27 research outputs found

    Systemic analysis of production scenarios for bioethanol produced from ligno-cellulosic biomass [abstract]

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    Defining alternatives for non-renewable energy sources constitutes a priority to the development of our societies. One of these alternatives is biofuels production starting from energy crops, agricultural wastes, forest products or wastes. In this context, a "second generation" biofuels production, aiming at utilizing the whole plant, including ligno-cellulosic (hemicelluloses, cellulose, lignin) fractions (Ogier et al., 1999) that are not used for human food, would allow the reduction of the drawbacks of bioethanol production (Schoeling, 2007). However, numerous technical, economical, ethical and environmental questions are still pending. One of the aims of the BioEtha2 project, directed by the Walloon Agricultural Research Centre, is to define the position of bioethanol produced from ligno-cellulosic biomass among the different renewable energy alternatives that could be developed in Wallonia towards 2020. With this aim, and in order to answer the numerous questions in this field, the project aims at using tools and methods coming from the concept of "forecasting scenarios" (Sebillotte, 2002; Slegten et al., 2007; For-learn, 2008). This concept, based on a contemporary reality, aims to explore different possible scenarios for the future development of alternative sources of energy production. The principle is to evaluate, explore, possible futures of the studied problematic, through the establishment of possible evolution trajectories. We contribute to this prospective through a systemic approach (Vanloqueren, 2007) that allows lightening the existing interactions within the system "ligno-cellulosic biomass chain" without isolating it from its environment. We explain and sketch the two contexts needed to identify primary stakes. The global context includes inter-dependant and auto-regulating fields such as society, politics, technology and economy. These four fields influence each part of the "chain" with specific tools. However, the interest and possible action fields lay within the intermediary context representing the "resources" such as agriculture, forestry, "driving" elements such as mobility, mediation elements such as territories and environment and concurrent elements such as non-cellulosic biomass, the energy mix and the non-energy valorization

    TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer.

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    PURPOSE: To infer the prognostic value of simultaneous androgen receptor (AR) and TP53 profiling in liquid biopsies from metastatic castration-resistant prostate cancer (mCRPC) patients starting a new line of AR signalling inhibitors (ARSi). EXPERIMENTAL DESIGN: Between March 2014 and April 2017, we recruited mCRPC patients (n=168) prior to ARSi in a cohort study encompassing 10 European centres. Blood samples were collected for comprehensive profiling of CellSearch-enriched circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA). Targeted CTC RNA-seq allowed the detection of eight AR splice variants (ARVs). Low-pass whole-genome and targeted gene-body sequencing of AR and TP53 was applied to identify amplifications, loss-of-heterozygosity, mutations and structural rearrangements in ctDNA. Clinical or radiological progression-free survival (PFS) was estimated by Kaplan-Meier analysis, and independent associations were determined using multivariable Cox-regression models. RESULTS: Overall, no single AR perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumour burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS. TP53 inactivation harbored independent prognostic value (HR 1.88, 95%CI 1.18-3.00, p = 0.008), and outperformed ARV expression and detection of genomic AR alterations. Using Cox coefficient analysis of clinical parameters and TP53 status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs 7.51 vs 2.62 months, p < 0.0001), which was validated in an independent mCRPC cohort (n=202) starting first-line ARSi (median, 14.3 vs 6.39 vs 2.23 months, p < 0.0001). CONCLUSIONS: In an all-comer cohort, tumour burden estimates and TP53 outperform any AR perturbation to infer prognosis

    Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis.

