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An array of approximately 300 different carbohydrate structures from select gut bacteria was generated and probed with mouse and rabbit IgG samples. The binding results indicate that galectins 3, 4 and 8 of the innate immune system can recognize certain microbes only if they express self-like antigens. Genomic approaches continue to provide unprecedented insight into the microbiome, yet host immune interactions with diverse microbiota can be difficult to study. We therefore generated a microbial microarray containing defined antigens isolated from a broad range of microbial flora to examine adaptive and innate immunity. Serological studies with this microarray show that immunoglobulins from multiple mammalian species have unique patterns of reactivity, whereas exposure of animals to distinct microbes induces specific serological recognition. Although adaptive immunity exhibited plasticity toward microbial antigens, immunological tolerance limits reactivity toward self. We discovered that several innate immune galectins show specific recognition of microbes that express self-like antigens, leading to direct killing of a broad range of Gram-negative and Gram-positive microbes. Thus, host protection against microbes seems to represent a balance between adaptive and innate immunity to defend against evolving antigenic determinants while protecting against molecular mimicry.

Identifying robust, patient-specific, and predictive biomarkers presents a major obstacle in precision oncology. To optimize patient-specific therapeutic strategies, here we couple pathway knowledge with large-scale drug sensitivity, RNAi, and CRISPR-Cas9 screening data from 460 cell lines. Pathway activity levels are found to be strong predictive biomarkers for the essentiality of 15 proteins, including the essentiality of MAD2L1 in breast cancer patients with high BRCA-pathway activity. We also find strong predictive biomarkers for the sensitivity to 31 compounds, including BCL2 and microtubule inhibitors (MTIs). Lastly, we show that Bcl-xL inhibition can modulate the activity of a predictive biomarker pathway and re-sensitize lung cancer cells and tumors to MTI therapy. Overall, our results support the use of pathways in helping to achieve the goal of precision medicine by uncovering dozens of predictive biomarkers. Predicting an individual's response to therapy is an important goal for precision medicine. Here, the authors use an algorithm that takes into account the interaction type and directionality of signalling pathways in protein–protein interactions and find that their pathway analysis can predict essential genes, which may be a target for therapy.

Molecular classification has transformed the management of brain tumors by enabling more accurate prognostication and personalized treatment. However, timely molecular diagnostic testing for patients with brain tumors is limited, complicating surgical and adjuvant treatment and obstructing clinical trial enrollment. In this study, we developed DeepGlioma, a rapid (<90 seconds), artificial-intelligence-based diagnostic screening system to streamline the molecular diagnosis of diffuse gliomas. DeepGlioma is trained using a multimodal dataset that includes stimulated Raman histology (SRH); a rapid, label-free, non-consumptive, optical imaging method; and large-scale, public genomic data. In a prospective, multicenter, international testing cohort of patients with diffuse glioma ( n  = 153) who underwent real-time SRH imaging, we demonstrate that DeepGlioma can predict the molecular alterations used by the World Health Organization to define the adult-type diffuse glioma taxonomy (IDH mutation, 1p19q co-deletion and ATRX mutation), achieving a mean molecular classification accuracy of 93.3 ± 1.6%. Our results represent how artificial intelligence and optical histology can be used to provide a rapid and scalable adjunct to wet lab methods for the molecular screening of patients with diffuse glioma. DeepGlioma, a multimodal deep learning approach for intraoperative diagnostic screening of diffuse glioma, trained on stimulated Raman histology and large-scale public genomic data, can predict molecular alterations for diffuse glioma diagnosis with high accuracy.

Over the past two decades, religious websites have gained immense popularity and have become dynamic platforms for sparking discourse, practice, and modes of leadership. The internet has allowed religious leaders to reach more believers than ever before and compete for online followership. How do religious leaders negotiate their authority through online information outlets? This study explores religious “Ask the Rabbi” websites specializing in religious Jewish knowledge. The corpus is composed of 50,799 Q&A public messages between rabbis and laypeople, asked and posted from 2005 to 2019. The findings point to a shift in the authority of religious Q&A websites from the initial authority endowed to the websites through the institutionally well-known rabbis who participated on the platform. Over time, however, these websites became public spheres of learning where little-known rabbis could establish their popularity. Textual analysis revealed that the writing style evolved from short answers with few cited sources to richly sourced essays. This may suggest that online religious Q&As have shifted from being viewed as a way to contact well-known rabbis to a legitimate forum for religious discourse and selecting spiritual guidance. The discussion centers on this socio-religious change in the information age where clerics harness the web to hone their craft, recruit their flock, and ultimately, constitute their authority.

