Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood.

Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty-one patients with suspected NAFLD ingested heavy water (2 H2 O, 50-mL aliquots) two to three times daily for 3-5 weeks prior to a clinically indicated liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican FSR were measured based on 2 H labeling using tandem mass spectrometry. Patients were classified by histology for fibrosis stage (F0-F4) and as having nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). Magnetic resonance elastography measurements of liver stiffness were also performed. Hepatic collagen FSR in NAFLD increased with advancing disease stage (e.g., higher in NASH than nonalcoholic fatty liver, positive correlation with fibrosis score and liver stiffness) and correlated with hemoglobin A1C. In addition, plasma lumican FSR demonstrated a significant correlation with hepatic collagen FSR.ConclusionUsing a well-characterized cohort of patients with biopsy-proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78-88)

Ocean acidification reduces mechanical properties of the Portuguese oyster shell with impaired microstructure: a hierarchical analysis

Abstract. The rapidly intensifying process of ocean acidification (OA) in coastal areas due to anthropogenic CO2 is not only depleting carbonate ions necessary for calcification but also causing acidosis and disrupting internal pH homeostasis in several marine organisms. These negative consequences of OA on marine communities, particularly to shellfish oyster species, has been very well documented in recent studies, however, the consequences of these reduced or impaired calcification processes on the end-product, shells or skeletons, still remains one of the major research gaps. Shells produced by marine organisms under OA are expected to be corroded with disorganized or impaired crystal orientation or microstructures with reduced mechanical property. To bridge this knowledge gap and to test the above hypothesis, we investigated the effect of OA on shell of the commercially important oyster species (Crassostrea angulata) at ecologically and climatically relevant OA levels (using pH 8.1, 7.8, 7.5, 7.2 as proxies). In decreased pH conditions, a drop of shell hardness and stiffness was revealed by nanoindentation tests, while an evident loosened internal microstructure was detected by scanning electron microscopy (SEM). In contrary, the crystallographic orientation of oyster shell showed no significant difference with decreasing pH by Electron Back Scattered Diffraction (EBSD) analyses. These results indicate the loosened internal microstructure may be the cause of the OA induced reduction in shell hardness and stiffness. Micro-computed tomography analysis (Micro-CT) indicated that an overall "down-shifting" of mineral density in the shell with decreasing pH, which implied the loosened internal microstructure may run through the shell, thus inevitably limiting the effectiveness of the shell defensive function. This study surfaces potential bottom-up deterioration induced by OA on oyster shells, especially in their early juvenile life stage. This knowledge is critical to forecast the survival and production of edible oysters in future ocean. </jats:p

Assistive robotic hand with bi-directional soft actuator for hand impaired patients

Soft wearable robotic hand can assist with hand function for the performance of activities of daily living (ADL). However, existing robotic hands lack a mathematical way to quantify the grip force generated for better controlling the grasp of objects during the performance of ADL. To address this issue, this article presents a soft wearable robotic hand with active control of finger flexion and extension through an elastomeric-based bi-directional soft actuator. This actuator bends and extends by pneumatic actuation at lower air pressure, and a flex sensor embedded inside the actuator measures the angles of the fingers in real-time. Analytical models are established to quantify the kinematic and tip force for gripping of the actuator in terms of the relationship between the input pressure and the bending angle, as well as the output force, and are validated experimentally and by the finite element method. Furthermore, the ability of the soft robotic hand to grasp objects is validated with and without being worn on a human hand. The robotic hand facilitates hand opening and closing by the wearer and successfully assists with grasping objects with sufficient force for ADL-related tasks, and the grip force provided by the actuator is further estimated by the analytical models on two healthy subjects. Results suggest the possibility of the soft robotic hand in providing controllable grip strength in rehabilitation and ADL assistance

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

The mechanisms of Yu Ping Feng San in tracking the cisplatin-resistance by regulating ATP-binding cassette transporter and glutathione S-transferase in lung cancer cells

Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs

Solar Thermochemical Energy Storage Through Carbonation Cycles of SrCO₃/SrO Supported on SrZrO₃

