gebhart/patrepeval huggingface dataset:
Intracellular Bacteria as Targets and Carriers for Vaccination (2001)

In this review we discuss intracellular bacteria as targets and carriers for vaccines. For clarity and ease of comprehension, we focus on three microbes, Mycobacterium tuberculosis, Listeria monocytogenes and Salmonella, with an emphasis on tuberculosis, one of the leading causes of death from infectious disease. Novel vaccination strategies against these pathogens are currently being considered. One approach favors the use of live attenuated vaccines and vaccine carrier strains thereof, either for heterologous antigen presentation or DNA vaccine delivery. This strategy includes both the improvement of attenuated vaccine strains as well as the 'de novo' generation of attenuated variants of virulent pathogens. An alternative strategy relies on the application of subunit immunizations, either as nucleic acid vaccines or protein antigens of the pathogen. Finally, we present a short summary of the vaccination strategies against tuberculosis.
High performance virtual machine migration with RDMA over modern interconnects (2007)

One of the most useful features provided by virtual machine (VM) technologies is the ability to migrate running OS instances across distinct physical nodes. As a basis for many administration tools in modern clusters and data-centers, VM migration is desired to be extremely efficient to reduce both migration time and performance impact on hosted applications. Currently, most VM environments use the Socket interface and the TCP/IP protocol to transfer VM migration traffic. In this paper, we propose a high performance VM migration design by using RDMA (Remote Direct Memory Access). RDMA is a feature provided by many modern high speed interconnects that are currently being widely deployed in data-centers and clusters. By taking advantage of the low software overhead and the one-sided nature of RDMA, our design significantly improves the efficiency of VM migration. We also contribute a set of micro-benchmarks and application-level benchmark evaluations aimed at evaluating important metrics of VM migration. The evaluations using our prototype implementation over Xen and InfiniBand show that RDMA can drastically reduce the migration overhead: up to 80% on total migration time and up to 77% on application observed downtime.
Measuring information quality of web sites: development of an instrument (1999)

Web sites have been extensively used to provide information to consumers. While practitioners and researchers have proposed different criteria for effective Web site design based on common sense, intuition, and rules-ofthumb, effective Web site design focusing on the quality of the information it provides has rarely been studied. In this research, we propose a framework and develop an instrument to measure the information quality of individual or personal Web sites. The theoretical foundation of this research is the information quality framework. The proposed framework and instrument were tested in an individual or personal Web site context.
Mechanics of Epithelial Tissue Homeostasis and Morphogenesis (2013)

Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.
Kinetics of the Titanium Isopropoxide Decomposition in Supercritical Isopropyl Alcohol (1996)

The formation of TiO2 powder from Ti(O-iC3H7)4 dissolved in supercritical isopropyl alcohol has been studied. Kinetic data were obtained in a temperature range of 531−568 K. A reaction mechanism has been proposed, based on a hydrolytic decomposition of Ti(O-iC3H7)4 by water produced in a catalytic dehydration of the isopropyl alcohol used as solvent and where the limiting steps are the decomposition reactions of the formed titanium hydroxides. In accordance with experimental results, such a mechanism leads to a first order kinetics relative to the precursor concentration. The activation energy was determined equal to 113 ± 16 kJ·mol-1, and an increase in the supercritical fluid density was found to decrease the overall reaction rate. The obtained results will be used to optimize the working of a continuous reactor producing submicronic TiO2 powder at a laboratory pilot scale.
Signaling and regulation of G protein-coupled receptors in airway smooth muscle (2003)

Signaling through G protein-coupled receptors (GPCRs) mediates numerous airway smooth muscle (ASM) functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that have been identified in ASM cells, and discuss the extent to which signaling via these GPCRs has been characterized and linked to distinct ASM functions. In addition, we examine the role of GPCR signaling and its regulation in asthma and asthma treatment, and suggest an integrative model whereby an imbalance of GPCR-derived signals in ASM cells contributes to the asthmatic state.
Shape-Adaptable Water-Soluble Conjugated Polymers (2003)

Cationic water-soluble conjugated polymers with a non "rigid-rod" aspect ratio can be prepared by Suzuki coupling condensation polymerization of 2,7-dibromo-9,9-bis(6'-bromohexyl)fluorene and varying ratios of p- and m-phenyl diboronic acids, followed by reaction with trimethylamine. The resulting polymers are designated MnPm+, where the subscripts in Mn and Pm correspond to the ratio of meta and para linkages, respectively. Absorption and fluorescence spectra indicate facile energy transfer via interachain or intrachain mechanisms. The emission of MnPm+ with m > 50 matches that of M0P100+. Excitations ultimately reside in the polymer segments with largest number of para linkages. FRET experiments show that the polymers with a more flexible structure are better donors to fluorescein-labeled double-stranded DNA. Similar results are obtained when intercalated ethidium bromide is used as the acceptor. These results indicate that there is better spatial registry between the flexible conjugated polymers and the secondary structure of DNA.
Arrhenius parameters for the alkaline hydrolysis of esters in aqueous solution. Part III. Methyl betaine methyl ester (1968)

