A direct approach to the evaluation of structural shakedown limit considering limited kinematic hardening and non-isothermal effect

This paper presents a novel direct method for the structural shakedown analysis considering limited kinematic hardening and non-isothermal effect. The Melan’s static shakedown theorem is extended to consider limited kinematic hardening material and implemented into the Linear Matching Method (LMM) shakedown module. Instead of using a specific kinematic hardening rule and an explicit back stress field, the general nonlinear hardening laws are considered by using a two-surface hardening model. A two-stage procedure is developed in the extended LMM algorithm, which can generate the limited hardening shakedown envelope and the unlimited hardening curve efficiently and accurately. Also, the material non-isothermal effect is considered during the computation process of the shakedown limit by proposing a temperature-dependent hardening factor, in place of a constant and fictitious one. To validate the extended LMM method, a numerical test on a thin cylinder pipe with temperature-independent material properties is performed, and the results match well with ones from literature. Then, a numerical study on a typical aero-engine turbine disk is conducted to investigate the influence of temperature-dependent material properties and operating conditions. Several shakedown curves considering kinematic hardening effect are derived and adequately discussed. As a result, the extended LMM shakedown module is proven to be a robust, efficient and versatile tool for practical industrial problems

MILP-Based Automatic Search Algorithms for Differential and Linear Trails for Speck

In recent years, Mixed Integer Linear Programming (MILP) has been successfully applied in searching for differential characteristics and linear approximations in block ciphers and has produced the significant results for some ciphers such as SIMON (a family of lightweight and hardware-optimized block ciphers designed by NSA) etc. However, in the literature, the MILP-based automatic search algorithm for differential characteristics and linear approximations is still infeasible for block ciphers such as ARX constructions. In this paper, we propose an MILP-based method for automatic search for differential characteristics and linear approximations in ARX ciphers. By researching the properties of differential characteristic and linear approximation of modular addition in ARX ciphers, we present a method to describe the differential characteristic and linear approximation with linear inequalities under the assumptions of independent inputs to the modular addition and independent rounds. We use this representation as an input to the publicly available MILP optimizer Gurobi to search for differential characteristics and linear approximations for ARX ciphers. As an illustration, we apply our method to Speck, a family of lightweight and software-optimized block ciphers designed by NSA, which results in the improved differential characteristics and linear approximations compared with the existing ones. Moreover, we provide the improved differential attacks on Speck48, Speck64, Speck96 and Speck128, which are the best attacks on them in terms of the number of rounds

hSef potentiates EGF-mediated MAPK signaling through affecting EGFR trafficking and degradation

Sef (similar expression to fgf genes) was identified as an effective antagonist of fibroblast growth factor (FGF) in vertebrates. Previous reports have demonstrated that Sef interacts with FGF receptors (FGFRs) and inhibits FGF signaling, however, its role in regulating epidermal growth factor receptor (EGFR) signaling remains unclear. In this report, we found that hSef localizes to the plasma membrane (PM) and is subjected to rapid internalization and well localizes in early/recycling endosomes while poorly in late endosomes/lysosomes. We observed that hSef interacts and functionally colocalizes with EGFR in early endosomes in response to EGF stimulation. Importantly, we demonstrated that overexpression of hSef attenuates EGFR degradation and potentiates EGF-mediated mitogen-activated protein kinase (MAPK) signaling by interfering EGFR trafficking. Finally, our data showed that, with overexpression of hSef, elevated levels of Erk phosphorylation and differentiation of rat pheochromocytoma (PC12) cells occur in response to EGF stimulation. Taken together, these data suggest that hSef plays a positive role in the EGFR-mediated MAPK signaling pathway. This report, for the first time, reveals opposite roles for Sef in EGF and FGF signalings

Silencing SARS-CoV Spike protein expression in cultured cells by RNA interference

AbstractThe severe acute respiratory syndrome (SARS) has been one of the most epidemic diseases threatening human health all over the world. Based on clinical studies, SARS-CoV (the SARS-associated coronavirus), a novel coronavirus, is reported as the pathogen responsible for the disease. To date, no effective and specific therapeutic method can be used to treat patients suffering from SARS-CoV infection. RNA interference (RNAi) is a process by which the introduced small interfering RNA (siRNA) could cause the degradation of mRNA with identical sequence specificity. The RNAi methodology has been used as a tool to silence genes in cultured cells and in animals. Recently, this technique was employed in anti-virus infections in human immunodeficiency virus and hepatitis C/B virus. In this study, RNAi technology has been applied to explore the possibility for prevention of SARS-CoV infection. We constructed specific siRNAs targeting the S gene in SARS-CoV. We demonstrated that the siRNAs could effectively and specifically inhibit gene expression of Spike protein in SARS-CoV-infected cells. Our study provided evidence that RNAi could be a tool for inhibition of SARS-CoV

Prognosis and Characterization of Immune Microenvironment in Acute Myeloid Leukemia Through Identification of an Autophagy-Related Signature

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has an unfavorable outcome and a high rate of relapse. Autophagy plays a vital role in the development of and therapeutic responses to leukemia. This study identifies a potential autophagy-related signature to monitor the prognoses of patients of AML. Transcriptomic profiles of AML patients (GSE37642) with the relevant clinical information were downloaded from Gene Expression Omnibus (GEO) as the training set while TCGA-AML and GSE12417 were used as validation cohorts. Univariate regression analyses and multivariate stepwise Cox regression analysis were respectively applied to identify the autophagy-related signature. The univariate Cox regression analysis identified 32 autophagy-related genes (ARGs) that were significantly associated with the overall survival (OS) of the patients, and were mainly rich in signaling pathways for autophagy, p53, AMPK, and TNF. A prognostic signature that comprised eight ARGs (BAG3, CALCOCO2, CAMKK2, CANX, DAPK1, P4HB, TSC2, and ULK1) and had good predictive capacity was established by LASSO–Cox stepwise regression analysis. High-risk patients were found to have significantly shorter OS than patients in low-risk group. The signature can be used as an independent prognostic predictor after adjusting for clinicopathological parameters, and was validated on two external AML sets. Differentially expressed genes analyzed in two groups were involved in inflammatory and immune signaling pathways. An analysis of tumor-infiltrating immune cells confirmed that high-risk patients had a strong immunosuppressive microenvironment. Potential druggable OS-related ARGs were then investigated through protein–drug interactions. This study provides a systematic analysis of ARGs and develops an OS-related prognostic predictor for AML patients. Further work is needed to verify its clinical utility and identify the underlying molecular mechanisms in AML

Salivary and fecal microbiota: potential new biomarkers for early screening of colorectal polyps

ObjectiveGut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of CRC-associated microbes. Multiple studies have identified gut and fecal microbiome-derived biomarkers for precursors lesions of CRC detection. However, few studies have used salivary samples to predict colorectal polyps. Therefore, in order to find new noninvasive colorectal polyp biomarkers, we searched into the differences in fecal and salivary microbiota between patients with colorectal polyps and healthy controls.MethodsIn this case–control study, we collected salivary and fecal samples from 33 patients with colorectal polyps (CP) and 22 healthy controls (HC) between May 2021 and November 2022. All samples were sequenced using full-length 16S rRNA sequencing and compared with the Nucleotide Sequence Database. The salivary and fecal microbiota signature of colorectal polyps was established by alpha and beta diversity, Linear discriminant analysis Effect Size (LEfSe) and random forest model analysis. In addition, the possibility of microbiota in identifying colorectal polyps was assessed by Receiver Operating Characteristic Curve (ROC).ResultsIn comparison to the HC group, the CP group’s microbial diversity increased in saliva and decreased in feces (p < 0.05), but there was no significantly difference in microbiota richness (p > 0.05). The principal coordinate analysis revealed significant differences in β-diversity of salivary and fecal microbiota between the CP and HC groups. Moreover, LEfSe analysis at the species level identified Porphyromonas gingivalis, Fusobacterium nucleatum, Leptotrichia wadei, Prevotella intermedia, and Megasphaera micronuciformis as the major contributors to the salivary microbiota, and Ruminococcus gnavus, Bacteroides ovatus, Parabacteroides distasonis, Citrobacter freundii, and Clostridium symbiosum to the fecal microbiota of patients with polyps. Salivary and fecal bacterial biomarkers showed Area Under ROC Curve of 0.8167 and 0.8051, respectively, which determined the potential of diagnostic markers in distinguishing patients with colorectal polyps from controls, and it increased to 0.8217 when salivary and fecal biomarkers were combined.ConclusionThe composition and diversity of the salivary and fecal microbiota were significantly different in colorectal polyp patients compared to healthy controls, with an increased abundance of harmful bacteria and a decreased abundance of beneficial bacteria. A promising non-invasive tool for the detection of colorectal polyps can be provided by potential biomarkers based on the microbiota of the saliva and feces

Effects of Aging Method and Time on Meat Quality of High-grade Fattening Angus Beef

This study was conducted to explore the aging technology of high-grade beef, a total of 12 high-grade fattening Angus longissimus dorsi were selected and aged in dry or wet environment for 3, 5 and 7 d, and the meat basic physicochemical indexes, free amino acids and volatile flavor compounds were compared and analyzed. The results showed that the pH of beef with dry-aging for 3 and 5 days was significantly lower than that with wet-aging, the pH of beef with dry-aging for 7 d was significantly higher than that with wet-aging (P<0.05). The share force of beef with dry-aging for 3 d was significantly lower than that with wet-aging (P<0.05). The contents of serine, valine, methionine, isoleucine, tyrosine, leucine, phenylalanine, arginine, lysine, total sweet free amino acids, total bitter free amino acids and total free amino acids of beef with both dry-aging and wet-aging for 7 d were significantly higher than those for 3 and 5 days (P<0.05). The contents of aspartic acid, glutamic acid, alanine and total umami free amino acids of beef with dry-aging for 7 d were significantly higher than those with wet-aging (P<0.05). The nonanal, octanal and octenol were key volatile flavor compounds in both dry-aging and wet-aging beef according to the relative odor activity value, and heptanal was the volatile flavor compounds only existed in beef with wet-aging, the octanal, phenylethanal, undecanal, tetradecyl aldehyde and limonene of beef with dry-aging for 7 d was significantly higher than those with wet-aging (P<0.05). In conclusion, beef with aging for 7 d is beneficial to enhance flavor richness of Angus beef, and dry-aging is better than wet-aging to improve the flavor of high-grade Angus beef

Auditor of State Mary Mosiman today released a reaudit report on the Mason City Community School District (District) for the period July 1, 2014 through June 30, 2015. The reaudit also covered items applicable to the years ended June 30, 2016 and June 30, 2017.

Auditor of State Mary Mosiman today released a reaudit report on the Mason City Community School District (District) for the period July 1, 2014 through June 30, 2015. The reaudit also covered items applicable to the years ended June 30, 2016 and June 30, 2017