gebhart/patrepeval huggingface dataset:
Disruption of the murine procollagen C-proteinase enhancer 2 gene causes accumulation of pro-apoA-I and increased HDL levels (2011)

Given the increased prevalence of cardiovascular disease in the world, the search for genetic variations that impact risk factors associated with the development of this disease continues. Multiple genetic association studies demonstrate that procollagen C-proteinase enhancer 2 (PCPE2) modulates HDL levels. Recent studies revealed an unexpected role for this protein in the proteolytic processing of pro-apolipoprotein (apo) A-I by enhancing the cleavage of the hexapeptide extension present at the N-terminus of apoA-I. To investigate the role of the PCPE2 protein in an in vivo model, PCPE2-deficient (PCPE2 KO) mice were examined, and a detailed characterization of plasma lipid profiles, apoA-I, HDL speciation, and function was done. Results of isoelectric focusing (IEF) electrophoresis together with the identification of the amino terminal peptides DEPQSQWDK and WHVWQQDEPQSQWDVK, representing mature apoA-I and pro-apoA-I, respectively, in serum from PCPE2 KO mice confirmed that PCPE2 has a role in apoA-I maturation. Lipid profiles showed a marked increase in plasma apoA-I and HDL-cholesterol (HDL-C) levels in PCPE2 KO mice compared with wild-type littermates, regardless of gender or diet. Changes in HDL particle size and electrophoretic mobility observed in PCPE2 KO mice suggest that the presence of pro-apoA-I impairs the maturation of HDL. ABCA1-dependent cholesterol efflux is defective in PCPE2 KO mice, suggesting that the functionality of HDL is altered.
Experimental Chemotherapy of Tuberculosis. IV. 2-Piperazinecarboxylic Acid and Related Compounds (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExperimental Chemotherapy of Tuberculosis. IV. 2-Piperazinecarboxylic Acid and Related CompoundsF. L. Bach Jr., S. Kushner, and J. H. WilliamsCite this: J. Am. Chem. Soc. 1955, 77, 22, 6049–6051Publication Date (Print):November 1, 1955Publication History Published online1 May 2002Published inissue 1 November 1955https://pubs.acs.org/doi/10.1021/ja01627a075https://doi.org/10.1021/ja01627a075research-articleACS PublicationsRequest reuse permissionsArticle Views102Altmetric-Citations6LEARN 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
A Prospective Double-Blind Study of Side Effects Associated with the Administration of Amantadine for Influenza A Virus Prophylaxis (1980)

During a study of efficacy of amantadine prophylaxis of influenza A virus infection in young adults, gross and subtle side effects were monitored. Eighty-eight students were randomly selected to receive either amantadine or placebo for four weeks or both in a sequential crossover design of two weeks each. Side effects (i.e., dizziness, nervousness, and insomnia) occurred in 33% of those receiving amantadine and in 10% of those receiving placebo (P less than 0.005). Although side effects were well tolerated by most subjects, six volunteers discontinued amantadine because of marked complaints. Cessation of side effects occurred in more than half of those continuing amantadine. Sixteen students receiving amantadine had decreased performance on sustained attention tasks as compared with ones receiving placebo (P less than 0.05). Gross and subtle side effects of amantadine observed in this study on currently recommended dosage are higher than previously reported, which may be an important factor in consideration of mass prophylaxis.
Shotgun Sequencing of the Human Genome (1998)

The recent public announcement by TIGR and Perkin-Elmer that they intend to form a new company whose goal is to sequence the human genome four years faster and at lower cost than the government-backed Human Genome Project caught the immediate attention of the community. Venter
 et al. now describe the scientific rationale for their proposal and outline the business plan of the company.
DNA‐Compatible Chemistry (2014)

This chapter discusses chemistries used to piece the building blocks together. It focuses on chemistries proven to work in the presence of DNA oligomers, and on chemistries thought to have potential value. The chapter provides the foundation needed to design DNA-Encoded Libraries (DELs) capable of providing valuable ligands in a drug-discovery setting. DEL-compatible chemistry requires methodologies that are robust, work in the presence of protic solvents, do not require strong acidic conditions, and will not degrade DNA. The chapter provides methodologies for reactions shown to work in the presence of DNA. It also provides an example that utilizes these known reactions to produce a structurally diverse DEL. The chapter surveys the literature and provides examples of reactions expected to have a reasonable likelihood of success.
The Crystal Structure of Fibroblast Growth Factor (FGF) 19 Reveals Novel Features of the FGF Family and Offers a Structural Basis for Its Unusual Receptor Affinity, (2003)

