Abstract: Grapevine is a well-studied, economically relevant crop, whose associated bacteria could influence its organoleptic properties. In this study, the spatial and temporal dynamics of the bacterial communities associated with grapevine organs (leaves, flowers, grapes, and roots) and soils were characterized over two growing seasons to determine the influence of vine cultivar, edaphic parameters, vine developmental stage (dormancy, flowering, preharvest), and vineyard. Belowground bacterial communities differed significantly from those aboveground, and yet the communities associated with leaves, flowers, and grapes shared a greater proportion of taxa with soil communities than with each other, suggesting that soil may serve as a bacterial reservoir. A subset of soil microorganisms, including root colonizers significantly enriched in plant growth-promoting bacteria and related functional genes, were selected by the grapevine. In addition to plant selective pressure, the structure of soil and root microbiota was significantly influenced by soil pH and C:N ratio, and changes in leaf- and grape-associated microbiota were correlated with soil carbon and showed interannual variation even at small spatial scales. Diazotrophic bacteria, e.g., Rhizobiaceae and Bradyrhizobium spp., were significantly more abundant in soil samples and root samples of specific vineyards. Vine-associated microbial assemblages were influenced by myriad factors that shape their composition and structure, but the majority of organ-associated taxa originated in the soil, and their distribution reflected the influence of highly localized biogeographic factors and vineyard management. IMPORTANCE Vine-associated bacterial communities may play specific roles in the productivity and disease resistance of their host plant. Also, the bacterial communities on grapes have the potential to influence the organoleptic properties of the wine, contributing to a regional terroir. Understanding that factors that influence these bacteria may provide insights into management practices to shape and craft individual wine properties. We show that soil serves as a key source of vine-associated bacteria and that edaphic factors and vineyard-specific properties can influence the native grapevine microbiome preharvest.

Abstract: Atomic force microscopy (AFM) is a powerful, multifunctional imaging platform that allows biological samples, from single molecules to living cells, to be visualized and manipulated. Soon after the instrument was invented, it was recognized that in order to maximize the opportunities of AFM imaging in biology, various technological developments would be required to address certain limitations of the method. This has led to the creation of a range of new imaging modes, which continue to push the capabilities of the technique today. Here, we review the basic principles, advantages and limitations of the most common AFM bioimaging modes, including the popular contact and dynamic modes, as well as recently developed modes such as multiparametric, molecular recognition, multifrequency and high-speed imaging. For each of these modes, we discuss recent experiments that highlight their unique capabilities.

Abstract: Given two consecutive frames, video interpolation aims at generating intermediate frame(s) to form both spatially and temporally coherent video sequences. While most existing methods focus on single-frame interpolation, we propose an end-to-end convolutional neural network for variable-length multi-frame video interpolation, where the motion interpretation and occlusion reasoning are jointly modeled. We start by computing bi-directional optical flow between the input images using a U-Net architecture. These flows are then linearly combined at each time step to approximate the intermediate bi-directional optical flows. These approximate flows, however, only work well in locally smooth regions and produce artifacts around motion boundaries. To address this shortcoming, we employ another U-Net to refine the approximated flow and also predict soft visibility maps. Finally, the two input images are warped and linearly fused to form each intermediate frame. By applying the visibility maps to the warped images before fusion, we exclude the contribution of occluded pixels to the interpolated intermediate frame to avoid artifacts. Since none of our learned network parameters are time-dependent, our approach is able to produce as many intermediate frames as needed. To train our network, we use 1,132 240-fps video clips, containing 300K individual video frames. Experimental results on several datasets, predicting different numbers of interpolated frames, demonstrate that our approach performs consistently better than existing methods.

Abstract: We introduce a new loss function for the weakly-supervised training of semantic image segmentation models based on three guiding principles: to seed with weak localization cues, to expand objects based on the information about which classes can occur in an image, and to constrain the segmentations to coincide with object boundaries. We show experimentally that training a deep convolutional neural network using the proposed loss function leads to substantially better segmentations than previous state-of-the-art methods on the challenging PASCAL VOC 2012 dataset. We furthermore give insight into the working mechanism of our method by a detailed experimental study that illustrates how the segmentation quality is affected by each term of the proposed loss function as well as their combinations.

