Scientific questions for the exploration of the terrestrial planets and Jupiter - Advanced planetary missions technology program Progress report

Scientific questions and experimental design for planetary exploration of Jupiter, Mars, Mercury, and Venu

Xanthine oxidoreductase regulates macrophage IL1β secretion upon NLRP3 inflammasome activation.

Activation of the NLRP3 inflammasome by microbial ligands or tissue damage requires intracellular generation of reactive oxygen species (ROS). We present evidence that macrophage secretion of IL1β upon stimulation with ATP, crystals or LPS is mediated by a rapid increase in the activity of xanthine oxidase (XO), the oxidized form of xanthine dehydrogenase, resulting in the formation of uric acid as well as ROS. We show that XO-derived ROS, but not uric acid, is the trigger for IL1β release and that XO blockade results in impaired IL1β and caspase1 secretion. XO is localized to both cytoplasmic and mitochondrial compartments and acts upstream to the PI3K-AKT signalling pathway that results in mitochondrial ROS generation. This pathway represents a mechanism for regulating NLRP3 inflammasome activation that may have therapeutic implications in inflammatory diseases

Detecting, Preventing, and Responding to “Fraudsters” in Internet Research: Ethics and Tradeoffs

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111094/1/jlme12200.pd

A new model to determine the dispersion of fatigue damage evaluations

Reliable predictions of remaining lives of civil or mechanical structures subjected to fatigue damage are very difficult to be made. In general, fatigue damage is extremely sensitive to the random variations of material mechanical properties, environment and loading. These variations may induce large dispersions when the structural fatigue life has to be predicted. Wirsching (1970) mentions dispersions of the order of 30 to 70 % of the mean calculated life. The presented paper introduces a model to estimate the fatigue damage dispersion based on known statistical distributions of the fatigue parameters (material properties and loading). The model is developed by expanding into Taylor series the set of equations that describe fatigue damage for crack initiation

Genetic Modifiers of Mendelian Monogenic Collagen IV Nephropathies in Humans and Mice

Familial hematuria is a clinical sign of a genetically heterogeneous group of conditions, accompanied by broad inter- and intrafamilial variable expressivity. The most frequent condition is caused by pathogenic (or likely pathogenic) variants in the collagen-IV genes, COL4A3/A4/A5. Pathogenic variants in COL4A5 are responsible for the severe X-linked glomerulopathy, Alport syndrome (AS), while homozygous or compound heterozygous variants in the COL4A3 or the COL4A4 gene cause autosomal recessive AS. AS usually leads to progressive kidney failure before the age of 40-years when left untreated. People who inherit heterozygous COL4A3/A4 variants are at-risk of a slowly progressive form of the disease, starting with microscopic hematuria in early childhood, developing Alport spectrum nephropathy. Sometimes, they are diagnosed with benign familial hematuria, and sometimes with autosomal dominant AS. At diagnosis, they often show thin basement membrane nephropathy, reflecting the uniform thin glomerular basement membrane lesion, inherited as an autosomal dominant condition. On a long follow-up, most patients will retain normal or mildly affected kidney function, while a substantial proportion will develop chronic kidney disease (CKD), even kidney failure at an average age of 55-years. A question that remains unanswered is how to distinguish those patients with AS or with heterozygous COL4A3/A4 variants who will manifest a more aggressive kidney function decline, requiring prompt medical intervention. The hypothesis that a subgroup of patients coinherit additional genetic modifiers that exacerbate their clinical course has been investigated by several researchers. Here, we review all publications that describe the potential role of candidate genetic modifiers in patients and include a summary of studies in AS mouse models

Improving BDD Based Symbolic Model Checking with Isomorphism Exploiting Transition Relations

Symbolic model checking by using BDDs has greatly improved the applicability of model checking. Nevertheless, BDD based symbolic model checking can still be very memory and time consuming. One main reason is the complex transition relation of systems. Sometimes, it is even not possible to generate the transition relation, due to its exhaustive memory requirements. To diminish this problem, the use of partitioned transition relations has been proposed. However, there are still systems which can not be verified at all. Furthermore, if the granularity of the partitions is too fine, the time required for verification may increase. In this paper we target the symbolic verification of asynchronous concurrent systems. For such systems we present an approach which uses similarities in the transition relation to get further memory reductions and runtime improvements. By applying our approach, even the verification of systems with an previously intractable transition relation becomes feasible.Comment: In Proceedings GandALF 2011, arXiv:1106.081

Gender Differences in Acute and Chronic Pain in the Emergency Department: Results of the 2014 Academic Emergency Medicine Consensus Conference Pain Section

Pain is a leading public health problem in the United States, with an annual economic burden of more than $630 billion, and is one of the most common reasons that individuals seek emergency department (ED) care. There is a paucity of data regarding sex differences in the assessment and treatment of acute and chronic pain conditions in the ED. The Academic Emergency Medicine consensus conference convened in Dallas, Texas, in May 2014 to develop a research agenda to address this issue among others related to sex differences in the ED. Prior to the conference, experts and stakeholders from emergency medicine and the pain research field reviewed the current literature and identified eight candidate priority areas. At the conference, these eight areas were reviewed and all eight were ratified using a nominal group technique to build consensus. These priority areas were: 1) gender differences in the pharmacological and nonpharmacological interventions for pain, including differences in opioid tolerance, side effects, or misuse; 2) gender differences in pain severity perceptions, clinically meaningful differences in acute pain, and pain treatment preferences; 3) gender differences in pain outcomes of ED patients across the life span; 4) gender differences in the relationship between acute pain and acute psychological responses; 5) the influence of physician-patient gender differences and characteristics on the assessment and treatment of pain; 6) gender differences in the influence of acute stress and chronic stress on acute pain responses; 7) gender differences in biological mechanisms and molecular pathways mediating acute pain in ED populations; and 8) gender differences in biological mechanisms and molecular pathways mediating chronic pain development after trauma, stress, or acute illness exposure. These areas represent priority areas for future scientific inquiry, and gaining understanding in these will be essential to improving our understanding of sex and gender differences in the assessment and treatment of pain conditions in emergency care settings

Presentation of the 9th Edition of the Model Checking Contest.

International audience; The Model Checking Contest (MCC) is an annual competition of software tools for model checking. Tools must process an increasing benchmark gathered from the whole community and may participate in various examinations: state space generation, computation of global properties, computation of some upper bounds in the model, evaluation of reachability formulas, evaluation of CTL formulas, and evaluation of LTL formulas.For each examination and each model instance, participating tools are provided with up to 3600 s and 16 gigabyte of memory. Then, tool answers are analyzed and confronted to the results produced by other competing tools to detect diverging answers (which are quite rare at this stage of the competition, and lead to penalties).For each examination, golden, silver, and bronze medals are attributed to the three best tools. CPU usage and memory consumption are reported, which is also valuable information for tool developers