Hypoxic Incubation Chamber

In developing a model to test anti-tumor drugs, Dr. Christopher Heylman’s lab requires the ability to culture cells in a hypoxic environment. The purpose of this project was to make this possible. Funding for this project comes from the Biomedical Engineering Department, the Hannah-Forbes Fund, and Dr. Heylman’s lab. The chamber must be able to reach a user-defined oxygen concentration and hold that concentration for 48 hours while creating an environment conducive to cell culture. Importantly, the chamber must also be sterilizable and cleanable for repeated use. While several products exist to create hypoxic environments for cell culture, they are either too expensive or too simple. The timeline of this project has been largely dictated by the BMED senior project class and its deadlines, culminating in the Final Report and Presentation given on March 9th. Several different ideas were generated to meet the customer requirements in various ways. The final design of the chamber is a rectangular box with a detachable door that is held onto the chamber by 3 latches. The door uses a rubber gasket with neoprene to prevent air from escaping or entering the chamber. Gas is allowed into the chamber through two different tubes- one supplying oxygen as an “up” control and one supplying a nitrogen and carbon dioxide mixture as a “down” control of the oxygen concentration. Flow through the tubes is regulated by two needle valves. A check valve on the side of the chamber allows excess gas to exit if the pressure passes 0.5 psi. An oxygen sensor sits in the top of the chamber that gives a continuous oxygen reading to a connected computer through an Arduino Uno. The only manufacturing required was that of the chamber, but because the chamber is a pressure vessel, the manufacturing had to be quite precise. Tests were to be conducted on the sealability of the chamber, the accuracy of setting the O2 level, the oxygen sensor itself and more. Due to time constraints, the only test that was able to be carried out to any significant extent was a Modified Maintain Oxygen Level test which determined what the best method of sealing the chamber was to maximize the amount of time the chamber was able to hold a given oxygen concentration. More work needs to be done for this project to be useful in a research setting. The chamber needs a way to be heated and held at a temperature conducive to cell proliferation. Additionally, active control of the valves will need to be introduced to hold the oxygen concentration within spec for 48 hours

Lipid nanoparticle-encapsulated, chemically modified anti-adenoviral siRNAs inhibit hepatic adenovirus infection in immunosuppressed Syrian hamsters

RNA interference has demonstrated its potential as an antiviral therapy for treatment of human adenovirus (hAd) infections. The only existing viral vector-based system for delivery of anti-adenoviral artificial microRNAs available for in vivo use, however, has proven to be inefficient in therapeutic applications. In this study, we investigated the potential of stabilized small interfering RNA (siRNA) encapsulated in lipid nanoparticles (LNPs) for treatment of hepatic hAd serotype 5 (hAd5) infection in an hAd infection model using immunosuppressed Syrian hamsters. The siRNA sipTPmod directed against the adenoviral pre-terminal protein (pTP) and containing 2′-O-methyl modifications as well as phosphorothioate linkages effectively inhibited hAd5 infection in vitro. In light of this success, sipTPmod was encapsulated in LNPs containing the cationic lipid XL-10, which enables hepatocyte-specific siRNA transfer, and injected intravenously into hAd5-infected immunosuppressed Syrian hamsters. This resulted in a significant reduction of liver hAd5 titers, a trend toward reduced liver injury and inflammation, and reduction of viral titers in the blood and spleen compared with hAd5-infected animals that received a non-silencing siRNA. These effects were demonstrated in animals infected with low and moderate doses of hAd5. These data demonstrate that hepatic hAd5 infection can be successfully treated with anti-adenoviral sipTPmod encapsulated in LNPs

Social Provisioning Process and Socio-Economic Modeling

The radical difference between orthodox and heterodox economics emanates from the different views of the capitalist socio-economic system. Economics as the science of social provisioning felicitously describes the heterodox view that economy is part of the evolving social order; social agency is embedded in the social and cultural context; a socio-economic change is driven by technical and cultural changes; and the provisioning process is open-ended. Such a perspective on economy offers ample methodological and theoretical implications for modeling the capitalist economy in a realistic manner. It lends itself especially to the micro-macro synthetic approach. Thus the objective of this paper is twofold: 1) to examine how the concept of the social provisioning process can be clarified and expanded by virtue of recent development in heterodox methodology and 2) to discuss how methodological development would nourish the heterodox modeling and theorizing of the capitalist social provisioning process

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

The Mouse Cytomegalovirus Gene m42 Targets Surface Expression of the Protein Tyrosine Phosphatase CD45 in Infected Macrophages

The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264.7 macrophage cell line led to comparable regulation of CD45 expression. In immunocompetent mice infected with an m42 deletion mutant lower viral titers were observed in all tissues examined when compared to wildtype MCMV, indicating an important role of m42 for viral replication in vivo. The m42 gene product was identified as an 18 kDa protein expressed with early kinetics and is predicted to be a tailanchored membrane protein. Tracking of surface-resident CD45 molecules revealed that m42 induces internalization and degradation of CD45. The observation that the amounts of the E3 ubiquitin ligases Itch and Nedd4 were diminished in cells expressing m42 and that disruption of a PY motif in the N-terminal part of m42 resulted in loss of function, suggest that m42 acts as an activator or adaptor for these Nedd4-like ubiquitin ligases, which mark CD45 for lysosomal degradation. In conclusion, the down-modulation of CD45 expression in MCMV-infected myeloid cells represents a novel pathway of virus-host interaction

Messianic Scientism: Technocracy, 1919-1960.

PhDSocial structureUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/179598/2/6304950.pd