The 22 members of the FGF family have been implicated in cell proliferation, differentiation, survival, and migration. They are required for both development and maintenance of vertebrates, demonstrating an exquisite pattern of affinities for both protein and proteoglycan receptors. FGF19, one of the most divergent human FGFs, is unique in binding solely to one receptor, FGFR4. We have used molecular replacement to solve the crystal structure of FGF19 at 1.3 A resolution using five superimposed FGF structures as the search model. The structure shows that two novel disulfide bonds found in FGF19, one of which appears to be conserved among several of the other FGFs, stabilize extended loops. The key heparin-binding loops of FGF19 have radically different conformations and charge patterns, compared to other FGFs, correlating with the unusually low affinity of FGF19 for heparin. A model for the complex of FGF19 with FGFR4 demonstrates that unique sequences in both FGF19 and FGFR4 are key to the formation of the complex. The structure therefore offers a clear explanation for the unusual affinity of FGF19 for FGFR4 alone.
A protein chip system for parallel analysis of multi-tumor markers and its application in cancer detection. (2004)

This protein chip system is a potential tool for assisting cancer diagnosis and for screening cancer in high-risk populations.
Structural Characteristics of Activated Carbons and Ibuprofen Adsorption Affected by Bovine Serum Albumin (2004)

Structural characteristics of a series of MAST carbons were studied using scanning electron microscopy images and the nitrogen adsorption isotherms analyzed with several models of pores and different adsorption equations. A developed model of pores as a mixture of gaps between spherical nanoparticles and slitlike pores was found appropriate for MAST carbons. Adsorption of ibuprofen [2-(4-isobutylphenyl)propionic acid] on activated carbons possessing different pore size distributions in protein-free and bovine serum albumin (BSA)-containing aqueous solutions reveals the importance of the contribution of mesopores to the total porosity of adsorbents. The influence of the mesoporosity increases when considering the removal of the drug from the protein-containing solution. Cellulose-coated microporous carbon Norit RBX adsorbs significantly smaller amounts of ibuprofen than uncoated micro/mesoporous MAST carbons whose adsorption capability increases with increasing mesoporosity and specific surface area, burnoff dependent variable. A similar effect of broad pores is observed on adsorption of fibrinogen on the same carbons. Analysis of the ibuprofen adsorption data using Langmuir and D'Arcy-Watt equations as the kernel of the Fredholm integral equation shows that the nonuniformity of ibuprofen adsorption complexes diminishes with the presence of BSA. This effect may be explained by a partial adsorption of ibuprofen onto protein molecules immobilized on carbon particles and blocking of a portion of narrow pores.
Does Heparin Coating Improve Patency or Reduce Infection of Tunneled Dialysis Catheters? (2009)

Heparin coating decreases the frequency of catheter-related bacteremia but does not reduce the frequency of catheter malfunction.
Cell-Free DNA as a Noninvasive Acute Rejection Marker in Renal Transplantation (2009)

Given that renal biopsy is the gold standard for detecting AR, analysis of both plasma tCF-DNA and PCT could permit a more selective use of this invasive procedure.
Heterocyclic β‐Enamino Esters, 481) Heterocondensed Pyridines by Cycloaddition‐Extrusion Sequence of Bi‐ and Tricyclic 1,3‐Oxazinones with N,N‐Diethyl‐1‐propynylamine (1987)

Abstract Dihalotriphenylphosphoranes convert the N ‐benzoylated ethyl 2‐amino‐4,5‐dihydrofuran‐ ( 5b ), ‐pyrrole‐ ( 7b ), ‐isoxazole‐ ( 9b ), and ‐oxazole‐3‐ or‐4‐carboxylates ( 11b ) into heterocondensed 1,3‐oxazinones 6, 8, 10 , and 12 . Treatment with N,N ‐diethyl‐1‐propynylamine of these compounds as well as the already known 1,3‐oxazinones 1a,b, 2a,b , and 3 results in a regiospecific cycloaddition‐extrusion sequence to afford the corresponding heterocondensed pyridines 13a,b, 14a,b, 15a,b , and 16–21 . Of these 15b and the 4‐oxonaphthyridines 16, 17 represent examples of insertion of the acetylene reagent.
Destabilization of phosphatidylethanolamine-containing liposomes: hexagonal phase and asymmetric membranes (1987)

