gebhart/patrepeval huggingface dataset:
VEWL: A Framework for Building a Windowing Interface in a Virtual Environment. (2003)

Abstract: VEWL (Virtual Environment Windowing Library) is a library designed to provide a highly flexible interface metaphor for building window-based interfaces within a virtual environment. VEWL was built on top of DIVERSE and uses the object-oriented paradigm of signals and slots through the use of Qt. In addition to the windowing metaphor presented this library was designed to provide an API (Application Programming Interface) to allow rapid development of new interfaces. This paper will describe the design and implementation of this library and provide preliminary results of a brief usability study.
GeneCards: a novel functional genomics compendium with automated data mining and query reformulation support. (1998)

cards@bioinformatics.weizmann.ac.il
Diverse Access to Artificial Superhydrophobic Surfaces Using Block Copolymers (2005)

The creation of an artificial superhydrophobic surface with micro- and nanostructures has been demonstrated using a block copolymer micelle solution and silica nanoparticles. The unique technique of a nanoparticle-supported micelle stabilization together with changes in the solvent power guarantees the precise morphology control of certain block copolymer-mediated surfaces. The approaches presented here provide a new strategy for the fabrication of a wettability-controlled organic-inorganic hybrid or organic coatings.
Teaching optimal control theory to distill robust pulses even under experimental constraints (2002)

Optimal control theory (OCT) has wide applicability in the quest for seeking optimal laser pulses in coherent control of quantum phenomena. We have revised OCT making it possible to distill robust electric fields realizable via femtosecond pulse-shaping technology. The simple pulse structures offer direct physical insight into the control mechanism and selectively isolate the most stable pathways involving only few frequencies. Moreover, a generalized functional makes a vital extension in including the laser system used in control experiments.
The Relative Burden of Dry Eye in Patients’ Lives: Comparisons to a U.S. Normative Sample (2004)

These results indicate dry eye's negative impact on everyday life, particularly in daily activities. Further research using disease-specific measures to examine dry eye's impact is underway.
A Critical Analysis of the Pharmacology of AZT and its Use in AIDS (1999)

The triphosphorylated form of the nucleoside analogue 3'-azido-3'-deoxythymidine (Zidovudine, AZT) is claimed to interrupt the HIV replication cycle by a selective inhibition of viral reverse transcriptase, thereby preventing the formation of new proviral DNA in permissive, uninfected cells. Given that initial HIV infection of an individual instigates abundant HIV replication from inception until death, and that the life of infected T-cells is only several days, the administration of AZT should lead both in vitro and in vivo (i) to decreased formation of proviral DNA; and thus (ii) to decreased frequencies of 'HIV isolation' (detection of p24 or reverse transcription or both) in stimulated cultures/cocultures of T-cells from seropositive individuals; (iii) to decreased synthesis of HIV p24 and RNA ('antigenaemia', 'plasma viraemia', 'viral load') ultimately resulting in low or absent levels of all three parameters; and (iv) to a perfect and direct correlation between all these parameters. A critical analysis of the presently available data shows that no such evidence exists, an outcome not unexpected given the pharmacological data on AZT. HIV experts all agree that only the triphosphorylated form of AZT (AZTTP) and not the unphosphorylated form administered to patients, nor its mono- or diphosphate, is the active agent. Furthermore, the mechanism of action is the ability of AZTTP to halt the formation of HIV-DNA (chain termination). However, although this claim was posited from the outset, AZT underwent clinical trials and was introduced as a specific anti-HIV drug many years before there were any data proving that the cells of patients are able to triphosphorylate the parent compound to a level considered sufficient for its putative pharmacological action. Notwithstanding, from the evidence published since 1991 it has become apparent that no such phosphorylation takes place and thus AZT cannot possess an anti-HIV effect. However, the scientific literature does elucidate: (i) a number of biochemical mechanisms which predicate the likelihood of widespread, serious toxicity from use of this drug; (ii) in vitro data proving that AZT has significant antibacterial and antiviral properties which confound interpretation of its effects when administered to patients. Based on all these data it is difficult if not impossible to explain why AZT was introduced and still remains the most widely recommended and used anti-HIV drug.
Transnational Evidence Gathering and Local Prosecution of International Cybercrime, 20 J. Marshall J. Computer & Info. L. 347 (2002) (2002)

By analyzing two high-profile cybercrime cases, the authors discuss legal and procedural issues involved when gathering evidence across national borders. In US v. Gorshkov, the FBI was asked to investigate a series of intrusions into the computer systems of businesses in the US from Russia. The second incident is when system administrators at the Rom Air Development Center at Griffis Air Force Base in New York discovered hackers had installed password sniffer programs on all system networks. One of the hackers was identified to be a British citizen. The first thing to start a transnational evidence gathering is to determine what formal and informal devices are available to search for and/or seize evidence located in another country. Then, he needs to identify any mutual legal assistance treaty between the US and the target country. Third, it is critical to determine whether the evidence being sought pertains t conduct that is illegal in the target country. The Department of State, the National Institute of Justice's International Center, Interpol, the United Nations, to name a few, provide excellent resources to assist investigators in a wide range of information. Even with these tools and resources, the authors are quick to point out the difficulties that prosecutors face in investigating cybercrimes. The crimes are no longer local or regional. The DA's offices lack funding and proper protocols to meet such international challenges. In addition, without strategic planning, local prosecutors are in a uphill battle against cybercrimes.
Effect of Interaction between Hepatitis C Virus NS5A and NS5B on Hepatitis C Virus RNA Replication with the Hepatitis C Virus Replicon (2004)

Hepatitis C virus (HCV) NS5A has been reported to be important for the establishment of replication by adaptive mutations or localization, although its role in viral replication remains unclear. It was previously reported that NS5A interacts with NS5B via two regions of NS5A in the isolate JK-1 and modulates the activity of NS5B RdRp (Y. Shirota et al., J. Biol. Chem., 277:11149-11155, 2002), but the biological significance of this interaction has not been determined. In this study, we addressed the effect of this interaction on HCV RNA replication with an HCV replicon system derived from the isolate M1LE (H. Kishine et al., Biochem. Biophys. Res. Commun., 293:993-999, 2002). We constructed three internal deletion mutants, M1LE/5Adel-1 and M1LE/5Adel-2, each encoding NS5A which cannot bind NS5B, and M1LE/5Adel-3, encoding NS5A that can bind NS5B. After transfection into Huh-7 cells, M1LE/5Adel-3 was replication competent, but both M1LE/5Adel-1 and M1LE/5Adel-2 were not. Next we prepared 20 alanine-substituted clustered mutants within both NS5B-binding regions and examined the effect of these mutants on HCV RNA replication. Only 5 of the 20 mutants were replication competent. Subsequently, we introduced a point mutation, S225P, a deletion of S229, or S232I into NS5A and prepared cured Huh-7 cells that were cured of RNA replication by alpha interferon. Finally, with these point mutations and cured cells, we established a highly improved replicon system. In this system, only the same five mutants were replication competent. These results strongly suggest that the interaction between NS5A and NS5B is critical for HCV RNA replication in the HCV replicon system.
Detection of DNA point mutations with DNA mismatch repair enzymes (1994)

We have developed a simple and reliable procedure to screen gene mutations using DNA mismatch repair (MR) specific mut Y enzyme of Escherichia coli and thymidine DNA glycosylase from HeLa cells. The mut Y enzyme cleaves A of G/A mismatches in DNA duplex and thymidine glycosylase cleaves T at G/T mismatches. Previously, we showed the determination of G:C-->T:A mutations in the N-ras gene in two human tumor samples with mut Y G/A MR enzyme. As low as 1-2% mutant DNAs in a sample of mutant and wild-type DNA can be detected with a synthetic DNA to create G/A mispairing for the assay. In this paper, we simplify the assay, include G/T MR thymidine glycosylase from HeLa cells and evaluate the application for screening DNA point mutations of p53 and ras genes. In this method, DNA fragments amplified from normal and mutated genes by polymerase chain reaction (PCR) were mixed and annealed to create DNA mismatches for cleavage by mismatch repair enzymes. The cleaved products and the substrates were separated by gel electrophoresis and detected by autoradiography. In theory, the enzymes that cut G/A or G/T mispairs will detect the mutations of G:C-->A:T, A:T-->G:C, G:C-->T:A and T:A-->G:C. Several human tumor samples were examined for p53 or K-ras mutations with G/A and G/T mismatch repair enzymes. The reliability of mutation detection was evaluated by comparing the results with reported mutations or confirmed by DNA sequencing of the same PCR-amplified DNA fragments. Our data showed that, following mismatch repair enzyme cleavage, all mutated DNA samples yielded cleaved products with sizes as expected. In addition, our assay is able to characterize the nature of mutation by 5' end-labeling of 32P on mutant or wild-type DNA fragments. The low background, reliability and the determination of the sites of mutations as well as the types of DNA base changes indicate the advantages of the method over other techniques in testing DNA mutants.
The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation. (1995)

IP-10 is a member of the chemokine family of cytokines and is induced in a variety of cells in response to interferon gamma and lipopolysaccharide. The self-aggregation common to many chemokines, including IP-10, has hindered the identification of a specific IP-10 receptor. Using an IP-10 alkaline phosphatase fusion protein that fortuitously blocks this self-aggregation, we have identified an IP-10 binding site on a variety of cells including endothelial, epithelial, and hematopoietic cells. This binding site has a Kd of 25 nM, is inhibited by recombinant murine or human IP-10, and is dependent on the presence of cell surface heparan sulfate proteoglycans (HSPG). This conclusion is based on the findings that IP-10 binding to cells is: (a) inhibited by heparin and heparan sulfate; (b) sensitive to a 1 M NaCl wash; (c) eliminated by treatment with heparinase and trypsin; and (d) absent on mutant CHO cells that do not express cell surface HSPG. Platelet factor 4 (PF4), but not IL-8, monocyte chemoattractant protein-1, RANTES, monocyte inflammatory protein (MIP)-1 alpha, or MIP-1 beta, can compete effectively with IP-10 for binding to the cell surface. Furthermore, IP-10 shares with PF4 the ability to inhibit endothelial cell proliferation (IC50 = 150 nM). These studies demonstrate specificity in the interaction of chemokines and HSPG, and they define IP-10 and PF4 as a distinct subset of chemokines sharing an HSPG-binding site and angiostatic properties.
Hemodynamic effects in dogs after intramuscular administration of a combination of dexmedetomidine-butorphanol-tiletamine-zolazepam or dexmedetomidine-butorphanol-ketamine (2012)

In healthy dogs, both DBTZ and DBK maintained oxygen delivery and oxygen consumption to tissues and blood lactate concentrations within the reference range. However, ventilation should be carefully monitored and assisted when necessary to prevent hypoventilation.
Evaluation of Aqueous Enteric Coated Granules Prepared by Moisture Control Method in Tumbling Fluidized Bed Process. (1994)

Based on the moisture control system developed previously, we have already reported that the operational moisture content during aqueous polymeric coating by a type of fluidized bed should be controlled for a better coating efficiency.In this paper, effects of operational moisture content and agitator rotational speed on the properties of granules prepared by the aqueous polymeric coating were investigated experimentally, and optimization of this process was conducted. Core granules (mean diameter 600 μM) containing a model drug, pigment Blue No. 1, were coated with the aqueous dispersion of enteric polymer (Eudragit L30D) by the tumbling fluidized bed with controlling the operational moisture content. The coated granules were evaluated by dissolution tests in JP 1st (pH 1.2) and 2nd fluid (pH 6.8) and by agglomeration tendency. Film thickness and specific surface area of the granules were examined to discuss the film forming process. Based on the evaluation, effects of the operational variables on the drug release rate and agglomeration tendency were investigated. It was found that the drug release rate was suppressed with increase in moisture content at any rotational speed in the JP 1st and 2nd fluid, and the agglomeration tendency was prevented with increase in moisture content and agitator rotational speed. It was concluded from the results that the aqueous coating with the enteric polymer by the tumbling fluidized bed process should be carried out under a condition of moisture content between 12 and 14% with agitation below 5 rps.
N-glycan Cryptic Antigens as Active Immunological Targets in Prostate Cancer Patients (2012)

Although tumor-associated abnormal glycosylation has been recognized for decades, information regarding host recognition of the evolving tumor glycome remains elusive. We report here a carbohydrate microarray analysis of a number of tumor-associated carbohydrates for their serum antibody reactivities and potential immunogenicity in humans. These are the precursors, cores and internal sequences of <i>N</i>-glycans. They are usually masked by other sugar moieties and belong to a class of glyco-antigens that are normally "cryptic". However, viral expression of these carbohydrates may trigger host immune responses. For examples, HIV-1 and SARS-CoV display Man9 clusters and tri- or multi-antennary type II (Galβ1→4GlcNAc) chains (Tri/m-II), respectively; viral neutralizing antibodies often target these sugar moieties. We asked, therefore, whether prostate tumor expression of corresponding carbohydrates triggers antibody responses <i>in vivo</i>. Using carbohydrate microarrays, we analyzed a panel of human sera, including 17 samples from prostate cancer patients and 12 from men with Benign Prostatic Hyperplasia (BPH). We observed that IgG antibodies targeting the Man9- or Tri-/m-II-autoantigens are readily detectable in the sera of men with BPH, as well as those with cancer. Importantly, these antibody activities were selectively increased in prostate cancer patients. Thus, human immune systems actively recognize these <i>N</i>-glycan cryptic carbohydrates and produce targeting antibodies. This finding shads a light on a class of previously less studied immunological targets of human cancers. Identifying the diagnostic, prognostic and therapeutic values of these targets will require further investigation.
Studies on New Acidic Azoles as Glucose-Lowering Agents in Obese, Diabetic db/db Mice (1995)

Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles, isoxazol-3- and -5-ones and a pyrazol-3-one, showed significant plasma glucose-lowering activity (17-42% reduction) in genetically obese, diabetic db/db mice at a dose of 100 mg/kg/day x4. Structure-activity relationship studies determined that 5-alkyl-4-(arylmethyl)pyrazol-3-ones, which exist in solution as aromatic enol/iminol tautomers, were the most promising new class of potential antidiabetic agent (32-45% reduction at 20 mg/kg/d x4). Included in this work are convenient syntheses for several types of acidic azoles that may find use as new acidic bioisosteres in medicinal chemistry such as the antidiabetic lead 5-(trifluoromethyl)pyrazol-3-one (hydroxy tautomer) and aza homologs of the pyrazolones, 1,2,3-triazol-5-ones (hydroxy tautomer) and 1,2,3,4-tetrazol-5-one heterocycles. log P and pKa data for 15 potential acidic bioisosteres, all appended to a 2-naphthalenylmethyl residue so as to maintain a similar distance between the acidic hydrogen and arene nucleus, are presented. This new data set allows comparison of a wide variety of potential acid mimetics (pKa 3.78-10.66; log P -0.21 to 2.76) for future drug design.
Alternative functional in vitro models of human intestinal epithelia (2013)

