We present an analysis of spectroscopic and astrometric data from APOGEE-2 and Gaia DR2 to identify structures toward the Orion Complex. By applying a hierarchical clustering algorithm to the ...six-dimensional stellar data, we identify spatially and/or kinematically distinct groups of young stellar objects with ages ranging from 1 to 12 Myr. We also investigate the star-forming history within the Orion Complex and identify peculiar subclusters. With this method we reconstruct the older populations in the regions that are currently largely devoid of molecular gas, such as Orion C (which includes the Ori cluster) and Orion D (the population that traces Ori OB1a, OB1b, and Orion X). We report on the distances, kinematics, and ages of the groups within the Complex. The Orion D group is in the process of expanding. On the other hand, Orion B is still in the process of contraction. In λ Ori the proper motions are consistent with a radial expansion due to an explosion from a supernova; the traceback age from the expansion exceeds the age of the youngest stars formed near the outer edges of the region, and their formation would have been triggered when they were halfway from the cluster center to their current positions. We also present a comparison between the parallax and proper-motion solutions obtained by Gaia DR2 and those obtained toward star-forming regions by the Very Long Baseline Array.
Neutrophil granule serine proteases contribute to immune responses through cleavage of microbial toxins and structural proteins. They induce tissue damage and modulate inflammation if levels exceed ...their inhibitors. Here, we show that the intracellular protease inhibitors Serpinb1a and Serpinb6a contribute to monocyte and neutrophil survival in steady-state and inflammatory settings by inhibiting cathepsin G (CatG). Importantly, we found that CatG efficiently cleaved gasdermin D (GSDMD) to generate the signature N-terminal domain GSDMD-p30 known to induce pyroptosis. Yet GSDMD deletion did not rescue neutrophil survival in Sb1a.Sb6a−/− mice. Furthermore, Sb1a.Sb6a−/− mice released high levels of pro-inflammatory cytokines upon endotoxin challenge in vivo in a CatG-dependent manner. Canonical inflammasome activation in Sb1a.Sb6a−/− macrophages showed increased IL-1β release that was dependent on CatG and GSDMD. Together, our findings demonstrate that cytosolic serpins expressed in myeloid cells prevent cell death and regulate inflammatory responses by inhibiting CatG and alternative activation of GSDMD.
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•Serpinb1a and Serpinb6a prevent cathepsin G-dependent neutrophil death•Cathepsin G cleaves gasdermin D at Leu274 to generate a p30 fragment•Serpin deficiency leads to high inflammation via cathepsin G and gasdermin D•Gasdermin D does not regulate neutrophil death in serpin deficiency
Burgener et al. show that cytosolic protease inhibitors Serpinb1a and Serpinb6a inhibit the granule serine protease cathepsin G to prevent neutrophil and monocyte death and cytokine release upon LPS challenge. Mechanistically, activation of gasdermin D by cathepsin G is required for inflammation but not for neutrophil death.
We present a novel framework to evaluate multi‐agent crowd simulation algorithms based on real‐world observations of crowd movements. A key aspect of our approach is to enable fair comparisons by ...automatically estimating the parameters that enable the simulation algorithms to best fit the given data. We formulate parameter estimation as an optimization problem, and propose a general framework to solve the combinatorial optimization problem for all parameterized crowd simulation algorithms. Our framework supports a variety of metrics to compare reference data and simulation outputs. The reference data may correspond to recorded trajectories, macroscopic parameters, or artist‐driven sketches. We demonstrate the benefits of our framework for example‐based simulation, modeling of cultural variations, artist‐driven crowd animation, and relative comparison of some widely‐used multi‐agent simulation algorithms.
Machine learning (ML) and artificial intelligence (AI) are rapidly becoming the most talked about and controversial topics in radiology and medicine. Over the past few years, the numbers of ML- or ...AI-focused studies in the literature have increased almost exponentially, and ML has become a hot topic at academic and industry conferences. However, despite the increased awareness of ML as a tool, many medical professionals have a poor understanding of how ML works and how to critically appraise studies and tools that are presented to us. Thus, we present a brief overview of ML, explain the metrics used in ML and how to interpret them, and explain some of the technical jargon associated with the field so that readers with a medical background and basic knowledge of statistics can feel more comfortable when examining ML applications.
Attention to sample size, overfitting, underfitting, cross validation, as well as a broad knowledge of the metrics of machine learning, can help those with little or no technical knowledge begin to assess machine learning studies. However, transparency in methods and sharing of algorithms is vital to allow clinicians to assess these tools themselves.
We estimated national-level trends in the prevalence of probable active syphilis in adult women using the Spectrum Sexually Transmitted Infections (STI) model to inform program planning, ...target-setting, and progress evaluation in STI control. The model fitted smoothed-splines polynomial regressions to data from antenatal clinic surveys and screening and representative household surveys, adjusted for diagnostic test performance and weighted by national coverage. Eligible countries had ≥1 data point from 2010 or later and ≥3 from 2000 or later from adult populations considered representative of the general female population (pregnant women or community-based studies). Between 2012 and 2016, the prevalence of probable active syphilis in women decreased in 54 (41%) of 132 eligible countries; this decrease was substantive (≥10% proportionally, ≥0.10% percentage-point absolute difference and non-overlapping 95% confidence intervals in 2012 and 2016) in 5 countries. Restricting eligible data to prevalence measurements of dual treponemal and non-treponemal testing limited estimates to 85 countries; of these, 45 countries (53%) showed a decrease. These standardized trend estimates highlight the need for increased investment in national syphilis surveillance and control efforts if the World Health Organization target of a 90% reduction in the incidence of syphilis between 2018 and 2030 is to be met.
Recent work on the initial switches that trigger cell death has revealed surprising inventions of nature that ensure the ordered suicide of a cell that has been selected for demise. Particularly ...intriguing is how a signal--the release of cytochrome c from the mitochondria--is translated into the activation of the death cascade, which leads to a point of no return. Now there is new understanding of how this crucial process is delicately handled by a cytosolic signalling platform known as the apoptosome. The formation of the apoptosome and the activation of its effector, caspase-9, reveals a sophisticated mechanism that might be more common than was initially thought.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
7.
The Hybrid Reciprocal Velocity Obstacle Snape, J.; van den Berg, J.; Guy, S. J. ...
IEEE transactions on robotics,
08/2011, Letnik:
27, Številka:
4
Journal Article
Recenzirano
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We present the hybrid reciprocal velocity obstacle for collision-free and oscillation-free navigation of multiple mobile robots or virtual agents. Each robot senses its surroundings and acts ...independently without central coordination or communication with other robots. Our approach uses both the current position and the velocity of other robots to compute their future trajectories in order to avoid collisions. Moreover, our approach is reciprocal and avoids oscillations by explicitly taking into account that the other robots sense their surroundings as well and change their trajectories accordingly. We apply hybrid reciprocal velocity obstacles to iRobot Create mobile robots and demonstrate direct, collision-free, and oscillation-free navigation.
