1,762 research outputs found

    Influence of Niche-Specific Nutrients on Secondary Metabolism in <i>Vibrionaceae</i>

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    Many factors, such as the substrate and the growth phase, influence biosynthesis of secondary metabolites in microorganisms. Therefore, it is crucial to consider these factors when establishing a bioprospecting strategy. Mimicking the conditions of the natural environment has been suggested as a means of inducing or influencing microbial secondary metabolite production. The purpose of the present study was to determine how the bioactivity of Vibrionaceae was influenced by carbon sources typical of their natural environment. We determined how mannose and chitin, compared to glucose, influenced the antibacterial activity of a collection of Vibrionaceae strains isolated because of their ability to produce antibacterial compounds but that in subsequent screenings seemed to have lost this ability. The numbers of bioactive isolates were 2- and 3.5-fold higher when strains were grown on mannose and chitin, respectively, than on glucose. As secondary metabolites are typically produced during late growth, potential producers were also allowed 1 to 2 days of growth before exposure to the pathogen. This strategy led to a 3-fold increase in the number of bioactive strains on glucose and an 8-fold increase on both chitin and mannose. We selected two bioactive strains belonging to species for which antibacterial activity had not previously been identified. Using ultrahigh-performance liquid chromatography–high-resolution mass spectrometry and bioassay-guided fractionation, we found that the siderophore fluvibactin was responsible for the antibacterial activity of Vibrio furnissii and Vibrio fluvialis. These results suggest a role of chitin in the regulation of secondary metabolism in vibrios and demonstrate that considering bacterial ecophysiology during development of screening strategies will facilitate bioprospecting. IMPORTANCE A challenge in microbial natural product discovery is the elicitation of the biosynthetic gene clusters that are silent when microorganisms are grown under standard laboratory conditions. We hypothesized that, since the clusters are not lost during proliferation in the natural niche of the microorganisms, they must, under such conditions, be functional. Here, we demonstrate that an ecology-based approach in which the producer organism is allowed a temporal advantage and where growth conditions are mimicking the natural niche remarkably increases the number of Vibrionaceae strains producing antibacterial compounds

    DAMP: Doubly Aligned Multilingual Parser for Task-Oriented Dialogue

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    Modern virtual assistants use internal semantic parsing engines to convert user utterances to actionable commands. However, prior work has demonstrated that semantic parsing is a difficult multilingual transfer task with low transfer efficiency compared to other tasks. In global markets such as India and Latin America, this is a critical issue as switching between languages is prevalent for bilingual users. In this work we dramatically improve the zero-shot performance of a multilingual and codeswitched semantic parsing system using two stages of multilingual alignment. First, we show that constrastive alignment pretraining improves both English performance and transfer efficiency. We then introduce a constrained optimization approach for hyperparameter-free adversarial alignment during finetuning. Our Doubly Aligned Multilingual Parser (DAMP) improves mBERT transfer performance by 3x, 6x, and 81x on the Spanglish, Hinglish and Multilingual Task Oriented Parsing benchmarks respectively and outperforms XLM-R and mT5-Large using 3.2x fewer parameters.Comment: 9 Pages; ACL Main Conference 202

    Time-resolved spectral densities of non-thermal electrons in gold

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    Noble-metal nanoparticles for photocatalysis have become a major research object in recent years due to their plasmon-enhanced strong light-matter interaction. The dynamics of the hot electrons in the noble metal are crucial for the efficiency of the photocatalysis and for the selective control of reactions. In this work, we present a kinetic description of the non-equilibrium electron distribution created by photoexcitation, based on full energy-resolved Boltzmann collision integrals for the laser excitation as well as for the electron-electron thermalization. The laser-induced electronic non-equilibrium and the inherently included secondary electron generation govern the dynamics of non-thermal electrons. Applying our method to gold, we show a significant dependence of hot electron dynamics on kinetic energy. Specifically, the timescales of the relaxation as well as the qualitative behavior are depending on the evaluated energy window. During the thermalization processes there are cases of increasing electron density as well as of decreasing electron density. Studying the influence of excitation parameters, we find that the photon energy and the fluence of the exciting laser can be tuned to influence not only the initial excitation but also the subsequent characteristics of the time-resolved electronic spectral density dynamics. The electronic thermalization including secondary electron generation leads to time-dependent spectral densities which differ from their specific final equilibrium values for picoseconds after irradiation ended

