gebhart/patrepeval huggingface dataset:
Clearance of Infection with<i>Mycobacterium bovis</i>BCG in Mice Is Enhanced by Treatment with S28463 (R-848), and Its Efficiency Depends on Expression of Wild-Type<i>Nramp1</i>(Resistance Allele) (2001)

The mouse bcg host resistance gene is known to control the activation of host macrophages for killing of intracellular parasites like Leishmania donovani as well as intracellular bacteria, including Mycobacterium bovis BCG and Salmonella enterica serovar Typhimurium. The Nramp1 gene has been mapped to this locus and affects the efficiency of macrophage activation. It has been shown that imidazoquinoline compounds, including S28463, are able to improve the clearance of a number of intracellular pathogens such as herpes simplex virus 2, human papillomavirus, and Leishmania. The goal of this study was to determine whether S28463 is efficient against infection with another intracellular pathogen, M. bovis BCG, and to determine the molecular basis underlying this effect. To achieve this, B10A.Nramp1(r) and B10A.Nramp1(-/-) mice were infected with M. bovis BCG and treated with S28463. The bacterial content in the spleen from these mice was assayed by a colony-forming assay. In addition, in vitro experiments were performed using bone marrow-derived macrophage cell lines from these mice. These cells were treated with S28463 and/or gamma interferon (IFN-gamma), and nitric oxide (NO) production was measured. Our study was able to show that S28463 acts in synergy with IFN-gamma to increase the production of NO in vitro. We were also able to demonstrate that mice that carried the resistant allele of the Nramp1 gene and were infected with M. bovis BCG responded to treatment with S28463, resulting in a decreased bacterial load after 2 weeks of treatment. Mice that do not express the Nramp1 gene responded only to a very large dose of S28463, and the response was not as efficient as that observed in mice carrying a wild-type Nramp1 allele. Our data provide evidence for the potential of S28463 as an immunomodulator that may be helpful in designing efficient strategies to improve host defense against mycobacterial infection.
Conditional mutagenesis using site-specific recombination in <i>Plasmodium berghei</i> (2004)

Reverse genetics in Plasmodium, the genus of parasites that cause malaria, still faces major limitations. Only red blood cell stages of this haploid parasite can be transfected. Consequently, the function of many essential genes in these and subsequent stages, including those encoding vaccine candidates, cannot be addressed genetically. Here, we establish conditional mutagenesis in Plasmodium by using site-specific recombination and the Flp/FRT system of yeast. Site-specific recombination is induced after cross-fertilization in the mosquito vector of two clones containing either the target sequence flanked by two FRT sites or the Flp recombinase. Parasites that have undergone recombination are recognized in the cross progeny through the expression of a fluorescence marker. This approach should permit to dissect the function of any essential gene of Plasmodium during the haploid phase of its life, i.e., during infection of salivary glands in the mosquito and infection of both the liver and red blood cells in the mammal.
Effects of hydrogen in the annealing environment on photoluminescence from Si nanoparticles in SiO2 (1999)

The role of hydrogen in enhancing the photoluminescence (PL) yield observed from Si nanocrystals embedded in SiO2 has been studied. SiO2 thermal oxides and bulk fused silica samples have been implanted with Si and subsequently annealed in various ambients including hydrogen or deuterium forming gases (Ar+4%H2 or Ar+4%D2) or pure Ar. Results are presented for annealing at temperatures between 200 and 1100 °C. Depth and concentration profiles of H and D at various stages of processing have been measured using elastic recoil detection. Hydrogen or deuterium is observed in the bulk after annealing in forming gas but not after high temperature (1100 °C) anneals in Ar. The presence of hydrogen dramatically increases the broad PL band centered in the near infrared after annealing at 1100 °C but has almost no effect on the PL spectral distribution. Hydrogen is found to selectively trap in the region where Si nanocrystals are formed, consistent with a model of H passivating surface states at the Si/SiO2 interface that leads to enhanced PL. The thermal stability of the trapped H and the PL yield observed after a high temperature anneal have been studied. The hydrogen concentration and PL yield are unchanged for subsequent anneals up to 400 °C. However, above 400 °C the PL decreases and a more complicated H chemistry is evident. Similar concentrations of H or D are trapped after annealing in H2 or D2 forming gas; however, no differences in the PL yield or spectral distribution are observed, indicating that the electronic transitions resulting in luminescence are not dependent on the mass of the hydrogen species.
11?-Hydroxysteroid dehydrogenase Type 1 as a novel therapeutic target in metabolic and neurodegenerative disease (2003)

11β-Hydroxysteroid dehydrogenase Type 1 (11HSD1) catalyses regeneration of active 11-hydroxy glucocorticoids from inactive 11-keto metabolites within target tissues. Inhibition of 11HSD1 has been proposed as a novel strategy to lower intracellular glucocorticoid concentrations, without affecting circulating glucocorticoid levels and their responsiveness to stress. Increased 11HSD1 activity may be pathogenic, for example, in adipose tissue in obesity. Experiments in transgenic mice and using prototype inhibitors in humans show benefits of 11HSD1 inhibition in liver, adipose and brain tissue in treating features of the metabolic syndrome and cognitive dysfunction with ageing. The clinical development of potent selective 11HSD1 inhibitors is now a high priority.
The Adaptor Protein Shb Binds to Tyrosine 1175 in Vascular Endothelial Growth Factor (VEGF) Receptor-2 and Regulates VEGF-dependent Cellular Migration (2004)

Previous studies have shown that the adaptor protein Shb is involved in receptor tyrosine kinase signaling. In this study, we demonstrate that Shb is phosphorylated in an Src-dependent manner upon vascular endothelial growth factor (VEGF) stimulation using porcine aortic endothelial cells expressing the human VEGF receptor 2 (VEGFR-2) (KDR). In co-immunoprecipitation experiments, we could detect an interaction between Shb and the VEGFR-2 in human telomerase-immortalized microvascular endothelial cells. Furthermore, in a glutathione S-transferase pull-down assay, the Src homology 2 domain of Shb was shown to interact with phosphorylated tyrosine 1175 in the C-terminal tail of VEGFR-2. VEGF-induced Shb phosphorylation was lost in porcine aortic endothelial cells expressing a chimeric murine VEGFR-2 (Flk-1) with a mutation at the corresponding position. Shb expression was specifically decreased by 80%, in a transient manner, by using the short interfering RNA technique. Reduced Shb expression led to a loss of stimulation of phosphatidylinositol 3-kinase, phosphorylation of focal adhesion kinase at tyrosine 576, the generation of focal adhesions, and stress fiber formation in response to VEGF. Furthermore, we show that VEGF-induced migration is inhibited in Shb short interfering RNA-treated cells. Our data demonstrate that Shb is important for VEGF signaling in endothelial cells. This is achieved by Shb binding to tyrosine 1175 in the VEGFR-2, which regulates VEGF-induced formation of focal adhesions and cell migration, of which the latter occurs in a phosphatidylinositol 3-kinase-dependent manner.
Effect of a teat sealer on coliform mastitis (1981)

The practice of disinfecting teat ends after milking has become an important tool in the control of intramammary infection due to Streptococcus spp. and Staphylococcus spp. but has shown little benefit in controlling mastitis due to coliforms. It has been theorized that since at least part of the coliform infection occurs in the period between milkings, a mechanical teat sealer may assist in preventing this type of infection. The effect of a teat sealer which contained no germicide was studied. The ability of the film to prevent environmental bacterial contamination between milkings was studied by comparing bacterial numbers present after the film was removed with unsealed teats. The effect on growth of bacteria sealed under such a film was studied by dipping over staphylococcus-contaminated teats, removing the dip and comparing the numbers with controls.
Grafted NiO on natural olivine for dry reforming of methane (2002)

