The B-cell receptor (BCR) is a key survival molecule for normal B cells and for most B-cell malignancies. Recombinatorial and mutational patterns in the clonal immunoglobulin (Ig) of chronic ...lymphocytic leukemia (CLL) have revealed 2 major IgMD-expressing subsets and an isotype-switched variant, each developing from distinct B-cell populations. Tracking of conserved stereotypic features of Ig variable regions characteristic of U-CLL indicate circulating naive B cells as the likely cells of origin. In CLL, engagement of the BCR by antigen occurs in vivo, leading to down-regulated expression and to an unanticipated modulation of glycosylation of surface IgM, visible in blood cells, especially in U-CLL. Modulated glycoforms of sIgM are signal competent and could bind to environmental lectins. U-CLL cases express more sIgM and have increased signal competence, linking differential signaling responses to clinical behavior. Mapping of BCR signaling pathways identifies targets for blockade, aimed to deprive CLL cells of survival and proliferative signals. New inhibitors of BCR signaling appear to have clinical activity. In this Perspective, we discuss the functional significance of the BCR in CLL, and we describe strategies to target BCR signaling as an emerging therapeutic approach.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Since the publication of the Revised European-American Classification of mature lymphoid neoplasms in 1994, subsequent updates of the classification of mature lymphoid neoplasms have been generated ...through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress in the characterization of malignancies of the immune system in the last years, with many new insights provided by genomic studies, have led to the current proposal. We have followed the same process that was successfully used for the 3rd and 4th editions of the WHO classification of hematological neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional are now upgraded to definite entities. Terminology of some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification (ICC) of mature lymphoid, histiocytic, and dendritic cell tumors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Octalithium ceramics with their high stoichiometric concentration of lithium offer exceptionally high tritium breeding ratios (TBRs) in comparison with other candidate breeder materials for tokamak ...fusion reactors, this is especially true with incorporation of a neutron multiplier into the crystal structures. Although, there are concerns surrounding the stability of these materials at operational temperatures. Therefore in this paper, we explore the thermodynamic properties of a selection of candidate octalithium ceramics in low and high temperature regimes (0-1200 K) using density functional perturbation theory (DFPT). Enthalpies as well as Gibbs formation energies were used to distinguish candidates which may or may not be susceptible to degradation.
Abstract
The Euclid telescope, due for launch in 2021, will perform an imaging and slitless spectroscopy survey over half the sky, to map baryon wiggles and weak lensing. During the survey, Euclid is ...expected to resolve 100 000 strong gravitational lens systems. This is ideal to find rare lens configurations, provided they can be identified reliably and on a reasonable time-scale. For this reason, we have developed a convolutional neural network (CNN) that can be used to identify images containing lensing systems. CNNs have already been used for image and digit classification as well as being used in astronomy for star-galaxy classification. Here, our CNN is trained and tested on Euclid-like and KiDS (Kilo-Degree Survey)-like simulations from the Euclid Strong Lensing Group, successfully classifying 77 per cent of lenses, with an area under the ROC curve of up to 0.96. Our CNN also attempts to classify the lenses in COSMOS Hubble Space Telescope F814W-band images. After convolution to the Euclid resolution, we find we can recover most systems that are identifiable by eye. The python code is available on Github.
Vegetation structural complexity (VSC)—the three‐dimensional distribution of plants within an ecosystem—is an important ecological trait. To date, research has focused primarily on the effects of VSC ...on ecological patterns and processes, but comparatively little is known about what drives variation in VSC.
Recent advances in active remote sensing technology, particularly light detection and ranging and radio detection and ranging, have allowed the measurement of VSC at unprecedented spatial scales and resolutions. Out of this and earlier work has emerged evidence that VSC is typically associated with greater ecosystem functioning (especially microclimate regulation, productivity, faunal diversity and habitat provisioning), making restoration of vegetation complexity a potentially powerful restoration tool.
Recent studies of VSC across natural and experimental gradients of plant diversity have also revealed that more diverse plant communities tend to be more structurally complex. However, the shape and generality of this relationship—and the mechanism(s) by which phytodiversity might contribute to structural complexity—remain poorly understood.
