49 research outputs found

    Aerodynamic Performance of Micro Aerial Wing Structures at Low Reynolds Number

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    Corrugations are folds on a surface as found on wings of dragon fly insects. Although they fly at relatively lower altitudes its wings are adapted for better aerodynamic and aero-elastic characteristics. In the present work, three airfoil geometries were studied using the 2-D panel method to evaluate the aerodynamic performance for low Reynolds number. The experiments were conducted in wind tunnel for incompressible flow regime to demonstrate the coefficients of lift drag and glide ratio at two Reynolds numbers 1.9x104 and 1.5x105 and for angles of attack ranging between 00 and 160. The panel method results have been validated using the current and existing experiment data as well as with the computational work from cited literature. A good agreement between the experimental and the panel methods were found for low angles of attack. The results showed that till 80 angle of attack higher lift coefficient and lower drag coefficient are obtainable for corrugated airfoils as compared to NACA 0010. The validation of surface pressure coefficients for all three airfoils using the panel method at 40 angles of attack was done. The contours of the non-dimensional pressure and velocity are illustrated from -100 to 200 angles of attack. A good correlation between the experiment data and the computational methods revealed that the corrugated airfoils exhibit better aerodynamic performance than NACA 0010

    Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin

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    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and has become a global health threat. No HCV vaccine is currently available and treatment with antiviral therapy is associated with adverse side effects. Moreover, there is no preventive therapy for recurrent hepatitis C post liver transplantation. The NS3 serine protease is necessary for HCV replication and represents a prime target for developing anti HCV therapies. Recently we described a therapeutic approach for eradication of HCV infected cells that is based on protein delivery of two NS3 protease-activatable recombinant toxins we named “zymoxins”. These toxins were inactivated by fusion to rationally designed inhibitory peptides via NS3-cleavable linkers. Once delivered to cells where NS3 protease is present, the inhibitory peptide is removed resulting in re-activation of cytotoxic activity. The zymoxins we described suffered from two limitations: they required high levels of protease for activation and had basal activities in the un-activated form that resulted in a narrow potential therapeutic window. Here, we present a solution that overcame the major limitations of the “first generation zymoxins” by converting MazF ribonuclease, the toxic component of the E. coli chromosomal MazEF toxin-antitoxin system, into an NS3-activated zymoxin that is introduced to cells by means of gene delivery. We constructed an expression cassette that encodes for a single polypeptide that incorporates both the toxin and a fragment of its potent natural antidote, MazE, linked via an NS3-cleavable linker. While covalently paired to its inhibitor, the ribonuclease is well tolerated when expressed in naïve, healthy cells. In contrast, activating proteolysis that is induced by even low levels of NS3, results in an eradication of NS3 expressing model cells and HCV infected cells. Zymoxins may thus become a valuable tool in eradicating cells infected by intracellular pathogens that express intracellular proteases

    Engineered Toxins “Zymoxins” Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain

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    The synthesis of inactive enzyme precursors, also known as “zymogens,” serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV) as a model, we designed two HCV NS3 protease-activated “zymogenized” chimeric toxins (which we denote “zymoxins”). In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA) and Ricin A chain (RTA), respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the “zymoxin” approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected

    Evaluation of fast pyrolysis feedstock conversion with a mixing paddle reactor

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    © 2017 We have developed a pyrolysis reactor based on a unique auger-paddle configuration with heat transfer material (HTM) and proved to achieve high heating rates and fast pyrolysis. We tested ten different biomass types and obtained bio-oil yields ranging from approximately 40% for thermally treated wood, to approximately 57% for crop residues (corn stover) and 67% yield for woody feedstocks (tulip poplar). These results, as well as the solid char yields, are similar to those obtained for the same feedstock using a circulating fluidized bed. Tests conducted without HTM resulted in lower bio-oil yields (ranging from 8 to 18% decrease in yield) and higher char yields with similar changes in magnitude, which is indicative of slow pyrolysis. In addition, a comprehensive study and analysis of the material residence time and mixing characteristics of the novel auger-paddle system is presented. These results demonstrate that an auger-paddle configuration is capable of achieving the high heating rates required for fast pyrolysis

    Irradiation up-regulates CD80 expression through two different mechanisms in spleen B cells, B lymphoma cells, and dendritic cells

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    We have previously demonstrated irradiation-induced up-regulation of CD80 expression in A20-HL B lymphoma cells by inducing expression of tumour necrosis factor-α (TNF-α) and CD154. In the present study, we investigated whether irradiation also up-regulates CD80 expression in mouse spleen B cells. Because freshly prepared spleen B cells are highly sensitive to irradiation, we employed spleen B cells stimulated with lipopolysaccharide (LPS-B cells). X-irradiation (8 Gy) followed by incubation (9–12 hr) highly and selectively up-regulated CD80 expression in LPS-B cells, whereas the same treatment slightly increased expression of CD54 and did not affect expression of CD86, major histocompatibility complex class II, CD11a or surface immunoglobulin M. The irradiation-induced up-regulation of CD80 expression resulted in enhanced APC function of LPS-B cells. Up-regulation of CD80 expression on LPS-B cells was accompanied by an increase in CD80 mRNA accumulation and nuclear factor (NF)-κB activation. Activation of NF-κB was shown to be critical for up-regulation of CD80 expression as pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, severely decreased the observed up-regulation. X-irradiation of LPS-B cells induced expression of TNF-α but not CD154. However, anti-TNF-α monoclonal antibody (mAb) with anti-CD154 mAb did not inhibit X-irradiation-induced up-regulation of CD80 expression in LPS-B cells, whereas these mAbs almost completely inhibited this up-regulation in A20-HL cells and bone marrow-derived dendritic cells (DCs). In contrast, a thiol antioxidant, N-acetyl-l-cysteine, completely blocked X-irradiation-induced up-regulation of CD80 expression in LPS-B cells, but not in A20-HL cells or in DCs. Based on these findings, we concluded that X-irradiation up-regulates CD80 expression not only in A20-HL cells and DCs but also in LPS-B cells, and that this up-regulation in LPS-B cells via NF-κB activation is dependent on the generation of reactive oxygen species, while that in A20-HL cells and DCs is not
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