Physiologically relevant sources of absorptive intestinal epithelial cells are crucial for human drug transport studies. Human adenocarcinoma-derived intestinal cell lines, such as Caco-2, offer conveniences of easy culture maintenance and scalability, but do not fully recapitulate in vivo intestinal phenotypes. Additional sources of renewable physiologically relevant human intestinal cells would provide a much needed tool for drug discovery and intestinal physiology. We compared two alternative sources of human intestinal cells, commercially available primary human intestinal epithelial cells (hInEpCs) and induced pluripotent stem cell (iPSC)-derived intestinal cells to Caco-2, for use in in vitro transwell monolayer intestinal transport assays. To achieve this for iPSC-derived cells, intestinal organogenesis was adapted to transwell differentiation. Intestinal cells were assessed by marker expression through immunocytochemical and mRNA expression analyses, monolayer integrity through Transepithelial Electrical Resistance (TEER) measurements and molecule permeability, and functionality by taking advantage the well-characterized intestinal transport mechanisms. In most cases, marker expression for primary hInEpCs and iPSC-derived cells appeared to be as good as or better than Caco-2. Furthermore, transwell monolayers exhibited high TEER with low permeability. Primary hInEpCs showed molecule efflux indicative of P-glycoprotein (Pgp) transport. Primary hInEpCs and iPSC-derived cells also showed neonatal Fc receptor-dependent binding of immunoglobulin G variants. Primary hInEpCs and iPSC-derived intestinal cells exhibit expected marker expression and demonstrate basic functional monolayer formation, similar to or better than Caco-2. These cells could offer an alternative source of human intestinal cells for understanding normal intestinal epithelial physiology and drug transport.
Genetics of esterases and 6-phosphogluconate dehydrogenase in the Anopheles maculatus complex. (1986)

Electromorphic variation for some esterases and 6-phosphogluconate dehydrogenase enzymes in the Anopheles maculatus complex is controlled by four loci which are unlinked to sex. Esterase loci are linked to each other: Est-1-36%-Est-4-16.5%-Est-3; but unlinked to Pgd-2. Linkage data were obtained by selfing the F1 generation from selected parents and analysing genotypes in the F2; the classical dihybrid-cross. The analysis consists of testing observed data for goodness of fit to a) ratios expected from Mendelian ratios without linkage and b) if they do not fit then computing a likely degree of linkage and computing expected ratios with such linkage for further tests. Confidence limits are given for the most likely levels of linkage. This method can provide useful information for population-genetic studies on anopheline mosquitoes, whose laboratory rearing is generally difficult. Through indirect evidence, the enzyme loci are correlated to polytene chromosomes. The esterases probably lie on chromosome three (polytene arms 3 and 4) and Pgd-2 on the second chromosome (arms 2 and 5).
Functional Cloning of the cDNA for a Human Hyaluronan Synthase (1996)

Hyaluronan is a constituent of the extracellular matrix of connective tissue and is actively synthesized during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of hyaluronan are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, hyaluronan has been implicated as an important substrate for migration of adhesion of leukocytes during inflammation. A human hyaluronan synthase (HuHAS1) cDNA was isolated by a functional expression cloning approach. Transfection of CHO cells conferred hyaluronidase-sensitive adhesiveness of a mucosal T cell line via the lymphocyte hyaluronan receptor, CD44, as well as increased hyaluronan levels in the cultures of transfected cells. The HuHAS1 amino acid sequence shows considerable homology to the hasA gene product of Streptococcus pyogenes, a glycosaminoglycan synthetase from Xenopus laevis (DG42), and is the human homolog of a recently described murine hyaluronan synthase.
EGFR gene amplification ‐ rearrangement in human glioblastomas (1995)

Immunostaining using an affinity-purified rabbit polyclonal antibody against the extracellular domain of the epidermal-growth-factor receptor (EGFR) showed over-expression occurring in a fraction of tumor cells in 17 out of 18 human glioblastomas and in a majority of cells in 7 of the 18. Southern-blotting technique using a full-length EGFR cDNA probe showed a variable degree of amplification in 10 of the 17 glioblastomas, which was associated with EGFR over-expression in each case. In 2 of the glioblastomas with EGFR gene amplification, a rearrangement of the gene affecting the extracellular domain of the receptor was identified and DNA sequence analyses revealed an identical deletion-rearrangement of 801 base pairs between exons 2 to 7, resulting in an in-frame fusion of exons 1 and 8.