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Localized thinning for strain concentration in suspended germanium membranes and optical method for precise thickness measurement

We deposited Ge layers on (001) Si substrates by molecular beam epitaxy and used them to fabricate suspended membranes with high uniaxial tensile strain. We demonstrate a CMOS-compatible fabrication strategy to increase strain concentration and to eliminate the Ge buffer layer near the Ge/Si hetero-interface deposited at low temperature. This is achieved by a two-steps patterning and selective etching process. First, a bridge and neck shape is patterned in the Ge membrane, then the neck is thinned from both top and bottom sides. Uniaxial tensile strain values higher than 3% were measured by Raman scattering in a Ge membrane of 76 nm thickness. For the challenging thickness measurement on micrometer-size membranes suspended far away from the substrate a characterization method based on pump-and-probe reflectivity measurements was applied, using an asynchronous optical sampling technique.EC/FP7/628197/EU/Heat Propagation and Thermal Conductivity in Nanomaterials for Nanoscale Energy Management/HEATPRONAN

Future challenges in cephalopod research

We thank Anto´nio M. de Frias Martins, past President of the Unitas Malacologica and Peter Marko, President of the American Malacological Society for organizing the 2013 World Congress of Malacology, and the Cephalopod International Advisory Committee for endorsing a symposium held in honour of Malcolm R. Clarke. In particular, we would like to thank the many professional staff from the University of the Azores for their hospitality, organization, troubleshooting and warm welcome to the Azores. We also thank Malcolm Clarke’s widow, Dorothy, his daughter Zoe¨, Jose´ N. Gomes-Pereira and numerous colleagues and friends of Malcolm’s from around the world for joining us at Ponta Delgada. We are grateful to Lyndsey Claro (Princeton University Press) for granting copyright permissions.Peer reviewedPublisher PD

The Earth as an extrasolar transiting planet - II: HARPS and UVES detection of water vapor, biogenic O2_2, and O3_3

The atmospheric composition of transiting exoplanets can be characterized during transit by spectroscopy. For the transit of an Earth twin, models predict that biogenic $O_2$ and $O_3$ should be detectable, as well as water vapour, a molecule linked to habitability as we know it on Earth. The aim is to measure the Earth radius versus wavelength $\lambda$ - or the atmosphere thickness $h(\lambda)$ - at the highest spectral resolution available to fully characterize the signature of Earth seen as a transiting exoplanet. We present observations of the Moon eclipse of 21-12-2010. Seen from the Moon, the Earth eclipses the Sun and opens access to the Earth atmosphere transmission spectrum. We used HARPS and UVES spectrographs to take penumbra and umbra high-resolution spectra from 3100 to 10400 Ang. A change of the quantity of water vapour above the telescope compromised the quality of the UVES data. We corrected for this effect in the data processing. We analyzed the data by 3 different methods. The 1st method is based on the analysis of pairs of penumbra spectra. The 2nd makes use of a single penumbra spectrum, and the 3rd of all penumbra and umbra spectra. Profiles $h(\lambda)$ are obtained with the three methods for both instruments. The 1st method gives the best result, in agreement with a model. The second method seems to be more sensitive to the Doppler shift of solar spectral lines with respect to the telluric lines. The 3rd method makes use of umbra spectra which bias the result, but it can be corrected for this a posteriori from results with the first method. The 3 methods clearly show the spectral signature of the Rayleigh scattering in the Earth atmosphere and the bands of H$_2$O, O$_2$, and O$_3$. Sodium is detected. Assuming no atmospheric perturbations, we show that the E-ELT is theoretically able to detect the $O_2$ A-band in 8~h of integration for an Earth twin at 10pc.Comment: Final version accepted for publication in A&A - 21 pages, 27 figures. Abstract above slightly shortened wrt the original. The ArXiv version has low resolution figures, but a version with full resolution figures is available here: http://www.obs-hp.fr/~larnold/publi_to_download/eclipse2010_AA_v5_final.pd

Hematopoietic IKBKE limits the chronicity of inflammasome priming and metaflammation

Obesity increases the risk of developing life-threatening metabolic diseases including cardiovascular disease, fatty liver disease, diabetes, and cancer. Efforts to curb the global obesity epidemic and its impact have proven unsuccessful in part by a limited understanding of these chronic progressive diseases. It is clear that low-grade chronic inflammation, or metaflammation, underlies the pathogenesis of obesity-associated type 2 diabetes and atherosclerosis. However, the mechanisms that maintain chronicity and prevent inflammatory resolution are poorly understood. Here, we show that inhibitor of κB kinase epsilon (IKBKE) is a novel regulator that limits chronic inflammation during metabolic disease and atherosclerosis. The pathogenic relevance of IKBKE was indicated by the colocalization with macrophages in human and murine tissues and in atherosclerotic plaques. Genetic ablation of IKBKE resulted in enhanced and prolonged priming of the NLRP3 inflammasome in cultured macrophages, in hypertrophic adipose tissue, and in livers of hypercholesterolemic mice. This altered profile associated with enhanced acute phase response, deregulated cholesterol metabolism, and steatoheptatitis. Restoring IKBKE only in hematopoietic cells was sufficient to reverse elevated inflammasome priming and these metabolic features. In advanced atherosclerotic plaques, loss of IKBKE and hematopoietic cell restoration altered plaque composition. These studies reveal a new role for hematopoietic IKBKE: to limit inflammasome priming and metaflammation

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment