Efficient Algorithms for Load Shuffling in Split-Platform AS/RS

We address the issue of shuffling loads in Automated Storage/Retrieval Systems (AS/RS) in this paper. The objective is to pre-sort the loads into any specified locations in order to minimize the response time of retrievals. 1D, 2D and 3D AS/RS racks have been designed in order to achieve the shuffling efficiently. The shuffling algorithms are described in detail. The response time of retrieval, the lower and upper bounds of energy consumption are also derived. Results of the analysis and numerical experiments show that the shuffling algorithms are quite efficient.Singapore-MIT Alliance (SMA

A Cell-Based Assay for RNA Synthesis by the HCV Polymerase Reveals New Insights on Mechanism of Polymerase Inhibitors and Modulation by NS5A

RNA synthesis by the genotype 1b hepatitis C virus (HCV) polymerase (NS5B) transiently expressed in Human embryonic kidney 293T cells or liver hepatocytes was found to robustly stimulate RIG-I-dependent luciferase production from the interferon β promoter in the absence of exogenously provided ligand. This cell-based assay, henceforth named the 5BR assay, could be used to examine HCV polymerase activity in the absence of other HCV proteins. Mutations that decreased de novo initiated RNA synthesis in biochemical assays decreased activation of RIG-I signaling. In addition, NS5B that lacks the C-terminal transmembrane helix but remains competent for RNA synthesis could activate RIG-I signaling. The addition of cyclosporine A to the cells reduced luciferase levels without affecting agonist-induced RIG-I signaling. Furthermore, non-nucleoside inhibitor benzothiadiazines (BTDs) that bind within the template channel of the 1b NS5B were found to inhibit the readout from the 5BR assay. Mutation M414T in NS5B that rendered the HCV replicon resistant to BTD was also resistant to BTDs in the 5BR assay. Co-expression of the HCV NS5A protein along with NS5B and RIG-I was found to inhibit the readout from the 5BR assay. The inhibition by NS5A was decreased with the removal of the transmembrane helix in NS5B. Lastly, NS5B from all six major HCV genotypes showed robust activation of RIG-I in the 5BR assay. In summary, the 5BR assay could be used to validate inhibitors of the HCV polymerase as well as to elucidate requirements for HCV-dependent RNA synthesis

Mental health of Chinese people during the COVID-19 pandemic: associations with infection severity of region of residence and filial piety

This study aims to investigate mental health among Chinese people living in areas with differing levels of infection severity during the COVID-19 outbreak. It also assesses the association between reciprocal and authoritarian filial piety and mental health in times of crises. A sample of 1,201 Chinese participants was surveyed between April and June 2020. Wuhan city (where 23.4% of participants resided), Hubei province outside Wuhan (13.4% of participants), and elsewhere in China (63.1% of participants) were categorized into high, moderate, and low infection severity areas, respectively. The Depression, Anxiety, and Stress Scale’s severity cut-points were used to categorize participants. In the overall sample, 20.9, 34.2, and 29.0% of the participants showed elevated (mild to extremely severe) levels of stress, anxiety, and depression. Those in the highest infection severity group were significantly more likely to be categorized as having elevated levels of stress, anxiety, and depression. General linear modeling was performed on a composite mental distress variable (taking into account stress, anxiety, and depression scores). This model indicated that, even after adjusting for group differences in age, gender, education, and filial piety, the high infection severity group displayed more mental distress than the low infection severity groups. The model also found reciprocal filial piety to have a negative association with mental distress. Conversely, authoritarian filial piety was found to be unrelated to mental distress when controlling for the other variables in the model. No evidence was found for an interaction between either authoritarian or reciprocal filial piety and infection severity, which suggests that the negative association observed between reciprocal filial piety and mental distress was relatively consistent across the three infection severity groups. The findings suggest that future public health programs may integrate the promotion of filial piety as a strategy to help Chinese people maintain good mental health in the face of pandemic crises

The relationship between mindfulness and mental distress in Chinese people during the COVID-19 pandemic: Moderating effects of infection severity of region and mediating effects of resilience and self-efficacy

