关键词： Finite elements   Multiscale mechanical problems   Geometrical and physical nonlinearity  

摘要： In this study, we present an alternative finite element to multiscale analysis. In this strategy, strain energy comes only from semi-discrete or lattice elements immersed in a continuum without stiffness, enabling mechanical analysis from molecular scales to macroscopic scales. Some characteristics of the proposed element are: (1) geometrically non-linear exact description that allows the presence of large displacements and large strain, (2) general mapping that allows curved and distorted elements generation with automatic immersions, (3) total compatibility with standard finite elements, and (4) huge degrees of freedom reduction with a small loss of continuum mobility. Throughout the text, the proposed strategy is presented in detail and applied in the determination of suitable meshes for any scale of analysis, which is an important information for future applications. To be direct, a Lennard-Jones-like (LJL) potential is chosen to build different crystalline-like structures that, when immersed in finite elements without stiffness, results in the desired continuous behavior. In this sense, some space of the paper is used to determine the energy constant of the LJL potential for these different "crystalline" structures at any scale. Taking advantage of the total compatibility of the proposed element with continuum elements, the multiscale strategy is straightforward applied. Selected examples are used to demonstrate the good behavior of the proposed element and its applicability. Future developments to enhance applications are commented at the conclusion section.

关键词： Adaptor protein   alternative translation start site   CpG DNA   macrophage   protein translation   Toll-like receptor  

摘要： Toll-like receptor (TLR) signaling relies on Toll/interleukin-1 receptor homology (TIR) domain-containing adaptor proteins that recruit downstream signaling molecules to generate tailored immune responses. In addition, the palmitoylated transmembrane adaptor protein family member Scimp acts as a non-TIR-containing adaptor protein in macrophages, scaffolding the Src family kinase Lyn to enable TLR phosphorylation and proinflammatory signaling responses. Here we report the existence of a smaller, naturally occurring translational variant of Scimp (Scimp TV1), which is generated through leaky scanning and translation at a downstream methionine. Scimp TV1 also scaffolds Lyn, but in contrast to full-length Scimp, it is basally rather than lipopolysaccharide (LPS)-inducibly phosphorylated. Macrophages from mice that selectively express Scimp TV1, but not full-length Scimp, have impaired sustained LPS-inducible cytokine responses. Furthermore, in granulocyte macrophage colony-stimulating factor-derived myeloid cells that express high levels of Scimp, selective overexpression of Scimp TV1 enhances CpG DNA-inducible cytokine production. Unlike full-length Scimp that localizes to the cell surface and filopodia, Scimp TV1 accumulates in intracellular compartments, particularly the Golgi. Moreover, this variant of Scimp is not inducibly phosphorylated in response to CpG DNA, suggesting that it may act via an indirect mechanism to enhance TLR9 responses. Our findings thus reveal the use of alternative translation start sites as a previously unrecognized mechanism for diversifying TLR responses in the innate immune system.

关键词： Immunology   Biomedicine   general  

关键词： MRSA   bacteremia   susceptibility testing   vancomycin   MIC  

摘要： Objectives: Variability in minimum inhibitory concentration (MIC) with automated susceptibility testing instruments may influence methicillin-resistant Staphylococcus aureus (MRSA) treatment. The purpose of this study was to evaluate the difference in vancomycin MIC values and the impact on vancomycin alternative therapy for MRSA bacteremia using the MicroScan and VITEK 2 automated systems. Methods: This was a retrospective multicenter cohort study of adult patients with MRSA bacteremia. Patients were stratified by susceptibility testing with MicroScan (May 2013-December 2016) or VITEK 2 (June 2017-February 2020). The primary outcome was vancomycin alternative therapy use. Secondary endpoints included MRSA MIC, 30-day mortality, 30-and 90-day readmission, and hospital length of stay (LOS). Results: A total of 193 patients were included for analysis: 89 in the MicroScan group and 104 in the VITEK 2 group. Vancomycin alternative therapy use was higher in the MicroScan group than the VITEK 2 group (56.2% vs 20.2%;p < 0.001). Median MIC value was 2 mg/L and 1 mg/L for MicroScan and VITEK 2, respectively ( p < 0.001). Median hospital LOS was shorter in the VITEK 2 period (16 vs 12 days;p = 0.02). Thirty-day mortality (10.1% vs 7.7%;p = 0.555) and 90-day readmission (34.8% vs 29.8%;p = 0.457) did not significantly differ between MicroScan and VITEK 2 groups. Conclusions: VITEK 2 use was associated with lower reported vancomycin MICs and less use of vancomycin alternative therapy. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://***/licenses/by-nc-nd/4.0/ )

关键词： Alternative pathway   Complement system   Dendritic cells   Macrophages   Properdin   Viable   death cells  

摘要： Properdin, the only known positive regulator of the complement system, stabilizes the C3 convertase, thereby increasing its half-life. In contrast to most other complement factors, properdin is mainly produced extrahepatically by myeloid cells. Recent data suggest a role for properdin as a pattern recognition molecule. Here, we confirmed previous findings of properdin binding to different necrotic cells including Jurkat T cells. Binding can occur independent of C3, as demonstrated by HAP-1 C3 KO cells, excluding a role for endogenous C3. In view of the cellular source of properdin, interaction with myeloid cells was examined. Properdin bound to the surface of viable monocyte-derived pro- and anti-inflammatory macrophages, but not to DCs. Binding was demonstrated for purified properdin as well as fractionated P2, P3, and P4 properdin oligomers. Binding contributed to local complement activation as determined by C3 and C5b-9 deposition on the cell surfaces and seems a prerequisite for alternative pathway activation. Interaction of properdin with cell surfaces could be inhibited with the tick protein Salp20 and by different polysaccharides, depending on sulfation and chain length. These data identify properdin as a factor interacting with different cell surfaces, being either dead or alive, contributing to the local stimulation of complement activation.