Solar thermochemical energy storage has enormous potential for enabling cost-effective concentrated solar power (CSP). A thermochemical storage system based on a SrO/SrCO₃ carbonation cycle offers the ability to store and release high temperature (≈1200 °C) heat. The energy density of SrCO₃/SrO systems supported by zirconia-based sintering inhibitors was investigated for 15 cycles of exothermic carbonation at 1150 °C followed by decomposition at 1235 °C. A sample with 40 wt % of SrO supported by yttria-stabilized zirconia (YSZ) shows good energy storage stability at 1450 MJ m⁻³ over fifteen cycles at the same cycling temperatures. After further testing over 45 cycles, a decrease in energy storage capacity to 1260 MJ m⁻³ is observed during the final cycle. The decrease is due to slowing carbonation kinetics, and the original value of energy density may be obtained by lengthening the carbonation steps.Keywords: energy storage, strontium oxide, concentrated solar power, reactive stabilit

The Physics of turbulent and dynamically unstable Herbig-Haro jets

The overall properties of the Herbig-Haro objects such as centerline velocity, transversal profile of velocity, flow of mass and energy are explained adopting two models for the turbulent jet. The complex shapes of the Herbig-Haro objects, such as the arc in HH34 can be explained introducing the combination of different kinematic effects such as velocity behavior along the main direction of the jet and the velocity of the star in the interstellar medium. The behavior of the intensity or brightness of the line of emission is explored in three different cases : transversal 1D cut, longitudinal 1D cut and 2D map. An analytical explanation for the enhancement in intensity or brightness such as usually modeled by the bow shock is given by a careful analysis of the geometrical properties of the torus.Comment: 17 pages, 10 figures. Accepted for publication in Astrophysics & Spac

Effect of calcification on the mechanical stability of plaque based on a three-dimensional carotid bifurcation model

Background: This study characterizes the distribution and components of plaque structure by presenting a three-dimensional blood-vessel modelling with the aim of determining mechanical properties due to the effect of lipid core and calcification within a plaque. Numerical simulation has been used to answer how cap thickness and calcium distribution in lipids influence the biomechanical stress on the plaque.Method: Modelling atherosclerotic plaque based on structural analysis confirms the rationale for plaque mechanical examination and the feasibility of our simulation model. Meaningful validation of predictions from modelled atherosclerotic plaque model typically requires examination of bona fide atherosclerotic lesions. To analyze a more accurate plaque rupture, fluid-structure interaction is applied to three-dimensional blood-vessel carotid bifurcation modelling

Exploring deep microbial life in coal-bearing sediment down to ~2.5 km below the ocean floor

Peer reviewedPostprin

Analyses of the Microbial Diversity across the Human Microbiome

Analysis of human body microbial diversity is fundamental to understanding community structure, biology and ecology. The National Institutes of Health Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine microbial diversity within and across body habitats and individuals through pyrosequencing-based profiling of 16 S rRNA gene sequences (16 S) from habits of the oral, skin, distal gut, and vaginal body regions from over 200 healthy individuals enabling the application of statistical techniques. In this study, two approaches were applied to elucidate the nature and extent of human microbiome diversity. First, bootstrap and parametric curve fitting techniques were evaluated to estimate the maximum number of unique taxa, Smax, and taxa discovery rate for habitats across individuals. Next, our results demonstrated that the variation of diversity within low abundant taxa across habitats and individuals was not sufficiently quantified with standard ecological diversity indices. This impact from low abundant taxa motivated us to introduce a novel rank-based diversity measure, the Tail statistic, (“τ”), based on the standard deviation of the rank abundance curve if made symmetric by reflection around the most abundant taxon. Due to τ’s greater sensitivity to low abundant taxa, its application to diversity estimation of taxonomic units using taxonomic dependent and independent methods revealed a greater range of values recovered between individuals versus body habitats, and different patterns of diversity within habitats. The greatest range of τ values within and across individuals was found in stool, which also exhibited the most undiscovered taxa. Oral and skin habitats revealed variable diversity patterns, while vaginal habitats were consistently the least diverse. Collectively, these results demonstrate the importance, and motivate the introduction, of several visualization and analysis methods tuned specifically for next-generation sequence data, further revealing that low abundant taxa serve as an important reservoir of genetic diversity in the human microbiome