Pharmacologic inhibition of RGD-binding integrins ameliorates fibrosis and improves function following kidney injury

Fibrosis is a final common pathway for many causes of progressive chronic kidney disease (CKD). Arginine-glycine-aspartic acid (RGD)-binding integrins are important mediators of the pro-fibrotic response by activating latent TGF-β at sites of injury and by providing myofibroblasts information about the composition and stiffness of the extracellular matrix. Therefore, blockade of RGD-binding integrins may have therapeutic potential for CKD. To test this idea, we used small-molecule peptidomimetics that potently inhibit a subset of RGD-binding integrins in a murine model of kidney fibrosis. Acute kidney injury leading to fibrosis was induced by administration of aristolochic acid. Continuous subcutaneous administration of CWHM-12, an RGD integrin antagonist, for 28 days improved kidney function as measured by serum creatinine. CWHM-12 significantly reduced Collagen 1 (Col1a1) mRNA expression and scar collagen deposition in the kidney. Protein and gene expression markers of activated myofibroblasts, a major source of extracellular matrix deposition in kidney fibrosis, were diminished by treatment. RNA sequencing revealed that inhibition of RGD integrins influenced multiple pathways that determine the outcome of the response to injury and of repair processes. A second RGD integrin antagonist, CWHM-680, administered once daily by oral gavage was also effective in ameliorating fibrosis. We conclude that targeting RGD integrins with such small-molecule antagonists is a promising therapeutic approach in fibrotic kidney disease

Accuracy in evaluation of view factors between small and far surfaces

The contribution describes an approach that can be used during evaluation of a view factor between complex emitter and planar absorber surfaces. Rather than sophisticated mathematical attitude, practical way is offered. The source surface is divided into smaller parts with same surface normal and using some minor assumptions, summary view factor is calculated. The contribution is aimed on an error that can be caused considering these assumptions and further on, on a case study (evaluation of a view factor between ceramic plaques source surface and a photometric sensor), real differences are shown

On the relation between shape and downward radiation of overhead radiant heaters

The paper aims on evaluating and assessing of the influence of a shape of overhead luminous infrared heater’s burner on heat distribution to the ambient. These devices are mainly used for heating of industrial or other large space buildings. The contribution is based on comparison between the experimental results and created mathematical model. The latest experimental results show that the maximum of radiant intensity does not lay right below the radiant heater. Actually, there exists a ring of maximal values around heater’s midpoint axis. Results prove that instead of reflectors’ geometry, very complicated shape of gas luminous heater’s burner plays the most significant role in radiant heat transfer from the luminous heater. It was evaluated that the position of the radiant intensity maximum is around 10° from the radiating surface’s normal direction. All the findings can be summarized in conclusion that uniform distribution of radiant intensity required for thermal comfort of occupants can be maintained just by optimizing of the shape of radiant heater’s burner. Besides this conclusion, it is also apparent that adding the reflector actually increases summary radiant heat flux to the desired zone and therefore radiant efficiency increases. It is also clear that varying the reflector shape, different improvement of the efficiency can be expected

Design optimization study for an infrared heater using CFD and sensitivity analysis

Sensitivity analysis (SA) has become a very popular technique for various application areas. However, not many studies concern SA using CFD (computational fluid dynamics). The main problem appears to be the large number of model executions when using the Monte Carlo method of SA. The computing resources and time needed for such a SA in combination with CFD (in which one model execution could take several hours) can be enormous. Nevertheless, this paper describes an approach of using SA in such cases. The recommendations are obvious: simplifying the model as much as possible; considering just a key part of the model; and take more care about the speed of convergence. On this basis a case study on "Optimization of gas infrared heater radiation geometry" has been performed. The most interesting result is that the shape of the heater and the reflector material do not significantly influence the heat delivery to the occupied zone. The main conclusion is that Monte Carlo sensitivity analysis is not suitable for large CFD models with low level of abstraction. In order to obtain good results, we recommend to select a smaller part of the overall domain and/or to significantly simplify it