Natural olivine is used for gasification of biomass in a fluidised bed. Characterisations by X-raydiffraction and electron microscopies (SEM and TEM) have proved the presence of a (Mg,Fe)2SiO4 structure (Mg/Fe ratio: 9/1) with a rather broad distribution in elemental composition. Temperature programmed reduction has revealed equally the presence of iron oxides outside of this structure. The nature of free iron oxides can be both modified by increasing the temperature of calcination and confirmed by measurements of magnetism.The introduction of nickel oxide upon natural olivine is obtained by impregnation with a nitrate salt. The type of interaction of nickel oxide with olivine is different depending upon the preparationmethod and the calcination temperature. For calcination at 1100 ºC, the effects of the amount ofNiO and the number of impregnation have been studied. At a high temperature of calcination (1400 ºC), NiO is integrated into the olivine structure and the amount of free iron increases. Integrated NiO on olivine is non-reducible, resulting in an inactive catalyst. At lower calcination temperatures grafted NiO is formed, a species which is reduced under catalytic test conditions without aggregation of particles. A single impregnation of nickel (5.5 wt% of NiO) gives a stable catalyst activated directly under reaction conditions (CH4 + CO2) yielding 96% CO and 76% H2. Catalysts with lower amounts of NiO or a double impregnation of nickel salt lead to a less stable system.Analysis reveals that no change in olivine structure nor size of nickel deposit occurs under test conditions. Equally there are no carbon deposits formed on these catalysts. A model of the evolution of each catalytic system arising from the different preparation methods is proposed. The observed deactivation of such catalysts is attributed to the increase in the amount of free iron, which favours the oxidative properties of the catalytic system.
Wetting of metal surfaces with a liquid metal using a plasma interaction technique (1984)

Materials such as tungsten, molybdenum, stainless steel, etc., which have low solubility in mercury (Hg) are difficult to be wetted or coated with the liquid metal. This paper describes a general technique for wetting and coating such metals with Hg. The method involves plasma etching the substrate and making the liquid metal interact with the plasma before it contacts the substrate surface, by delivering it to the substrate through the glow discharge, to successfully wet the above metals. Elkonite (70% W and 30% Cu) was also wetted successfully by this technique. A model has been presented to qualitatively explain the observed results. The discharge is postulated to create reactive species on the substrate surface and to produce reactive Hg species as Hg travels through the plasma. Further, the surface free energies of the substrate and the liquid metal are altered suitably to favor wetting and surface complexing as described by Young’s equation.
Functional Impacts of the Intestinal Microbiome in the Pathogenesis of Inflammatory Bowel Disease (2014)

: The human intestinal microbiome plays a critical role in human health and disease, including the pathogenesis of inflammatory bowel disease (IBD). Numerous studies have identified altered bacterial diversity and abundance at varying taxonomic levels through biopsies and fecal samples of patients with IBD and diseased model animals. However, inconsistent observations regarding the microbial compositions of such patients have hindered the efforts in assessing the etiological role of specific bacterial species in the pathophysiology of IBD. These observations highlight the importance of minimizing the confounding factors associated with IBD and the need for a standardized methodology to analyze well-defined microbial sampling sources in early IBD diagnosis. Furthermore, establishing the linkage between microbiota compositions with their function within the host system can provide new insights on the pathogenesis of IBD. Such research has been greatly facilitated by technological advances that include functional metagenomics coupled with proteomic and metabolomic profiling. This review provides updates on the composition of the microbiome in IBD and emphasizes microbiota dysbiosis-involved mechanisms. We highlight functional roles of specific bacterial groups in the development and management of IBD. Functional analyses of the microbiome may be the key to understanding the role of microbiota in the development and chronicity of IBD and reveal new strategies for therapeutic intervention.
APOL1 variants change C-terminal conformational dynamics and binding to SNARE protein VAMP8 (2017)

APOL1 variants in African populations mediate resistance to trypanosomal infection but increase risk for kidney diseases through unknown mechanisms. APOL1 is expressed in glomerular podocytes and does not vary with underlying kidney disease diagnoses or APOL1 genotypes, suggesting that the kidney disease-associated variants dysregulate its function rather than its localization or abundance. Structural homology searches identified vesicle-associated membrane protein 8 (VAMP8) as an APOL1 protein interactor. VAMP8 colocalizes with APOL1 in the podocyte, and the APOL1:VAMP8 interaction was confirmed biochemically and with surface plasmon resonance. APOL1 variants attenuate this interaction. Computational modeling of APOL1's 3-dimensional structure, followed by molecular dynamics simulations, revealed increased motion of the C-terminal domain of reference APOL1 compared with either variant, suggesting that the variants stabilize a closed or autoinhibited state that diminishes protein interactions with VAMP8. Changes in ellipticity with increasing urea concentrations, as assessed by circular dichroism spectroscopy, showed higher conformational stability of the C-terminal helix of the variants compared with the reference protein. These results suggest that reference APOL1 interacts with VAMP8-coated vesicles, a process attenuated by variant-induced reduction in local dynamics of the C-terminal. Disordered vesicular trafficking in the podocyte may cause injury and progressive chronic kidney diseases in susceptible African Americans subjects.
Chronicity in posttraumatic stress disorder (PTSD) and predictors of course of comorbid PTSD in patients with anxiety disorders (1999)

