Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells. © 2010 MacTavish et al

Defense Mechanisms of Hepatocytes Against Burkholderia pseudomallei

The Gram-negative facultative intracellular rod Burkholderia pseudomallei causes melioidosis, an infectious disease with a wide range of clinical presentations. Among the observed visceral abscesses, the liver is commonly affected. However, neither this organotropism of B. pseudomallei nor local hepatic defense mechanisms have been thoroughly investigated so far. Own previous studies using electron microscopy of the murine liver after systemic infection of mice indicated that hepatocytes might be capable of killing B. pseudomallei. Therefore, the aim of this study was to further elucidate the interaction of B. pseudomallei with these cells and to analyze the role of hepatocytes in anti-B. pseudomallei host defense. In vitro studies using the human hepatocyte cell line HepG2 revealed that B. pseudomallei can invade these cells. Subsequently, B. pseudomallei is able to escape from the vacuole, to replicate within the cytosol of HepG2 cells involving its type 3 and type 6 secretion systems, and to induce actin tail formation. Furthermore, stimulation of HepG2 cells showed that IFNγ can restrict growth of B. pseudomallei in the early and late phase of infection whereas the combination of IFNγ, IL-1β, and TNFα is required for the maximal antibacterial activity. This anti-B. pseudomallei defense of HepG2 cells did not seem to be mediated by inducible nitric oxide synthase-derived nitric oxide or NADPH oxidase-derived superoxide. In summary, this is the first study describing B. pseudomallei intracellular life cycle characteristics in hepatocytes and showing that IFNγ-mediated, but nitric oxide- and reactive oxygen species-independent, effector mechanisms are important in anti-B. pseudomallei host defense of hepatocytes

Deformation and phase transformation in polycrystalline cementite (Fe3_{3}C) during single- and multi-pass sliding wear

Cementite (Fe$_{3}$C) plays a major role in the tribological performance of rail and bearing steels. Nonetheless, the current understanding of its deformation behavior during wear is limited because it is conventionally embedded in a matrix. Here, we investigate the deformation and chemical evolution of bulk polycrystalline cementite during single-pass sliding at a contact pressure of 31 GPa and reciprocating multi-pass sliding at 3.3 GPa. The deformation behavior of cementite was studied by electron backscatter diffraction for slip trace analysis and transmission electron microscopy. Our results demonstrate activation of several deformation mechanisms below the contact surface: dislocation slip, shear band formation, fragmentation, grain boundary sliding, and grain rotation. During sliding wear, cementite ductility is enhanced due to the confined volume, shear/compression domination, and potentially frictional heating. The microstructural alterations during multi-pass wear increase the subsurface nanoindentation hardness by up to 2.7 GPa. In addition, we report Hägg carbide (Fe$_{5}$C$_{2}$) formation in the uppermost deformed regions after both sliding experiments. Based on the results of electron and X-ray diffraction, as well as atom probe tomography, we propose potential sources of excess carbon and mechanisms that promote the phase transformation

Gasaustausch zwischen einem Helium enthaltenden Behälter und der Umgebung über ein nach unten abgehendes Rohr und dessen Relevanz für den HTR Modu

After a fracture of the fuel charge tube {$\varnothing$ = 65 mm) of a HTR-Modul-Reactor a rapid depressurization of the primary circuit occurs and thereafter a long-range gas exchange between primary circuit and containment takes place. Experiments related to the problem of gas exchange between a vessel and the environment via a vertically installed tube were carried out. For the calculation of the gas exchange rates a computer code was developed, which takes into account all mechanisms influencing the exchange rate in the experiment. The calculated values were in good agreement with the experimental results. The transformation of the results to a HTR-Modul shows that the gas exchange rate in the case of a charge tube fracture is only determined by gas expansion and contraction in the primary circuit. Therefore the amount of air entering the primary circuit is very small

Ausström- und Gasaustauschvorgänge nach Lecks im Primärkreislauf von Hochtemperaturreaktoren

The occurrence of leaks in the pressurized enclosure of an Helium cooled High Temperature Reactor leads in a first step to a rapid outflow of the cooling gas. After loss of pressure gas exchange processes start governd by convection, diffusion and the so called 'breathing'of the primary circuit. Theoretical models for the treatment of the processes are presented. Further experimental investigations are reported. The phenomena are discussed and theory and experiments are compared

Seroprevalence of Zika virus in wild African green monkeys and baboons

ABSTRACT Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive “sentinel” macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and those studying ZIKV in primates in particular. Podcast: A podcast concerning this article is available

Operating Cabled Underwater Observatories in Rough Shelf-Sea Environments:A Technological Challenge

Cabled coastal observatories are often seen as future-oriented marine technology that enables science to conduct observational and experimental studies under water year-round, independent of physical accessibility to the target area. Additionally, the availability of (unrestricted) electricity and an Internet connection under water allows the operation of complex experimental setups and sensor systems for longer periods of time, thus creating a kind of laboratory beneath the water. After successful operation for several decades in the terrestrial and atmospheric research field, remote controlled observatory technology finally also enables marine scientists to take advantage of the rapidly developing communication technology. The continuous operation of two cabled observatories in the southern North Sea and off the Svalbard coast since 2012 shows that even highly complex sensor systems, such as stereo-optical cameras, video plankton recorders or systems for measuring the marine carbonate system, can be successfully operated remotely year-round facilitating continuous scientific access to areas that are difficult to reach, such as the polar seas or the North Sea. Experience also shows, however, that the challenges of operating a cabled coastal observatory go far beyond the provision of electricity and network connection under water. In this manuscript, the essential developmental stages of the "COSYNA Shallow Water Underwater Node" system are presented, and the difficulties and solutions that have arisen in the course of operation since 2012 are addressed with regard to technical, organizational and scientific aspects.</p

Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice

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The Coastal Observing System for Northern and Arctic Seas (COSYNA)

The Coastal Observing System for Northern and Arctic Seas (COSYNA) was established in order to better understand the complex interdisciplinary processes of northern seas and the Arctic coasts in a changing environment. Particular focus is given to the German Bight in the North Sea as a prime example of a heavily used coastal area, and Svalbard as an example of an Arctic coast that is under strong pressure due to global change. The COSYNA automated observing and modelling system is designed to monitor real-time conditions and provide short-term forecasts, data, and data products to help assess the impact of anthropogenically induced change. Observations are carried out by combining satellite and radar remote sensing with various in situ platforms. Novel sensors, instruments, and algorithms are developed to further improve the understanding of the interdisciplinary interactions between physics, biogeochemistry, and the ecology of coastal seas. New modelling and data assimilation techniques are used to integrate observations and models in a quasi-operational system providing descriptions and forecasts of key hydrographic variables. Data and data products are publicly available free of charge and in real time. They are used by multiple interest groups in science, agencies, politics, industry, and the public