There is paucity of data regarding the diagnostic yield and safety of skin biopsies in patients with acute myeloid leukemia (AML), though skin eruptions are common in these patients. We evaluated 216 patients treated in our hemato-oncology unit at a tertiary medical center between 2007 and 2018 and identified 35 patients who underwent 37 skin biopsies. The majority of biopsies were performed during induction treatment for AML (n = 26, 70%), whereas the remainder of biopsies were done prior to induction initiation (n = 8, 22%) or during consolidation chemotherapy (n = 3, 8%). Pathology findings were inconclusive in 13 cases (35%), while diagnostic biopsies were positive for drug eruptions (24%), leukemia cutis (16%), infections (11%), reactive processes (8%) and Sweet syndrome (5.5%). In almost half of cases (16/37) tissue cultures were performed. Of those, only a quarter (4/16) were positive. Histopathology and tissue culture results altered immediate patient care in 3 cases (8%), yet information obtained from biopsies had potential to affect long term patient care in 8 additional cases (21.6%). Although most skin biopsies were performed while patients had severe thrombocytopenia and neutropenia, only one patient had a complication due to the biopsy (fever and local bleeding). With the limitation of a retrospective analysis, our study suggests that skin biopsies in patients treated for AML are relatively safe. Although biopsy results infrequently alter immediate patient management, long term effect on patient care expand the potential diagnostic yield of skin biopsies.

A bstract Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a W or a Z boson or a pair of top quarks, and of the six decay modes H → ZZ, W W , γγ , ττ, bb , and μμ . All results are reported assuming a value of 125 . 09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton-proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fb −1 at s = 7 TeV and 20 fb −1 at s = 8 TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1 . 09 ± 0 . 11. The combined measurements lead to observed significances for the vector boson fusion production process and for the H → ττ decay of 5 . 4 and 5 . 5 standard deviations, respectively. The data are consistent with the Standard Model predictions for all parameterisations considered.

A bstract This paper describes a measurement of the Z / γ * boson transverse momentum spectrum using ATLAS proton-proton collision data at a centre-of-mass energy of s = 7 TeV at the LHC. The measurement is performed in the Z / γ * → e + e − and Z / γ * → μ + μ − channels, using data corresponding to an integrated luminosity of 4.7 fb −1 . Normalized differential cross sections as a function of the Z / γ * boson transverse momentum are measured for transverse momenta up to 800 GeV. The measurement is performed inclusively for Z / γ * rapidities up to 2.4, as well as in three rapidity bins. The channel results are combined, compared to perturbative and resummed QCD calculations and used to constrain the parton shower parameters of Monte Carlo generators.

Space radiation is a notable hazard for long-duration human spaceflight 1 . Associated risks include cancer, cataracts, degenerative diseases 2 and tissue reactions from large, acute exposures 3 . Space radiation originates from diverse sources, including galactic cosmic rays 4 , trapped-particle (Van Allen) belts 5 and solar-particle events 6 . Previous radiation data are from the International Space Station and the Space Shuttle in low-Earth orbit protected by heavy shielding and Earth’s magnetic field 7 , 8 and lightly shielded interplanetary robotic probes such as Mars Science Laboratory and Lunar Reconnaissance Orbiter 9 , 10 . Limited data from the Apollo missions 11 – 13 and ground measurements with substantial caveats are also available 14 . Here we report radiation measurements from the heavily shielded Orion spacecraft on the uncrewed Artemis I lunar mission. At differing shielding locations inside the vehicle, a fourfold difference in dose rates was observed during proton-belt passes that are similar to large, reference solar-particle events. Interplanetary cosmic-ray dose equivalent rates in Orion were as much as 60% lower than previous observations 9 . Furthermore, a change in orientation of the spacecraft during the proton-belt transit resulted in a reduction of radiation dose rates of around 50%. These measurements validate the Orion for future crewed exploration and inform future human spaceflight mission design. Measurements from the heavily shielded Orion spacecraft during the uncrewed Artemis I mission show dose-rate reductions due to shielding and orientation for Van Allen belt crossings and quantify the interplanetary cosmic-ray radiation in a human-rated spacecraft.

A bstract A search for squarks and gluinos in final states containing high- p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s = 8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20 . 3 fb −1 . Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R -parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2 m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector.

Baumard's perspective asserts that “opportunity is the mother of innovation,” in contrast to the adage ascribing this role to necessity. Drawing on behavioral ecology and cognition, we propose that both extremes – affluence and scarcity – can drive innovation. We suggest that the types of innovations at these two extremes differ and that both rely on mechanisms operating on different time scales.