Divergent Effects of Factors on Crash Severity under Autonomous and Conventional Driving Modes Using a Hierarchical Bayesian Approach

Influencing factors on crash severity involved with autonomous vehicles (AVs) have been paid increasing attention. However, there is a lack of comparative analyses of those factors between AVs and human-driven vehicles. To fill this research gap, the study aims to explore the divergent effects of factors on crash severity under autonomous and conventional (i.e., human-driven) driving modes. This study obtained 180 publicly available autonomous vehicle crash data, and 39 explanatory variables were extracted from three categories, including environment, roads, and vehicles. Then, a hierarchical Bayesian approach was applied to analyze the impacting factors on crash severity (i.e., injury or no injury) under both driving modes with considering unobserved heterogeneities. The results showed that some influencing factors affected both driving modes, but their degrees were different. For example, daily visitors\u27 flowrate had a greater impact on the crash severity under the conventional driving mode. More influencing factors only had significant impacts on one of the driving modes. For example, in the autonomous driving mode, mixed land use increased the severity of crashes, while daytime had the opposite effects. This study could contribute to specifying more appropriate policies to reduce the crash severity of both autonomous and human-driven vehicles especially in mixed traffic conditions

Microglia Prevent Beta-Amyloid Plaque Formation in the Early Stage of an Alzheimer\u27s Disease Mouse Model with Suppression of Glymphatic Clearance

BACKGROUND: Soluble beta-amyloid (Aβ) can be cleared from the brain through various mechanisms including enzymatic degradation, glial cell phagocytosis, transport across the blood-brain barrier, and glymphatic clearance. However, the relative contribution of each clearance system and their compensatory effects in delaying the pathological process of Alzheimer\u27s disease (AD) are currently unknown. METHODS: Fluorescent trace, immunofluorescence, and Western blot analyses were performed to compare glymphatic clearance ability and Aβ accumulation among 3-month-old APP695/PS1-dE9 transgenic (APP/PS1) mice, wild-type mice, aquaporin 4 knock out (AQP4−/−) mice, and AQP4−/−/APP/PS1 mice. The consequence of selectively eliminating microglial cells, or downregulating apolipoprotein E (apoE) expression, on Aβ burden, was also investigated in the frontal cortex of AQP4−/−/APP/PS1 mice and APP/PS1 mice. RESULTS: AQP4 deletion in APP/PS1 mice significantly exaggerated glymphatic clearance dysfunction, and intraneuronal accumulation of Aβ and apoE, although it did not lead to Aβ plaque deposition. Notably, microglia, but not astrocytes, increased activation and phagocytosis of Aβ in the cerebral cortex of AQP4−/−/APP/PS1 mice, compared with APP/PS1 mice. Selectively eliminating microglia in the frontal cortex via local injection of clodronate liposomes resulted in deposition of Aβ plaques in AQP4−/−/APP/PS1 mice, but not APP/PS1 mice. Moreover, knockdown of apoE reduced intraneuronal Aβ levels in both APP/PS1 mice and AQP4−/−/APP/PS1 mice, indicating an inhibitory effect of apoE on Aβ clearance. CONCLUSION: The above results suggest that the glymphatic system mediated Aβ and apoE clearance and microglia mediated Aβ degradation synergistically prevent Aβ plague formation in the early stages of the AD mouse model. Protecting one or both of them might be beneficial to delaying the onset of AD

Organization of chromosome ends in the rice blast fungus, Magnaporthe oryzae

Eukaryotic pathogens of humans often evade the immune system by switching the expression of surface proteins encoded by subtelomeric gene families. To determine if plant pathogenic fungi use a similar mechanism to avoid host defenses, we sequenced the 14 chromosome ends of the rice blast pathogen, Magnaporthe oryzae. One telomere is directly joined to ribosomal RNA-encoding genes, at the end of the ∼2 Mb rDNA array. Two are attached to chromosome-unique sequences, and the remainder adjoin a distinct subtelomere region, consisting of a telomere-linked RecQ-helicase (TLH) gene flanked by several blocks of tandem repeats. Unlike other microbes, M.oryzae exhibits very little gene amplification in the subtelomere regions—out of 261 predicted genes found within 100 kb of the telomeres, only four were present at more than one chromosome end. Therefore, it seems unlikely that M.oryzae uses switching mechanisms to evade host defenses. Instead, the M.oryzae telomeres have undergone frequent terminal truncation, and there is evidence of extensive ectopic recombination among transposons in these regions. We propose that the M.oryzae chromosome termini play more subtle roles in host adaptation by promoting the loss of terminally-positioned genes that tend to trigger host defenses

Data mining of Arabidopsis thaliana salt-response proteins based on bioinformatics analysis

Abstract Salt stress limits the growth and productivity of many plants. To further understand plant protein salt-response mechanisms, the proteins of model plant Arabidopisis thaliana was selected and mined based on bioinformatic analysis and experimental biology verification. With the features of salt-response, 292 of 10,835 reviewed Arabidopsis thaliana proteins were screened from Uniprot public proteins database. Among 292 salt-response proteins, 67, 71, and 54 proteins showed the cross-talk with cold, drought and heavy metal stress, respectively. Function classifications revealed the above four groups (292, 67, 71, and 54 proteins) were mainly associated with reactive oxygen species scavenging and defense, catalytic activity, signal transduction, and energy metabolism. Activities of superoxide dismutase and peroxidase in both Arabidopisis thaliana root and leaf were determined under salt (150mmol.L -1 NaCl), cold (10℃), drought (200mmol.L -1 mannitol), and heavy metal (10µmol.L -1 CdCl 2 ) stress. The experimental results were consistent with bioinformatic analysis. This work improves our knowledge of salt tolerance and provides clues to discover salt tolerance protein targets for plant growth and crop productivity

Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells

The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear. In this study, we reported the construction of the nuclear transport system, and we demonstrated that FN3R (three nuclear localization signals were fused to FRBT2098L with a FLAG tag), HF2S (two FKBP domains were in tandem and fused to the SH2 domain of Grb2 with an HA tag) and Bcr-Abl form a complexus upon AP21967. Bcr-Abl was imported into the nucleus successfully by the nuclear transport system. The nuclear transport system inhibited CML cell proliferation through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 5 (STAT5) pathways mainly by HF2S. It was proven that nuclear located Bcr-Abl induced CML cell (including imatinib-resistant K562G01 cells) apoptosis by activation of p73 and its downstream molecules. In summary, our study provides a new targeted therapy for the CML patients even with Tyrosine Kinase Inhibitor (TKI)-resistance

Real-World, Multicenter Case Series of Patients Treated with Isavuconazole for Invasive Fungal Disease in China

Background: The incidence of invasive fungal disease (IFD) has increased significantly, and IFD is a major cause of mortality among those with hematological malignancies. As a novel second-generation triazole antifungal drug offering both efficacy and safety, isavuconazole (ISA) is recommended by various guidelines internationally for the first-line treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM) infecting adults. Given that it was only approved in China at the end of 2021, there is currently a lack of statistical data regarding its usage in the Chinese population. The primary objective of this report is to describe early experiences with ISA for the treatment of IFD. Methods: This was a real-world, multicenter, observational case series study conducted in China. It included patients from three centers who received ISA treatment from January 2022 to April 2023. A retrospective assessment on patient characteristics, variables related to ISA administration, the treatment response of IFD to ISA, and potential adverse events attributed to ISA was conducted. Results: A total of 40 patients met the inclusion criteria. Among them, 12 (30%) were diagnosed with aspergillosis, 2 (5%) were diagnosed with candidiasis, 12 (30%) were diagnosed with mucormycosis, and 14 cases did not present mycological evidence. The predominant site of infection was the lungs (36), followed by the blood stream (8), sinuses (4), and respiratory tract (2). The overall response rate was 75% (30 patients), with male patients having a higher clinical response than female patients (24/24 versus 6/16, p = 0.000) and autologous stem cell transplant patients having a higher clinical response than allogeneic stem cell transplant patients (6/6 versus 4/10, p = 0.027). During the observation period, four patients experienced adverse effects associated with ISA, but none of them discontinued the treatment. Conclusions: Our findings suggest that ISA, a novel first-line treatment for IA and IM, is associated with a high clinical response rate, low incidence, and a low grade of adverse effects. Given the short time that ISA has been available in China, further research is needed to identify its efficacy and safety in the real world

Proteomic and phosphoproteomic analyses of NaCl stress-responsive proteins in <i>Arabidopsis</i> roots

<p>Salt is one of the major abiotic stresses limiting the productivity and the geographical distribution of crops. To gain a better understanding of NaCl stress responses in model plant <i>Arabidopsis</i> roots, the protein changes in the abundance (Coomassie Brilliant Blue R-350 stain) and phosphorylation (Pro-Q Diamond stain) were examined using two-dimensional electrophoresis coupled with mass spectrometry (MS). Seventeen unique proteins differentially changed in abundance, phosphorylation, or both in response to NaCl. Nonsynchronous differences were found between total proteins and phosphorylated proteins. Protein synthesis, proteolysis, post-translational modifications, and isoforms might cause the differential protein redundancies. The identified proteins are involved in binding, catalysis, signal transduction, transport, metabolisms of cell wall and energy, and reactive oxygen species (ROS) scavenging and defense. These protein changes provide new avenues of investigation into the underlying salt stress response in <i>Arabidopsis</i> roots and demonstrate the advantages of proteomic approach in plant biology studies.</p

Compressive Mechanical Properties and Shock-Induced Reaction Behavior of Zr/PTFE and Ti/PTFE Reactive Materials

Existing research on PTFE-based reactive materials (RMs) mostly focuses on Al/PTFE RMs. To explore further possibilities of formulation, the reactive metal components in the RMs can be replaced. In this paper, Zr/PTFE and Ti/PTFE RMs were prepared by cold isostatic pressing and vacuum sintering. The static and dynamic compressive mechanical properties of Zr/PTFE and Ti/PTFE RMs were investigated at different strain rates. The results show that the introduction of zirconium powder and titanium powder can increase the strength of the material under dynamic loading. Meanwhile, a modified J-C model considering strain and strain rate coupling was proposed. The parameters of the modified J-C model of Zr/PTFE and Ti/PTFE RMs were determined, which can describe and predict plastic flow stress. To characterize the impact-induced reaction behavior of Zr/PTFE and Ti/PTFE RMs, a quasi-sealed test chamber was used to measure the over-pressure induced by the exothermic reaction. The energy release characteristics of both materials were more intense under the higher impact