2,184 research outputs found

    Exhaustive generation of kk-critical H\mathcal H-free graphs

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    We describe an algorithm for generating all kk-critical H\mathcal H-free graphs, based on a method of Ho\`{a}ng et al. Using this algorithm, we prove that there are only finitely many 44-critical (P7,Ck)(P_7,C_k)-free graphs, for both k=4k=4 and k=5k=5. We also show that there are only finitely many 44-critical graphs (P8,C4)(P_8,C_4)-free graphs. For each case of these cases we also give the complete lists of critical graphs and vertex-critical graphs. These results generalize previous work by Hell and Huang, and yield certifying algorithms for the 33-colorability problem in the respective classes. Moreover, we prove that for every tt, the class of 4-critical planar PtP_t-free graphs is finite. We also determine all 27 4-critical planar (P7,C6)(P_7,C_6)-free graphs. We also prove that every P10P_{10}-free graph of girth at least five is 3-colorable, and determine the smallest 4-chromatic P12P_{12}-free graph of girth five. Moreover, we show that every P13P_{13}-free graph of girth at least six and every P16P_{16}-free graph of girth at least seven is 3-colorable. This strengthens results of Golovach et al.Comment: 17 pages, improved girth results. arXiv admin note: text overlap with arXiv:1504.0697

    A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

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    © 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

    Comparison of the CHU-9D and the EQ-5D-Y instruments in children and young people with cerebral palsy: A cross-sectional study

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    © Author(s) (or their employer(s)) 2020. Objective To compare the performance of the EuroQol 5D youth (EQ-5D-Y) and child health utility 9D (CHU-9D) for assessing health-related quality of life (HRQoL) in children and young people (CYP) with cerebral palsy (CP). Design Cross-sectional study. Setting England. Participants Sixty-four CYP with CP aged 10-19 years in Gross Motor Function Classification System (GMFCS) levels I-III. Main outcome measures Missing data were examined to assess feasibility. Associations between utility values and individual dimensions on each instrument were examined to assess convergent validity. Associations between utility values and GMFCS level were examined to assess known-group differences. Results Missing data were <5% for both instruments. Twenty participants (32.3%) and 11 participants (18.0%) reported full health for the EQ-5D-Y and CHU-9D, respectively. There was poor agreement between utilities from the two instruments (intraclass correlation coefficient=0.62; 95% limits of agreement -0.58 to 0.29). Correlations between EQ-5D-Y and CHU-9D dimensions were weak to moderate (r=0.25 to 0.59). GMFCS level was associated with EQ-5D-Y utility values but not CHU-9D utility values. Conclusion The EQ-5D-Y and CHU-9D are feasible measures of HRQoL in CYP with CP. However, the two instruments demonstrate poor agreement and should not be used to measure and value HRQoL in CYP with CP interchangeably. We propose that the CHU-9D may be preferable to use in this population as it assesses concepts that influence HRQoL among CYP with CP and provides less extreme utility values than the EQ-5D-Y.Action Medical Research; Chartered Society of Physiotherapy Charitable Trust; The Henry Smith Charity (GN2340)

    Nutrition Strategies for Triathlon

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    Contemporary sports nutrition guidelines recommend that each athlete develop a personalised, periodised and practical approach to eating that allows him or her to train hard, recover and adapt optimally, stay free of illness and injury and compete at their best at peak races. Competitive triathletes undertake a heavy training programme to prepare for three different sports while undertaking races varying in duration from 20 min to 10 h. The everyday diet should be adequate in energy availability, provide CHO in varying amounts and timing around workouts according to the benefits of training with low or high CHO availability and spread high-quality protein over the day to maximise the adaptive response to each session. Race nutrition requires a targeted and well-practised plan that maintains fuel and hydration goals over the duration of the specific event, according to the opportunities provided by the race and other challenges, such as a hot environment. Supplements and sports foods can make a small contribution to a sports nutrition plan, when medical supplements are used under supervision to prevent/treat nutrient deficiencies (e.g. iron or vitamin D) or when sports foods provide a convenient source of nutrients when it is impractical to eat whole foods. Finally, a few evidence-based performance supplements may contribute to optimal race performance when used according to best practice protocols to suit the triathlete’s goals and individual responsiveness

    The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial

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    Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015

    Water induced sediment levitation enhances downslope transport on Mars

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    On Mars, locally warm surface temperatures (~293 K) occur, leading to the possibility of (transient) liquid water on the surface. However, water exposed to the martian atmosphere will boil, and the sediment transport capacity of such unstable water is not well understood. Here, we present laboratory studies of a newly recognized transport mechanism: “levitation” of saturated sediment bodies on a cushion of vapor released by boiling. Sediment transport where this mechanism is active is about nine times greater than without this effect, reducing the amount of water required to transport comparable sediment volumes by nearly an order of magnitude. Our calculations show that the effect of levitation could persist up to ~48 times longer under reduced martian gravity. Sediment levitation must therefore be considered when evaluating the formation of recent and present-day martian mass wasting features, as much less water may be required to form such features than previously thought

    Radiation-hypersensitive cancer patients do not manifest protein expression abnormalities in components of the nonhomologous end-joining (NHEJ) pathway

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    Radiation therapy (RT) is utilised for the treatment of around half of all oncology patients during the course of their illness. Despite great clinical progress in the rational deployment of RT, the underlying molecular basis for its efficacy and toxicity are currently imperfectly understood. In this study, we took a biochemical approach to evaluate the potential role of key ionising radiation repair proteins in the treatment outcomes of patients with severe acute or late RT side effects. Lymphoblastoid cell lines were established from blood samples from 36 radiosensitive cases and a number of controls (the latter had had RT but did not develop significant toxicity). The expression level and migration of key proteins from the nonhomologous end-joining (NHEJ) pathway was evaluated by Western blot analysis on cases and controls. We did not observe any abnormalities in expression level or migration pattern of the following NHEJ proteins in radiosensitive cancer cases: Ku70, Ku80, XRCC4, DNA Ligase IV. These important negative results provide evidence that mutations that affect protein expression of these NHEJ components are unlikely to underlie clinical radiation sensitivity

    Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

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    Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics
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