We have measured the temperature of the L alpha-HII phase transition, TH, for several types of phosphatidylethanolamine (PE), their binary mixtures, and several PE/cholesteryl hemisuccinate (CHEMS) mixtures. We have shown for liposomes composed of pure PE and in mixtures with CHEMS that there is an aggregation-mediated destabilization which is greatly enhanced at and above TH. We now ask the question: How well can a dioleoylphosphatidylethanolamine/CHEMS liposome, for example, destabilize TPE (transesterified from egg phosphatidylcholine)/CHEMS liposome and vice versa? We use Ca2+ and H+ to induce aggregation and to provide different values of TH: the TH of the PE/CHEMS mixture is much lower at low pH than with Ca2+. We find that if the temperature is above the TH of one lipid mixture, e.g., A, and below the TH of the other lipid mixture, e.g., B, then the destabilization sequence [measured by the fluorescent 1-aminonaphthalene-3,6,8-trisulfonic acid/p-xylylenebis(pyridinium bromide) leakage assay] is AA greater than AB much greater than BB. That is, the bilayer of the lipid A (which on its own would end up in the HII phase) destabilizes itself better than it destabilizes the bilayer of lipid B (which on its own would remain in the L alpha phase). The BB contact is the least unstable. From these experiments, we conclude that the enhanced destabilization of membranes provided by the polymorphism accessible to these lipids above TH is effective even if only one of the apposed outer monolayers is HII phase competent. The surprising result is that if the temperature is above the TH of both lipid mixtures, then the destabilization sequence is AB greater than AA, BB. That is, the mixed bilayers are destabilized more by contact than either of the pure pairs. We believe that this is due to specific differences in the kinetics of aggregation or close approach of the membranes. Similar results were obtained with pure PE liposomes induced to aggregate by Ca2+ at pH 9.5. We also found that the kinetics of low-pH-induced leakage from PE/CHEMS liposomes were initially faster when the CHEMS on both sides of the bilayer is fully protonated. However, in a citrate buffer, which cannot cross intact membranes, the leakage was eventually faster. Flip-flop of the protonated CHEMS to the inner monolayer can explain this observation.
Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor beta subunit in human breast tissue and breast carcinoma. (1995)

Breast carcinomas are known to express platelet-derived growth factor (PDGF), a known connective tissue mitogen. In order to further evaluate the potential role of PDGF in these epithelial tumors, expression of the PDGF B chain (PDGF-B) and the PDGF receptor beta subunit (PDGFR) was analyzed by immunocytochemistry and in situ hybridization in 49 benign and malignant breast tissues. PDGF-B expression was analyzed with respect to the expression of the proliferating cell nuclear antigen, as well as tumor grade, p53 overexpression, estrogen receptor, progesterone receptor, and c-erbB-2 expression. Expression of PDGF-B protein and mRNA was restricted to the breast epithelium and tumor cells except for scattered tissue macrophages. A strong correlation was found between increasing proliferating cell nuclear antigen indices and PDGF-B expression in both nonmalignant (P = 0.01) and malignant (P = 0.02) breast specimens. Decreased PDGF-B expression was found in postmenopausal atrophic breast tissue compared with normal breast tissue (P = 0.04). Within the subgroup of malignant tumors, no correlations were found between PDGF-B expression and tumor grade or p53 overexpression. In 16 of the malignant tumors evaluated for estrogen/progesterone receptor status and c-erbB-2 overexpression, no correlations with PDGF-B expression were found. Membranous PDGFR immunostaining was present within the fibroblastic cell population in all of the tissues examined but not in the nonmalignant breast epithelium. Six malignant specimens had detectable cytoplasmic expression of PDGFR. There was no correlation between this PDGFR expression and proliferating cell nuclear antigen indices, but a correlation was noted between increasing estrogen receptor expression and PDGFR cytoplasmic expression (P = 0.04). The results support a paracrine role for PDGF-B in malignant and benign breast epithelial cell proliferation.
Prognostic significance of circumferential cell surface immunoreactivity of glypican‐3 in hepatocellular carcinoma (2010)

Circumferential membranous GPC3 immunoreactivity in HCC indicates poorer prognosis particularly in patients with HCV infection.
Serum levels of tissue inhibitor of metalloproteinases in patients with mixed connective tissue disease. (2003)

These results suggest that TIMP-1 is involved in the pathogenesis of MCTD, and that TIMP-1 may be a serological marker for the presence of esophageal involvement in these patients.
Discovery of Potent Mcl-1/Bcl-xL Dual Inhibitors by Using a Hybridization Strategy Based on Structural Analysis of Target Proteins (2013)

Mcl-1 and Bcl-xL are crucial regulators of apoptosis, therefore dual inhibitors of both proteins could serve as promising new anticancer drugs. To design Mcl-1/Bcl-xL dual inhibitors, we performed structure-guided analyses of the corresponding selective Mcl-1 and Bcl-xL inhibitors. A cocrystal structure of a pyrazolo[1,5-a]pyridine derivative with Mcl-1 protein was successfully determined and revealed the protein-ligand binding mode. The key structure for Bcl-xL inhibition was further confirmed through the substructural analysis of ABT-263, a representative Bcl-xL/Bcl-2/Bcl-w inhibitor developed by Abbott Laboratories. On the basis of the structural data from this analysis, we designed hybrid compounds by tethering the Mcl-1 and Bcl-xL inhibitors together. The results of X-ray crystallographic analysis of hybrid compound 10 in complexes with both Mcl-1 and Bcl-xL demonstrated its binding mode with each protein. Following further optimization, compound 11 showed potent Mcl-1/Bcl-xL dual inhibitory activity (Mcl-1, IC50 = 0.088 μM; and Bcl-xL, IC50 = 0.0037 μM).
Vertical Integration of Stacked DRAM and High-Speed Logic Device Using SMAFTI Technology (2009)

A multistrata dynamic random access memory (DRAM) vertically integrated with a complementary metal oxide semiconductor (CMOS) logic device using through-silicon vias (TSVs) and a unique interposer technology was developed for high-performance, power-efficient, and scalable computing. SMAFTI (SMArt chip connection with FeedThrough Interposer) technology, featuring an ultra-thin organic interposer with high-density feedthrough conductive vias, was used for interconnecting the three-dimensionally stacked DRAM and the CMOS logic device . A DRAM-compatible TSV manufacturing process was realized through the use of a ldquovia-firstrdquo process and highly doped poly-Si TSVs for vertical traces inside memory dice. A multilayer ultra-thin die stacking process with micro-bump interconnection using a solid-liquid interdiffusion technique was also developed. The thermal aging reliability of the micro-bump interconnection was evaluated by a unique analysis method and its basic reliability was confirmed. Finally, we fabricated a prototype package including stacked DRAM and a CMOS logic device, and observed the combined operation. High-speed 3 Gbit/s signals were successfully transmitted through the fine interposer between the memory and logic.
The geography of science: disciplinary and national mappings (1985)

Chaque annee l'Institut for Scientific Information (ISI) entreprend une analyse de sa banque de donnees, derivee du Science Citation Index et du Social Science Citation Index. Le but de cette analyse est de creer des «cartes de la science» qui montrent la topographie des sciences a divers niveaux d'agregation. Cette technique est encore dans l'enfance mais fait apparaitre des structures interessantes. Une analyse de ces cartes et de la methode utilisee est proposee. (INTD)
Bioconjugated Janus Particles Prepared by in Situ Click Chemistry (2009)

Janus silica particles decorated with biotin molecules and poly(ethylene oxide) PEO chains on two hemispheres were prepared by two-step click reactions. Polystyrene (PS) particles coated with azide modified silica particles were used as templates. On the PS surface one hemisphere of a silica particle was exposed to the solvent and the other one was embedded in PS. The alkynated biotin molecules were grafted onto the exposed side of the silica particle by click reaction. After removal of PS, the embedded part of the silica particle was released, and alkynated PEO chains were grafted to the particle by click reaction. FT-IR, TGA, and TEM were employed to characterize the Janus particles. The Janus particles show strong interaction with avidin.
Computer assisted leukocyte adhesion measurement in intravital microscopy. (1989)

