Periodic gamma-ray emissions from Geminga at or = 10(12) eV

Analysis of data from an atmospheric Cerenkov telescope indicated the periodic emission of gamma rays of energy 10 to the 12th power eV, at 60.25 second period, from 2CG 195+4. The gamma ray flux at 99% confidence level is estimated to be 9.5 x 10 to 12 photons/sq cm/s

Comparative performance of some popular ANN algorithms on benchmark and function approximation problems

We report an inter-comparison of some popular algorithms within the artificial neural network domain (viz., Local search algorithms, global search algorithms, higher order algorithms and the hybrid algorithms) by applying them to the standard benchmarking problems like the IRIS data, XOR/N-Bit parity and Two Spiral. Apart from giving a brief description of these algorithms, the results obtained for the above benchmark problems are presented in the paper. The results suggest that while Levenberg-Marquardt algorithm yields the lowest RMS error for the N-bit Parity and the Two Spiral problems, Higher Order Neurons algorithm gives the best results for the IRIS data problem. The best results for the XOR problem are obtained with the Neuro Fuzzy algorithm. The above algorithms were also applied for solving several regression problems such as cos(x) and a few special functions like the Gamma function, the complimentary Error function and the upper tail cumulative $\chi^2$-distribution function. The results of these regression problems indicate that, among all the ANN algorithms used in the present study, Levenberg-Marquardt algorithm yields the best results. Keeping in view the highly non-linear behaviour and the wide dynamic range of these functions, it is suggested that these functions can be also considered as standard benchmark problems for function approximation using artificial neural networks.Comment: 18 pages 5 figures. Accepted in Pramana- Journal of Physic

Differential expression of a new isoform of DLG2 in renal oncocytoma

BACKGROUND: Renal oncocytoma, a benign tumour of the kidney, may pose a differential diagnostic problem due to overlapping phenotype with chromophobe renal cell carcinoma or other types of renal cell tumours. Therefore, identification of molecular markers would be of great value for molecular diagnostics of this tumour type. METHODS: In the current study we applied various techniques, including Affymetrix microarray hybridization and semiquantitative RT-PCR, to identify genes expressed differentially in renal oncocytomas. Subsequently, we used RACE and Northern blot hybridization to characterize the potential candidates for molecular diagnosis. RESULTS: We have identified new isoform of DLG2 gene, which contains 3'-end exons of the known DLG2 gene along with the hypothetical gene FLJ37266. The new isoform is specifically upregulated in renal oncocytoma, whereas the known DLG2 gene is downregulated in this type of kidney tumour. CONCLUSION: The new isoform of DLG2 is the promising candidate gene for molecular differential diagnostics of renal oncocytoma

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma

BACKGROUND Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. METHODS We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. RESULTS Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2'antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). CONCLUSIONS Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renalcell carcinoma consisted of at least three subtypes based on molecular and phenotypic features

A taxonomy of epithelial human cancer and their metastases

<p>Abstract</p> <p>Background</p> <p>Microarray technology has allowed to molecularly characterize many different cancer sites. This technology has the potential to individualize therapy and to discover new drug targets. However, due to technological differences and issues in standardized sample collection no study has evaluated the molecular profile of epithelial human cancer in a large number of samples and tissues. Additionally, it has not yet been extensively investigated whether metastases resemble their tissue of origin or tissue of destination.</p> <p>Methods</p> <p>We studied the expression profiles of a series of 1566 primary and 178 metastases by unsupervised hierarchical clustering. The clustering profile was subsequently investigated and correlated with clinico-pathological data. Statistical enrichment of clinico-pathological annotations of groups of samples was investigated using Fisher exact test. Gene set enrichment analysis (GSEA) and DAVID functional enrichment analysis were used to investigate the molecular pathways. Kaplan-Meier survival analysis and log-rank tests were used to investigate prognostic significance of gene signatures.</p> <p>Results</p> <p>Large clusters corresponding to breast, gastrointestinal, ovarian and kidney primary tissues emerged from the data. Chromophobe renal cell carcinoma clustered together with follicular differentiated thyroid carcinoma, which supports recent morphological descriptions of thyroid follicular carcinoma-like tumors in the kidney and suggests that they represent a subtype of chromophobe carcinoma. We also found an expression signature identifying primary tumors of squamous cell histology in multiple tissues. Next, a subset of ovarian tumors enriched with endometrioid histology clustered together with endometrium tumors, confirming that they share their etiopathogenesis, which strongly differs from serous ovarian tumors. In addition, the clustering of colon and breast tumors correlated with clinico-pathological characteristics. Moreover, a signature was developed based on our unsupervised clustering of breast tumors and this was predictive for disease-specific survival in three independent studies. Next, the metastases from ovarian, breast, lung and vulva cluster with their tissue of origin while metastases from colon showed a bimodal distribution. A significant part clusters with tissue of origin while the remaining tumors cluster with the tissue of destination.</p> <p>Conclusion</p> <p>Our molecular taxonomy of epithelial human cancer indicates surprising correlations over tissues. This may have a significant impact on the classification of many cancer sites and may guide pathologists, both in research and daily practice. Moreover, these results based on unsupervised analysis yielded a signature predictive of clinical outcome in breast cancer. Additionally, we hypothesize that metastases from gastrointestinal origin either remember their tissue of origin or adapt to the tissue of destination. More specifically, colon metastases in the liver show strong evidence for such a bimodal tissue specific profile.</p

Integrated Molecular Characterization of Testicular Germ Cell Tumors

We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance—KIT, KRAS, and NRAS—exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas. Shen et al. identify molecular characteristics that classify testicular germ cell tumor types, including a separate subset of seminomas defined by KIT mutations. This provides a set of candidate biomarkers for risk stratification and potential therapeutic targeting

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations

Claude Marcel (1793–1876) : a neglected applied linguist?

This article contributes to the as yet underexplored field of applied linguistic historiography by surveying the life and achievements of Claude Marcel (1793–1876), author of a two-volume study of language education published in London in 1853 under the title Language as a Means of Mental Culture and International Communication. The question of whether Marcel was an applied linguist 'avant la lettre' is addressed, as are possible reasons for the contemporary and subsequent neglect of his work. It is suggested that the identification of precursors depends on one's view of the nature of applied linguistics, and that there are alternatives to a linguistics-focused conception. Indeed, a consideration of Marcel's writings — and the contemporary and subsequent neglect of them — highlights the way language teaching theory has tended, for the last 120 years or more, to be dominated by linguistic much more than educational considerations