The purpose of this study was to examine the course of comorbid posttraumatic stress disorder (PTSD) in 54 patients with another anxiety disorder. Using a prospective longitudinal design, the present study found that during the first 5 years of follow-up the probability of full remission from a chronic episode of PTSD was .18. Findings from this and other research confirm clinical impressions that a substantial number of people never fully remit from their PTSD even after many years. Variables associated with a longer time to remit from an episode of chronic PTSD were a history of alcohol abuse and a history of childhood trauma.
Phylogenomic Analysis of Natural Products Biosynthetic Gene Clusters Allows Discovery of Arseno-Organic Metabolites in Model Streptomycetes (2016)

Natural products from microbes have provided humans with beneficial antibiotics for millennia. However, a decline in the pace of antibiotic discovery exerts pressure on human health as antibiotic resistance spreads, a challenge that may better faced by unveiling chemical diversity produced by microbes. Current microbial genome mining approaches have revitalized research into antibiotics, but the empirical nature of these methods limits the chemical space that is explored.Here, we address the problem of finding novel pathways by incorporating evolutionary principles into genome mining. We recapitulated the evolutionary history of twenty-three enzyme families previously uninvestigated in the context of natural product biosynthesis in Actinobacteria, the most proficient producers of natural products. Our genome evolutionary analyses where based on the assumption that expanded-repurposed enzyme families-from central metabolism, occur frequently and thus have the potential to catalyze new conversions in the context of natural products biosynthesis. Our analyses led to the discovery of biosynthetic gene clusters coding for hidden chemical diversity, as validated by comparing our predictions with those from state-of-the-art genome mining tools; as well as experimentally demonstrating the existence of a biosynthetic pathway for arseno-organic metabolites in Streptomyces coelicolor and Streptomyces lividans, Using a gene knockout and metabolite profile combined strategy.As our approach does not rely solely on sequence similarity searches of previously identified biosynthetic enzymes, these results establish the basis for the development of an evolutionary-driven genome mining tool termed EvoMining that complements current platforms. We anticipate that by doing so real 'chemical dark matter' will be unveiled.
The Theory of a Fluidic Diode Autonomous Inflow Control Device (2013)

Abstract Traditionally, first-generation inflow control devices (ICDs) were designed to balance completion pressure differential with reservoir pressure differential so that even flow across production zones could be maintained. The purpose of maintaining even flow was to delay influx of unwanted fluids, and thus, help maximize oil production. However, if low-viscosity fluids were present and did succeed in breaking through, a traditional passive ICD could not control the flow, and the unwanted fluid flow would take over. To provide more effective control in these conditions, a newly developed, autonomous Inflow- control device (AICD) has been introduced to theIndustry. This device will improve production by balancing desired production fluids across the completion, while restricting the production from zones with unwanted fluids. This paper discusses 1) how the AICD detects the fluid properties and 2) how the production of the undesired fluid can be restricted without the use of any moving parts. The autonomous ICD is designed to function without moving parts, without intervention, without electronics, and without control lines. It is a solid-state design with improved reliability, erosion resistance, corrosion resistance, and plugging resistance that can maintain high mechanical integrity. An autonomous ICD operates by detecting whether the production fluid is undesirable, and then, if unwanted, it restricts the production of the unwanted fluid. The fluidic diode-type AICD operates using a combination of fluid mechanics, computer modeling, and measured performance data, and this paper explains how these devices are capable of restricting undesirable fluid breakthrough without intervention so that a well can continue to produce the desirable hydrocarbon. Testing procedures and results, which include numerical simulation and experimental testing, also will be presented.
Polar Networks Control Oligomeric Assembly in Membranes (2006)