    Comparison of mortality with home hemodialysis and center hemodialysis: A national study

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    Comparison of mortality with home hemodialysis and center hemodialysis: A national study. We sought to determine whether lower mortality rates reported with hemodialysis (HD) at home compared to hemodialysis in dialysis centers (center HD) could be explained by patient selection. Data are from the United States Renal Data System (USRDS) Special Study Of Case Mix Severity, a random national sample of 4,892 patients who started renal replacement therapy in 1986 to 1987. Intent-to-treat analyses compared mortality between home HD (N =70) and center HD patients (N = 3,102) using the Cox proportional hazards model. Home HD patients were younger and had a lower frequency of comorbid conditions. The unadjusted relative risk (RR) of death for home HD patients compared to center HD was 0.37 (P < 0.001). The RR adjusted for age, sex, race and diabetes, was 44% lower in home HD patients (RR = 0.56, P = 0.02). When additionally adjusted for comorbid conditions, this RR increased marginally (RR = 0.58, P = 0.03). A different analysis using national USRDS data from 1986/7 and without comorbid adjustment showed patients with training for self care hemodialysis at home or in a center (N = 418) had a lower mortality risk (RR = 0.78, P = 0.001) than center HD patients (N = 43,122). Statistical adjustment for comorbid conditions in addition to age, sex, race, and diabetes explains only a small amount of the lower mortality with home HD

    In situ formation of suspended graphene windows for lab-based XPS in liquid and gas environments

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    Environmental cells sealed with photoelectron-transparent graphene windows are promising for extending X-ray photoelectron spectroscopy (XPS) to liquid and high-pressure gas environments for in situ and operando studies. However, the reliable production of graphene windows that are sufficiently leak-tight for extended measurements remains a challenge. Here we demonstrate a PDMS/Au(100 nm)-supported transfer method that reliably produces suspended graphene on perforated silicon nitride membranes without significant contamination. A yield of ~95% is achieved based on single-layer graphene covering >98% of the holes in the silicon nitride membrane. Even higher coverages are achieved for stacked bilayer graphene, allowing wet etching (aqueous KI/I2) of the Au support to be observed in a conventional lab-based XPS system, thereby demonstrating the in situ formation of leak-tight, suspended graphene windows. Furthermore, these windows allow gas-phase measurements at close to atmospheric pressure, showing future promise for XPS under higher-pressure gas environments in conventional lab-based systems

    Balanced hydroxyethylstarch (HES 130/0.4) impairs kidney function in-vivo without inflammation

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    Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6h. After 24h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1–4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansio

    Restriction landmark genomic scanning (RLGS) spot identification by second generation virtual RLGS in multiple genomes with multiple enzyme combinations.

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    BackgroundRestriction landmark genomic scanning (RLGS) is one of the most successfully applied methods for the identification of aberrant CpG island hypermethylation in cancer, as well as the identification of tissue specific methylation of CpG islands. However, a limitation to the utility of this method has been the ability to assign specific genomic sequences to RLGS spots, a process commonly referred to as "RLGS spot cloning."ResultsWe report the development of a virtual RLGS method (vRLGS) that allows for RLGS spot identification in any sequenced genome and with any enzyme combination. We report significant improvements in predicting DNA fragment migration patterns by incorporating sequence information into the migration models, and demonstrate a median Euclidian distance between actual and predicted spot migration of 0.18 centimeters for the most complex human RLGS pattern. We report the confirmed identification of 795 human and 530 mouse RLGS spots for the most commonly used enzyme combinations. We also developed a method to filter the virtual spots to reduce the number of extra spots seen on a virtual profile for both the mouse and human genomes. We demonstrate use of this filter to simplify spot cloning and to assist in the identification of spots exhibiting tissue-specific methylation.ConclusionThe new vRLGS system reported here is highly robust for the identification of novel RLGS spots. The migration models developed are not specific to the genome being studied or the enzyme combination being used, making this tool broadly applicable. The identification of hundreds of mouse and human RLGS spot loci confirms the strong bias of RLGS studies to focus on CpG islands and provides a valuable resource to rapidly study their methylation
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