Abstract: With the success of new computational architectures for visual processing, such as convolutional neural networks (CNN) and access to image databases with millions of labeled examples (e.g., ImageNet, Places), the state of the art in computer vision is advancing rapidly. One important factor for continued progress is to understand the representations that are learned by the inner layers of these deep architectures. Here we show that object detectors emerge from training CNNs to perform scene classification. As scenes are composed of objects, the CNN for scene classification automatically discovers meaningful objects detectors, representative of the learned scene categories. With object detectors emerging as a result of learning to recognize scenes, our work demonstrates that the same network can perform both scene recognition and object localization in a single forward-pass, without ever having been explicitly taught the notion of objects.

Abstract: Background Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea. Methods We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging. Results The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two g...

Abstract: Covid-19 affected higher educational institutions not just in Wuhan, China where the virus originated but all other higher educational institutions in 188 countries as of April 06, 2020. Educational countermeasures are taken to continue educating the students despite the COVID-19 predicaments. Based on the author’s experiences, research, observations in the academe, COVID-19 guidelines, and the need for alternative solutions, this article introduces how higher education is affected and how it can respond to future challenges. This article recommends to educational institutions to produce studies to proliferate and document the impact of the pandemic to the educational system. There is also a greater need for educational institutions to strengthen the practices in the curriculum and make it more responsive to the learning needs of the students even beyond the conventional classrooms.

Abstract: Lipid nanoparticles (LNPs) have attracted special interest during last few decades. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are two major types of Lipid-based nanoparticles. SLNs were developed to overcome the limitations of other colloidal carriers, such as emulsions, liposomes and polymeric nanoparticles because they have advantages like good release profile and targeted drug delivery with excellent physical stability. In the next generation of the lipid nanoparticle, NLCs are modified SLNs which improve the stability and capacity loading. Three structural models of NLCs have been proposed. These LNPs have potential applications in drug delivery field, research, cosmetics, clinical medicine, etc. This article focuses on features, structure and innovation of LNPs and presents a wide discussion about preparation methods, advantages, disadvantages and applications of LNPs by focusing on SLNs and NLCs.

Abstract: The genetic enhancement of wild animals and plants for characteristics that benefit human populations has been practiced for thousands of years, resulting in impressive improvements in commercially valuable species. Despite these benefits, genetic manipulations are rarely considered for noncommercial purposes, such as conservation and restoration initiatives. Over the last century, humans have driven global climate change through industrialization and the release of increasing amounts of CO2, resulting in shifts in ocean temperature, ocean chemistry, and sea level, as well as increasing frequency of storms, all of which can profoundly impact marine ecosystems. Coral reefs are highly diverse ecosystems that have suffered massive declines in health and abundance as a result of these and other direct anthropogenic disturbances. There is great concern that the high rates, magnitudes, and complexity of environmental change are overwhelming the intrinsic capacity of corals to adapt and survive. Although it is important to address the root causes of changing climate, it is also prudent to explore the potential to augment the capacity of reef organisms to tolerate stress and to facilitate recovery after disturbances. Here, we review the risks and benefits of the improvement of natural and commercial stocks in noncoral reef systems and advocate a series of experiments to determine the feasibility of developing coral stocks with enhanced stress tolerance through the acceleration of naturally occurring processes, an approach known as (human)-assisted evolution, while at the same time initiating a public dialogue on the risks and benefits of this approach.

Abstract: To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)+HLA-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

Abstract: A novel crystal configuration of sandwiched S-Mo-Se structure (Janus SMoSe) at the monolayer limit has been synthesized and carefully characterized in this work. By controlled sulfurization of monolayer MoSe2 the top layer of selenium atoms are substituted by sulfur atoms while the bottom selenium layer remains intact. The peculiar structure of this new material is systematically investigated by Raman, photoluminescence and X-ray photoelectron spectroscopy and confirmed by transmission-electron microscopy and time-of-flight secondary ion mass spectrometry. Density-functional theory calculations are performed to better understand the Raman vibration modes and electronic structures of the Janus SMoSe monolayer, which are found to correlate well with corresponding experimental results. Finally, high basal plane hydrogen evolution reaction (HER) activity is discovered for the Janus monolayer and DFT calculation implies that the activity originates from the synergistic effect of the intrinsic defects and structural strain inherent in the Janus structure.

