Application of direct inverse analogy method (DIVA) and viscous design optimization techniques

A direct-inverse approach to the transonic design problem was presented in its initial state at the First International Conference on Inverse Design Concepts and Optimization in Engineering Sciences (ICIDES-1). Further applications of the direct inverse analogy (DIVA) method to the design of airfoils and incremental wing improvements and experimental verification are reported. First results of a new viscous design code also from the residual correction type with semi-inverse boundary layer coupling are compared with DIVA which may enhance the accuracy of trailing edge design for highly loaded airfoils. Finally, the capabilities of an optimization routine coupled with the two viscous full potential solvers are investigated in comparison to the inverse method

Environmental tolerance of a H4N6 avian-origin type A influenza virus

Detection of avian-origin type A influenza virus infections has been well documented within domestic and wild bird populations. However, research focused on the ability of these viruses to remain viable under naturally fluctuating environmental conditions, which we have termed "environmental tolerance" (ET), has led to untested hypotheses about the existence of an environmental viral reservoir. By measuring ET, we can determine the potential importance of an environmental reservoir. We developed three microcosms (soil, water, and water-soil interface) using soil, water, and field data collected from Waterfowl Lake at the Cleveland Metroparks Zoo during the summer of 2008 to construct a controlled environmental model quantifying the ET of influenza A viruses. Focusing on the effect of mean, minimum and maximum summer temperatures recorded in Waterfowl Lake, we spiked three replicates of each microcosm with a known quantity of a H4N6 avian influenza virus. An aquarium with soil and water that was not spiked served as a negative viral control for the microcosms. We hypothesized that there would be both qualitative and quantifiable differences in virus viability among our microcosms and temperature treatments. Samples were collected over four weeks and tested for the presence of viable virus using virus isolation in 10-day old embryonating chicken eggs. Surprisingly, viral infectivity generally surpassed four weeks. Therefore, we demonstrated that type A influenza viruses have sufficient ET to remain viable for at least 30 days in a pond under summer environmental conditions and concluded that ponds could serve as an environmental reservoir for influenza A viruses and should therefore be considered when managing bird collections. Currently, we are determining the mean egg infective dose concentration (EID50) of virus in our samples to attempt to detect quantitative changes in virus concentration over time.No embarg

The non-structural protein 5A (NS5A) of hepatitis c virus interacts with the SH3 domain of human Bin1 using non-canonical binding sites

The hepatitis C virus (HCV) is a major human pathogen that causes severe diseases such as chronic hepatitis, liver cirrhosis and finally hepatocellular carcinoma. Although no enzymatic activity could be attributed yet to the HCV non-structural protein 5A (NS5A), it is indispensable for viral replication and particle assembly. Furthermore, it is associated with a variety of cellular pathways, although their relevance for viral pathogenesis still has to be elucidated. To fulfil its function NS5A interacts with a large number of different proteins including both viral and human ones. NS5A is organized into three domains, which are connected via two low complexity sequences (LCS). The first domain is highly conserved among different HCV genotypes and forms a well-defined globular structure [1]. The domains 2 (D2) and 3 (D3) are less conserved and intrinsically disordered. Nonetheless, three segments in LCS-I and D2 show significant propensities to adopt a-helical structures as could be shown by nuclear magnetic resonance (NMR) chemical shift and 15 N relaxation data [2]. The LCS-II connecting D2 and D3 contains two directly neighbored class II PxxP-motifs, which are important for interactions with Src homology 3 (SH3) domains. SH3 domains mediate protein-protein interactions, often via binding to polyproline II helices. Recent studies also revealed alternative binding mechanisms, mainly involving helical motifs and positively charged amino acid residues. The SH3 domain of the bridging integrator 1 (Bin1) is known to interact with NS5A not only via its PxxP-motifs, but also via two non-canonical binding sites, which will be further described here [3]

The non-structural protein 5A (NS5A) of hepatitis C virus interacts with the SH3 domain of human Bin1 using non-canonical binding sites

The hepatitis C virus (HCV) is a major human pathogen that causes severe diseases such as chronic hepatitis, liver cirrhosis and finally hepatocellular carcinoma. Although no enzymatic activity could be attributed yet to the HCV non-structural protein 5A (NS5A), it is indispensable for viral replication and particle assembly. Furthermore, it is associated with a variety of cellular pathways, although their relevance for viral pathogenesis still has to be elucidated. To fulfil its function NS5A interacts with a large number of different proteins including both viral and human ones. NS5A is organized into three domains, which are connected via two low complexity sequences (LCS). The first domain is highly conserved among different HCV genotypes and forms a well-defined globular structure [1]. The domains 2 (D2) and 3 (D3) are less conserved and intrinsically disordered. Nonetheless, three segments in LCS-I and D2 show significant propensities to adopt a-helical structures as could be shown by nuclear magnetic resonance (NMR) chemical shift and 15 N relaxation data [2]. The LCS-II connecting D2 and D3 contains two directly neighbored class II PxxP-motifs, which are important for interactions with Src homology 3 (SH3) domains. SH3 domains mediate protein-protein interactions, often via binding to polyproline II helices. Recent studies also revealed alternative binding mechanisms, mainly involving helical motifs and positively charged amino acid residues. The SH3 domain of the bridging integrator 1 (Bin1) is known to interact with NS5A not only via its PxxP-motifs, but also via two non-canonical binding sites, which will be further described here [3]

