The cost of solving linear differential equations on a quantum computer: fast-forwarding to explicit resource counts

How well can quantum computers simulate classical dynamical systems? There is increasing effort in developing quantum algorithms to efficiently simulate dynamics beyond Hamiltonian simulation, but so far exact running costs are not known. In this work, we provide two significant contributions. First, we provide the first non-asymptotic computation of the cost of encoding the solution to linear ordinary differential equations into quantum states -- either the solution at a final time, or an encoding of the whole history within a time interval. Second, we show that the stability properties of a large class of classical dynamics can allow their fast-forwarding, making their quantum simulation much more time-efficient. We give a broad framework to include stability information in the complexity analysis and present examples where this brings several orders of magnitude improvements in the query counts compared to state-of-the-art analysis. From this point of view, quantum Hamiltonian dynamics is a boundary case that does not allow this form of stability-induced fast-forwarding. To illustrate our results, we find that for homogeneous systems with negative log-norm, the query counts lie within the curves $11900 \sqrt{T} \log(T)$ and $10300 T \log(T)$ for $T \in [10^6, 10^{15}]$ and error $\epsilon = 10^{-10}$, when outputting a history state.Comment: 8+22 pages, 3 figures. Comments welcome

Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain

BACKGROUND: Cross-sectional studies suggest that the microbes in the human gut have a role in obesity by influencing thehuman body’s ability to extract and store calories. The aim of this study was to assess if there is a correlation between change inbody weight over time and gut microbiome composition.METHODS: We analysed 16S ribosomal RNA gene sequence data derived from the faecal samples of 1632 healthy females fromTwinsUK to investigate the association between gut microbiome measured cross-sectionally and longitudinal weight gain (adjustedfor caloric intake and baseline body mass index). Dietary fibre intake was investigated as a possible modifier.RESULTS: Less than half of the variation in long-term weight change was found to be heritable (h2 = 0.41 (0.31, 0.47)). Gutmicrobiota diversity was negatively associated with long-term weight gain, whereas it was positively correlated with fibre intake.Nine bacterial operational taxonomic units (OTUs) were significantly associated with weight gain after adjusting for covariates,family relatedness and multiple testing (false discovery rate o0.05). OTUs associated with lower long-term weight gain includedthose assigned to Ruminococcaceae (associated in mice with improved energy metabolism) and Lachnospiraceae. A Bacterioidesspecies OTU was associated with increased risk of weight gain but this appears to be driven by its correlation with lower levels ofdiversity.CONCLUSIONS: High gut microbiome diversity, high-fibre intake and OTUs implicated in animal models of improved energymetabolism are all correlated with lower term weight gain in humans independently of calorie intake and other confounders

Motorcyclists and pillion passengers with open lower-limb fractures: a study using TARN data 2007-2014

Introduction We aimed to identify population demographics of motorcyclists and pillion passengers with isolated open lower-limb fractures, to ascertain the impact of the revised 2009 British Orthopaedic Association/British Association of Plastic Reconstructive and Aesthetic Surgeons joint standards for the management of open fractures of the lower limb (BOAST 4), in terms of time to skeletal stabilisation and soft-tissue coverage, and to observe any impact on patient movement. Methods Retrospective cohort data was collected by the Trauma Audit and Research Network (TARN). A longitudinal analysis was performed between two timeframes in England (pre-and post-BOAST 4 revision): 2007-2009 and 2010-2014. Results A total of 1564 motorcyclists and 64 pillion passengers were identified. Of these, 93% (1521/1628) were male. The median age for males was 30.5 years and 36.7 years for females. There was a statistically significant difference in the number of patients who underwent skeletal stabilisation (49% vs 65%, P < 0.0001), the time from injury to skeletal stabilisation (7.33 hours vs 14.3 hours, P < 0.0001) and the proportion receiving soft-tissue coverage (26% vs 43%, P < 0.0001). There was no difference in the time from injury to soft-tissue coverage (62.3 hours vs 63.7 hours, P = 0.726). The number of patients taken directly to a major trauma centre (or its equivalent) increased between the two timeframes (12.5% vs, 41%, P < 0.001). Conclusions Since the 2009 BOAST 4 revision, there has been no difference in the time taken from injury to soft-tissue coverage but the time from injury to skeletal stabilisation is longer. There has also been an increase in patient movement to centres offering joint orthopaedic and plastic care

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling

BACKGROUND/OBJECTIVES: Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence VF development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM. SUBJECTS/METHODS: In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the ‘VFM diet score’ in the remainder of the sample. Using linear regression (adjusted for covariates, including BMI and total fat mass) we investigated associations between the VFM diet score, the blood metabolomics profile and the faecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (greater than or equal to1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence. RESULTS: Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (Beta[s.e.]: 0.281[0.091]; P=0.002), butyrylcarnitine (0.199[0.087]; P=0.023) and hippurate (−0.297[0.095]; P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042[0.011], P=8.47 × 10−5), VFM (0.057[0.019], P=2.73 × 10−3) and hippurate (−0.075[0.032], P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016[0.004], P=9.82 × 10−6). CONCLUSION: We linked a dietary VFM score and VFM to Eubacterium dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM

Heritable components of the human fecal microbiome are associated with visceral fat

Background: Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures.Results: We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity.Conclusions: Our results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies

GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation

COPI is a key mediator of protein trafficking within the secretory pathway. COPI is recruited to the membrane primarily through binding to Arf GTPases, upon which it undergoes assembly to form coated transport intermediates responsible for trafficking numerous proteins, including Golgi-resident enzymes. Here, we identify GORAB, the protein mutated in the skin and bone disorder gerodermia osteodysplastica, as a component of the COPI machinery. GORAB forms stable domains at the trans-Golgi that, via interactions with the COPI-binding protein Scyl1, promote COPI recruitment to these domains. Pathogenic GORAB mutations perturb Scyl1 binding or GORAB assembly into domains, indicating the importance of these interactions. Loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor, and support the view that defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica.Peer reviewe

Promotion of Hendra virus replication by microRNA 146a

Hendra virus is a highly pathogenic zoonotic paramyxovirus in the genus Henipavirus. Thirty-nine outbreaks of Hendra virus have been reported since its initial identification in Queensland, Australia, resulting in seven human infections and four fatalities. Little is known about cellular host factors impacting Hendra virus replication. In this work, we demonstrate that Hendra virus makes use of a microRNA (miRNA) designated miR-146a, an NF-&kappa;B-responsive miRNA upregulated by several innate immune ligands, to favor its replication. miR-146a is elevated in the blood of ferrets and horses infected with Hendra virus and is upregulated by Hendra virus in human cells in vitro. Blocking miR-146a reduces Hendra virus replication in vitro, suggesting a role for this miRNA in Hendra virus replication. In silico analysis of miR-146a targets identified ring finger protein (RNF)11, a member of the A20 ubiquitin editing complex that negatively regulates NF-&kappa;B activity, as a novel component of Hendra virus replication. RNA interference-mediated silencing of RNF11 promotes Hendra virus replication in vitro, suggesting that increased NF-&kappa;B activity aids Hendra virus replication. Furthermore, overexpression of the I&kappa;B superrepressor inhibits Hendra virus replication. These studies are the first to demonstrate a host miRNA response to Hendra virus infection and suggest an important role for host miRNAs in Hendra virus disease

Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet and relationship to metabolic syndrome

Reduced gut microbiome diversity is associated with multiple disorders including metabolic syndrome (MetS) features, though metabolomic markers have not been investigated. Our objective was to identify blood metabolite markers of gut microbiome diversity, and explore their relationship with dietary intake and MetS. We examined associations between Shannon diversity and 292 metabolites profiled by the untargeted metabolomics provider Metabolon Inc. in 1529 females from TwinsUK using linear regressions adjusting for confounders and multiple testing (Bonferroni: P < 1.71 × 10−4). We replicated the top results in an independent sample of 420 individuals as well as discordant identical twin pairs and explored associations with self-reported intakes of 20 food groups. Longitudinal changes in circulating levels of the top metabolite, were examined for their association with food intake at baseline and with MetS at endpoint. Five metabolites were associated with microbiome diversity and replicated in the independent sample. Higher intakes of fruit and whole grains were associated with higher levels of hippurate cross-sectionally and longitudinally. An increasing hippurate trend was associated with reduced odds of having MetS (OR: 0.795[0.082]; P = 0.026). These data add further weight to the key role of the microbiome as a potential mediator of the impact of dietary intake on metabolic status and health

Diurnal changes in middle atmospheric H2O and O3: Observations in the Alpine region and climate models

International audienceIn this paper we investigate daily variations in middle atmospheric water vapor and ozone based on data from two ground-based microwave radiometers located in the Alpine region of Europe. Temperature data are obtained from a lidar located near the two stations and from the SABER experiment on the TIMED satellite. This unique set of observations is complemented by three different three-dimensional (3-D) chemistry-climate models (Monitoring of Stratospheric Depletion of the Ozone Layer (MSDOL), Laboratoire de Météorologie Dynamique Reactive Processes Ruling the Ozone Budget in the Stratosphere (LMDz-REPROBUS), and Solar Climate Ozone Links (SOCOL)) and the 2-D atmospheric global-scale wave model (GSWM). The first part of the paper is focused on the first Climate and Weather of the Sun-Earth System (CAWSES) tidal campaign that consisted of a period of intensive measurements during September 2005. Variations in stratospheric water vapor are found to be in the order of 1% depending on altitude. Meridional advection of tidal nature is likely to be the dominant driving factor throughout the whole stratosphere, while vertical advection becomes more important in the mesosphere. Observed ozone variations in the upper stratosphere and lower mesosphere show amplitudes of several percent in accordance with photochemical models. Variations in lower stratospheric ozone are not solely governed by photochemistry but also by dynamics, with the temperature dependence of the photochemistry becoming more important. The second part presents an investigation of the seasonal dependence of daily variations. Models tend to underestimate the H2O diurnal amplitudes, especially during summer in the upper stratosphere. Good agreement between models and observations is found for ozone in the upper stratosphere, which reflects the fact that the O3 daily variations are driven by the photochemistry that is well modeled

Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry

Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV