Empirical relationships between stream flow and ecological responses (flow–ecology relationships) are essential for establishing environmental flows and evaluating tradeoffs between instream values ...and out‐of‐stream uses. Establishing the shape of flow–ecology relationships (i.e. slope, linearity versus nonlinearity) is particularly important to avoid crossing ecological thresholds in water management.
This review focuses on ecological responses to discharge at low summer flows when out‐of‐stream water demand is often highest, and identifying ecological contexts where nonlinearities are most likely. Most physical attributes (temperature, dissolved oxygen, available habitat) and ecological responses (energy flow, fish survival, recruitment, community structure) show at least some evidence of nonlinear relationships with flow, although assumptions of linearity may be reasonable across limited discharge ranges which may include low flows.
Nonlinearities are most likely in systems that are near existing thresholds (e.g. cold‐water transitional fish communities that are close to upper thermal tolerances). The probability of nonlinearities is likely to increase under future landuse and climate change scenarios, particularly in combination with other stressors, such as eutrophication, which may greatly accelerate temperature‐related decline in dissolved oxygen under climate warming.
Managers need to anticipate changes in flow–ecology relationships and develop management systems that are robust to change. Field programmes to establish the slope and linearity of local flow–ecology relationships are essential for regional management, but developing generalisable flow–ecology relationships that are transferrable to regions with limited resources also needs to be a priority.
Generalised relationships can be generated through meta‐analysis of empirical flow–ecology relationships, and may prove especially useful if they can capture how environmental and ecological context (channel size and morphology, landuse, flow regime, antecedent conditions, habitat or taxonomic guild) affect flow–ecology relationships. For instance, linking empirical data from flow–ecology relationships to available habitat predicted by physical habitat simulation models (e.g. PHABSIM) may provide a better mechanistic basis for modelling ecological responses, while providing much needed validation for habitat simulation approaches. This would also help bridge the gap between emerging holistic environmental flow modelling approaches and more traditional habitat simulation methods.
Natural killer cell deficiency Orange, Jordan S., MD, PhD
Journal of allergy and clinical immunology,
09/2013, Letnik:
132, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Natural killer (NK) cells are part of the innate immune defense against infection and cancer and are especially useful in combating certain viral pathogens. The utility of NK cells in human health ...has been underscored by a growing number of persons who are deficient in NK cells and/or their functions. This can be in the context of a broader genetically defined congenital immunodeficiency, of which there are more than 40 presently known to impair NK cells. However, the abnormality of NK cells in certain cases represents the majority immunologic defect. In aggregate, these conditions are termed NK cell deficiency. Recent advances have added clarity to this diagnosis and identified defects in 3 genes that can cause NK cell deficiency, as well as some of the underlying biology. Appropriate consideration of these diagnoses and patients raises the potential for rational therapeutic options and further innovation.
The natural killer (NK)-cell immunological synapse is the dynamic interface formed between an NK cell and its target cell. Formation of the NK-cell immunological synapse involves several distinct ...stages, from the initiation of contact with a target cell to the directed delivery of lytic-granule contents for target-cell lysis. Progression through the individual stages is regulated, and this tight regulation underlies the precision with which NK cells select and kill susceptible target cells (including virally infected cells and cancerous cells) that they encounter during their routine surveillance of the body.
Summary
The factors responsible for the spectrum of coronavirus 19 (COVID‐19) disease severity and the genesis and nature of protective immunity against COVID‐19 remain elusive. Multiple studies have ...investigated the immune responses to COVID‐19 in various populations, including those without evidence of COVID‐19 infection. Information regarding innate and adaptive immune responses to the novel severe respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has evolved rapidly. Data are accumulating defining disease phenotypes that aid in rational and informed development of new therapeutic approaches for the treatment of patients infected with SARS‐CoV‐2 and the development of novel vaccines. In this paper, data on important innate immune responses are summarized, including cytokines, specifically interleukin (IL)‐6 and complement, and potential treatments are explored. Adaptive immune responses and derivative therapeutics such as monoclonal antibodies directed at spike proteins are also examined. Finally, data on real‐time assessments of adaptive immune responses are explored, which include CD4+/CD8+ T cells, natural killer (NK) T cells, memory B cells and T follicular cells with specificities for COVID‐19 peptides in infected and normal individuals. Data of two novel vaccines have been released, both showing > 95% efficacy in preventing SARS‐CoV‐2 infection. Analysis of humoral and cellular responses to the vaccines will determine the robustness and durability of protection. In addition, long‐term assessment of SARS‐CoV‐2 memory B and T cell‐mediated immune responses in patients recovering from an infection or those with cross‐reactive immunological memory will help to define risk for future SARS‐CoV infections. Finally, patients recovering from SARS‐CoV‐2 infection may experience prolonged immune activation probably due to T cell exhaustion. This will be an important new frontier for study.
