strain genomes specify functions that play a role in the release of virions from some cell types, at least one other function (which is defective in the Bartha strain but not in the Norden strain) also affects release of virus from these cells. Since restoration to the Bartha strain of an intact Us restores to the virus both the ability to grow in chicken brains (B. Lomniczi, S. Watanabe, T. Ben-Porat, and A. S. Kaplan, J. Virol. 52:198-205, 1984) and to be released from RK cells, the possibility that the lack of virulence of the Bartha vaccine strain may be related to its limited release from some target cells is discussed.