Wind tunnel testing of a generic telescope enclosure

The design of future large optical telescopes must take into account the wind-induced buffeting of the telescope structure caused by large-scale flow structures and turbulence inside the dome. However, estimating the resulting degradation in image quality is difficult due to our relatively poor understanding of the flow inside the dome. Data has been collected in a scaled wind-tunnel test of a telescope enclosure to understand the flow-field around the region near the dome opening where the secondary mirror and supporting structure would be subjected to wind loads. Digital particle image velocimetry (DPIV) data was collected in a vertical plane near the dome opening to obtain mean velocity and fluctuation kinetic energy. In addition, hotwire data was collected along the telescope axis to obtain temporal spectra of the velocity, and flow visualization was used to determine the general flow patterns. In addition to its direct use in telescope modeling and design, this data is of particular value in validation of computational fluid dynamic (CFD) analyses, so that CFD can be used with confidence in future design work

Methods for Analyzing Early Stage Naval Distributed Systems Designs, Employing Simplex, Multislice, and Multiplex Networks.

Naval ships are some of the most complex systems ever engineered. The process by which they are designed is similarly complex. The complexity and disjointedness of this process leads to the creation of disparate and incomplete ship design information created by different systems of analysis, completed by different design groups, using different tools, at different levels of fidelity. Distributed system design decisions based off this disparate and incomplete information lead to unnecessary complexity when the design is transitioned from the early design stage to the detailed design stage. This dissertation presents novel network theory-based methods for better understanding and analyzing the implications of early stage distributed system design decisions. This new method introduces network theory concepts such as degree distribution, system interdependence, and community to the field of distributed systems design as metrics for determining system robustness, as well as develops new techniques for representing physical systems as networks. Additionally, a personnel movement modeling and analysis method, derived from the network concept of betweenness centrality, is developed. This dissertation documents the first use of multislice and multiplex structures in the analysis of physical systems. System design evolutions are analyzed using multislice network structures and the interactions between systems are investigated using multiplex network structures. These two structures are combined into a novel time-dependent multiplex network structure that is developed in this work. This new structure is used to track the evolution of systems interactions. A new network complexity metric based on the concepts of planarity and network communities is created for this research in a response to lack of methods for studying the planar and near planar networks that often arise in the study of real systems. The methods presented in this dissertation do not require complex 3D CAD models or simulations. Therefore, they can be used by a single naval architect to gain insight into the implications of design decisions in the early design stages. This will result in improved naval distributed systems designs that are easier to design, maintain, and upgrade.PhDNaval Architecture and Marine EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108838/1/rigterin_1.pd

IL-2 limits IL-12 enhanced lymphocyte proliferation during \u3ci\u3eLeishmania amazonensis\u3c/i\u3e infection

C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44hiCD4+ T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44hiCD4+ T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4+ T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional Treg cells

IL-2 limits IL-12 enhanced lymphocyte proliferation during \u3ci\u3eLeishmania amazonensis\u3c/i\u3e infection

C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44hiCD4+ T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44hiCD4+ T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4+ T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional Treg cells

Ubiquitination and proteasomal degradation of ATG12 regulates its proapoptotic activity

During macroautophagy, conjugation of ATG12 to ATG5 is essential for LC3 lipidation and autophagosome formation. Additionally, ATG12 has ATG5-independent functions in diverse processes including mitochondrial fusion and mitochondrial-dependent apoptosis. In this study, we investigated the regulation of free ATG12. In stark contrast to the stable ATG12–ATG5 conjugate, we find that free ATG12 is highly unstable and rapidly degraded in a proteasome-dependent manner. Surprisingly, ATG12, itself a ubiquitin-like protein, is directly ubiquitinated and this promotes its proteasomal degradation. As a functional consequence of its turnover, accumulation of free ATG12 contributes to proteasome inhibitor-mediated apoptosis, a finding that may be clinically important given the use of proteasome inhibitors as anticancer agents. Collectively, our results reveal a novel interconnection between autophagy, proteasome activity, and cell death mediated by the ubiquitin-like properties of ATG12

Wind tunnel testing of a generic telescope enclosure

The design of future large optical telescopes must take into account the wind-induced buffeting of the telescope structure caused by large-scale flow structures and turbulence inside the dome. However, estimating the resulting degradation in image quality is difficult due to our relatively poor understanding of the flow inside the dome. Data has been collected in a scaled wind-tunnel test of a telescope enclosure to understand the flow-field around the region near the dome opening where the secondary mirror and supporting structure would be subjected to wind loads. Digital particle image velocimetry (DPIV) data was collected in a vertical plane near the dome opening to obtain mean velocity and fluctuation kinetic energy. In addition, hotwire data was collected along the telescope axis to obtain temporal spectra of the velocity, and flow visualization was used to determine the general flow patterns. In addition to its direct use in telescope modeling and design, this data is of particular value in validation of computational fluid dynamic (CFD) analyses, so that CFD can be used with confidence in future design work

Parenting trans and nonbinary youth

The Oklahoma Cooperative Extension Service periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311

Divergent drivers of carbon dioxide and methane dynamics in an agricultural coastal floodplain: post-flood hydrological and biological drivers

Many coastal floodplains have been artificially drained for agriculture, altering hydrological connectivity and the delivery of groundwater-derived solutes including carbon dioxide (CO2) and methane (CH4) to surface waters. Here, we investigated the drivers of CO2 and CH4 within the artificial drains.of a coastal floodplain under sugarcane plantation and quantify the contribution of groundwater discharge to CO2 and CH4 dynamics over a flood event (290 mm of rainfall). High temporal resolution, in situ observations of dissolved CO2 and CH4, carbon stable isotopes of CH4 (delta C-13-CH4), and the natural groundwater tracer radon (Rn-222) allowed us to quantify. CO2, CH4 and groundwater dynamics during the rapid recession of a flood over a five day period. Extreme super-saturation of free CO2 ([CO2*]) up to 2,951 mu M (25,480% of atmospheric equilibrium) was driven by large groundwater input into the drains (maximum 87 cm day-(1)), caused by a steep hydraulic head in the adjacent water table. Groundwater input sustained between 95 and 124% of the surface [CO2*] flux during the flood recession by delivering high carbonate alkalinity groundwater (DIC = 10,533 mu M, similar to pH = 7.05) to acidic surface water (pH <4), consequently transforming all groundwater-derived DIC to [CO2*]. In contrast, groundwater was not a major direct driver of CH4 contributing only 14% of total CH4 fluxes. A progressive increase in CH4 concentrations of up to similar to 2400 nM day-(1) occurred as a combination of increased substrate availability delivered by post-flood drainage water and longer residence times, which allowed for a biogenic CH4 signal to develop. The progressive enrichment in delta C-13-CH4 values (- 70%. to-48%.) and increase in CH4 concentrations (46-2460 nM) support coupled production-oxidation, with concentrations and delta C-13 values remaining higher (2,798 nM and-47%.) than pre-flood conditions (534 nM and-55 parts per thousand) three weeks after the flood. Our findings demonstrate how separate processes can drive the aquatic CO2 and CH4 response to a flood event in a drained coastal floodplain, and the key role groundwater had in post-flood [CO2*] evasion to the atmosphere, but not CH4. (C) 2016 Elsevier B.V. All rights reserved

T. brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes

Aims: African trypanosomiasis, caused by Trypanosoma brucei species, leads to both neurological and cardiac dysfunction and can be fatal if untreated. While the neurological-related pathogenesis is well studied, the cardiac pathogenesis remains unknown. The current study exposed isolated ventricular cardiomyocytes and adult rat hearts to T. brucei to test whether trypanosomes can alter cardiac function independent of a systemic inflammatory/immune response. Methods and results: Using confocal imaging, T. brucei and T. brucei culture media (supernatant) caused an increased frequency of arrhythmogenic spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release (Ca2+ waves) in isolated adult rat ventricular cardiomyocytes. Studies utilising inhibitors, recombinant protein and RNAi all demonstrated that this altered SR function was due to T. brucei cathepsin-L (TbCatL). Separate experiments revealed that TbCatL induced a 10–15% increase of SERCA activity but reduced SR Ca2+ content, suggesting a concomitant increased SR-mediated Ca2+ leak. This conclusion was supported by data demonstrating that TbCatL increased Ca2+ wave frequency. These effects were abolished by autocamtide-2-related inhibitory peptide, highlighting a role for CaMKII in the TbCatL action on SR function. Isolated Langendorff perfused whole heart experiments confirmed that supernatant caused an increased number of arrhythmic events. Conclusion: These data demonstrate for the first time that African trypanosomes alter cardiac function independent of a systemic immune response, via a mechanism involving extracellular cathepsin-L-mediated changes in SR function

Development of analytical characterization tools for process monitoring of adenovirus-based vaccines (ChAdOx and Ad5)

Product quality understanding is a critical part of viral vector vaccine manufacturing and regulation. Mass spectrometry is a technique that has widely been applied to protein-based therapeutics and could be used as a characterisation tool to monitor viral vector vaccine product quality. The ultimate objective of this Bill and Melinda Gates Foundation funded project is to enable vaccine manufacturing in Low and Middle-income countries (LMIC) through increased scientific understanding of viral vector vaccine manufacturing bottlenecks and therefore de-risking of vaccine development and manufacturing. Please click Download on the upper right corner to see the full abstract