关键词： Complex coacervation   double emulsion   microstructure   plant protein   riboflavin  

摘要： Compared to animal proteins, this paper describes the use of plant proteins as alternative emulsifiers in double emulsion (DE) fabrication followed by complex coacervation. This is an additional way to improve stability, sustainability and lower production costs. In this study, kappa-carrageenan (k-carr) was used in complex coacervation with DE stabilised by pea protein isolate (PPI), mung bean protein isolate and chickpea protein concentrate (CPC) at pH 2 and 3 to form microcapsules (DECC). By investigating the particle sizes, microstructures and visual observations over 9 days at 4 degrees C, PPI/k-carr DECC and CPC/k-carr DECC at pH 2 were the most stable. Riboflavin encapsulation in PPI/k-carr DECC achieved an encapsulation efficiency of 65.46%, preserving similar to 20% of riboflavin across the storage period. As compared to DE systems, complex coacervation significantly improved riboflavin encapsulation stability. The results highlight the potential of PPI as an alternative emulsifier in DECC for the delivery of bioactive compounds.

关键词： Anabolic androgenic steroids   Dehydrochloromethyltestosterone   Phase -II metabolite   Glucuronide   High-resolution mass spectrometry   Anti-doping  

摘要： ABS TRACT Dehydrochloromethyltestosterone (DHCMT) is one of the most detected illicit used anabolic-androgenic steroids in professional sports. Therefore, a fast and accurate analysis of this substance is of great importance for a constructive fight against doping abuse. The conventional method for the analysis of this drug, GC-MSMS, is very sensitive and selective but also very time-and resource-consuming. With the presented work, a new approach for simple detection with LC-HRMSMS without any sample preparation is introduced. The method is based on the direct analysis of two newly described phase-II metabolites of the DHCMT long-term metabolite 4-chloro-18-nor-17(i-hydroxymethyl-17 alpha-methyl-5(i-androst-13-en-3 alpha-ol (M3). LC-HRMSMS, GC-MSMS, fractionation and deriv-atization experiments are combined to identify and characterize for the first time two different glucuronide-acid conjugates of this metabolite in positive human urine samples. In addition, a third glucuronide metabolite was identified, however without isomeric structure determination. The detection of these metabolites is particularly interesting for confirmation analyses, as the method is rapid and requires little sample material.

关键词： Surgical Oncology   Oncology   Surgery  

关键词： Lithium-ion batteries   Anode   Lithium zinc titanate  

摘要： Cr-doped and undoped lithium zinc titanate (LZTO), Li2ZnCrxTi3-xO8 (x = 0, 0.1, 0.3, 0.5) has been prepared as alternative anode using a simple and facile high-temperature solid-state ball-milling route followed by calcination in the air atmosphere. The cubic spinel structure with P4(3)32 space group is confirmed through X-ray Diffraction (XRD) for all compositions indicating doping of Cr3+ does not cause any changes within the lattice as well as maintain the phase structure up to an optimized doping. The study of morphology and distribution of the particles in the synthesized LZTO and doped LZTO compositions are carried out via scanning electron microscopy and transmission electron microscopy (TEM). It reveals the formation of polyhedron-shaped spherical facets in the sub-micron to nanometer range as observed by TEM. The particle size reduces toward the nanometer range as the amount of Cr doping increases and it also decreases the agglomeration of particles. All the samples doped with Cr indicate good electrochemical performance as compared to pristine LZTO. Sample Li2ZnCr0.3Ti2.7O8 doped with Cr content 0.3 displays higher discharge capacity, better cyclability, and lower polarization among all other Cr doped samples. Li2ZnCr0.3Ti2.7O8 delivered excellent rate performances attaining capacities of 251.73 +/- 4, 184.34 +/- 5, 157.42 +/- 5, and 119.03 +/- 4 mAh g(-1) at 0.1C, 0.5C, 1, and 2C, respectively, which is higher than the pristine LZTO sample. Electrochemical impedance spectroscopy shows Li2ZnCr0.3Ti2.7O8 acquired a lower value of charge-transfer resistance and the fastest Li-ion diffusivity which enhances its capacity at higher current rates and makes it suitable as an alternative anode for lithium-ion batteries.

关键词： continuous glucose monitoring   dietary intervention   exercise intervention   glycaemic control   insulin therapy   type 1 diabetes  

摘要： Aim To investigate the accuracy and acceptability of the FreeStyle Libre Flash continuous glucose monitoring system (FSL-CGM) at alternative sites during free living and under experimental conditions. Materials and Methods Participants with type 1 diabetes were provided with three FSL-CGM sensors applied to the upper arm, the lower back, and the anterior chest. On day 2 or 3, FSL-CGM sensor glucose was compared with venous glucose following a standard meal, during and after an exercise test, and after skin cooling. Participants completed 14-day use of the sensors with concomitant sensor scanning at all sites and capillary glucose tests. The primary outcome was accuracy between sensor sites of 14-day mean glucose. Clarke's error grids, precision absolute relative deviation, and mean absolute relative deviation were calculated. Results In the 20 participants, compared with the arm sensor, the accuracy of the back sensor and the chest sensor was 97.9% and 98%, respectively. Under experimental conditions, the arm sensor was more accurate than that of the back and chest. All the sensors recorded higher glucose concentration than venous samples during exercise. The arm and chest sites were most preferred, with the greatest sensor failures from the back. Conclusions The FSL-CGM is clinically accurate when the sensors are applied to alternate chest or back sites. Greater variability occurs during rapid changes in glucose concentration with all sensor sites compared with venous glucose. Understanding these variabilities allows appropriate use of an economically viable continuous glucose monitor.