The role of retinoic acid related orphan receptor alpha in age-related macular degeneration

Age-related macular degeneration (AMD) is a prevalent cause of vision loss and irreversible blindness that affects more than 11 million Americans. AMD is a multifactorial disease with a number of genetic, demographic, and environmental risk factors. Currently the etiology of AMD is still unclear and there are no effective cure for this devastating disease, but recent studies have demonstrated that RORA is a candidate gene involved in AMD pathophysiology. RORA is a critical regulator of multiple biological processes and has been implicated in various physiological processes including circadian rhythm, lipid metabolism, photoreceptor development, autism, and inflammation. Our current study will explore in depth the role of RORA in AMD. We will look at the effects of RORA in the retina of mice. Localization studies of retinal tissues obtained from mice with a conditional knockout of RORA in epithelial cells showed little effect of RORA on structural cells of the retina. However, there was a decrease in VEGF and TGF-B proteins in RORA knockout. This is an interesting finding because VEGF and TGF-B has an important function in angiogenesis and neovascularization which are pathophysiological effects of AMD. In addition, we will try to identify gene targets of RORA that have also been linked with AMD. By identifying the targets of RORA and discovering how RORA regulates these targets, we hope to better understand the role of RORA in AMD pathophysiology. ChIP-seq and software analysis of the data was performed to identify all genomic targets of RORA linked with AMD. A number of promising genes were found in both RORA and AMD networks. The next step of this study is to perform quantitative analysis of these genes and how their expression is affected by RORA. Also, we will perform additional conditional RORA knockout models in cone cells and developing retinal cells to further understand the role of RORA in the retina and AMD pathogenesis

A knowledge-based system with learning for computer communication network design

Computer communication network design is well-known as complex and hard. For that reason, the most effective methods used to solve it are heuristic. Weaknesses of these techniques are listed and a new approach based on artificial intelligence for solving this problem is presented. This approach is particularly recommended for large packet switched communication networks, in the sense that it permits a high degree of reliability and offers a very flexible environment dealing with many relevant design parameters such as link cost, link capacity, and message delay

Pathogenicity and diagnostics of non-group A porcine rotaviruses

Rotavirus-associated diarrhea is a common enteric disease in piglets. Group A, B, and C rotaviruses have been implicated in US swine. While group A rotaviruses have been widely studied and attributed as a major cause of the disease, little known about group B and C rotaviruses with respect to their pathogenicity/pathogenesis as well as diagnostics and prevention/control. To address such shortfalls, three studies were carried out. The objective of the first study was producing monoclonal antibodies (MAbs) against PoRV A, B, and C. To that goal, full-length VP6 protein gene of each serogroup was cloned from feces positive for respective virus and expressed in a baculovirus system using Bac-to-Bac cloning and expression kits. The recombinant proteins, purified in their native conditions, were used to immunize mice. A VP6-based ELISA and an indirect fluorescent antibody test using Sf9 cells expressing VP6 of PoRV A, B or C were used to screen hybridomas. The protein specificity of selected MAbs were further verified by Western immunoblot, and the isotype of each MAb was determined using a commercial murine antibody isotyping kit. Based on all these evaluations, MAb 10A11, 10B1 and 11H3, which were of IgG isotype, were selected for PoRV A, B and C, respectively. The MAbs specific for PoRV A and C were proven to be useful for immunohistochemical staining to detect these viruses in formalin-fixed intestinal tissues, which can aid more accurate diagnostic investigation of rotavirus-associated diarrhea. The second study was to compare the pathogenicity of porcine rotavirus (PoRV) A, B and C individually or in combinations in immunologically naïve newborn piglets. Forty-eight one-day-old Cesarean-Derived Colostrum-Deprived (CDCD) pigs were divided into eight groups. Pigs in each group were challenged with rotaviruses that belong to individual group A, B, C or all combinations. Clinical

Folding model study of the elastic α+α\alpha + \alpha scattering at low energies

The folding model analysis of the elastic $\alpha + \alpha$ scattering at the incident energies below the reaction threshold of 34.7 MeV (in the lab system) has been done using the well-tested density dependent versions of the M3Y interaction and realistic choices for the $^4$He density. Because the absorption is negligible at the energies below the reaction threshold, we were able to probe the $\alpha + \alpha$ optical potential at low energies quite unambiguously and found that the $\alpha + \alpha$ overlap density used to construct the density dependence of the M3Y interaction is strongly distorted by the Pauli blocking. This result gives possible explanation of a long-standing inconsistency of the double-folding model in its study of the elastic $\alpha + \alpha$ and $\alpha$-nucleus scattering at low energies using the same realistic density dependent M3Y interaction