The pathogenetic role of the leukocytes in the development of postischemic injury is not yet understood. Therefore a model was developed which allows for in vivo quantification of leukocyte-endothelium interaction in the awake animal. The velocity of leukocytes was measured by means of intravital microscopy and interactive digital image analysis. An adhesion coefficient (AC) was calculated which characterizes the degree of the leukocyte-endothelium interaction. A special procedure of automatically taking image samples for the leukocyte velocity measurement reduces observer bias. As shown in a validation experiment, this procedure yields reproducible results and therefore allows to quantify the influence of prophylactic and therapeutic measures on postischemic leukocyte-endothelium interaction.
An in-depth map of polyadenylation sites in cancer (2012)

We present a comprehensive map of over 1 million polyadenylation sites and quantify their usage in major cancers and tumor cell lines using direct RNA sequencing. We built the Expression and Polyadenylation Database to enable the visualization of the polyadenylation maps in various cancers and to facilitate the discovery of novel genes and gene isoforms that are potentially important to tumorigenesis. Analyses of polyadenylation sites indicate that a large fraction (∼30%) of mRNAs contain alternative polyadenylation sites in their 3' untranslated regions, independent of the cell type. The shortest 3' untranslated region isoforms are preferentially upregulated in cancer tissues, genome-wide. Candidate targets of alternative polyadenylation-mediated upregulation of short isoforms include POLR2K, and signaling cascades of cell-cell and cell-extracellular matrix contact, particularly involving regulators of Rho GTPases. Polyadenylation maps also helped to improve 3' untranslated region annotations and identify candidate regulatory marks such as sequence motifs, H3K36Me3 and Pabpc1 that are isoform dependent and occur in a position-specific manner. In summary, these results highlight the need to go beyond monitoring only the cumulative transcript levels for a gene, to separately analysing the expression of its RNA isoforms.
PPAR-α agonists are still on the rise: an update on clinical and experimental findings (2017)

Non-fasting plasma triglyceride (TG) and remnant cholesterol levels, cholesterol content of triglyceride-rich lipoproteins, have been suggested to be an additional cause of cardiovascular diseases; thus, pharmacological TG-lowering with fibrates, activators of PPAR-alpha system, has been linked to risk reduction. Areas covered: This manuscript reviews available evidence on clinical trials involving highly selective PPAR-α agonists (i.e., pemafibrate) and drugs used in the pre-clinical and experimental setting (e.g., WY14,643). Original publications in English were selected, as well as Abstracts of international meetings' presentations. Clinical trials were identified using the clinicaltrial.gov database and the EU Clinical Trials Register (clinicaltrialsregister.eu). Expert opinion: In addition to the aim of improving lipid profile with fibrates, the interest in new PPAR-α activators stems from the need to overcome some of the clinical problems encountered with dose-dependent adverse events; a rise of plasma creatinine, gallstone formation, drug-drug interactions (i.e. gemfibrozil), and myopathy. New PPAR-α agonists improved TG and HDL-C levels as well as other parameters related to TG metabolism (remnant cholesterol and apoB), without raising liver enzymes. Although the use of fibrates is rated 'second choice' by many clinicians, new PPAR-α agonists may offer a more accessible route to the management of hypertriglyceridemia, a frequent clinical condition.
An observability-based code coverage metric for functional simulation (1996)

Functional simulation is the most widely used method for design verification. At various levels of abstraction, e.g., behavioral, register-transfer level and gate level, the designer simulates the design using a large number of vectors attempting to debug and verify the design. A major problem with functional simulation is the lack of good metrics and tools to evaluate the quality of a set of functional vectors. Metrics used currently are based on instruction counts and are quite simplistic. Designers are forced to use ad-hoc methods to terminate functional simulation, e.g., CPU time limitations, We propose a new metric for measuring the extent of design verification provided by a set of functional simulation vectors. This metric is universal, and can be used uniformly for all designs. Our metric computes observability information to determine whether effects of errors that are activated by the program stimuli can be observed at the circuit outputs. We provide preliminary experimental evidence that supports the validity of the proposed metric. We believe that using this metric in design verification will result in higher-quality functional tests and improved correctness checking.