The 2DECOMP&FFT library: an update with new CPU/GPU capabilities

The 2DECOMP&FFT library is a software framework written in modern Fortran to build large-scale parallel applications. It is designed for applications using three-dimensional structured meshes with a particular focus on spatially implicit numerical algorithms. However, the library can be easily used with other discretisation schemes based on a structured layout and where pencil decomposition can apply. It is based on a general-purpose 2D pencil decomposition for data distribution and data Input Output (I/O). A 1D slab decomposition is also available as a special case of the 2D pencil decomposition. The library includes a highly scalable and efficient interface to perform three-dimensional Fast Fourier Transforms (FFTs). The library has been designed to be user-friendly, with a clean application programming interface hiding most communication details from application developers, and portable with support for modern CPUs and NVIDIA GPUs (support for AMD and Intel GPUs to follow)

Transient Increase in Intrahepatic Pressure Mediates Successful Treatment of the Gunn Rat with Reduced Doses of Lentiviral Vector

Lentiviral vectors can stably transduce hepatocytes and are promising tools for gene therapy of hepatic diseases. Although hepatocytes are accessible to blood-borne viral vectors through fenestrations of the hepatic endothelium, improved liver transduction after delivery of vectors to the blood stream is needed. As the normal endothelial fenestration and lentiviral vectors are similar in size (150 nm), we hypothesized that a transient increase in hepatic blood pressure may enhance in vivo gene transfer to hepatocytes. We designed a simple surgical procedure, by which the liver is temporarily excluded from blood flow. Lentiviral vectors were injected in a large volume to increase intrahepatic pressure. We demonstrated that in the Gunn rat, a model of Crigler–Najjar disease, the administration of low vector doses (corresponding to a multiplicity of infection of 0.2) by this procedure resulted in therapeutic correction of hyperbilirubinemia, without toxicity. The correction was sustained for 10 months (end of study). The same vector amounts yielded only partial correction after intraportal delivery. We believe that this new and clinically applicable strategy may broaden the range of genetic liver diseases accessible to gene therapy

Lentiviral Vectors That Express UGT1A1 in Liver and Contain Mir-142 Target Sequences Normalize Hyperbilirubinemia in Gunn Rats

Background & AimsCrigler–Najjar type 1 (CN-I) is an inherited liver disease caused by an absence of bilirubin–uridine 5′-diphosphate–glucuronosyltransferase (UGT1A1) activity. It results in life-threatening levels of unconjugated bilirubin, and therapeutic options are limited. We used adult Gunn rats (an animal model of the disease) to evaluate the efficiency of lentiviral-based gene therapy to express UGT1A1 in liver. Methods Gunn rats were given intraportal injections of VSVG-pseudotyped lentiviral vectors that encode UGT1A1 under the control of a liver-specific transthyretin promoter (mTTR.hUGT1A1); this vector does not contain target sequences for miR-142, a microRNA that is expressed specifically in hematopoietic cells. Rats were also injected with the vector mTTR.hUGT1A1.142T, which contains 4 copies of the miR-142 target sequences; its messenger RNA should be degraded in antigen-presenting cells. Bilirubinemia was monitored, and the presence of transduced hepatocytes was analyzed by quantitative polymerase chain reaction. Vector expression was tested in vitro in rat hematopoietic cells. Results In Gunn rats, bilirubin levels normalized 2 weeks after administration of mTTR.hUGT1A1. However, hyperbilirubinemia resumed 8 weeks after vector administration, concomitant with the induction of an immune response. In contrast, in rats injected with mTTR-UGT1A1.142T, bilirubin levels normalized for up to 6 months and transduced cells were not eliminated. Conclusions Lentiviral vectors that express UGT1A1 reduce hyperbilirubinemia in immunocompetent Gunn rats for at least 6 months. The immune response against virally expressed UGT1A1 can be circumvented by inclusion of miR-142 target sequences, which reduce vector expression in antigen-presenting cells. This lentiviral-based gene therapy approach might be developed to treat patients with CN-I

On the origin of leprosy.

International audienceLeprosy, a chronic human disease with potentially debilitating neurological consequences, results from infection with Mycobacterium leprae. This unculturable pathogen has undergone extensive reductive evolution, with half of its genome now occupied by pseudogenes. Using comparative genomics, we demonstrated that all extant cases of leprosy are attributable to a single clone whose dissemination worldwide can be retraced from analysis of very rare single-nucleotide polymorphisms. The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years

DNS of channel flow with conjugate heat transfer - Budgets of turbulent heat fluxes and temperature variance

International audienceBudgets of turbulent heat fluxes and temperature variance obtained from the Direct Numerical Simulation of an incompressible periodic channel flow with a Reynolds number of 150 (based on friction velocity) and a Prandtl number of 0.71 are presented and analysed for three cases: imposed temperature, imposed heat flux and 3D conjugate heat transfer. The dissipation rate associated with the temperature variance is strongly impacted by the thermal boundary condition

Electrostatic multipole for electrical resistivity measurements at the decimetric scale

International audienceNon-invasive electrical resistivity studies at the decimetric scale can be achieved by using electrostatic multipoles. The reduction of the influence of electromagnetic induction at this scale facilitates the choice of frequency. We first present the hexapole instrument (six poles) comprising one transmitting current pair of poles and two different voltage pairs corresponding to two different depths of analysis: roughly 7 and 15 cm. Two different examples are then presented, illustrating the wide range of possible applications of this technique. Firstly, by measuring the electrical resistivity of the stone blocks of an historical building, it is possible to verify whether its builders took into account the stresses these blocks had to support, when choosing their position. Secondly, the characterisation and monitoring of cultivated soil compaction is illustrated on an experimental plot of land