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    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.BACKGROUND: There are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited. METHODS: A combination of targeted and low-pass whole genome sequencing was performed on plasma cell-free DNA and matched white blood cell germline DNA in 364 blood samples from 217 metastatic prostate cancer patients. RESULTS: ctDNA was detected in 85.9% of baseline samples, correlated to line of therapy and was mirrored by circulating tumor cell enumeration of synchronous blood samples. Comprehensive profiling of the androgen receptor (AR) revealed a continuous increase in the fraction of patients with intra-AR structural variation, from 15.4% during first-line metastatic castration-resistant prostate cancer therapy to 45.2% in fourth line, indicating a continuous evolution of AR during the course of the disease. Patients displayed frequent alterations in DNA repair deficiency genes (18.0%). Additionally, the microsatellite instability phenotype was identified in 3.81% of eligible samples (≥ 0.1 ctDNA fraction). Sequencing of non-repetitive intronic and exonic regions of PTEN, RB1, and TP53 detected biallelic inactivation in 47.5%, 20.3%, and 44.1% of samples with ≥ 0.2 ctDNA fraction, respectively. Only one patient carried a clonal high-impact variant without a detectable second hit. Intronic high-impact structural variation was twice as common as exonic mutations in PTEN and RB1. Finally, 14.6% of patients presented false positive variants due to clonal hematopoiesis, commonly ignored in commercially available assays. CONCLUSIONS: ctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenges the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials.The Belgian Foundation Against Cancer (grant number C/2014/227); Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society (grant number 00000000116000000206); Royal College of Surgeons/Cancer Research UK (C19198/A1533); The Cancer Research Funds of Radiumhemmet, through the PCM program at KI (grant number 163012); The Erling-Persson family foundation (grant number 4-2689-2016); the Swedish Research Council (grant number K2010-70X-20430-04-3), and the Swedish Cancer Foundation (grant number 09-0677)

    Diagnosis and Treatment of Lichen Sclerosus

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    Competitive and stereoselective histamine H1 antagonistic effect of cicletanide in guinea-pig isolated ileum.

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    The histamine H1 antagonistic effects of the racemic form and the enantiomers of cicletanide, a new antihypertensive furopyridine derivative, were investigated in guinea-pig isolated ileum. Both the racemic and the (-) enantiomer behaved as competitive histamine antagonists (pA2 values of 6.8 and 7.2, respectively). The (+) enantiomer was at least 100 times less potent than the (-) enantiomer. The H1-blocking effect of cicletanide is the most potent and is the only stereoselective property so far reported for the drug

    Notice explicative de la carte de Tintigny-Etalle

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    La feuille de Tintigny-Etalle couvre 160 km2 d'une région située en Belgique aux confins sud de la province de Luxembourg. Située à cheval sur l'Ardenne et la Gaume, elle exprime un relief assez contrasté trahissant les grandes structures géologiques de son sous-sol. Le socle paléozoïque est représenté, sur une portion restreinte au nord de la feuille, par des terrains datés du Praguien (Dévonien inférieur), principalement des massifs schisteux à barres quartzitiques, et plissés au cours de l'orogenèse varisque. La partie sud, pour l'essentiel, est couverte par des séries sédimentaires mésozoïques déposées sur un socle émergé par plusieurs transgressions marines successives sur des périodes qui s'échelonnent du Trias supérieur au Jurassique inférieur. D'allure régulière et monoclinale en pente vers le sud, elles comportent des terrains cohérents ou non très variés qui forment la marge nord-est du Bassin de Paris et reposent en discordance sur le versant sud du massif ardennais. L'ossature du relief est marquée par deux lignes parallèles de cuestas, appelées rhétienne et sinémurienne, plus ou moins bien exprimées dans le paysage et localement perturbées par le cours de la Semois et de la Rulles. Les dépôts quaternaires sont représentés par des alluvions déposées par la Semois et ses affluents dans les vallées ou abandonnées sur des terrasses. L'exploitation des sables, grès, marnes et argiles et schistes constitue un secteur important de l'économie régionale d'hier et d'aujourd'hui

    Notice explicative de la carte de Messancy-Saint Léger Musson-Le Fays Houwald

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    La feuille Saint-Léger – Messancy, Musson – Le Fays et Houwald située en Lorraine belge entre les frontières luxembourgeoise et française couvre l'extrême sud-est de la Belgique. En marge du Bassin de Paris, la région est couverte de roches sédimentaires mésozoïques d'allure monoclinale. Les couches de très faible pendage sud-est sont affectées de nombreuses failles de direction NE-SW à ENE-WSW. L'allure des couches ainsi que la nature contrastée des roches composant le sous-sol lorrain a déterminé un paysage typique de cuestas. Cette structure du relief affectée, dès le Tertiaire, par le climat et le réseau hydrographique cède la place à des vallées asymétriques (région de Saint-Léger), des buttes témoins et des plateaux ou terrasses alluviales. Les témoins de ces événements sont visibles entre autres par les anciennes alluvions et par des cuirassements ferrugineux ou siliceux. Parmi les nombreuses exploitations du sous-sol lorrain, celle du fer a principalement influencé le développement de la région d'Athus. Actuellement seuls le sable et l'eau des différents aquifères sont encore exploités
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