The cellular stress response has a vital role in regulating homeostasis by modulating cell survival and death. Stress granules are cytoplasmic compartments that enable cells to survive various ...stressors. Defects in the assembly and disassembly of stress granules are linked to neurodegenerative diseases, aberrant antiviral responses and cancer
. Inflammasomes are multi-protein heteromeric complexes that sense molecular patterns that are associated with damage or intracellular pathogens, and assemble into cytosolic compartments known as ASC specks to facilitate the activation of caspase-1. Activation of inflammasomes induces the secretion of interleukin (IL)-1β and IL-18 and drives cell fate towards pyroptosis-a form of programmed inflammatory cell death that has major roles in health and disease
. Although both stress granules and inflammasomes can be triggered by the sensing of cellular stress, they drive contrasting cell-fate decisions. The crosstalk between stress granules and inflammasomes and how this informs cell fate has not been well-studied. Here we show that the induction of stress granules specifically inhibits NLRP3 inflammasome activation, ASC speck formation and pyroptosis. The stress granule protein DDX3X interacts with NLRP3 to drive inflammasome activation. Assembly of stress granules leads to the sequestration of DDX3X, and thereby the inhibition of NLRP3 inflammasome activation. Stress granules and the NLRP3 inflammasome compete for DDX3X molecules to coordinate the activation of innate responses and subsequent cell-fate decisions under stress conditions. Induction of stress granules or loss of DDX3X in the myeloid compartment leads to a decrease in the production of inflammasome-dependent cytokines in vivo. Our findings suggest that macrophages use the availability of DDX3X to interpret stress signals and choose between pro-survival stress granules and pyroptotic ASC specks. Together, our data demonstrate the role of DDX3X in driving NLRP3 inflammasome and stress granule assembly, and suggest a rheostat-like mechanistic paradigm for regulating live-or-die cell-fate decisions under stress conditions.
The Second APOKASC Catalog: The Empirical Approach Pinsonneault, Marc H.; Elsworth, Yvonne P.; Tayar, Jamie ...
The Astrophysical journal. Supplement series,
12/2018, Letnik:
239, Številka:
2
Journal Article
Recenzirano
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We present a catalog of stellar properties for a large sample of 6676 evolved stars with Apache Point Observatory Galactic Evolution Experiment spectroscopic parameters and Kepler asteroseismic data ...analyzed using five independent techniques. Our data include evolutionary state, surface gravity, mean density, mass, radius, age, and the spectroscopic and asteroseismic measurements used to derive them. We employ a new empirical approach for combining asteroseismic measurements from different methods, calibrating the inferred stellar parameters, and estimating uncertainties. With high statistical significance, we find that asteroseismic parameters inferred from the different pipelines have systematic offsets that are not removed by accounting for differences in their solar reference values. We include theoretically motivated corrections to the large frequency spacing (Δ ) scaling relation, and we calibrate the zero-point of the frequency of the maximum power ( max) relation to be consistent with masses and radii for members of star clusters. For most targets, the parameters returned by different pipelines are in much better agreement than would be expected from the pipeline-predicted random errors, but 22% of them had at least one method not return a result and a much larger measurement dispersion. This supports the usage of multiple analysis techniques for asteroseismic stellar population studies. The measured dispersion in mass estimates for fundamental calibrators is consistent with our error model, which yields median random and systematic mass uncertainties for RGB stars of order 4%. Median random and systematic mass uncertainties are at the 9% and 8% level, respectively, for red clump stars.
Genome sequences are known for two archaic hominins—Neanderthals and Denisovans—which interbred with anatomically modern humans as they dispersed out of Africa. We identified high-confidence archaic ...haplotypes in 161 new genomes spanning 14 island groups in Island Southeast Asia and New Guinea and found large stretches of DNA that are inconsistent with a single introgressing Denisovan origin. Instead, modern Papuans carry hundreds of gene variants from two deeply divergent Denisovan lineages that separated over 350 thousand years ago. Spatial and temporal structure among these lineages suggest that introgression from one of these Denisovan groups predominantly took place east of the Wallace line and continued until near the end of the Pleistocene. A third Denisovan lineage occurs in modern East Asians. This regional mosaic suggests considerable complexity in archaic contact, with modern humans interbreeding with multiple Denisovan groups that were geographically isolated from each other over deep evolutionary time.
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•A new dataset of 161 genomes covering the understudied Indonesia-New Guinea region•Introgressing Denisovans comprise at least three genetically divergent groups•Papuans carry haplotypes from two Denisovan groups, with one unique to Oceania•Some Denisovan introgression was recent and likely occurred in New Guinea or Wallacea
Genome sequences from Island Southeast Asia suggest two independent Denisovan lineages, distinct from the Altai Denisovan, that have contributed to modern Papuan genomes, with one group potentially present east of the Wallace Line and thus capable of crossing geographical barriers.
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