An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm

Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1. The HDAC9–MALAT1–BRG1 complex binds chromatin and represses contractile protein gene expression in association with gain of histone H3-lysine 27 trimethylation modifications. Disruption of Malat1 or Hdac9 restores contractile protein expression, improves aortic mural architecture, and inhibits experimental aneurysm growth. Thus, we highlight a shared epigenetic pathway responsible for VSMC dysfunction in both forms of TAA, with potential therapeutic implication for other known HDAC9-associated vascular diseases

Minimization of Drug Shortages in Pharmaceutical Supply Chains: A Simulation-Based Analysis of Drug Recall Patterns and Inventory Policies

The drug shortage crisis in the last decade not only increased health care costs but also jeopardized patients’ health across the United States. Ensuring that any drug is available to patients at health care centers is a problem that official health care administrators and other stakeholders of supply chains continue to face. Furthermore, managing pharmaceutical supply chains is very complex, as inevitable disruptions occur in these supply chains (exogenous factors), which are then followed by decisions members make after such disruptions (internal factors). Disruptions may occur due to increased demand, a product recall, or a manufacturer disruption, among which product recalls—which happens frequently in pharmaceutical supply chains—are least studied. We employ a mathematical simulation model to examine the effects of product recalls considering different disruption profiles, e.g., the propagation in time and space, and the interactions of decision makers on drug shortages to ascertain how these shortages can be mitigated by changing inventory policy decisions. We also measure the effects of different policy approaches on supply chain disruptions, using two performance measures: inventory levels and shortages of products at health care centers. We then analyze the results using an approach similar to data envelopment analysis to characterize the efficient frontier (best inventory policies) for varying cost ratios of the two performance measures as they correspond to the different disruption patterns. This analysis provides insights into the consequences of choosing an inappropriate inventory policy when disruptions take place

Dynamic Modeling and Control of Grid-Connected Photovoltaic Systems based on Amplitude-Phase Transformation

A voltage source inverter (VSI) is widely used as an interface for distributed generation (DG) systems. However, high-power applications with increasing voltage levels require an extra power converter to reduce costs and complications. Thus, a current source inverter (CSI) is used. This study presents a precise phasor modeling and control details for a VSI-based system for DG and compares it with a CSI-based system. First, the dynamic characteristics of the system based on amplitude-phase transformation are investigated via small signal analysis in the synchronous reference frame. Moreover, the performance of the grid-connected system is determined by adopting the closed-loop control method based on the obtained dynamic model. The control strategies employ an outer active-power loop cascaded with an inner reactive-power loop, which the inner loop is a single-input single-output system without coupling terms. The sensitivity analysis of the linearized model indicates the dynamic features of the system. The simulation results for the different conditions confirm proposed model and design of the controller

Effects of mannan oligosaccharide and <i>Curcuma xanthorrhiza</i> essential oil on the intestinal morphologyand stress indicators of broilers subjected to cyclic heat stress

An experiment was carried out that was intended to explore the growth performance, nutrient retention, and heat stress biomarkers of finishing broilers under cyclic heat stress (HS) as modulated by the supplementation of mannan oligosaccharide (MOS) and <i>Curcuma xanthorrhiza</i> essential oil (CXEO). Two hundred and forty 21-day-old Ross 308 male broilers were allocated to four experimental treatments, each of which was replicated six times with 10 broilers per replicate. The diets included a control (CON), CON + 5 g of MOS kg⁻¹, CON + 400 mg of CXEO kg⁻¹ of feed, and CON + 5 g of MOS kg⁻¹ + 400 mg of CXEO kg⁻¹. From day 22 to 42, birds were subjected to cyclic HS by exposing them to 33 °C for 10 h (from 07:00 to 17:00 LT) and 22 °C from 17:00 to 07:00. Dietary treatments did not have an effect on average daily feed intake, feed conversion ratio, the duodenal histomorphology, and relative visceral weights. Body weight, average daily gain, villus length, crypt depth, and the villus-length-to-crypt-depth ratio in the jejunum were significantly increased in birds fed MOS or MOS + CXEO diets (<i>p</i>&thinsp;&lt;&thinsp;0.05). The relative bursa weight of the control birds was lower (<i>p</i>&thinsp;&lt;&thinsp; 0.05) compared to those fed the MOS diet. Compared with CON, dietary treatments reduced corticosterone and creatine kinase levels, the heterophile-to-lymphocyte ratio, and mRNA levels of heat shock protein 70 in the breast muscle and jejunum (<i>p</i>&thinsp;&lt;&thinsp;0.05). It was concluded that dietary supplementation of either MOS or CXEO alone or in combination may reduce some of the harmful effects of HS in broiler chickens