Here, we review how active remote sensing has facilitated recent VSC research and shaped our understanding of the relationship between vegetation complexity and ecosystem function. We then present a theoretical framework for the relationship between phytodiversity and VSC based on classic biodiversity‐ecosystem functioning principles. Finally, we evaluate the evidence for the notion that diverse plant assemblages tend to be more structurally complex and explore the shape of the relationship between phytodiversity and VSC using data from 13 recent remote sensing studies.
Synthesis. The relationship between phytodiversity and VSC appears to be almost universally positive. Preliminary evidence further suggests that the most common relationships between phytodiversity and VSC are linear or saturating, indicating that the extent of functional redundancy between species varies across plant communities and ecosystems. In contrast, we find little evidence for exponential or negative relationships between plant diversity and VSC, suggesting that even modest increases in plant diversity could markedly increase structural complexity. Additional investigations of phytodiversity‐VSC relationships are necessary to establish whether the observed positive relationships are causal (and, if so, in which direction) and to clarify the potential impact of plant community restoration on structural complexity and broader ecosystem function.
Vegetation structural complexity (VSC) is an important ecosystem trait that is typically associated with greater ecological functioning. Recent studies have also revealed that more diverse plant communities tend to be more structurally complex. However, the shape and generality of this relationship—and the mechanism(s) by which phytodiversity might contribute to structural complexity—remain poorly understood. We propose a theoretical framework for the relationship between phytodiversity and VSC based on classic biodiversity‐ecosystem functioning principles. Using data from recently published studies that compare VSC across phytodiversity gradients, we find that the relationship between phytodiversity and VSC appears to be almost universally positive.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The largest cohort of critically ill patients evaluating intragastric and small intestinal delivery of nutrients was recently reported. This systematic review included recent data to compare the ...effects of small bowel and intragastric delivery of enteral nutrients in adult critically ill patients.
This is a systematic review of all randomised controlled studies published between 1990 and March 2013 that reported the effects of the route of enteral feeding in the critically ill on clinically important outcomes.
Data from 15 level-2 studies were included. Small bowel feeding was associated with a reduced risk of pneumonia (Relative Risk, RR, small intestinal vs. intragastric: 0.75 (95% confidence interval 0.60 to 0.93); P=0.01; I2=11%). The point estimate was similar when only studies using microbiological data were included. Duration of ventilation (weighted mean difference: -0.36 days (-2.02 to 1.30); P=0.65; I2=42%), length of ICU stay (WMD: 0.49 days, (-1.36 to 2.33); P=0.60; I2=81%) and mortality (RR 1.01 (0.83 to 1.24); P=0.92; I2=0%) were unaffected by the route of feeding. While data were limited, and there was substantial statistical heterogeneity, there was significantly improved nutrient intake via the small intestinal route (% goal rate received: 11% (5 to 16%); P=0.0004; I2=88%).
Use of small intestinal feeding may improve nutritional intake and reduce the incidence of ICU-acquired pneumonia. In unselected critically ill patients other clinically important outcomes were unaffected by the site of the feeding tube.
Plastic pollution and climate change have commonly been treated as two separate issues and sometimes are even seen as competing. Here we present an alternative view that these two issues are ...fundamentally linked. Primarily, we explore how plastic contributes to greenhouse gas (GHG) emissions from the beginning to the end of its life cycle. Secondly, we show that more extreme weather and floods associated with climate change, will exacerbate the spread of plastic in the natural environment. Finally, both issues occur throughout the marine environment, and we show that ecosystems and species can be particularly vulnerable to both, such as coral reefs that face disease spread through plastic pollution and climate-driven increased global bleaching events. A Web of Science search showed climate change and plastic pollution studies in the ocean are often siloed, with only 0.4% of the articles examining both stressors simultaneously. We also identified a lack of regional and industry-specific life cycle analysis data for comparisons in relative GHG contributions by materials and products. Overall, we suggest that rather than debate over the relative importance of climate change or marine plastic pollution, a more productive course would be to determine the linking factors between the two and identify solutions to combat both crises.
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•Plastic pollution and climate change crises compete for public and policy attention.•These issues are linked, with some marine species and ecosystems vulnerable to both.•The root cause of both crises is the same, the overconsumption of finite resources.•Engagement in solving plastic pollution can increase action against climate change.•Integrated approaches include conserving blue carbon and a circular economy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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