Economic development, demographic characteristics, road network and traffic accidents in Zhongshan, China: gradient boosting decision tree model

This paper explores the joint effects of economic development, demographic characteristics and road network on road safety. Although extensive efforts have been undertaken to model safety effects of various influential factors, little evidence is provided on the relative importance of explanatory variables by accounting for their mutual interactions and non-linear effects. We present an innovative gradient boosting decision tree (GBDT) model to explore joint effects of comprehensive factors on four traffic accident indicators (the number of traffic accidents, injuries, deaths, and the economic loss). A total of 27 elaborated influential factors in Zhongshan, China during 2000–2016 are collected. Results show that GBDT not only presents high prediction accuracy, but can also handle the multicollinearity between explanatory variables; more importantly, it can rank the influential factors on traffic accidents. We also investigate the partial effects of key influential factors. Based on key findings, we highlight the practical insights for planning practice

An SMT Encoding of LLVM’s Memory Model for Bounded Translation Validation

© 2021, The Author(s).Several automatic verification tools have been recently developed to verify subsets of LLVM’s optimizations. However, none of these tools has robust support to verify memory optimizations. In this paper, we present the first SMT encoding of LLVM’s memory model that 1) is sufficiently precise to validate all of LLVM’s intra-procedural memory optimizations, and 2) enables bounded translation validation of programs with up to hundreds of thousands of lines of code. We implemented our new encoding in Alive2, a bounded translation validation tool, and used it to uncover 21 new bugs in LLVM memory optimizations, 10 of which have been already fixed. We also found several inconsistencies in LLVM IR’s official specification document (LangRef) and fixed LLVM’s code and the document so they are in agreement.N

Alive2: Bounded translation validation for LLVM

© 2021 ACM.We designed, implemented, and deployed Alive2: a bounded translation validation tool for the LLVM compiler's intermediate representation (IR). It limits resource consumption by, for example, unrolling loops up to some bound, which means there are circumstances in which it misses bugs. Alive2 is designed to avoid false alarms, is fully automatic through the use of an SMT solver, and requires no changes to LLVM. By running Alive2 over LLVM's unit test suite, we discovered and reported 47 new bugs, 28 of which have been fixed already. Moreover, our work has led to eight patches to the LLVM Language Reference-the definitive description of the semantics of its IR-and we have participated in numerous discussions with the goal of clarifying ambiguities and fixing errors in these semantics. Alive2 is open source and we also made it available on the web, where it has active users from the LLVM community.N

Estradiol mediates colonic epithelial protection in aged mice after stroke and is associated with shifts in the gut microbiome

ABSTRACTThe gut is a major source of bacteria and antigens that contribute to neuroinflammation after brain injury. Colonic epithelial cells (ECs) are responsible for secreting major cellular components of the innate defense system, including antimicrobial proteins (AMP) and mucins. These cells serve as a critical regulator of gut barrier function and maintain host-microbe homeostasis. In this study, we determined post-stroke host defense responses at the colonic epithelial surface in mice. We then tested if the enhancement of these epithelial protective mechanisms is beneficial in young and aged mice after stroke. AMPs were significantly increased in the colonic ECs of young males, but not in young females after experimental stroke. In contrast, mucin-related genes were enhanced in young females and contributed to mucus formation that maintains the distance between the host and gut bacteria. Bacterial community profiling was done using universal amplification of 16S rRNA gene sequences. The sex-specific colonic epithelial defense responses after stroke in young females were reversed with ovariectomy and led to a shift from a predominately mucin response to the enhanced AMP expression seen in males after stroke. Estradiol (E2) replacement prior to stroke in aged females increased mucin gene expression in the colonic ECs. Interestingly, we found that E2 treatment reduced stroke-associated neuronal hyperactivity in the insular cortex, a brain region that interacts with visceral organs such as the gut, in parallel to an increase in the composition of Lactobacillus and Bifidobacterium in the gut microbiota. This is the first study demonstrating sex differences in host defense mechanisms in the gut after brain injury

CD11b B Cells Increase after Stroke and Regulate Microglia

Recent studies have highlighted the deleterious contributions of B cells to post-stroke recovery and cognitive decline. Different B cell subsets have been proposed on the basis of expression levels of transcription factors (e.g., T-bet) as well as specific surface proteins. CD11b (α-chain of integrin) is expressed by several immune cell types and is involved in regulation of cell motility, phagocytosis, and other essential functions of host immunity. Although B cells express CD11b, the CD11b subset of B cells has not been well characterized, especially in immune dysregulation seen with aging and after stroke. Here, we investigate the role of CD11b B cells in immune responses after stroke in young and aged mice. We evaluated the ability of CD11b B cells to influence pro- and anti-inflammatory phenotypes of young and aged microglia (MG). We hypothesized that CD11b B cells accumulate in the brain and contribute to neuroinflammation in aging and after stroke. We found that CD11b B cells are a heterogeneous subpopulation of B cells predominantly present in naive aged mice. Their frequency increases in the brain after stroke in young and aged mice. Importantly, CD11b B cells regulate MG phenotype and increase MG phagocytosis in both ex vivo and in vivo settings, likely by production of regulatory cytokines (e.g., TNF-α). As both APCs and adaptive immune cells with long-term memory function, B cells are uniquely positioned to regulate acute and chronic phases of the post-stroke immune response, and their influence is subset specific

Stabilizing histamine release in gut mast cells mitigates peripheral and central inflammation after stroke

Abstract Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and improve stroke outcomes. We used the transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in aged (18 mo) male mice to investigate the role of MC in neuroinflammation post-stroke. After MCAO we treated mice with 25 mg/kg body weight of cromolyn (MC stabilizer) by oral gavage. Cromolyn was administered at 3 h, 10 h, 24 h and every 24 h for 3 days post-stroke. Three control groups were used. One group underwent a sham surgery and was treated with cromolyn, one received sham surgery with PBS vehicle and the third underwent MCAO with PBS vehicle. Mice were euthanized at 24 h and 3 days post-stroke. Cromolyn administration significantly reduced MC numbers in the brain at both 24 h and 3 days post-stroke. Infarct volume was not significantly different between groups, however improved functional outcomes were seen at 3 days post-stroke in mice that received cromolyn. Treatment with cromolyn reduced plasma histamine and IL-6 levels in both the 24-h and 3-day cohorts. Gut MCs numbers were significantly reduced after cromolyn treatment at 24 h and 3 days after stroke. To determine if MC trafficking from the gut to the brain occurred after injury, GFP+MCs were adoptively transferred to c-kit−/− MC knock-out animals prior to MCAO. 24 h after stroke, elevated MC recruitment was seen in the ischemic brain. Preventing MC histamine release by cromolyn improved gut barrier integrity and an improvement in stroke-induced dysbiosis was seen with treatment. Our results show that preventing MC histamine release possesses prevents post-stroke neuroinflammation and improves neurological and functional outcomes. Graphical abstrac