Proposing a Revised Pedestrian Walkway Level of Service Based on Characteristics of Pedestrian Interactive Behaviours in China

The objective of this study is to analyse characteristics of Pedestrian Interactive Behaviours (PIBs) in order to propose a revised pedestrian walkway Level of Service (LOS) in China. Field data on overtaking and evasive behaviours were collected at a metro station walkway in Shanghai, China to calculate macro and micro indicators. Occurrence intensities of these two PIBs initially increased with moderate density and later decreased with high density that reduced available space. PIBs were also analysed in terms of sideways behaviours to account for the varying difficulties of PIBs at different densities. It was found that available space for PIBs was the main factor contributing to the intensity features. Moreover, the different space demands of the two PIBs resulted in different features between them. Finally, a revised pedestrian walkway LOS was proposed based on the macro and micro characteristics of PIBs in China.</p

Analysis of pig serum proteins based on shotgun liquid chromatography-tandem mass spectrometry

Recent advances in proteomics technologies have opened up significant opportunities for future applications. We used shotgun liquid chromatography, coupled with tandem mass spectrometry (LC-MS/MS) to determine the proteome profile of healthy pig serum. Samples of venous blood were collected and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis separation and in-gel trypsin digestion. The peptides were then processed using shotgun LC-MS/MS. Serum proteins were subjected to protein identification and bioinformatics analysis. A total of 392 proteins were identified, and 179 were annotated according to their molecular functions and biological processes, excluding 142 hypothetical proteins and 71 immune globulins. To the best of our knowledge, this represents the first porcine serum proteomics analysis based on shotgun LC-MS/MS. This method and the resulting proteomics information may prove valuable for ensuring good animal welfare practice and for monitoring swine health and disease status.Keywords: Analysis, pig serum, shotgun coupled with tandem mass spectrometry (LC-MS/MS

Investigation of nonlinear wave-induced seabed response around mono-pile foundation

YesStability and safety of offshore wind turbines with mono-pile foundations, affected by nonlinear wave effect and dynamic seabed response, are the primary concerns in offshore foundation design. In order to address these problems, the nonlinear wave effect on dynamic seabed response in the vicinity of mono-pile foundation is investigated using an integrated model, developed using OpenFOAM, which incorporates both wave model (waves2Foam) and Biot’s poro-elastic model. The present model was validated against several laboratory experiments and promising agreements were obtained. Special attention was paid to the systematic analysis of pore water pressure as well as the momentary liquefaction in the proximity of mono-pile induced by nonlinear wave effects. Various embedment depths of mono-pile relevant for practical engineering design were studied in order to attain the insights into nonlinear wave effect around and underneath the mono-pile foundation. By comparing time-series of water surface elevation, inline force, and wave-induced pore water pressure at the front, lateral, and lee side of mono-pile, the distinct nonlinear wave effect on pore water pressure was shown. Simulated results confirmed that the presence of mono-pile foundation in a porous seabed had evident blocking effect on the vertical and horizontal development of pore water pressure. Increasing embedment depth enhances the blockage of vertical pore pressure development and hence results in somewhat reduced momentary liquefaction depth of the soil around the mono-pile foundation.Energy Technology Partnership (ETP), Wood Group Kenny, and University of Aberdeen; the National Science Fund for Distinguished Young Scholars (51425901) and the 111 project (B12032)

Melatonin Mitigates Salt Stress in Wheat Seedlings by Modulating Polyamine Metabolism

Melatonin, a small molecular weight indoleamine molecule, is involved in various biological processes and responses to environmental cues in plants. However, its function in abiotic stress response and the underlying mechanisms is less clear. In this study, we investigated the effect of melatonin on wheat seedlings growth under salt stress condition. Exogenous melatonin pretreatment partially mitigated the salt-induced inhibition of whole-plant growth as judged from shoot dry weight, IAA content, leaf photosynthesis rate, maximum photochemistry efficiency of photosystem II, and chlorophyll. The mitigation was also observed in reduced accumulation of H2O2 in melatonin-pretreated wheat seedlings exposed to salt stress. Exogenous melatonin increased endogenous melatonin content by evaluating the levels of TaSNAT transcript, which encodes a key regulatory enzyme in the melatonin biosynthetic pathway. Furthermore, melatonin increased polyamine contents by accelerating the metabolic flow from the precursor amino acids arginine and methionine to polyamines; melatonin also decreased the degradation of salt-induced polyamines. Taken together, these results provide the evidence that melatonin mitigates salt stress mainly through its regulation on polyamine metabolism of wheat seedlings

Prognosis for patients with apical hypertrophic cardiomyopathy: A multicenter cohort study based on propensity score matching

Background: Apical hypertrophic cardiomyopathy (AHCM) is a subtype of HCM, and few studies on the prognosis in AHCM are available.Aims: This study aimed to explore the clinical prognosis for AHCM and non-AHCM patients through clinical data based on propensity score matching (PSM) in a large cohort of Chinese HCM patients.Methods: The cohort study included 2268 HCM patients, 226 AHCM and 2042 non-AHCM patients from 13 tertiary hospitals, who were treated between 1996 and 2021. Fifteen demographic and clinical variables of 226 AHCM patients and 2042 non-AHCM patients were matched using 1:2 PSM. A Cox proportional hazard regression model was constructed to assess the effect of AHCM on mortality.Results: During a median follow-up of 5.1 (2.4–8.4) years, 353 (15.6%) of the 2268 HCM patients died, of whom 205 died due to cardiovascular mortality/cardiac transplantation and 94 experienced sudden cardiac death (SCD). In the matched cohort, the ACHM patients had lower rates of all-cause mortality (P = 0.003), cardiovascular mortality/cardiac transplantation (P = 0.03), and SCD (P = 0.02) than the non-AHCM patients. Furthermore, the Cox proportional hazard regression model showed that AHCM was an independent prognostic predictor of all-cause HCM mortality (P = 0.004) and a univariable prognostic predictor of cardiovascular mortality/cardiac transplantation (P = 0.03) and for SCD (P = 0.03). However, AHCM was not significant in multivariable Cox regression models in relation to cardiovascular mortality/cardiac transplantation and SCD.Conclusion: AHCM had a favorable prognosis both before and after matching, with lower all-cause mortality, cardiovascular mortality/cardiac transplantation, and SCD than non-AHCM

Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2

Activation of the transient receptor potential melastatin 2 (TRPM2) channel occurs during the response to oxidative stress under physiological conditions as well as in pathological processes such as ischemia and diabetes. Accumulating evidence indicates that adenosine diphosphate ribose (ADPR) is the most important endogenous ligand of TRPM2. However, although it is known that ADPR binds to the NUDT9 homology (NUDT9-H) domain in the intracellular C-terminal region, the molecular mechanism underlying ADPR binding and activation of TRPM2 remains unknown. In this study, we generate a structural model of the NUDT9-H domain and identify the binding pocket for ADPR using induced docking and molecular dynamics simulation. We find a subset of 11 residues—H1346, T1347, T1349, L1379, G1389, S1391, E1409, D1431, R1433, L1484, and H1488—that are most likely to directly interact with ADPR. Results from mutagenesis and electrophysiology approaches support the predicted binding mechanism, indicating that ADPR binds tightly to the NUDT9-H domain, and suggest that the most significant interactions are the van der Waals forces with S1391 and L1484, polar solvation interaction with E1409, and electronic interactions (including π–π interactions) with H1346, T1347, Y1349, D1431, and H1488. These findings not only clarify the roles of a range of newly identified residues involved in ADPR binding in the TRPM2 channel, but also reveal the binding pocket for ADPR in the NUDT9-H domain, which should facilitate structure-based drug design for the TRPM2 channel

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN