Microbial burden prediction model program

Model supplements biological surveys of spacecraft by simulating microbial burden accumulation process during periods when surveys are not taken. Important application of model is to predict microbial loading on spacecraft landing capsule immediately prior to terminal heat sterilization

A study program on the development of mathematical model/s/ for microbial burden prediction. Volume 1 - Technical report Final report

Mathematical models and computer program for microbial burden prediction - phases 1, 2,

Human cytomegalovirus-encoded pUL7 is a novel CEACAM1-like molecule responsible for promotion of angiogenesis.

UNLABELLED: Persistent human cytomegalovirus (HCMV) infection has been linked to several diseases, including atherosclerosis, transplant vascular sclerosis (TVS), restenosis, and glioblastoma. We have previously shown that factors secreted from HCMV-infected cells induce angiogenesis and that this process is due, at least in part, to increased secretion of interleukin-6 (IL-6). In order to identify the HCMV gene(s) responsible for angiogenesis promotion, we constructed a large panel of replication-competent HCMV recombinants. One HCMV recombinant deleted for UL1 to UL10 was unable to induce secretion of factors necessary for angiogenesis. Fine mapping using additional HCMV recombinants identified UL7 as a viral gene required for production of angiogenic factors from HCMV-infected cells. Transient expression of pUL7 induced phosphorylation of STAT3 and ERK1/2 MAP kinases and production of proangiogenic factors, including IL-6. Addition of recombinant pUL7 to cells was sufficient for angiogenesis and was again associated with increased IL-6 expression. Analysis of the UL7 structure revealed a conserved domain similar to the immunoglobulin superfamily domain and related to the N-terminal V-like domain of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Our report therefore identifies UL7 as a novel HCMV-encoded molecule that is both structurally and functionally related to cellular CEACAM1, a proangiogenic factor highly expressed during vasculogenesis. IMPORTANCE: A hallmark of cytomegalovirus (CMV) infection is its ability to modulate the host cellular machinery, resulting in the secretion of factors associated with long-term diseases such as vascular disorders and cancer. We previously demonstrated that HCMV infection alters the types and quantities of bioactive proteins released from cells (designated the HCMV secretome) that are involved in the promotion of angiogenesis and wound healing. A key proangiogenic and antiapoptotic factor identified from a proteomic-based approach was IL-6. In the present report, we show for the first time that HCMV UL7 encodes a soluble molecule that is a structural and functional homologue of the CEACAM1 proangiogenic cellular factor. This report thereby identifies a critical component of the HCMV secretome that may be responsible, at least in part, for the vascular dysregulation associated with persistent HCMV infection

4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection.

BackgroundChagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice.Methodology/principal findingsBoth acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart.Conclusions/significanceThe positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of safe re-administration of the medication during the lifespan of a Chagas disease patient. A medication that reduces parasite burden may halt or slow progression of cardiomyopathy and therefore improve both life expectancy and quality of life

Curating Tempelhof: negotiating the multiple histories of Berlin's ‘symbol of freedom’

Despite its National Socialist origins, the post-war use of Berlin’s Tempelhof Airport has seen it recast as a ‘symbol of freedom’. Since the airport’s 2008 closure the site has been caught between calls for increased engagement with its use under the Third Reich and economic incentives to repackage it as an attractive events location. Through analysing the different strategies through which Tempelhof’s past is negotiated, this article will highlight the contested nature of Berlin’s relationship with the past and the complex interaction between memory politics and more pragmatic issues

Integrating microalgae production with anaerobic digestion: a biorefinery approach

This is the peer reviewed version of the following article: [Uggetti, E. , Sialve, B. , Trably, E. and Steyer, J. (2014), Integrating microalgae production with anaerobic digestion: a biorefinery approach. Biofuels, Bioprod. Bioref, 8: 516-529. doi:10.1002/bbb.1469], which has been published in final form at https://doi.org/10.1002/bbb.1469. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingIn the energy and chemical sectors, alternative production chains should be considered in order to simultaneously reduce the dependence on oil and mitigate climate change. Biomass is probably the only viable alternative to fossil resources for production of liquid transportation fuels and chemicals since, besides fossils, it is one of the only available sources of carbon-rich material on Earth. Over recent years, interest in microalgae biomass has grown in both fundamental and applied research fields. The biorefinery concept includes different technologies able to convert biomass into added-value chemicals, products (food and feed) and biofuels (biodiesel, bioethanol, biohydrogen). As in oil refinery, a biorefinery aims at producing multiple products, maximizing the value derived from differences in biomass components, including microalgae. This paper provides an overview of the various microalgae-derived products, focusing on anaerobic digestion for conversion of microalgal biomass into methane. Special attention is paid to the range of possible inputs for anaerobic digestion (microalgal biomass and microalgal residue after lipid extraction) and the outputs resulting from the process (e.g. biogas and digestate). The strong interest in microalgae anaerobic digestion lies in its ability to mineralize microalgae containing organic nitrogen and phosphorus, resulting in a flux of ammonium and phosphate that can then be used as substrate for growing microalgae or that can be further processed to produce fertilizers. At present, anaerobic digestion outputs can provide nutrients, CO2 and water to cultivate microalgae, which in turn, are used as substrate for methane and fertilizer generation.Peer ReviewedPostprint (author's final draft

How Free is Free Indirect Discourse? Empirical Approaches to the Anchoring Mechanisms of Perspective-taking

This dissertation presents a discussion and empirical investigation of the anchoring mechanisms of free indirect discourse. Its main focus is on the claim that a discourse referent must be sufficiently activated in a linguistic context in order to serve as the anchor for a sentence in free indirect discourse mode. This issue becomes particularly pressing whenever more than one discourse referent is available as the perspectival center. I want to argue that whenever several referents compete, the referent with the highest activation is preferred as the perspectival center, while a sentence in FID mode anchored to a less activated referent sounds rather unnatural. To approach this claim, I provide a number of examples that illustrate that the anchoring of free indirect discourse is related to linguistic activation. The observations indicate that: (i) referents in subject position are preferred as anchors over referents in object position, (ii) referents that are introduced with a proper name are preferred as anchors over referents that are introduced with an indefinite noun phrase, (iii) referents that are activated in a larger context are preferred over referents that are activated in the sentence preceding the free indirect discourse, and (iv) referents that are assigned particular verbal features are preferred over competing referents. In order to account for these observations, I present the results of a series of psycholinguistic experiments that indicate an effect of grammatical function, referential expression, global activation, and verbal features assigned to the referents by the verb in the preceding context on the anchoring of free indirect discourse. Ultimately, the findings presented in this thesis indicate that the anchoring of free indirect discourse is not arbitrary but determined by referential activation