The kinetics of the alkaline hydrolysis of methyl betaine methyl ester have been studied using a pH-stat in aqueous solution, over a range of hydroxide ion concentrations at 0, 25, and 42°, and at an ionic strength of 0·1M. The results show the presence of a very small but detectable water rate at 25 and 42° but not at 0°. The effect of ionic strength has been studied. Rate constants and the energy and entropy of activation all show the expected dependence on ionic strength. Methyl betaine methyl ester has been shown to hydrolyse approximately three times faster at 25° than ethyl betaine ethyl ester. The Arrhenius parameters for both reactions are discussed. A comparison of ethyl betaine ethyl ester with glycine ethyl ester shows the effect of introducing both charge and substituent, while a comparison with the reaction of the protonated glycine ethyl ester shows the effect of substitution only. Such comparisons indicate that, though the introduction of a charge on the N atom has a major effect on the rate, substitution at this centre has little effect. This is also discussed with reference to the Arrhenius parameters for the relevant reactions.
Disinfection of selected Aspergillus spp. using ultraviolet germicidal irradiation (2004)

These results may not be directly correlated to the effect of UVGI on airborne fungal spores, but they indicate that current technology may not be efficacious as a supplement to ventilation unless it can provide higher doses of UVGI to kill spores traveling through the irradiated zone.
Distinct Mechanisms of Glucose Lowering by Specific Agonists for Peroxisomal Proliferator Activated Receptor γ and Retinoic Acid X Receptors (2005)

Agonists for the nuclear receptor peroxisomal proliferator-activated receptor-gamma (PPARgamma) and its heterodimeric partner, retinoid X receptor (RXR), are effective agents for the treatment of type 2 diabetes. To gain insight into the antidiabetic action of these compounds, we treated female Zucker diabetic rats (ZFF) with AGN194204, which we show to be a homodimer-specific RXR agonist, or the PPARgamma agonist, troglitazone. Hyperinsulinemic-euglycemic clamps in ZFF showed that troglitazone and AGN194204 reduced basal endogenous glucose production (EGP) approximately 30% and doubled the insulin suppression of EGP. AGN194204 had no effect on peripheral glucose utilization, whereas troglitazone increased insulin-stimulated glucose utilization by 50%, glucose uptake into skeletal muscle by 85%, and de novo skeletal muscle glycogen synthesis by 300%. Troglitazone increased skeletal muscle Irs-1 and phospho-Akt levels following in vivo insulin treatment, whereas AGN194204 increased hepatic Irs-2 and insulin stimulated phospho-Akt in liver. Gene profiles of AGN194204-treated mouse liver analyzed by Ingenuity Pathway Analysis identified increases in fatty acid synthetic genes, including Srebp-1 and fatty acid synthase, a pathway previously shown to be induced by RXR agonists. A network of down-regulated genes containing Foxa2, Foxa3, and G-protein subunits was identified, and decreases in these mRNA levels were confirmed by quantitative reverse transcription-PCR. Treatment of HepG2 cells with AGN194204 resulted in inhibition of glucagon-stimulated cAMP accumulation suggesting the G-protein down-regulation may provide an additional mechanism for hepatic insulin sensitization by RXR. These studies demonstrate distinct molecular events lead to insulin sensitization by high affinity RXR and PPARgamma agonists.
Western blots using stained protein gels. (1992)

A general method is described for the electrophoretic transfer of proteins from stained gels to membranes and subsequent Western detection of specific proteins on the stained membranes. Proteins are separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and the gels are stained using either of two different methods followed by electrophoretic transfer to nitrocellulose or Immobilon-P membranes. The transferred proteins remain stained during immunodetection, providing a set of background markers for protein location and size determination.
Neuroendocrine dysfunction in the acute phase of traumatic brain injury (2004)

Our data show that post-traumatic neuroendocrine abnormalities occur early and with high frequency, which may have significant implications for recovery and rehabilitation of TBI patients.
Structure-activity study of hCGRP8-37, a calcitonin gene-related peptide receptor antagonist (1992)

