Von Hippel-Lindau (VHL) disease is the main cause of inherited clear-cell renal cell carcinoma (ccRCC) and is caused by germline mutations in the VHL tumor suppressor gene. Bi-allelic VHL alterations lead to inactivation of pVHL, which plays a major role by downstream activation of the hypoxia inducible factor (HIF) pathway. Somatic VHL mutations occur in 80% of sporadic ccRCC cases and the second most frequently mutated gene is polybromo 1 (PBRM1). As there is currently no data regarding PBRM1 involvement in VHL disease-associated ccRCC, the aim of the present study was to assess the PBRM1 mutational status, and PBRM1 and HIF expression in VHL disease-associated ccRCC series compared with a sporadic series. PBRM1 gene was screened by Sanger sequencing for 23 VHL-disease-associated ccRCC and 22 sporadic ccRCC cases. Immunohistochemical studies were performed to detect the expression of PBRM1, HIF1 and HIF2 for all cases. In VHL-associated tumors, 13.0% (n=3/23) had PBRM1 somatic mutations and 17.4% (n=4/23) had a loss of PBRM1 nuclear expression. In sporadic cases, 27.3% (n=6/22) showed PBRM1 somatic mutations and 45.5% (n=10/22) had a loss of PBRM1 nuclear expression. Loss of PBRM1 was associated with an advanced tumor stage. HIF1-positive tumors were observed more frequently in the VHL-associated ccRCC than in the sporadic series. Furthermore, in the VHL cohort, PBRM1 expression appeared to be associated more with HIF1 than with HIF2. Given that hereditary tumors tend to be less aggressive, these results would suggest that co-expression
Deploying neural networks on constrained hardware platforms such as 32-bit microcontrollers is a challenging task because of the large memory, computing and energy requirements of their inference process. To tackle these issues, several convolution primitives have been proposed to make the standard convolution more computationally efficient. However, few of these primitives are really implemented for 32-bit microcontrollers. In this work, we collect different state-of-the-art convolutional primitives and propose an implementation for ARM Cortex-M processor family with an open source deployment platform (NNoM). Then, we carry out experimental characterization tests on these implementations. Our benchmark reveals a linear relationship between theoretical MACs and energy consumption. Thus showing the advantages of using computationally efficient primitives like shift convolution. We discuss about the significant reduction in latency and energy consumption due to the use of SIMD instructions and highlight the importance of data reuse in those performance gains. For reproducibility purpose and further experiments, codes and experiments are publicly available 4 .
Le rôle antiviral du complexe MRN La réplication, l'héritabilité et le maintien fidèle de l'ADN génomique sont indispensables à la vie. Les mécanismes de réparation de l'ADN, qui sont présents de la levure à l'homme, permettent de protéger le génome, notamment en réagissant aux cassures double brin (CDB) de l'ADN, qui peuvent mener à une instabilité génomique et à la tumorigenèse. Les cassures double brin sont détectées par le complexe MRN composé des protéines MRE11, RAD50 et NBS1 (Figure 1A). Ce complexe induit la formation de foyers de réponses aux dommages à l'ADN (RDA), en recrutant et activant la kinase ataxia telangiectasia mutated (ATM). Le signal est
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