Response to communication of Paola Romagnani and Giuseppe Remuzzi

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Optimization of Finite-Differencing Kernels for Numerical Relativity Applications

A simple optimization strategy for the computation of 3D finite-differencing kernels on many-cores architectures is proposed. The 3D finite-differencing computation is split direction-by-direction and exploits two level of parallelism: in-core vectorization and multi-threads shared-memory parallelization. The main application of this method is to accelerate the high-order stencil computations in numerical relativity codes. Our proposed method provides substantial speedup in computations involving tensor contractions and 3D stencil calculations on different processor microarchitectures, including Intel Knight Landing

Wearable device for swim assessment: a new ecologic approach for communication and analysis

This paper describes a wearable system for the assessment of swim performance focusing on the description of the system and especially on the novel method for data transmission in water, and the algorithm used for extracting some parameters for the qualitative assessment of the performance. We placed a 3-axes Inertial Measurement Unit (IMU) on the athlete's back in a specific swimsuit, which also allows for recording 1-lead ECG. The system and the algorithm have been tested on 13 trials with 10 subjects comparing the results with data extracted from video recording. The system demonstrated able and reliable to measure time and kinematic parameters of swimming

Doping of silicon by phosphorus end-terminated polymers: drive-in and activation of dopants

An effective doping technology for precise control of P atom injection and activation into a semiconductor substrate is presented

Molecular Portrait of Clear Cell Renal Cell Carcinoma: An Integrative Analysis of Gene Expression and Genomic Copy Number Profiling

Renal cell carcinoma (RCC) incidence accounts for about 3 to 10 cases per 100,000 individuals with a predilection for adult males over 60 year old (1.6:1 male/female ratio) (Chow, 2010; Nese, 2009). In Europe, about 60,000 individuals are affected by RCC every year, with a mortality rate of about 18,000 subjects and an incidence rate for all stages steadily rising over the last three decades. Although inherited forms occur in a number of familial cancer syndromes, as the well-known von Hippel-Lindau (VHL) syndrome, RCC is commonly sporadic (Cohen & McGovern, 2005; Kaelin, 2007) and, as recently highlighted by the National Cancer Institute (NCI), influenced by the interplay between exposure to environmental risk factors and genetic susceptibility of exposed individuals (Chow et al., 2010). Being poorly symptomatic in early phases, many cases become clinically detectable only when already advanced and, as such, therapy-resistant (Motzer, 2011). Based on histology, RCC can be classified into several subtypes, i.e., clear cell (80% of cases), papillary (10%), chromophobe (5%) and oncocytoma (5%), each one characterized by specific histo- pathological features, malignant potential and clinical outcome (Cohen & McGovern, 2005). Patient stratification is normally achieved using prognostic algorithms and nomograms based on multiple clinico-pathological factors such as TNM stage, Fuhrman nuclear grade, tumor size, performance status, necrosis and other hematological indices (Flanigan et al., 2011), although the most efficient predictors of survival and recurrence are based on nuclear grade alone (Nese et al., 2009). As recently reviewed by Brannon et al. (Brannon & Rathmell, 2010), a finer RCC subtype classification could be obtained exploiting the vast amount of genomic and transcriptional data that have been presented in numerous studies. For instance, several authors proposed a molecular classification of RCC based on differential gene expression profiles, with any subtype characterized by the activation of distinct gene sets (Brannon, 2010; Furge, 2004; Skubitz, 2006; Su\u308ltmann, 2005; Zhang, 2008), while others identified RCC-specific biomarkers (e.g. CA9, ki67, VEGF proteins, phosphorylated AKT, PTEN, HIF-1). Lately, it has been reported that microRNAs, a small class of non coding RNA molecules, could contribute to RCC development at different levels and may represent a new group of potential tumor biomarkers (Redova et al., 2011). Despite the numerous efforts in dissecting the molecular features of RCC through functional genomics, not a single transcriptional signature or biomarker has gained approval for clinical application yet (Arsanious, 2009; Eichelberg, 2009; Lam, 2007; Yin-Goen, 2006), so that the identification of novel molecular markers to improve early diagnosis and prognostic prediction and of candidate targets to develop new therapeutic approaches remains of primary importance for this pathology

Modulation of cell growth and cisplatin sensitivity by membrane gamma-glutamyltransferase in melanoma cells.

The plasma membrane enzyme c-glutamyltransferase (GGT) is regarded as critical for the maintenance of intracellular levels of glutathione (GSH). GGT expression has been implicated in drug resistance through elevation of intracellular GSH. The dependence of intracellular GSH on GGT expression was not conclusively ascertained. The present study was designed to investigate the role of GGT and of intracellular GSH levels in modulating proliferation and sensitivity to cisplatin of melanoma cells. GGT transfection resulted in increased growth, both in vitro and in tumour xenografts. In addition, GGT-transfected cells exhibited reduced sensitivity to cisplatin associated with lower DNA platination. A decrease in intracellular GSH levels, rather than an increase, was observed in GGT-transfected cells; moreover, in cysteine-deficient conditions, the expression of GGT did not provide transfected cells with the ability of utilising extracellular GSH. In conclusion, these results indicate that GGTactivity confers a growth advantage unrelated with intracellular glutathione supply, and are consistent with the interpretation that cisplatin resistance is the consequence of modifications of cellular pharmacokinetics as a result of extracellular drug inactivation by thiol metabolites originated by GGT-mediated GSH cleavage

Genome-wide screening of copy number alterations and LOH events in renal cell carcinomas and integration with gene expression profile

<p>Abstract</p> <p>Background</p> <p>Clear cell renal carcinoma (RCC) is the most common and invasive adult renal cancer. For the purpose of identifying RCC biomarkers, we investigated chromosomal regions and individual genes modulated in RCC pathology. We applied the dual strategy of assessing and integrating genomic and transcriptomic data, today considered the most effective approach for understanding genetic mechanisms of cancer and the most sensitive for identifying cancer-related genes.</p> <p>Results</p> <p>We performed the first integrated analysis of DNA and RNA profiles of RCC samples using Affymetrix technology. Using 100K SNP mapping arrays, we assembled a genome-wide map of DNA copy number alterations and LOH areas. We thus confirmed the typical genetic signature of RCC but also identified other amplified regions (e.g. on chr. 4, 11, 12), deleted regions (chr. 1, 9, 22) and LOH areas (chr. 1, 2, 9, 13). Simultaneously, using HG-U133 Plus 2.0 arrays, we identified differentially expressed genes (DEGs) in tumor vs. normal samples. Combining genomic and transcriptomic data, we identified 71 DEGs in aberrant chromosomal regions and observed, in amplified regions, a predominance of up-regulated genes (27 of 37 DEGs) and a trend to clustering. Functional annotation of these genes revealed some already implicated in RCC pathology and other cancers, as well as others that may be novel tumor biomarkers.</p> <p>Conclusion</p> <p>By combining genomic and transcriptomic profiles from a collection of RCC samples, we identified specific genomic regions with concordant alterations in DNA and RNA profiles and focused on regions with increased DNA copy number. Since the transcriptional modulation of up-regulated genes in amplified regions may be attributed to the genomic alterations characteristic of RCC, these genes may encode novel RCC biomarkers actively involved in tumor initiation and progression and useful in clinical applications.</p

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues

<p>Abstract</p> <p>Background</p> <p>Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues.</p> <p>Methods</p> <p>We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation).</p> <p>Results</p> <p>A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed.</p> <p>Conclusions</p> <p>ccRCC primary cultures are a reliable <it>in vitro </it>model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches aimed to study genes or pathways involved in ccRCC etiopathogenesis and to identify novel clinical markers or therapeutic targets. Moreover, SNP array technology proved to be a powerful tool to better define the cell composition and homogeneity of RCC primary cultures.</p