This review summarizes published data on the relevant innate and adaptive immune responses to SARS‐CoV‐2. Data characterizing innate and adaptive immune responses have rapidly led to informed therapeutic interventions, including vaccine development and recognition of dysfunctional immune responses that are likely responsible for post‐COVID‐19 autoimmunity.
Human immunoglobulin preparations for intravenous or subcutaneous administration are the cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral immune ...system. Intravenous preparations have a number of important uses in the treatment of other diseases in humans as well, some for which acceptable treatment alternatives do not exist. We provide an update of the evidence-based guideline on immunoglobulin therapy, last published in 2006. Given the potential risks and inherent scarcity of human immunoglobulin, careful consideration of its indications and administration is warranted.
•Polystyrene nanoparticles (PS NPs) crossed the zebrafish chorion.•PS NPs accumulated in numerous organs during development.•Bradycardia and hypoactivity were observed following exposure to PS NPs.
...Plastic pollution is a critical environmental concern and comprises the majority of anthropogenic debris in the ocean, including macro, micro, and likely nanoscale (less than 100nm in at least one dimension) plastic particles. While the toxicity of macroplastics and microplastics is relatively well studied, the toxicity of nanoplastics is largely uncharacterized. Here, fluorescent polystyrene nanoparticles (PS NPs) were used to investigate the potential toxicity of nanoplastics in developing zebrafish (Danio rerio), as well as to characterize the uptake and distribution of the particles within embryos and larvae. Zebrafish embryos at 6h post-fertilization (hpf) were exposed to PS NPs (0.1, 1, or 10ppm) until 120 hpf. Our results demonstrate that PS NPs accumulated in the yolk sac as early as 24 hpf and migrated to the gastrointestinal tract, gallbladder, liver, pancreas, heart, and brain throughout development (48–120 hpf). Accumulation of PS NPs decreased during the depuration phase (120–168 hpf) in all organs, but at a slower rate in the pancreas and gastrointestinal tract. Notably, exposure to PS NPs did not induce significant mortality, deformities, or changes to mitochondrial bioenergetics, but did decrease the heart rate. Lastly, exposure to PS NPs altered larval behavior as evidenced by swimming hypoactivity in exposed larvae. Taken together, these data suggest that at least some nanoplastics can penetrate the chorion of developing zebrafish, accumulate in the tissues, and affect physiology and behavior, potentially affecting organismal fitness in contaminated aquatic ecosystems.
LiDAR has become one of the primary 3D object detection sensors in autonomous driving. However, LiDAR's diverging point pattern with increasing distance results in a non-uniform sampled point cloud ...ill-suited to discretized volumetric feature extraction. Current methods either rely on voxelized point clouds or use inefficient farthest point sampling to mitigate detrimental effects caused by density variation but largely ignore point density as a feature and its predictable relationship with distance from the LiDAR sensor. Our proposed solution, Point Density-Aware Voxel network (PDV), is an end-to-end two stage LiDAR 3D object detection architecture that is designed to account for these point density variations. PDV efficiently localizes voxel features from the 3D sparse convolution backbone through voxel point centroids. The spatially localized voxel features are then aggregated through a density-aware RoI grid pooling module using kernel density estimation (KDE) and self attention with point density positional encoding. Finally, we exploit LiDAR's point density to distance relationship to refine our final bounding box confidences. PDV outperforms all state-of-the-art methods on the Waymo Open Dataset and achieves competitive results on the KITTI dataset.
An intermolecular, photocatalytic dicarbofunctionalization (DCF) of olefins enabled by the merger of Giese-type addition with Ni/photoredox dual catalysis has been realized. Capitalizing on the rapid ...addition of 3° radicals to alkenes and their reluctance toward single electron metalation to Ni complexes, regioselective alkylation and arylation of olefins is possible. This dual catalytic method not only permits elaborate species to be assembled from commodity materials, but also allows quaternary and tertiary centers to be installed in a singular, chemoselective olefin difunctionalization. This multicomponent process occurs under exceptionally mild conditions, compatible with a diverse range of functional groups and synthetic handles such as pinacolboronate esters. This technology was directly applied to the synthesis of an intermediate to a preclinical candidate (TK-666) and its derivatives.
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