Simulation of induction tempering process of carbon steel using finite element method

A numerical model was developed to simulate an induction tempering process, solving an electromagnetic-thermal coupled problem. The temperature distribution inside an alloy steel work-piece was computed and the final hardness was predicted using Jaffe and Gordon relation. The experiments were undertaken with different induction process settings at some industrial conditions. The effects of induction parameters i.e. input AC current density, coil velocity and coil stay time were investigated by employing the proposed model and the results were compared to the experimental data. The computed results are in a good agreement with the experimental data. As an example, the model predicted the final hardness at three given points 47, 45 and 37 HRC. For this tempering condition the experimental results were 51, 45 and 36 HRC, respectively. © 2011

Heat shock protein 70 mRNA expression and immune response of heat-stressed finishing broilers fed propolis (bee glue) supplementation

This 2&times;2 factorial experiment investigated the efficacy of propolis (bee glue; BG) in ameliorating heat-stress-induced impairment of growth performance, the hematological profile, intestinal morphology, and biomarkers of heat stress in broilers. Two hundred and forty 21-day old Ross 308 male broiler chicks were allocated to four experimental treatments in six replicates of 10 birds each. The main factors were composed of diet (basal diet or addition of 3 g kg⁻¹ of BG) and temperature (thermoneutral or heat stress). Broilers subjected to heat stress had reduced average daily gain (ADG) and average daily feed intake (ADFI); a higher heterophil level and heterophil-to-lymphocyte ratio, and a lower lymphocyte level; upregulated mRNA expression of 70 kDa heat shock protein (HSP70) levels in heart, kidney, and breast muscle; and shorter jejunal villus height, deeper crypt depth, and a lower ratio of villus-height-to-crypt-depth compared with those broilers raised in thermoneutral conditions. Supplemental BG increased ADG, jejunal villus height, and the villus-height-to-crypt-depth ratio and decreased the feed-to-gain ratio and creatine kinase and lactate dehydrogenase levels in breast muscle compared with the birds who received control diets. The inclusion of BG in diets significantly decreased the mRNA expression of HSP70 levels in heart, kidney, and breast muscle in birds subjected to heat challenge. These results indicate that the BG-supplemented diet was effective in partially ameliorating adverse effects in resistance to heat stress in broiler chickens

In silico analysis of Omp25 and BLS Brucella melitensis antigens for designing subunit vaccine

Brucellosis is a well-known infection in domestic animals which caused by Brucella bacterium. Due to serious economic and medical consequences of this disease, various efforts have been made to prevent the infection through the use of recombinant vaccines based on Brucella outer membrane protein (OMP) antigens. The objectives of the present study were cloning, sequencing and epitope prediction of Omp25 and BLS genes as two major Brucella melitensis antigens. The full-length open reading frame (ORF) of Omp25 and BLS genes were amplified and cloned into pTZ57R/T vector. Phylogenetic analysis of sequenced genes showed that both genes were nearly similar in different Brucella species. Several online prediction softwares were used to predict B and T-cells epitopes, secondary and tertiary structures, antigenicity ability and enzymatic degradation sites. Bioinformatic tools used in the current study were confirmed by the results of three different experimental epitope predictions. Bioinformatic analysis identified five and two B-cell and two and one T-cell epitopes for Omp25 and BLS antigens, respectively. Finally, according to the antigenicity ability and proteosomal recognition site common B and T-cell epitope was predicted for Omp25 (154-162 amino acids) and BLS (37-48 and 119-139 amino acids). Results of this study might be useful for recombinant vaccine development