Beam profile and beam time structure monitors for the extracted beams from the GANIL cyclotrons

International audienc

Interactively solving school timetabling problems using extensions of constraint programming

Timetabling problems have been frequently studied due to their wide range of applications. However, they are often solved manually because of the lack of appropriate computer tools. Although many approaches mainly based on local search or constraint programming seem to have been quite successful in recent years, they are often highly dedicated to specific problems and encounter difficulties to take the dynamic and over-constrained nature of such problems. We were confronted with such an over-constrained and dynamic problem in our institution. This paper deals with a timetabling system based on constraint programming with the use of explanations to offer a dynamic behaviour and to allow automatic relaxations of constraints. Our tool has successfully answered the needs of the current planner by providing solutions in a few minutes instead of a week of manual design.We present in this paper the techniques used, the results obtained and a discussion on the effects of the automation of the timetabling process

The persistence in the liver of residual duck hepatitis B virus covalently closed circular DNA is not dependent upon new viral DNA synthesis

AbstractResidual hepatitis B virus (HBV) DNA can be detected following the resolution of acute HBV infection. Our previous work using duck hepatitis B virus (DHBV) infected ducks, indicated that ~80% of residual DHBV DNA in the liver is in the covalently closed circular DNA (cccDNA) form, suggesting that viral DNA synthesis is suppressed. The current study asked more directly if maintenance of residual DHBV cccDNA is dependent upon ongoing viral DNA synthesis. Ducks that recovered from acute DHBV infection were divided into 2 groups and treated with the antiviral drug, Entecavir (ETV), or placebo. No major differences in the stability of cccDNA or levels of residual cccDNA were observed in liver biopsy tissues taken 95days apart from ETV treated and placebo control ducks. The data suggest that residual DHBV cccDNA is highly stable and present in a cell population with a rate of turnover similar to normal, uninfected hepatocytes

Androgen receptor signaling regulates the transcriptome of prostate cancer cells by modulating global alternative splicing

Androgen receptor (AR), is a transcription factor and a member of a hormone receptor superfamily. AR plays a vital role in the progression of prostate cancer and is a crucial target for therapeutic interventions. While the majority of advanced-stage prostate cancer patients will initially respond to the androgen deprivation, the disease often progresses to castrate-resistant prostate cancer (CRPC). Interestingly, CRPC tumors continue to depend on hyperactive AR signaling and will respond to potent second-line antiandrogen therapies, including bicalutamide (CASODEX®) and enzalutamide (XTANDI®). However, the progression-free survival rate for the CRPC patients on antiandrogen therapies is only 8–19 months. Hence, there is a need to understand the mechanisms underlying CRPC progression and eventual treatment resistance. Here, we have leveraged next-generation sequencing and newly developed analytical methodologies to evaluate the role of AR signaling in regulating the transcriptome of prostate cancer cells. The genomic and pharmacologic stimulation and inhibition of AR activity demonstrates that AR regulates alternative splicing within cancer-relevant genes. Furthermore, by integrating transcriptomic data from in vitro experiments and in prostate cancer patients, we found that a significant number of AR-regulated splicing events are associated with tumor progression. For example, we found evidence for an inadvertent AR-antagonist-mediated switch in IDH1 and PL2G2A isoform expression, which is associated with a decrease in overall survival of patients. Mechanistically, we discovered that the epithelial-specific splicing regulators (ESRP1 and ESRP2), flank many AR-regulated alternatively spliced exons. And, using 2D invasion assays, we show that the inhibition of ESRPs can suppress AR-antagonist-driven tumor invasion. Our work provides evidence for a new mechanism by which AR alters the transcriptome of prostate cancer cells by modulating alternative splicing. As such, our work has important implications for CRPC progression and development of resistance to treatment with bicalutamide and enzalutamide

L-Ilf3 and L-NF90 Traffic to the Nucleolus Granular Component: Alternatively-Spliced Exon 3 Encodes a Nucleolar Localization Motif

Ilf3 and NF90, two proteins containing double-stranded RNA-binding domains, are generated by alternative splicing and involved in several functions. Their heterogeneity results from posttranscriptional and posttranslational modifications. Alternative splicing of exon 3, coding for a 13 aa N-terminal motif, generates for each protein a long and short isoforms. Subcellular fractionation and localization of recombinant proteins showed that this motif acts as a nucleolar localization signal. Deletion and substitution mutants identified four arginines, essential for nucleolar targeting, and three histidines to stabilize the proteins within the nucleolus. The short isoforms are never found in the nucleoli, whereas the long isoforms are present in the nucleoplasm and the nucleoli. For Ilf3, only the posttranslationally-unmodified long isoform is nucleolar, suggesting that this nucleolar targeting is abrogated by posttranslational modifications. Confocal microscopy and FRAP experiments have shown that the long Ilf3 isoform localizes to the granular component of the nucleolus, and that L-Ilf3 and L-NF90 exchange rapidly between nucleoli. The presence of this 13 aminoacid motif, combined with posttranslational modifications, is responsible for the differences in Ilf3 and NF90 isoforms subcellular localizations. The protein polymorphism of Ilf3/NF90 and the various subcellular localizations of their isoforms may partially explain the various functions previously reported for these proteins

Constraint solving in uncertain and dynamic environments - a survey

International audienceThis article follows a tutorial, given by the authors on dynamic constraint solving at CP 2003 (Ninth International Conference on Principles and Practice of Constraint Programming) in Kinsale, Ireland. It aims at offering an overview of the main approaches and techniques that have been proposed in the domain of constraint satisfaction to deal with uncertain and dynamic environments

Performance of Coffea arabica F1 hybrids in agroforestry and full-sun cropping systems in comparison with American pure line cultivars

Coffea arabica F1 hybrids derived from crosses between wild Sudan-Ethiopian and American cultivars and propagated by somatic embryogenesis have been obtained in Central America. These new hybrids considerably enhanced the genetic diversity of coffee in the region. We conducted 15 trials to assess whether using hybrids represents substantial genetic progress in terms of productivity in agroforestry and full-sun cropping systems. The new germplasm was grown in the same conditions as the best American cultivar (homozygous pure lines). The results showed that yields of hybrids were earlier and superior to those of American cultivars. The hybrids were also more stable than the American cultivars in all environments. In the agroforestry system, the mean yield of hybrids was 58% higher than that of the American cultivars, while the mean yield of hybrids in the full-sun system was 34% higher. Coffee-based agroforestry systems (AS) are considered effective in protecting the environment in the volcanic cordilleras of Central America. We found that introducing hybrids in coffee-based AS can considerably increase productivity. This finding could be a convincing argument to encourage coffee growers who have adopted the full-sun cropping system to return to agroforestry cropping systems. Finally, the conditions for large-scale dissemination of those new hybrids—which represent a major innovation for C. arabica cropping—was analysed