A structure-activity study was carried out to determine the importance of the N-terminal amino acids of hCGRP8-37 in binding and antagonistic activity to CGRP receptors. Therefore, fragments of hCGRP8-37 as well as analogs obtained by the replacement of residues 9-12 by L-alanine were synthesized by solid-phase peptide synthesis, using BOP as a coupling reagent. The affinities of the peptides to CGRP receptors were evaluated in the rat brain, guinea pig atrium, and guinea pig vas deferens membrane preparations. Their antagonistic activities were measured in the guinea pig atria and rat vas deferens bioassays. The pharmacological characterization showed that arginine-11 and leucine-12 play a crucial role for the affinity of hCGRP8-37. Interestingly, it was observed that [Ala11]hCGRP8-37 was able to potentiate the twitch response of the electrically stimulated rat vas deferens. On the other hand, the substantial antagonistic potencies of analogs [Ala9]-, [Ala10]-, and [Ala12]hCGRP8-37, as compared to those of the fragments hCGRP10-37, hCGRP11-37, and hCGRP12-37, suggest that the side chains of Thr-9, His-10, and Leu-12 assume mainly a structural role. Accordingly, the conformational characterization of these peptides by circular dichroism spectroscopy revealed that the residues 9-12 are important for the integrity of the amphiphilic alpha-helix of hCGRP8-37.
Biochemical, Structural, and Biological Evaluation of Tranylcypromine Derivatives as Inhibitors of Histone Demethylases LSD1 and LSD2 (2010)

LSD1 and LSD2 histone demethylases are implicated in a number of physiological and pathological processes, ranging from tumorigenesis to herpes virus infection. A comprehensive structural, biochemical, and cellular study is presented here to probe the potential of these enzymes for epigenetic therapies. This approach employs tranylcypromine as a chemical scaffold for the design of novel demethylase inhibitors. This drug is a clinically validated antidepressant known to target monoamine oxidases A and B. These two flavoenzymes are structurally related to LSD1 and LSD2. Mechanistic and crystallographic studies of tranylcypromine inhibition reveal a lack of selectivity and differing covalent modifications of the FAD cofactor depending on the enantiomeric form. These findings are pharmacologically relevant, since tranylcypromine is currently administered as a racemic mixture. A large set of tranylcypromine analogues were synthesized and screened for inhibitory activities. We found that the common evolutionary origin of LSD and MAO enzymes, despite their unrelated functions and substrate specificities, is reflected in related ligand-binding properties. A few compounds with partial enzyme selectivity were identified. The biological activity of one of these new inhibitors was evaluated with a cellular model of acute promyelocytic leukemia chosen since its pathogenesis includes aberrant activities of several chromatin modifiers. Marked effects on cell differentiation and an unprecedented synergistic activity with antileukemia drugs were observed. These data demonstrate that these LSD1/2 inhibitors are of potential relevance for the treatment of promyelocytic leukemia and, more generally, as tools to alter chromatin state with promise of a block of tumor progression.
Ewen Bridge Replacement Pile Grouting (1995)

Construction of a new 170 metre long, four lane road bridge across the Hutt River at Ewen involved installing 2.4 metre diameter cast in situ piles to a depth of 22 metres below the river bed. The piles were founded in the Hutt Aquifer which provides 25 percent of Wellington's water supply and is artesian with a static water level 5 metre above river bed level. After it proved impossible to drive a single 2.4 metre casing with an internal shoe to founding level, casings with external shoes were adopted. These were expected to leave a gap between the casing and the ground behind the shoe. This paper describes the development and implementation of grouting procedures to effectively seal that gap to prevent release of the aquifer pressure.
Discontinuity-aware video object cutout (2012)

Existing video object cutout systems can only deal with limited cases. They usually require detailed user interactions to segment real-life videos, which often suffer from both inseparable statistics (similar appearance between foreground and background) and temporal discontinuities (e.g. large movements, newly-exposed regions following disocclusion or topology change). In this paper, we present an efficient video cutout system to meet this challenge. A novel directional classifier is proposed to handle temporal discontinuities robustly, and then multiple classifiers are incorporated to cover a variety of cases. The outputs of these classifiers are integrated via another classifier, which is learnt from real examples. The foreground matte is solved by a coherent matting procedure, and remaining errors can be removed easily by additive spatio-temporal local editing. Experiments demonstrate that our system performs more robustly and more intelligently than existing systems in dealing with various input types, thus saving a lot of user labor and time.
Interferon-α and -β inhibit the in vitro differentiation of immunocompetent human dendritic cells from CD14+ precursors (2000)

Dendritic cell (DC) precursors and immature DC reside in epithelium where they encounter pathogens and cytokines, which stimulate their differentiation. We hypothesized that type-I interferons (IFN-alpha and -beta), cytokines that are produced early in the innate immune response against viruses and some bacteria, may influence DC differentiation and function. To examine this possibility, we used an in vitro model of DC differentiation in which initial culture of human CD14(+) monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 generates immature DC, and subsequent culture with tumor necrosis factor (TNF)-alpha drives the final development into mature DC. We found in this model that IFN-alpha/beta, added from the initiation of the culture on, significantly reduced the survival and altered the morphology and differentiation of DC. TNF-alpha-dependent maturation of IFN-beta-treated immature DC led to cells with reduced expression of CD1a, CD40, CD54, and CD80 when compared with mature DC controls. IFN-alpha/beta-treated DC further had a reduced capacity to induce naive Th-cell proliferation through allostimulation or anti-CD3 monoclonal antibody stimulation. In addition, IFN-alpha/beta-treated DC secreted less IL-12 upon stimulation with Staphylococcus aureus Cowan strain or with CD4(+) T cells, and this decrease correlated directly with their inability to support CD4(+) T-cell secretion of IFN-gamma, even though T-cell lymphotoxin production was unaffected. These findings indicate that type-I IFNs can influence the generation of acquired immune responses by modifying T-helper cell differentiation through the regulation of DC differentiation and function.
Intercellular Adhesion Molecule 1 Discriminates Functionally Different Populations of Human Osteoblasts: Characteristic Involvement of Cell Cycle Regulators (2000)

The concept of differential regulation of certain adhesion molecules on different cell subsets and their relevance to cell functions has emerged in recent years. The initial event in bone remodeling is an increase in osteoclastic bone resorption and cell adhesion between osteoclastic precursors and bone marrow stromal cells or osteoblasts is known to commit the osteoclast development. Here, we show that human osteoblasts can be divided into two subsets based on the expression of the intercellular adhesion molecule (ICAM)-1; ICAM-1+ osteoblasts highly adhered to monocytes, including osteoclast precursors, produced osteoclast differentiation factor (ODF), and induced multinuclear osteoclast-like cell formation. Anti-ODF monoclonal antibody (mAb) did not inhibit the adhesion of monocytes to osteoblastic cells, whereas anti-leukocyte function-associated antigen (LFA)-1, a receptor for ICAM-1, mAb blocked the adhesion. We thereby propose that the higher affinity adhesion via LFA-1/ICAM-1 is prerequisite for efficient function of membrane-bound ODF during osteoclast maturation. The functional characteristics of ICAM-1+ osteoblasts were emphasized further by cell cycle regulation, as manifested by (i) up-regulation of p53 and p21, (ii) reduction of activity of cyclin-dependent kinase (cdk) 6, (iii) underphosphorylation of retinoblastoma protein, (iv) increased Fas but reduced bcl-2 expression, and (v) majority of cells remained at G0/G1 phase. Furthermore, ICAM-1+ osteoblasts were induced by interleukin-1beta (IL-1beta). Taken together, we propose that the differentiation of osteoblasts to ICAM-1+ subpopulation by inflammatory cytokines plays an important role in osteoporosis, which is observed in patients with chronic inflammation, because ICAM-1+ osteoblasts can bias bone turnover to bone resorption, committing osteoclast maturation through cell adhesion with its precursor, and the majority of ICAM-1+ osteoblasts arrested at G0/G1 phase. Such regulation of cell cycle arrest also is an important determinant of the life span of cells in bone in which continuous bone remodeling maintains its homeostasis.
Substituent Effects on the Mechanism-Based Inactivation of Prostatic Acid Phosphatase (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSubstituent Effects on the Mechanism-Based Inactivation of Prostatic Acid PhosphataseJason K. Myers, Jonathan D. Cohen, and Theodore S. WidlanskiCite this: J. Am. Chem. Soc. 1995, 117, 45, 11049–11054Publication Date (Print):November 1, 1995Publication History Published online1 May 2002Published inissue 1 November 1995https://pubs.acs.org/doi/10.1021/ja00150a002https://doi.org/10.1021/ja00150a002research-articleACS PublicationsRequest reuse permissionsArticle Views438Altmetric-Citations33LEARN 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
CLYBL is a polymorphic human enzyme with malate synthase and β-methylmalate synthase activity (2013)

CLYBL is a human mitochondrial enzyme of unknown function that is found in multiple eukaryotic taxa and conserved to bacteria. The protein is expressed in the mitochondria of all mammalian organs, with highest expression in brown fat and kidney. Approximately 5% of all humans harbor a premature stop polymorphism in CLYBL that has been associated with reduced levels of circulating vitamin B12. Using comparative genomics, we now show that CLYBL is strongly co-expressed with and co-evolved specifically with other components of the mitochondrial B12 pathway. We confirm that the premature stop polymorphism in CLYBL leads to a loss of protein expression. To elucidate the molecular function of CLYBL, we used comparative operon analysis, structural modeling and enzyme kinetics. We report that CLYBL encodes a malate/β-methylmalate synthase, converting glyoxylate and acetyl-CoA to malate, or glyoxylate and propionyl-CoA to β-methylmalate. Malate synthases are best known for their established role in the glyoxylate shunt of plants and lower organisms and are traditionally described as not occurring in humans. The broader role of a malate/β-methylmalate synthase in human physiology and its mechanistic link to vitamin B12 metabolism remain unknown.