Monitoring the dynamic behaviors of the Bosporus Bridge by GPS during Eurasia Marathon

International audienceEngineering structures, like bridges, dams and towers are designed by considering temperature changes, earthquakes, wind, traffic and pedestrian loads. However, generally, it can not be estimated that these structures may be affected by special, complex and different loads. So it could not be known whether these loads are dangerous for the structure and what the response of the structures would be to these loads. Such a situation occurred on the Bosporus Bridge, which is one of the suspension bridges connecting the Asia and Europe continents, during the Eurasia Marathon on 2 October 2005, in which 75 000 pedestrians participated. Responses of the bridge to loads such as rhythmic running, pedestrian walking, vehicle passing during the marathon were observed by a real-time kinematic (RTK) Global Positioning System (GPS), with a 2.2-centimeter vertical accuracy. Observed responses were discussed in both time domain and frequency domain by using a time series analysis. High (0.1?1 Hz) and low frequencies (0.00036?0.01172 Hz) of observed bridge responses under 12 different loads which occur in different quantities, different types and different time intervals were calculated in the frequency domain. It was seen that the calculated high frequencies are similar, except for the frequencies of rhythmic running, which causes a continuously increasing vibration. Any negative response was not determined, because this rhythmic effect continued only for a short time. Also when the traffic load was effective, explicit changes in the bridge movements were determined. Finally, it was seen that bridge frequencies which were calculated from the observations and the finite element model were harmonious. But the 9th natural frequency value of the bridge under all loads, except rhythmic running could not be determined with observations

Suborbital Payload Testing Aboard Level 3 Rocket Research Platform

Embry-Riddle Aeronautical University (ERAU) has launched several suborbital scientific payloads aboard Blue Origin’s New Shepard in 2017 and 2019. Students continue gaining hands-on experience in rocket design and construction, and payload integration and testing of future and more mature payloads to be launched into space. A Level 3 Rocket is being designed and developed at ERAU to serve as a scaled-down model research platform for launching and testing of payloads that will be later flown in commercial suborbital platforms such as Blue Origin’s New Shepard and PLD space Miura 1 rockets. Computer simulations were conducted to calculate the key parameters such as flight trajectory profiles, stability and flight velocities for different rocket motors configurations. A preliminary design of the rocket was developed using Computer-Aided Design (CAD) software. The rocket will accommodate multiple payloads (Cubesats, NanoLabs, TubeSats) designed and developed in the Payload Applied, Technology and Operations (PATO) laboratory. The rocket will be primarily constructed of carbon fiber composite as it has a high strength to weight ratio. These simulations are used to select a suitable motor for the rocket according to the flight requirements and landing restrictions. This prospective Level 3 Rocket is referred to as Suborbital Technology Experimental Vehicle for Exploration (STEVE). Rocket procedures and results from the design, simulation, construction and assembly will be presented

The role of lymphoid tissue SPARC in the pathogenesis and response to treatment of multiple myeloma.

BACKGROUND: Despite the significant progress in the treatment of multiple myeloma (MM), the disease remains untreatable and its cure is still an unmet clinical need. Neoplastic transformation in MM is initiated in the germinal centers (GCs) of secondary lymphoid tissue (SLT) where B cells experience extensive somatic hypermutation induced by follicular dendritic cells (FDCs) and T-cell signals. OBJECTIVE: We reason that secreted protein acidic and rich in cysteine (SPARC), a common stromal motif expressed by FDCs at the origin (SLTs) and the destination (BM) of MM, plays a role in the pathogenesis of MM, and, here, we sought to investigate this role. METHODS: There were 107 BM biopsies from 57 MM patients (taken at different time points) together with 13 control specimens assessed for SPARC gene and protein expression and compared with tonsillar tissues. In addition, regulation of myeloma-promoting genes by SPARC-secreting FDCs was assessed in in vitro GC reactions (GCRs). RESULTS: SPARC gene expression was confirmed in both human primary (BM) and secondary (tonsils) lymphoid tissues, and the expression was significantly higher in the BM. Sparc was detectable in the BM and tonsillar lysates, co-localized with the FDC markers in both tissues, and stimulation of FDCs in vitro induced significantly higher levels of SPARC expression than unstimulated controls. In addition, SPARC inversely correlated with BM PC infiltration, ISS staging, and ECOG performance of the MM patients, and in vitro addition of FDCs to lymphocytes inhibited the expression of several oncogenes associated with malignant transformation of PCs. CONCLUSION: FDC-SPARC inhibits several myelomagenic gene expression and inversely correlates with PC infiltration and MM progression. Therapeutic induction of SPARC expression through combinations of the current MM drugs, repositioning of non-MM drugs, or novel drug discovery could pave the way to better control MM in clinically severe and drug-resistant patients

Fatty Acid Composition of Growing Kiko X Spanish Crossbred Intact Male Goats Fed Varying Levels of Peanut Skins

Abstract The objective was to evaluate the effects of feeding peanut skins (PS) on fatty acid profile of goat meat. The diets used contained 0, 10, 20, and 30% of PS. After 92 days, longissimus muscle (LM), mesenteric adipose (MA), and subcutaneous (SA) tissue samples were analyzed for fatty acid profile. Eighteen (18), 21, and 21 fatty acids were detected in LM, MS and SC adipose tissues, respectively. No changes were detected in the fatty acid profile, but C18:0 increased linearly in LM (p \u3c 0.05) with increasing level of PS whereas C18:1 decreased in the similar manner (p = 0.05). Total saturated fatty acid and monounsaturated fatty acid percentage increased linearly (p \u3c 0.05) in LM fat, but polyunsaturated fatty acids were not different (p \u3e 0.05) among treatments. The results showed that the fatty acid composition of goat carcass can be altered with the dietary addition of PS. Keywords: Meat Goats, Peanut Skins, Fatty Acid

Structural Basis for Inhibition Promiscuity of Dual Specific Thrombin and Factor Xa Blood Coagulation Inhibitors

AbstractBackground: A major current focus of pharmaceutical research is the development of selective inhibitors of the blood coagulation enzymes thrombin or factor Xa to be used as orally bioavailable anticoagulant drugs in thromboembolic disorders and in the prevention of venous and arterial thrombosis. Simultaneous direct inhibition of thrombin and factor Xa by synthetic proteinase inhibitors as a novel approach to antithrombotic therapy could result in potent anticoagulants with improved pharmacological properties.Results: The binding mode of such dual specific inhibitors of thrombin and factor Xa was determined for the first time by comparative crystallography using human α-thrombin, human des-Gla (1–44) factor Xa and bovine trypsin as the ligand receptors. The benzamidine-based inhibitors utilize two different conformations for the interaction with thrombin and factor Xa/trypsin, which are evoked by the steric requirements of the topologically different S2 subsites of the enzymes. Compared to the unliganded forms of the proteinases, ligand binding induces conformational adjustments of thrombin and factor Xa active site residues indicative of a pronounced induced fit mechanism.Conclusion: The structural data reveal the molecular basis for a desired unselective inhibition of the two key components of the blood coagulation cascade. The 4-(1-methyl-benzimidazole-2-yl)-methylamino-benzamidine moieties of the inhibitors are able to fill both the small solvent accessible as well as the larger hydrophobic S2 pockets of factor Xa and thrombin, respectively. Distal fragments of the inhibitors are identified which fit into both the cation hole/aromatic box of factor Xa and the hydrophobic aryl binding site of thrombin. Thus, binding constants in the medium-to-low nanomolar range are obtained against both enzymes

Outer-Sphere Contributions to the Electronic Structure of Type Zero Copper Proteins

Bioinorganic canon states that active-site thiolate coordination promotes rapid electron transfer (ET) to and from type 1 copper proteins. In recent work, we have found that copper ET sites in proteins also can be constructed without thiolate ligation (called “type zero” sites). Here we report multifrequency electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), and nuclear magnetic resonance (NMR) spectroscopic data together with density functional theory (DFT) and spectroscopy-oriented configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1 centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Fungal model systems and the elucidation of pathogenicity determinants

This is the final version of the article. Available from Elsevier via the DOI in this record.Fungi have the capacity to cause devastating diseases of both plants and animals, causing significant harvest losses that threaten food security and human mycoses with high mortality rates. As a consequence, there is a critical need to promote development of new antifungal drugs, which requires a comprehensive molecular knowledge of fungal pathogenesis. In this review, we critically evaluate current knowledge of seven fungal organisms used as major research models for fungal pathogenesis. These include pathogens of both animals and plants; Ashbya gossypii, Aspergillus fumigatus, Candida albicans, Fusarium oxysporum, Magnaporthe oryzae, Ustilago maydis and Zymoseptoria tritici. We present key insights into the virulence mechanisms deployed by each species and a comparative overview of key insights obtained from genomic analysis. We then consider current trends and future challenges associated with the study of fungal pathogenicity.This review was carried out by members of the EU-Initial Training Network Ariadne (PITN-GA-2009-237936), which provided financial support for C.B., S.D., M.E.G., E.G., E.M., P.V.M., M.M., V.N., M.F.A.N., T.O., M.O.R., K.S. and L.W