The elastic modulus, shear modulus, and Poisson’s ratio of timber are the elastic constants characterizing its material properties. In this paper, the transient excitation method was used to ...dynamically measure the 10 elastic constants of the falling larch wood under the condition of the free board and cantilever board, that is, 3 elastic moduli E, 3 shear moduli G, and 4 Poisson’s ratios μ. The other two Poisson’s ratios μ were derived using the principle of orthogonality. At the same time, the elastic modulus, shear modulus, and Poisson’s ratio under static conditions were tested and verified by symmetrical four-point bending, asymmetrical four-point bending, and tensile methods. This study is expected to have good application value and practical significance for timber as an engineering structural material, which is widely used in architecture, decoration, furniture, transportation, musical instruments, and in other fields.
Physical fatigue is frequent for heavy manual laborers like construction workers, but it causes distraction and may lead to safety incidents. The purpose of this study is to develop predictive models ...for monitoring construction workers’ inattention caused by physical fatigue utilizing electrocardiograph (ECG) and galvanic skin response (GSR) sensors. Thirty participants were invited to complete an attention-demanding task under non-fatigued and physically fatigued conditions. Supervised learning algorithms were utilized to develop models predicting their attentional states, with heart rate variability (HRV) features derived from ECG signals and skin electric activity features derived from GSR signals as data inputs. The results demonstrate that using HRV features alone could obtain a prediction accuracy of 88.33%, and using GSR features alone could achieve an accuracy of 76.67%, both through the KNN algorithm. The accuracy increased to 96.67% through the SVM algorithm when combining HRV and GSR features. The findings indicate that ECG sensors used alone or in combination with GSR sensors can be applied to monitor construction workers’ inattention on job sites. The findings would provide an approach for detecting distracted workers at job sites. Additionally, it might reveal the relationships between workers’ physiological features and attention.
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Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most aggressive solid tumours in humans. Despite its high mortality rate, effective targeted therapeutic strategies ...remain limited due to incomplete understanding of the underlying biological mechanisms. The NAP1L gene family has been implicated in the development and progression of various human tumours. However, the specific function and role of NAP1L5 (nucleosome assembly protein-like 5) in PDAC have not been fully elucidated. Therefore, in this study, we aimed to investigate the role of NAP1L5 in PDAC and explore the regulatory relationship between NAP1L5 and its potential downstream molecule PHLPP1 (PH domain Leucine-rich repeat Protein Phosphatase 1) in PDAC. Our study revealed that NAP1L5 is notably upregulated in PDAC. Moreover, both in vivo and in vitro experiments demonstrated that knockdown of NAP1L5 suppressed the proliferation of PDAC cells. Mechanistically, NAP1L5 was found to promote PDAC progression by activating the AKT/mTOR signalling pathway in a PHLPP1-dependent manner. Specifically, NAP1L5 binds to PHLPP1 and facilitates the ubiquitination-mediated degradation of PHLPP1, ultimately resulting in reduced PHLPP1 expression. Notably, TRIM29, recruited by NAP1L5, was found to be involved in facilitating K48-linked ubiquitination of PHLPP1. Our findings indicate that NAP1L5 overexpression promotes the proliferation of PDAC cells by inhibiting PHLPP1 expression. These novel insights suggest that NAP1L5 may serve as a potential therapeutic target for PDAC.
Detecting xylene gas is an important means of avoiding human harm from gas poisoning. A precise measurement demands that the gas sensor used must have high sensitivity, high selectivity, and low ...working temperature. To meet these requirements, in this study, Sn2+-doped NiO flower-like microspheres (SNM) with different amounts of Sn2+ synthesized by a one-step hydrothermal process were investigated. The responses of gas sensors based on different Sn2+-doped NiO materials for various targeting gases were fully characterized. It was found that all of the synthesized materials exhibited the best gas response at a working temperature of 180 degrees, which was much lower than the previously reported working temperature range of 300–500 degrees. When exposed to 10 ppm xylene, the 8 at% Sn2+-doped NiO sensor (mol ratio) exhibited the highest response, with a value of 30 (Rg/Ra). More significantly, the detection limit of the 8 at% Sn2+-doped NiO sensor for xylene is down in the ppb level. The Sn2+-doped NiO material also exhibits excellent selectivity for other gases with long-term stability and repeatability. The significant improvement in the response to xylene can theoretically be attributed to a decrease in the intrinsic hole carrier concentration, higher amounts of adsorbed oxygen and active sites.
In order to strengthen the seismic design and diagnosis of glulam building structures, and improve the accuracy and reliability of building modal analysis, this paper uses the designed glulam frame ...structure as a research object to conduct experimental investigation on its dynamic properties. On the one hand, a computational modal analysis is carried out using ANSYS to determine the modal shapes and modal parameters of the glulam frame structure. On the other hand, transient excitation, steady-state contact excitation and steady-state non-contact excitation methods are used to test and analyze the experimental modalities of the field-built larch glulam frame structure. The research results show that the three experimental modal methods can all measure the biaxial(xy-) first-order bending, first-order torsion, and second-order bending modes of the glulam frame structure. The vibration shapes and modal frequencies are all consistent. The results of computational modal analysis and experimental modal analysis are combined in this article. Since the elastic constant input of components is measured by grading, the frequency values of the computational mode are larger. The error of the two analyses is about 15%. In the first-order bending mode in the x- and y-directions, both the computational and experimental modes show the characteristics of greater local stiffness in the gusset. In the uniaxial (x- or y-) torsional mode, the computational mode not only reflects the torsional characteristics of the upper beam region, but also shows first-order bending mode of the column, which is also consistent with the experimental mode.
Herein, we describe the clinical and hematological features of three genetically related families predisposed to myeloproliferative neoplasms (MPNs). Using whole-exome sequencing, we identified a ...c.1367delG mutation(p.Arg456fs) in CHST15 (NM_001270764), a gene encoding a type II transmembraneglycoproteinthat acts as a sulfotransferase and participates in the biosynthesis of chondroitin sulfate E, in germline and somatic cells in familial MPN. CHST15defects caused an increased JAK2V617F allele burden and upregulated p-Stat3 activity,leading to an increase in the proliferative and prodifferentiation potential of transgenic HEL cells. We demonstrated that mutant CHST15 is able to coimmmunoprecipitate the JAK2 protein,suggesting the presence of a CHST15-JAK2-Stat3 signaling axis in familial MPN. Gene expression profiling showed that the FREM1, IFI27 and C4B_2 genes are overexpressed in familial MPN, suggesting the activation of an "inflammatory response-extracellular matrix-immune regulation" signaling network in the CHST15 mutation background.We thus concluded that CHST15 is a novel gene that predisposes to familial MPN and increases the probability of disease development or transformation.
BRD4, an epigenetic regulator that recognizes and binds the acetylated lysine residues in histone, has been reported as a potential therapeutic target for cancers. Since the first BRD4 inhibitor JQ1 ...developed in 2010, numerous BRD4 inhibitors have been discovered in past five years. In this review, we have systematically summarized a series of BRD4 binding compounds, which are divided into five categories based on the similarity of their chemical structures and respectively referred as JQ1 derivatives, tetrahydroquinoline derivatives, 3,5- dimethylisoxazole derivatives, 2-thiazolidinone derivatives and others. The binding affinities for each class of compounds are also discussed.
Colorectal cancer (CRC) is the fourth most common cancer worldwide, with high morbidity and mortality rates. In recent years, high-fat diet has been shown to increase CRC morbidity, highlighting the ...possibility of the application of hypolipidemic drugs for CRC treatment. In this study, we preliminarily evaluated the effects and mechnisms of ezetimibe against CRC through the blockage of lipid absorption in small intesine.
In this study, CRC cell proliferation, invasion, apoptosis, and autophagy were evaluated using cellular and molecular assays. Fluorescent microscopy, and a flow cytometric assay were used to assess mitochondrial activity
. A subcutaneous xenograft mouse model was used to evaluate the effects of ezetimibe
.
We found that ezetimibe inhibited CRC cell proliferation, and migration, and facilitated autophage-associated apoptosis in HCT116 and Caco2 cells. Ezetimibe-induced mitochondrial dysfunction in CRC cells was found to be correlated with mTOR signaling activity.
Ezetimibe exhibits effects against CRC through the promotion of cancer cell death
mTOR signaling-dependent mitochondrial dysfunction, highlighting its potential value in CRC therapy.
Abstract
Identifying the exact epitope positions for a monoclonal antibody (mAb) is of critical importance yet highly challenging to the Ab design of biomedical research. Based on previous versions ...of SEPPA 3.0, we present SEPPA-mAb for the above purpose with high accuracy and low false positive rate (FPR), suitable for both experimental and modelled structures. In practice, SEPPA-mAb appended a fingerprints-based patch model to SEPPA 3.0, considering the structural and physic-chemical complementarity between a possible epitope patch and the complementarity-determining region of mAb and trained on 860 representative antigen-antibody complexes. On independent testing of 193 antigen-antibody pairs, SEPPA-mAb achieved an accuracy of 0.873 with an FPR of 0.097 in classifying epitope and non-epitope residues under the default threshold, while docking-based methods gave the best AUC of 0.691, and the top epitope prediction tool gave AUC of 0.730 with balanced accuracy of 0.635. A study on 36 independent HIV glycoproteins displayed a high accuracy of 0.918 and a low FPR of 0.058. Further testing illustrated outstanding robustness on new antigens and modelled antibodies. Being the first online tool predicting mAb-specific epitopes, SEPPA-mAb may help to discover new epitopes and design better mAbs for therapeutic and diagnostic purposes. SEPPA-mAb can be accessed at http://www.badd-cao.net/seppa-mab/.
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