Static friction between rigid fractal surfaces

Using spheropolygon-based simulations and contact slope analysis, we investigate the effects of surface topography and atomic scale friction on the macroscopically observed friction between rigid blocks with fractal surface structures. From our mathematical derivation, the angle of macroscopic friction is the result of the sum of the angle of atomic friction and the slope angle between the contact surfaces. The latter is obtained from the determination of all possible contact slopes between the two surface profiles through an alternative signature function. Our theory is validated through numerical simulations of spheropolygons with fractal Koch surfaces and is applied to the description of frictional properties of Weierstrass-Mandelbrot surfaces. The agreement between simulations and theory suggests that for interpreting macroscopic frictional behavior, the descriptors of surface morphology should be defined from the signature function rather than from the slopes of the contacting surfaces.Civil Engineering Research Development Scheme provided by the School of Civil Engineering at The University of Sydney

Mets-IR as a predictor of cardiovascular events in the middle-aged and elderly population and mediator role of blood lipids

BackgroundCardiovascular disease (CVD) is a global health concern, with a significant impact on morbidity and mortality rates. Using fasting glucose, fasting triglycerides, body mass index (BMI), and high-density lipoprotein cholesterol (HDL-C), the metabolic score of insulin resistance (Mets-IR), a novel index created by Mexican researchers to assess insulin sensitivity, is a more precise way to measure insulin sensitivity. This study aimes to explore the association between Mets-IR and CVD, as well as investigate the potential mediating role of of low-density lipoprotein cholesterol (LDL-C).MethodsThe study’s data came from the 2011 and 2018 China Health and Retirement Longitudinal Studies (CHARLS). We used three logistic regression models to account for the potential effects of ten factors on cardiovascular disease/stroke/heart disease. Moreover, We performed mediation analyses to evaluate the role of LDL-C in the association between Mets-IR and incident CVD.ResultsThis study comprised 4,540 participants, of whom 494 (10.88%) were found to develop disease (CVD). Each interquartile range (IQR) increased in Mets-IR raised the risk of developing CVD by 38% (OR=1.38; 95% CI, 1.21-1.56) and there was a linear dose-response relationship between Mets-IR and the risk of new-onset cardiovascular disease, stroke, and heart disease (Poverall<0.05, Pnon-linear>0.05). Approximately 5% (indirect effect/total effect) of the significant association of Mets-IR with stroke was mediated by LDL-C, respectively. With the addition of Mets-IR to the base model, the continuous net reclassification improvement and integrated discrimination improvement for predicting cardiovascular disease increased by 0.175 (P <0.001) and 0.006 (P <0.001), respectively.Conclusionets-IR is associated with an increased risk of cardiovascular disease/stroke/cardiac issues, with LDL-C mediating these relationships. Improving insulin sensitivity and lipid regulation may be essential and effective preventive measures for cardiovascular events

Constant-pH simulations with the polarizable atomic multipole AMOEBA force field

Accurately predicting protein behavior across diverse pH environments remains a significant challenge in biomolecular simulations. Existing constant-pH molecular dynamics (CpHMD) algorithms are limited to fixed-charge force fields, hindering their application to biomolecular systems described by permanent atomic multipoles or induced dipoles. This work overcomes these limitations by introducing the first polarizable CpHMD algorithm in the context of the Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) force field. Additionally, our implementation in the open-source Force Field X (FFX) software has the unique ability to handle titration state changes for crystalline systems including flexible support for all 230 space groups. The evaluation of constant-pH molecular dynamics (CpHMD) with the AMOEBA force field was performed on 11 crystalline peptide systems that span the titrating amino acids (Asp, Glu, His, Lys, and Cys). Titration states were correctly predicted for 15 out of the 16 amino acids present in the 11 systems, including for the coordination of Z

Biomimetic Metal-Organic Nanoparticles Prepared with a 3D-Printed Microfluidic Device as a Novel Formulation for Disulfiram-Based Therapy Against Breast Cancer

Disulfiram (DSF) is currently tested in several clinical trials for cancer treatment in combination with cop-per (Cu) ions. Usually, DSF and Cu are administered in two separate formulations. In the body, DSF andCu ions form diethyldithiocarbamate copper complex [Cu(DDC)2] which has potent antitumor activities.However, the “two formulation” approach often achieved low Cu(DDC)2 concentration at tumor regions and resulted in compromised anticancer efficacy. Therefore, preformed Cu(DDC)2 complex administered in a single formulation will have better anticancer efficacy. However, the poor aqueous solubility of Cu(DDC)2 is a significant challenge for its clinical use. In this work, a biomimetic nanoparticle formulation of Cu(DDC)2 was produced with a novel SMILE (Stabilized Metal Ion Ligand complex) method developed in our laboratory to address the drug delivery challenges. The Metal-organic Nanoparticle (MON) is composed of Cu(DDC)2 metal-organic complex core and surface decorated bovine serum albumin (BSA). Importantly, we designed a 3D-printed microfluidic device to further improve the fabrication of BSA/Cu(DDC)2 MONs. This method could precisely control the MON preparation process and also has great potential for large scale production of Cu(DDC)2 MON formulations. We also used a computational modeling approach to simulate the MON formation process in the microfluidic device. The optimized BSA/Cu(DDC)2 MONs demonstrated good physicochemical properties. The MONs also showed potent antitumor activities in the breast cancer cell monolayers as well as the 3D-cultured tumor spheroids. The BSA/Cu(DDC)2 MONs also effectively inhibited the growth of tumors in an orthotopic 4T1 breast tumor model. This current study provided a novel method to prepare a biomimetic MON formulation for DSF/Cu cancer therapy .© 2019 Elsevier Ltd. All rights reserved