Cultivating Community Resources to Address Language Barriers in Healthcare

This poster presentation describes a collaborative strategy to address language barriers in health care in central Ohio. A shortage of health care interpreters in the central Ohio region compromises the health of a significant portion of our region's most vulnerable population. A collaborative strategy implemented by South-Western City School District, The Ohio State University and Primary One Health responds to this challenge through the development of a high school career pathway program to train certified health care interpreters. The pathway includes a college preparatory sequence of Spanish courses in ninth and 10th grade, a 12-credit block of Advanced Spanish language courses offered through College Credit Plus, and an internship in a community health center serving a majority of Spanish-speaking patients. This presentation will focus on progress-to-date of participants and describe the potential impact of the project on the participants and the community. This presentation will be of interest to school district representatives, education policymakers, health care administrators, and language access coordinators. The presenters include faculty members and administrators from Ohio State and South-Western City School District, and interpreters and managers from Primary One and The Ohio State University Wexner Medical Center.AUTHOR AFFILIATION: Glenn Martinez, Professor, The Ohio State University, [email protected] (Corresponding Author); Ed Kennedy, Coordinator of EL Services, South-Western City Schools; Amy Schakat, Coordinator of Career-Technical Education, Southwestern City Schools; Michael Schwarten, Spanish Teacher; Milly Valverde, Director Interpretive Services, The Ohio State University.This poster presentation describes a collaborative strategy to address language barriers in health care in central Ohio. A shortage of health care interpreters in the central Ohio region compromises the health of a significant portion of our region's most vulnerable population. A collaborative strategy implemented by South-Western City School District, The Ohio State University and Primary One Health responds to this challenge through the development of a high school career pathway program to train certified health care interpreters

Mitophagy and the therapeutic clearance of damaged mitochondria for neuroprotection

Mitochondria are the foremost producers of the cellular energy currency ATP. They are also a significant source of reactive oxygen species and an important buffer of intracellular calcium. Mitochondrial retrograde signals regulate energy homeostasis and pro-survival elements whereas anterograde stimuli can trigger programmed cell death. Maintenance of a healthy, functional mitochondria network is therefore essential, and several mechanisms of mitochondrial quality control have been described. Mitochondrial dysfunction is linked to several neurodegenerative conditions including Parkinson, and Huntingdon diseases as well as Amyotrophic lateral sclerosis. Understanding the mechanisms governing mitochondrial quality control may reveal novel strategies for pharmacological intervention and disease therapy

Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition

Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation between dimerization and functional activity. We subsequently identified the dodecapeptide AR71, which prevents MIA dimerization and thereby acts as a MIA inhibitor. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy demonstrated the binding of AR71 to the MIA dimerization domain, in agreement with in vitro and in vivo data revealing reduced cell migration, reduced formation of metastases and increased immune response after AR71 treatment. We believe AR71 is a lead structure for MIA inhibitors. More generally, inhibiting MIA dimerization is a novel therapeutic concept in melanoma therapy

Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8

Cdc48/p97/VCP plays a ubiquitin-independent role during autophagosome formation in S. cerevisiae

No supra-additive effects of goserelin and radiotherapy on clonogenic survival of prostate carcinoma cells in vitro

<p>Abstract</p> <p>Background</p> <p>Oncological results of radiotherapy for locally advanced prostate cancer (PC) are significantly improved by simultaneous application of LHRH analoga (e.g. goserelin). As 85% of PC express LHRH receptors, we investigated the interaction of goserelin incubation with radiotherapy under androgen-deprived conditions in vitro.</p> <p>Methods</p> <p>LNCaP and PC-3 cells were stained for LHRH receptors. Downstream the LHRH receptor, changes in protein expression of c-fos, phosphorylated p38 and phosphorylated ERK1/2 were analyzed by means of Western blotting after incubation with goserelin and irradiation with 4 Gy. Both cell lines were incubated with different concentrations of goserelin in hormone-free medium. 12 h later cells were irradiated (0 – 4 Gy) and after 12 h goserelin was withdrawn. Endpoints were clonogenic survival and cell viability (12 h, 36 h and 60 h after irradiation).</p> <p>Results</p> <p>Both tested cell lines expressed LHRH-receptors. Changes in protein expression demonstrated the functional activity of goserelin in the tested cell lines. Neither in LNCaP nor in PC-3 any significant effects of additional goserelin incubation on clonogenic survival or cell viability for all tested concentrations in comparison to radiation alone were seen.</p> <p>Conclusion</p> <p>The clinically observed increase in tumor control after combination of goserelin with radiotherapy in PC cannot be attributed to an increase in radiosensitivity of PC cells by goserelin in vitro.</p