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Studies focusing on the kinematics of the ankle joint complex (AJC) have long been a key area of interest for biomechanists and orthopedic surgeons. However, it is not clear how additional weight-bearing walking affects the motion of the AJC compared to walking with a normal body weight (BW) or what adjustments the AJC would instinctively make to accommodate the additional load. To address this gap in knowledge, advanced dynamic biplane radiography combined with a model-based 2D-3D tracking technique was employed to elucidate the inherent kinematics of the AJC during the stance phase while walking with and without additional weight-bearing. It was found that walking with additional 50% body weight (BW + 50%) resulted in a greater dispersion of instantaneous axes of rotation in the talocrural and subtalar joints during the stance phase of gait. The talocrural joint is more plantarflexed and anteriorly translated during the early and late stance phases than during the midstance phases, which suggests that additional weight-bearing affects the stability of the AJC. Moreover, walking with BW + 50% showed that the center of rotation of the talocrural joint was positioned more superiorly and posteriorly during the foot flat to heel-off phase. This, accordingly, increases the ankle-foot gear ratio and the force of the dorsiflexors. [ABSTRACT FROM AUTHOR]

Commensal bacteria generate immensely diverse active metabolites to maintain gut homeostasis, however their fundamental role in establishing an immunotolerogenic microenvironment in the intestinal tract remains obscure. Here, we demonstrate that an understudied murine commensal bacterium, Dubosiella newyorkensis, and its human homologue Clostridium innocuum, have a probiotic immunomodulatory effect on dextran sulfate sodium-induced colitis using conventional, antibiotic-treated and germ-free mouse models. We identify an important role for the D. newyorkensis in rebalancing Treg/Th17 responses and ameliorating mucosal barrier injury by producing short-chain fatty acids, especially propionate and L-Lysine (Lys). We further show that Lys induces the immune tolerance ability of dendritic cells (DCs) by enhancing Trp catabolism towards the kynurenine (Kyn) pathway through activation of the metabolic enzyme indoleamine-2,3-dioxygenase 1 (IDO1) in an aryl hydrocarbon receptor (AhR)-dependent manner. This study identifies a previously unrecognized metabolic communication by which Lys-producing commensal bacteria exert their immunoregulatory capacity to establish a Treg-mediated immunosuppressive microenvironment by activating AhR-IDO1-Kyn metabolic circuitry in DCs. This metabolic circuit represents a potential therapeutic target for the treatment of inflammatory bowel diseases. Here, Zhang et al. identify a metabolic axis by which Lys-producing commensal bacterium Dubosiella newyorkensis mediates a Treg-mediated immunosuppressive microenvironment by activating AhR-IDO1-Kyn metabolic circuitry in dendritic cells. [ABSTRACT FROM AUTHOR]

Dynamic mechanical characteristics of coral sand is of vital importance for foundation compaction. In the present study, a series of tests were conducted to estimate the dynamic behaviors of coral sand under drop weight impact. The coral sands with original and uniform gradations were impacted with different energies and different repeating times. The test results show that the dynamic force–displacement or the stress–strain response roughly undergoes the initial intense fluctuation, quasi-free fall, subsequent descending fluctuation and the inverse rebound periods. The reduction in the void ratio of coral sand increases with single impact energy increasing, while it decreases with the repetition of impact. The breakage of coral sand under impacting is progressive along the height of the sample, revealing by the multiple yield points in the e-logp curve. It is found that the predominant size fraction of fragmented particles corresponds well to the inflection interval of its initial PSD curve. The ratio of the dissipated energy to the absorbed energy generally reduces as the repetition of impact loading. The breakage index can be closely correlated to the dissipated energy. As compared to the original coral sand, the uniform coral sand exhibits more sensitive behaviors in terms of compressibility, particle crushing and energy dissipation. Furthermore, the scenario of few impacts at high energy level is proved to be more efficient than that of multiple impacts at low energy level in the reinforcement of coral sand. [ABSTRACT FROM AUTHOR]