Abstract: We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section “other invertebrates” review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.

Abstract: Rapid reviews are a form of knowledge synthesis in which components of the systematic review process are simplified or omitted to produce information in a timely manner. Although numerous centers are conducting rapid reviews internationally, few studies have examined the methodological characteristics of rapid reviews. We aimed to examine articles, books, and reports that evaluated, compared, used or described rapid reviews or methods through a scoping review.

Abstract: Brain Autopsy Series in Patients with Covid-19 Eighteen brains of patients who died 0 to 32 days after the onset of symptoms of SARS-CoV-2 infection showed hypoxic–ischemic changes but no encephali...

Abstract: "Engagement" with digital behaviour change interventions (DBCIs) is considered important for their effectiveness. Evaluating engagement is therefore a priority; however, a shared understanding of how to usefully conceptualise engagement is lacking. This review aimed to synthesise literature on engagement to identify key conceptualisations and to develop an integrative conceptual framework involving potential direct and indirect influences on engagement and relationships between engagement and intervention effectiveness. Four electronic databases (Ovid MEDLINE, PsycINFO, ISI Web of Knowledge, ScienceDirect) were searched in November 2015. We identified 117 articles that met the inclusion criteria: studies employing experimental or non-experimental designs with adult participants explicitly or implicitly referring to engagement with DBCIs, digital games or technology. Data were synthesised using principles from critical interpretive synthesis. Engagement with DBCIs is conceptualised in terms of both experiential and behavioural aspects. A conceptual framework is proposed in which engagement with a DBCI is influenced by the DBCI itself (content and delivery), the context (the setting in which the DBCI is used and the population using it) and the behaviour that the DBCI is targeting. The context and "mechanisms of action" may moderate the influence of the DBCI on engagement. Engagement, in turn, moderates the influence of the DBCI on those mechanisms of action. In the research literature, engagement with DBCIs has been conceptualised in terms of both experience and behaviour and sits within a complex system involving the DBCI, the context of use, the mechanisms of action of the DBCI and the target behaviour.

Abstract: Importance Laparoscopic sleeve gastrectomy for treatment of morbid obesity has increased substantially despite the lack of long-term results compared with laparoscopic Roux-en-Y gastric bypass. Objective To determine whether laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are equivalent for weight loss at 5 years in patients with morbid obesity. Design, Setting, and Participants The Sleeve vs Bypass (SLEEVEPASS) multicenter, multisurgeon, open-label, randomized clinical equivalence trial was conducted from March 2008 until June 2010 in Finland. The trial enrolled 240 morbidly obese patients aged 18 to 60 years, who were randomly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period (last follow-up, October 14, 2015). Interventions Laparoscopic sleeve gastrectomy (n = 121) or laparoscopic Roux-en-Y gastric bypass (n = 119). Main Outcomes and Measures The primary end point was weight loss evaluated by percentage excess weight loss. Prespecified equivalence margins for the clinical significance of weight loss differences between gastric bypass and sleeve gastrectomy were −9% to +9% excess weight loss. Secondary end points included resolution of comorbidities, improvement of quality of life (QOL), all adverse events (overall morbidity), and mortality. Results Among 240 patients randomized (mean age, 48 [SD, 9] years; mean baseline body mass index, 45.9,[SD, 6.0]; 69.6% women), 80.4% completed the 5-year follow-up. At baseline, 42.1% had type 2 diabetes, 34.6% dyslipidemia, and 70.8% hypertension. The estimated mean percentage excess weight loss at 5 years was 49% (95% CI, 45%-52%) after sleeve gastrectomy and 57% (95% CI, 53%-61%) after gastric bypass (difference, 8.2 percentage units [95% CI, 3.2%-13.2%], higher in the gastric bypass group) and did not meet criteria for equivalence. Complete or partial remission of type 2 diabetes was seen in 37% (n = 15/41) after sleeve gastrectomy and in 45% (n = 18/40) after gastric bypass (P > .99). Medication for dyslipidemia was discontinued in 47% (n = 14/30) after sleeve gastrectomy and 60% (n = 24/40) after gastric bypass (P = .15) and for hypertension in 29% (n = 20/68) and 51% (n = 37/73) (P = .02), respectively. There was no statistically significant difference in QOL between groups (P = .85) and no treatment-related mortality. At 5 years the overall morbidity rate was 19% (n = 23) for sleeve gastrectomy and 26% (n = 31) for gastric bypass (P = .19). Conclusions and Relevance Among patients with morbid obesity, use of laparoscopic sleeve gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not meet criteria for equivalence in terms of percentage excess weight loss at 5 years. Although gastric bypass compared with sleeve gastrectomy was associated with greater percentage excess weight loss at 5 years, the difference was not statistically significant, based on the prespecified equivalence margins. Trial Registration clinicaltrials.gov Identifier:NCT00793143