Identification of Novel Retroid Agents in Danio rerio, Oryzias latipes, Gasterosteus aculeatus and Tetraodon nigroviridis

Retroid agents are genomes that encode a reverse transcriptase (RT) and replicate or transpose by way of an RNA intermediate. The Genome Parsing Suite (GPS) is software created to identify and characterize Retroid agents in any genome database (McClure et al. 2005). The detailed analysis of all Retroid agents found by the GPS in Danio rerio (zebrafish), Oryzias latipes (medaka), Gasterosteus aculeatus (stickleback) and Tetraodon nigroviridis (spotted green pufferfish) reveals extensive Retroid agent diversity in the compact genomes of all four fish. Novel Retroid agents were identified by the GPS software: the telomerase reverse transcriptase (TERT) in O. latipes, G. aculeatus and T. nigroviridis and a potential TERT in D. rerio, a retrotransposon in D. rerio, and multiple lineages of endogenous retroviruses (ERVs) in D. rerio, O. latipes and G. aculeatus

Applications of Perpendicular-To-Grain Compression Behavior in Real Wood Construction Assemblies

Compression perpendicular to grain (C┴) of wood is an important property and has a drastic effect on serviceability of the structure. Typical C┴ loading scenarios include the bottom chord of a truss resting on the top plate of a shear wall and chords of a shear wall resting on the bottom plate. Present design values for C┴ are based on stress at 1-mm deflection for an ASTM block test. However, in real applications, loading conditions and deflection limits are much different from that administered during the test. There is a need to characterize C┴ behavior of wood in construction applications and compare it with current design codes. This study addresses that by testing two different assemblies involving C┴ loading, each with two different species of wood, to quantify the design C┴ based on the desired application and compare it with current design codes. Also, the effect of species and aspect ratio of assembly was characterized. Results suggested that the ASTM values significantly differ from the assembly values. Species of wood did not have any effect on the performance of the assemblies. A 2% strain offset method was proposed to determine allowable value for C┴ for a desired application. Adjustment factors based on loading configurations were suggested for calculation of design values

Identifying The Health Needs In Rural Appalachian Ohio: Outcomes Of A Rural Community-Academic Partnership

To identify health issues in two rural counties, a needs assessment was developed by health officials and researchers. Focus groups (n = 32) and interviews (n = 8) were conducted among community leaders and a modified BRFFS survey was completed by 399 community members. Results indicated the health of the participants was influenced by: 1) rural Appalachian culture, 2) geography and access to health care, and 3) lack of access/knowledge about preventive health behaviors. These issues likely contributed to 30% obesity prevalence among the sample, which was prioritized as the main health issue for both counties.

The Regulation of the ospZ and ORF-2 promoters in the Shigella flexneri by the virulence factor VirB

Shigella flexneri is a pathogenic bacterium that is the causative agent of shigellosis, an illness characterized by severe dysentery. Shigella carries many of its virulence genes on a large virulence plasmid and consequently this plasmid is the focus of research in the Wing lab. My research focuses on the transcriptional regulation of a newly identified gene called ospZ. This gene’s protein product is secreted outside the bacterial cell and assists in polymorphonuclear leukocyte migration, a function that is believed to enhance the virulence of Shigella. Many genes encoded by the Shigella virulence plasmid are regulated by the transcription factor VirB, which is also encoded by the virulence plasmid. VirB regulates the expression of IcsP, a gene 1.6 kilobase pairs upstream of ospZ on the divergent strand. To determine the role VirB plays in the regulation of ospZ, reporter plasmids will be constructed in which the ospZ promoter region is fused to lacZ (a gene that encodes the enzyme betagalactosidase) and transformed into wild type and VirB mutant strains of Shigella. Promoter activity of ospZ will then be measured using beta-galactosidase assays. My hypothesis is that VirB, which binds to DNA 100 base pairs upstream of the ospZ gene, regulates the expression of this gene also