The Novel Immunosuppressive Protein Kinase C Inhibitor Sotrastaurin Has No Pro-Viral Effects on the Replication Cycle of Hepatitis B or C Virus

The pan-protein kinase C (PKC) inhibitor sotrastaurin (AEB071) is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV), major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases

CEDIMS: cloud ethical DICOM image Mojette storage

Dicom images of patients will necessarily been stored in Clouds. However, ethical constraints must apply. In this paper, a method which provides the two following conditions is presented: 1) the medical information is not readable by the cloud owner since it is distributed along several clouds 2) the medical information can be retrieved from any sufficient subset of clouds In order to obtain this result in a real time processing, the Mojette transform is used. This paper reviews the interesting features of the Mojette transform in terms of information theory. Since only portions of the original Dicom files are stored into each cloud, their contents are not reachable. For instance, we use 4 different public clouds to save 4 different projections of each file, with the additional condition that any 3 over 4 projections are enough to reconstruct the original file. Thus, even if a cloud is unavailable when the user wants to load a Dicom file, the other 3 are giving enough information for real time reconstruction. The paper presents an implementation on 3 actual clouds. For ethical reasons, we use a Dicom image spreaded over 3 public clouds to show the obtained confidentiality and possible real time recovery

Micro-patterned porous substrates for cell-based assays

10.1039/c2lc20696jLab on a Chip - Miniaturisation for Chemistry and Biology1291717-1722LCAH

Santi, culti e simboli nell'etā della secolarizzazione: (1815-1915)

Gli autori portano alla luce alcune questioni cruciali dell'Otto-Novecento, offrendo un preciso quadro della storia religiosa dell'epoca. Le modificazioni intervenute in ambito istituzionale e agiografico, la riproposizione di vecchi culti e il radicarsi di altri, l'affermazione di nuovi modelli di santità e la formazione di miti sacri e profani sono i grandi temi attraverso i quali gli autori dipingono svolte e contraddizioni del vissuto religioso dell'Otto-Novecento