Abstract: Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment of cancer metastasis. Numerous types of photothermal nanotherapeutics (PTN) have been developed with encouraging therapeutic efficacy on metastatic cancer in many preclinical animal experiments. We summarize the design and performance of various PTN in PTT alone and their combinational therapy. We also point out the lacking area and the most promising approaches in this challenging field. In conclusion, PTT or their combinational therapy can provide an essential promising therapeutic modality against cancer metastasis.

Abstract: In this work, we propose a method that combines a single hand-held camera and a set of Inertial Measurement Units (IMUs) attached at the body limbs to estimate accurate 3D poses in the wild. This poses many new challenges: the moving camera, heading drift, cluttered background, occlusions and many people visible in the video. We associate 2D pose detections in each image to the corresponding IMU-equipped persons by solving a novel graph based optimization problem that forces 3D to 2D coherency within a frame and across long range frames. Given associations, we jointly optimize the pose of a statistical body model, the camera pose and heading drift using a continuous optimization framework. We validated our method on the TotalCapture dataset, which provides video and IMU synchronized with ground truth. We obtain an accuracy of 26 mm, which makes it accurate enough to serve as a benchmark for image-based 3D pose estimation in the wild. Using our method, we recorded 3D Poses in the Wild (3DPW), a new dataset consisting of more than 51, 000 frames with accurate 3D pose in challenging sequences, including walking in the city, going up-stairs, having coffee or taking the bus. We make the reconstructed 3D poses, video, IMU and 3D models available for research purposes at http://virtualhumans.mpi-inf.mpg.de/3DPW.

Abstract: We present an approach to learn a dense pixel-wise labeling from image-level tags. Each image-level tag imposes constraints on the output labeling of a Convolutional Neural Network (CNN) classifier. We propose Constrained CNN (CCNN), a method which uses a novel loss function to optimize for any set of linear constraints on the output space (i.e. predicted label distribution) of a CNN. Our loss formulation is easy to optimize and can be incorporated directly into standard stochastic gradient descent optimization. The key idea is to phrase the training objective as a biconvex optimization for linear models, which we then relax to nonlinear deep networks. Extensive experiments demonstrate the generality of our new learning framework. The constrained loss yields state-of-the-art results on weakly supervised semantic image segmentation. We further demonstrate that adding slightly more supervision can greatly improve the performance of the learning algorithm.

Abstract: We demonstrate postsynthetic modification of CsPbBr3 nanocrystals by a thiocyanate salt treatment. This treatment improves the quantum yield of both freshly synthesized (PLQY ≈ 90%) and aged nanocrystals (PLQY ≈ 70%) to within measurement error (2–3%) of unity, while simultaneously maintaining the shape, size, and colloidal stability. Additionally, the luminescence decay kinetics transform from multiexponential decays typical of nanocrystalline semiconductors with a distribution of trap sites, to a monoexponential decay, typical of single energy level emitters. Thiocyanate only needs to access a limited number of CsPbBr3 nanocrystal surface sites, likely representing under-coordinated lead atoms on the surface, in order to have this effect.

Abstract: We introduce the fractional integral corresponding to the new concept of fractional derivative recently introduced by Caputo and Fabrizio and we study some related fractional differential equations.

Abstract: This study used national survey data to compare the prevalence symptoms of psychological distress and loneliness among US adults during the coronavirus disease 2019 (COVID-19) pandemic in April 2020 vs those reported in the National Health Interview Survey in 2018.

Abstract: We analyze randomized online survey experiments providing interactive, customized information on US income inequality, the link between top income tax rates and economic growth, and the estate tax. The treatment has large effects on views about inequality but only slightly moves tax and transfer policy preferences. An exception is the estate tax—informing respondents of the small share of decedents who pay it doubles support for it. The small effects for all other policies can be partially explained by respondents’ low trust in government and a disconnect between concerns about social issues and the public policies meant to address them. (JEL D31, D72, H23, H24)

Abstract: The therapeutic use of natural herbs is an ancient human civilization act and the numbers of people have reliance on their pharmacological properties and preferred to use the natural herbs. People also use to consume these herbs as supplements to energize, bolster, and eventually enhance sexual ability. Polyherbal formulation (PHF) is one of these herbal amalgams that can be used to treat sexual dysfunction including erectile dysfunction, impotence, ejaculation dysfunction, and hypogonadism. The pilot study was aimed at evaluating the capacity of PHF in enhancing the spermatogenic potential of oligospermic patients. Thirty-six male patients with oligospermia were enrolled and randomized either to treatment (n = 23) with PHF (750 mg/d in three doses for 90 days) or to placebo (n = 13) in the same protocol. The preintervention semen analysis was compared with posttreatment semen analysis. Based on the postintervention semen analysis, patients were advised to undergo either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) to assess their fertility status. After polyherbal treatment, there was a 256% increase in sperm concentration (9.59 ± 4.37 × 106/mL to 25.61 ± 8.6 × 106/mL; P ≤0.001), 154% increase in semen volume (1.7 ± 0.14 mL to 4.32 ± 0.38 mL; P ≤0.001), and 215% increase in sperm motility (15.43 ± 2.40% to 48.65 ± 5.10%; P ≤ 0.001) on day 90 from baseline. Furthermore, a significant improvement and regulation were also observed in serum hormone levels with PHF treatment as compared to the placebo group. The present study demonstrated the evidence on synergistic spermatogenic effect of PHF as attributed in ayurveda for the treatment of oligospermia leading to infertility.

Abstract: Given the results from early trials, COVID-19 vaccines will be available by 2021. However, little is known about what Americans think of getting immunized with a COVID-19 vaccine. Thus, the purpose of this study was to conduct a comprehensive and systematic national assessment of COVID-19 vaccine hesitancy in a community-based sample of the American adult population. A multi-item valid and reliable questionnaire was deployed online via mTurk and social media sites to recruit U.S. adults from the general population. A total of 1878 individuals participated in the study where the majority were: females (52%), Whites (74%), non-Hispanic (81%), married (56%), employed full time (68%), and with a bachelor's degree or higher (77%). The likelihood of getting a COVID-19 immunization in the study population was: very likely (52%), somewhat likely (27%), not likely (15%), definitely not (7%), with individuals who had lower education, income, or perceived threat of getting infected being more likely to report that they were not likely/definitely not going to get COVID-19 vaccine (i.e., vaccine hesitancy). In unadjusted group comparisons, compared to their counterparts, vaccine hesitancy was higher among African-Americans (34%), Hispanics (29%), those who had children at home (25%), rural dwellers (29%), people in the northeastern U.S. (25%), and those who identified as Republicans (29%). In multiple regression analyses, vaccine hesitancy was predicted significantly by sex, education, employment, income, having children at home, political affiliation, and the perceived threat of getting infected with COVID-19 in the next 1 year. Given the high prevalence of COVID-19 vaccine hesitancy, evidence-based communication, mass media strategies, and policy measures will have to be implemented across the U.S. to convert vaccines into vaccinations and mass immunization with special attention to the groups identified in this study.

Abstract: Using a large sample of Main Sequence stars with 7-D measurements supplied by Gaia and SDSS, we study the kinematic properties of the local (within ∼10 kpc from the Sun) stellar halo. We demonstrate that the halo’s velocity ellipsoid evolves strongly with metallicity. At the low [Fe/H] end, the orbital anisotropy (the amount of motion in the radial direction compared to the tangential one) is mildly radial with 0.2 < β < 0.4. However, for stars with [Fe/H]> −1.7 we measure extreme values of β ∼ 0.9. Across the metallicity range considered, i.e. −3 <[Fe/H]−1, the stellar halo’s spin is minimal, at the level of 20 < v¯θ(kms−1 ) < 30. Using a suite of cosmological zoom-in simulations of halo formation, we deduce that the observed acute anisotropy is inconsistent with the continuous accretion of dwarf satellites. Instead, we argue, the stellar debris in the inner halo were deposited in a major accretion event by a satellite with Mvir > 1010M⊙ around the epoch of the Galactic disc formation, i.e. between 8 and 11 Gyr ago. The radical halo anisotropy is the result of the dramatic radialisation of the massive progenitor’s orbit, amplified by the action of the growing disc.

Abstract: The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma (LUAC) are poorly characterized. We performed an integrative analysis of genomic, transcriptomic and proteomic data from early-stage and chemo-refractory LUAC and identified three robust subsets of KRAS-mutant LUAC dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP) and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further reveal biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules and improved relapse-free survival. Differences in drug sensitivity patterns were also observed; notably, KL cells showed increased vulnerability to HSP90-inhibitor therapy. This work provides evidence that co-occurring genomic alterations identify subgroups of KRAS-mutant LUAC with distinct biology and therapeutic vulnerabilities.

Abstract: The gut microbiota and its metabolic products interact with the host in many different ways, influencing gut homoeostasis and health outcomes. The species composition of the gut microbiota has been shown to respond to dietary change, determined by competition for substrates and by tolerance of gut conditions. Meanwhile, the metabolic outputs of the microbiota, such as SCFA, are influenced both by the supply of dietary components and via diet-mediated changes in microbiota composition. There has been significant progress in identifying the phylogenetic distribution of pathways responsible for formation of particular metabolites among human colonic bacteria, based on combining cultural microbiology and sequence-based approaches. Formation of butyrate and propionate from hexose sugars, for example, can be ascribed to different bacterial groups, although propionate can be formed via alternative pathways from deoxy-sugars and from lactate by a few species. Lactate, which is produced by many gut bacteria in pure culture, can also be utilised by certain Firmicutes to form butyrate, and its consumption may be important for maintaining a stable community. Predicting the impact of diet upon such a complex and interactive system as the human gut microbiota not only requires more information on the component groups involved but, increasingly, the integration of such information through modelling approaches.

Abstract: We derive constraints on cosmological parameters and tests of dark energy models from the combination of baryon acoustic oscillation (BAO) measurements with cosmic microwave background (CMB) data and a recent reanalysis of Type Ia supernova (SN) data. In particular, we take advantage of high-precision BAO measurements from galaxy clustering and the Lyman-alpha forest (LyaF) in the SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS). Treating the BAO scale as an uncalibrated standard ruler, BAO data alone yield a high confidence detection of dark energy; in combination with the CMB angular acoustic scale they further imply a nearly flat universe. Adding the CMB-calibrated physical scale of the sound horizon, the combination of BAO and SN data into an "inverse distance ladder" yields a measurement of H-0 = 67.3 +/- 1.1 km s(-1) Mpc(-1), with 1.7% precision. This measurement assumes standard prerecombination physics but is insensitive to assumptions about dark energy or space curvature, so agreement with CMB-based estimates that assume a flat Lambda CDM cosmology is an important corroboration of this minimal cosmological model. For constant dark energy (Lambda), our BAO + SN + CMB combination yields matter density Omega(m) = 0.301 +/- 0.008 and curvature Omega(k) = -0.003 +/- 0.003. When we allow more general forms of evolving dark energy, the BAO + SN + CMB parameter constraints are always consistent with flat Lambda CDM values at approximate to 1 sigma. While the overall chi(2) of model fits is satisfactory, the LyaF BAO measurements are in moderate (2-2.5 sigma) tension with model predictions. Models with early dark energy that tracks the dominant energy component at high redshift remain consistent with our expansion history constraints, and they yield a higher H-0 and lower matter clustering amplitude, improving agreement with some low redshift observations. Expansion history alone yields an upper limit on the summed mass of neutrino species, Sigma m(nu) < 0.56 eV (95% confidence), improving to Sigma m(nu) < 0.25 eV if we include the lensing signal in the Planck CMB power spectrum. In a flat Lambda CDM model that allows extra relativistic species, our data combination yields N-eff = 3.43 +/- 0.26; while the LyaF BAO data prefer higher N-eff when excluding galaxy BAO, the galaxy BAO alone favor N-eff approximate to 3. When structure growth is extrapolated forward from the CMB to low redshift, standard dark energy models constrained by our data predict a level of matter clustering that is high compared to most, but not all, observational estimates.