The Holst Action by the Spectral Action Principle

We investigate the Holst action for closed Riemannian 4-manifolds with orthogonal connections. For connections whose torsion has zero Cartan type component we show that the Holst action can be recovered from the heat asymptotics for the natural Dirac operator acting on left-handed spinor fields.Comment: We correct a sign mistake in Proposition 2.3. As a consequence the main result (Theorem 3.4) becomes more natura

The refined decentralized concept and development support

After the technical feasibility of the decentralized user support was demonstrated earlier, this study phase elaborated on questions with respect to the sharing of responsibilities and how to operate the different types of payloads. After having worked out an appropriate classification for payloads it is shown that a clear scheme about the distribution of responsibilities during the various phases of an experiment has been found and that the payload operation can be performed in the vicinity of the researcher. The aspect of development support has been picked up by the user support to minimize the development process. A list of the tasks to be performed in support of the development of experiments has been compiled with a detailed description for each payload class. © 1993.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

User support for the Columbus Precursor Missions

Based on the User Support Organization definition concept, this paper describes how user support for the precursor missions could be implemented. A survey of the facilities to be included in the Spacelab E1 and the EURECA 2 missions has been performed. Additionally, an overview of the national user support activities in Europe is given. It is assumed that this infrastructure can be applied for precursor mission support, as well. On the basis of the results of these two surveys, an exercise was executed to map the various support functions to be performed by the available Utilization Centres. In this work, the Facility Responsible Centre and Experiment Support Centre status was assigned to various centres. The results of the mapping exercise are presented in this paper. © 1993.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

HCV-Induced Epigenetic Changes Associated With Liver Cancer Risk Persist After Sustained Virologic Response

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is an important risk factor for hepatocellular carcinoma (HCC). Despite effective antiviral therapies, the risk for HCC is decreased but not eliminated after a sustained virologic response (SVR) to direct-acting antiviral (DAA) agents, and the risk is higher in patients with advanced fibrosis. We investigated HCV-induced epigenetic alterations that might affect risk for HCC after DAA treatment in patients and mice with humanized livers. METHODS: We performed genome-wide ChIPmentation-based ChIP-Seq and RNA-seq analyses of liver tissues from 6 patients without HCV infection (controls), 18 patients with chronic HCV infection, 8 patients with chronic HCV infection cured by DAA treatment, 13 patients with chronic HCV infection cured by interferon therapy, 4 patients with chronic hepatitis B virus infection, and 7 patients with nonalcoholic steatohepatitis in Europe and Japan. HCV-induced epigenetic modifications were mapped by comparative analyses with modifications associated with other liver disease etiologies. uPA/SCID mice were engrafted with human hepatocytes to create mice with humanized livers and given injections of HCV-infected serum samples from patients; mice were given DAAs to eradicate the virus. Pathways associated with HCC risk were identified by integrative pathway analyses and validated in analyses of paired HCC tissues from 8 patients with an SVR to DAA treatment of HCV infection. RESULTS: We found chronic HCV infection to induce specific genome-wide changes in H3K27ac, which correlated with changes in expression of mRNAs and proteins. These changes persisted after an SVR to DAAs or interferon-based therapies. Integrative pathway analyses of liver tissues from patients and mice with humanized livers demonstrated that HCV-induced epigenetic alterations were associated with liver cancer risk. Computational analyses associated increased expression of SPHK1 with HCC risk. We validated these findings in an independent cohort of patients with HCV-related cirrhosis (n = 216), a subset of which (n = 21) achieved viral clearance. CONCLUSIONS: In an analysis of liver tissues from patients with and without an SVR to DAA therapy, we identified epigenetic and gene expression alterations associated with risk for HCC. These alterations might be targeted to prevent liver cancer in patients treated for HCV infection