The current study investigated the moderating effects of COVD-19 infection severity of region of residence, and the mediating effects of resilience and self-efficacy, on the relationship between mindfulness and mental distress during the COVID-19 pandemic. A total of 1,220 participants from 107 cities in China took part in a cross-sectional survey. The data were collected during the early stages of the COVID-19 pandemic (from April 10 to June 10, 2020). The final sample comprised of 1,201 participants with a mean age of 29.62 (SD = 12.72; Range = 18–78). Participants were categorized into high, moderate, and low infection-severity areas according to the numbers of infected people and deaths in their residential areas as of April 16, 2020. The findings showed that mindfulness, resilience, and self-efficacy were negatively associated with the mental distress indicators of stress, anxiety, and depression and that mindfulness, resilience, and self-efficacy positively correlated to one another. COVID-19 infection severity in one's region of residence did not moderate the negative associations between mindfulness and stress, anxiety and depression, while resilience and self-efficacy mediated the negative relationship between mindfulness and mental distress. This study therefore sheds light on some of the mechanisms by which mindfulness helps individuals maintain good mental health in times of adversity. The inclusion of mindfulness, resilience, and self-efficacy in the design and implementation of mental health intervention in response to the pandemic and future public health crisis may help mitigate some of the mental problems related to the COVID-19 and future pandemics

LL37 and Cationic Peptides Enhance TLR3 Signaling by Viral Double-stranded RNAs

BACKGROUND:Toll-like Receptor 3 (TLR3) detects viral dsRNA during viral infection. However, most natural viral dsRNAs are poor activators of TLR3 in cell-based systems, leading us to hypothesize that TLR3 needs additional factors to be activated by viral dsRNAs. The anti-microbial peptide LL37 is the only known human member of the cathelicidin family of anti-microbial peptides. LL37 complexes with bacterial lipopolysaccharide (LPS) to prevent activation of TLR4, binds to ssDNA to modulate TLR9 and ssRNA to modulate TLR7 and 8. It synergizes with TLR2/1, TLR3 and TLR5 agonists to increase IL8 and IL6 production. This work seeks to determine whether LL37 enhances viral dsRNA recognition by TLR3. METHODOLOGY/PRINCIPAL FINDINGS:Using a human bronchial epithelial cell line (BEAS2B) and human embryonic kidney cells (HEK 293T) transiently transfected with TLR3, we found that LL37 enhanced poly(I:C)-induced TLR3 signaling and enabled the recognition of viral dsRNAs by TLR3. The presence of LL37 also increased the cytokine response to rhinovirus infection in BEAS2B cells and in activated human peripheral blood mononuclear cells. Confocal microscopy determined that LL37 could co-localize with TLR3. Electron microscopy showed that LL37 and poly(I:C) individually formed globular structures, but a complex of the two formed filamentous structures. To separate the effects of LL37 on TLR3 and TLR4, other peptides that bind RNA and transport the complex into cells were tested and found to activate TLR3 signaling in response to dsRNAs, but had no effect on TLR4 signaling. This is the first demonstration that LL37 and other RNA-binding peptides with cell penetrating motifs can activate TLR3 signaling and facilitate the recognition of viral ligands. CONCLUSIONS/SIGNIFICANCE:LL37 and several cell-penetrating peptides can enhance signaling by TLR3 and enable TLR3 to respond to viral dsRNA

22.運動負荷時の血小板機能とヘモレオロジー(第636回千葉医学会例会・第3回千葉大学第三内科懇話会)

Additional file 2. Changes of residual nitrate concentration during the experiments

Regulation of the hepatitis C virus RNA replicase by endogenous lipid peroxidation

Although oxidative tissue injury often accompanies viral infection, there is little understanding of how it influences virus replication. We show that multiple hepatitis C virus (HCV) genotypes are exquisitely sensitive to oxidative membrane damage, a property distinguishing them from other pathogenic RNA viruses. Lipid peroxidation, regulated in part through sphingosine kinase 2, severely restricts HCV replication in Huh-7 cells and primary human hepatoblasts. Endogenous oxidative membrane damage lowers the 50% effective concentration of direct-acting antivirals, suggesting critical regulation of the conformation of the NS3/4A protease and NS5B polymerase, membrane-bound HCV replicase components. Resistance to lipid peroxidation maps genetically to trans-membrane and membrane-proximal residues within these proteins, and is essential for robust replication in cell culture, as exemplified by the atypical JFH1 strain. Thus, the typical, wild-type HCV replicase is uniquely regulated by lipid peroxidation, providing a novel mechanism for attenuating replication in stressed tissue and possibly facilitating long-term viral persistence