Background: Gadolinium-based nanoparticles (GdNPs) are clinically used agents to increase the radiosensitivity of tumor cells. However, studies on the mechanisms and biological modeling of GdNP radio-enhancement are still preliminary. This study aims to investigate the mechanism of radio-enhancement of GdNPs for kilovoltage photons using Monte Carlo (MC) simulations, and to establish local effect model (LEM)-based biological model of GdNP radiosensitization. Methods: The spectrum and yield of secondary electrons and dose enhancement around a single GdNP and clustered GdNPs were calculated in a water cube phantom by MC track-structure simulations using TOPAS code. We constructed a partial shell-like cell geometry model of pancreatic cancer cell based on transmission electron microscope (TEM) observations. LEM-based biological modeling of GdNP radiosensitization was established based on the MC-calculated nano-scale dose distributions in the cell model to predict the cell surviving fractions after irradiation. Results: The yield of secondary electrons for GdNP was 0.16% of the yield for gold nanoparticle (GNP), whereas the average electron energy was 12% higher. The majority of the dose enhancement came from the contribution of Auger electrons. GdNP clusters had a larger range and extent of dose enhancement than single GdNPs, although GdNP clustering reduced radial dose per interacting photon significantly. For the dose range between 0 and 8 Gy, the surviving fraction predicted using LEM-based biological model laid within one standard deviation of the published experimental results, and the deviations between them were all within 25%. Conclusions: The mechanism of radio-enhancement of GdNPs for kilovoltage photons was investigated using MC simulations. The prediction results of the established LEM-based biological model for GdNP radiosensitization showed good agreement with published experimental results, although the deviation of simulation parameters can lead to large disparity in the results. To our knowledge, this was the first LEM-based biological model for GdNP radiosensitization. [ABSTRACT FROM AUTHOR]

The emerging technique of carbonization of polyimide (PI) by direct laser writing receives great attention for its flexibility, versatility, and ease-of-patterning capability in creating a variety of functional laser-induced graphene (LIG) sensors and devices. LIG prepared by CO2 laser irradiating of the PI film is characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscope (TEM), specific surface area analyzer, synchronous thermal analysis, and Raman spectroscopy with the focus on investigating the effects of laser parameters (e.g., power, scanning speed) on the microstructure, thickness, and sheet resistance of LIG. Both TEM and XRD indicate that LIG is composed of many graphene layers with a layer spacing of 0.34 nm. The specific surface area of LIG decreases with the increase of laser power. The ratio of the thickness of LIG over the depth of the carbonized PI film as the expansion ratio characterizes the expansibility of LIG. The influence of image resolution and off-focus value on the sheet resistance of LIG is explained by the superposition mechanism of laser scanning spots. [ABSTRACT FROM AUTHOR]

The porcine circovirus type 2 (PCV2) capsid protein (Cap) is an important antigen for the development of vaccines. To achieve high-level expression of recombinant PCV2 Cap in Pichia pastoris, the wild-type Cap (wt-Cap) and optimized Cap (opti-Cap) gene fragments encoding the same amino acid sequence of PCV2 were amplified by PCR using DNA from lymph nodes of postweaning multisystemic wasting syndrome-suffered pigs and synthesized based on the codon bias of the methylotrophic yeast P. pastoris, respectively. The wt-Cap and opti-Cap gene fragments were inserted into the site between EcoRI and NotI sites in pPIC9K, which was under the control of the alcohol oxidase 1 (AOX1) promoter and α-mating factor signal sequence from Saccharomyces cerevisiae. The recombinant plasmids, designated as pPIC9K-wt-Cap and pPIC9K-opti-Cap, were linearized using SacI and transformed into P. pastoris GS115 by electroporation. The expressed intracellular soluble opti-Cap reached 174 μg/mL without concentration in a shake flask and kept good reactivity to PCV2-specific positive sera, whereas the wt-Cap could not be detectable throughout three times electroporation. Strong specific PCV2-Cap antibodies were elicited from piglets immunized with vaccine based on opti-Cap. To the best of our knowledge, the achieved opti-Cap yield is the highest ever reported. Our results demonstrated that codon optimization play an important role on the high-level expression of a codon-optimized PCV2-Cap gene in P. pastoris, and the vaccine based on opti-Cap may be a potential subunit vaccine candidate. [ABSTRACT FROM AUTHOR]

The linkage of customer satisfaction, customer retention, and firm profitability has been well established in the marketing literature, and provides ample justification as to why customer satisfaction measurement (CSM) has been a focal point in marketing decision making. Although aggregate market level research on understanding the determinants of customer satisfaction is abundant, CSM decisions at segment level are possible only if the individual or market segment differences in the formation of overall satisfaction judgments and subsequent heterogeneity in the role these various determinants play are understood. Based on expectancy-disconfirmation theory in customer satisfaction, we propose a maximum likelihood based latent structure factor analytic methodology which visually depicts customer heterogeneity regarding the various major determinants of customer satisfaction judgments involving multiple attributes, and provides directions for segment-specific CSM decisions. We first describe the proposed model framework including the technical aspects of the model structure and subsequent maximum likelihood estimation. In an application to a consumer trade show, we then demonstrate how our proposed methodology can be gainfully employed to uncover the nature of such heterogeneity. We also empirically demonstrate the superiority of the proposed model over a number of different model specifications in this application. Finally, limitations and directions for future research are discussed. [ABSTRACT FROM AUTHOR]