Polar interactions have a profound influence on membrane stability and structure. A membrane-solubilized GCN4 peptide, MS-1, is used to study the impact of polar networks. Amide functionalities from amino acid side chains have been shown to promote peptide oligomerization, but lacked specificity. Herein, the hydrogen bonding interactions of an Asn side chain are coupled with the hydroxyl of Ser or Thr to generate a polar network. Analytical ultracentrifugation and fluorescence resonance energy transfer studies indicate that a trimer assembly is established where each membrane-embedded hydrogen bond contributes 1 kcal mol-1.
A New Threat to Honey Bees, the Parasitic Phorid Fly Apocephalus borealis (2012)

Honey bee colonies are subject to numerous pathogens and parasites. Interaction among multiple pathogens and parasites is the proposed cause for Colony Collapse Disorder (CCD), a syndrome characterized by worker bees abandoning their hive.
Chemical Transformations of Biomass-Derived C6-Furanic Platform Chemicals for Sustainable Energy Research, Materials Science, and Synthetic Building Blocks (2018)

Recent advances in the area of biomass-derived C6-furanic platform chemicals for sustainable biomass processing are analyzed focusing on chemical reactions important for development of practical applications and materials science. Among the chemical processes currently being studied, tuning the amount of oxygen-containing functional groups remains the most active research direction. Production of efficient fuels requires the removal of oxygen atoms (reduction reactions), whereas utilization of biomass-derived furanic derivatives in material science points out the importance of oxidation in order to form dicarboxylic derivatives. Stimulated by this driving force, oxidation and reduction of 5-(hydroxymethyl)furfural (HMF) are nowadays massively studied. Moreover, these fundamental transformations are often used as model reactions to test new catalysts, and HMF transformations guide the development of new catalytic systems. From the viewpoint of organic synthesis, highly diverse chemical reactivity is explored and a number of bioderived synthetic building blocks with different functional groups are now accessible. This Perspective covers the most recent literature (since Jan 2017) to highlight the emerging research trends.
Sidetap Optical Fibre Grating Filters (1999)

Simple physical models based on antenna theory are used to model, understand and optimise the performance of sidetap gratings for use as wavelength-dependent loss filters. Novel fibre structures are presented that are splice compatible with standard fibre, yet obtain a FWHM bandwidth of only 5 nm, minimal sidelobes, a symmetric response and complete extinction of the leaky mode resonance.
Differences in airway microbiome and metabolome of single lung transplant recipients (2020)

Allograft lungs have a distinct microbiome signature, a higher bacterial biomass and an increased Ac-PGP compared to the native lungs in SLTs compared to the native lungs in SLTs. Airway metabolome distinguishes the allografts from native lungs and is associated with distinct microbial communities, suggesting a functional relationship between the local microbiome and metabolome.
On the rate of boronate ester formation in<i>ortho</i>-aminomethyl-functionalised phenyl boronic acids (2012)

The role of the ortho-aminomethyl functional group in phenyl boronic acids for sugar complexation is a topic of debate. To decipher its effect on the kinetics of boronate ester formation, we first performed pseudo-first order kinetics analyses at five pH values up to 4 mM in fructose, revealing a first-order kinetic dependence upon fructose. Under these conditions, the reaction is in equilibrium and does not reach completion, but at 50 mM fructose saturation is achieved revealing zero-order dependence upon fructose. This indicates rate-determining creation of an intermediate prior to reaction with fructose, which we propose involves leaving group departure of inserted solvent. Further, the region of kinetics displaying zero-order dependence has a kinetic isotope effect (KIE) of 1.42, showing involvement of a proton transfer in the leaving group departure. The ratio of forward and reverse rate constants branching from the intermediate shows that fructose is several thousand times more nucleophilic than the solvent. Overall, the data supports a mechanism where the o-aminomethyl group lowers the pK(a) of the proximal boronic acid and acts as a general-acid (as an ammonium) to facilitate leaving group departure. Consequently, by microscopic reversibility the resulting amine must perform general-base catalysis to deliver fructose.