The Impact of the Multi-core Revolution on Signal Processing

This paper analyzes the influence of new multi- core and many-core architectures on Signal Processing. The article covers both the architectural design and the programming models of current general-purpose multi-core processors and graphics processors (GPU), with the goal of identifying their possibilities and impact on signal processing applications

Relating multivariate shapes to genescapes using phenotype-biological process associations for craniofacial shape.

Realistic mappings of genes to morphology are inherently multivariate on both sides of the equation. The importance of coordinated gene effects on morphological phenotypes is clear from the intertwining of gene actions in signaling pathways, gene regulatory networks, and developmental processes underlying the development of shape and size. Yet, current approaches tend to focus on identifying and localizing the effects of individual genes and rarely leverage the information content of high-dimensional phenotypes. Here, we explicitly model the joint effects of biologically coherent collections of genes on a multivariate trait - craniofacial shape - in a sample of n = 1145 mice from the Diversity Outbred (DO) experimental line. We use biological process Gene Ontology (GO) annotations to select skeletal and facial development gene sets and solve for the axis of shape variation that maximally covaries with gene set marker variation. We use our process-centered, multivariate genotype-phenotype (process MGP) approach to determine the overall contributions to craniofacial variation of genes involved in relevant processes and how variation in different processes corresponds to multivariate axes of shape variation. Further, we compare the directions of effect in phenotype space of mutations to the primary axis of shape variation associated with broader pathways within which they are thought to function. Finally, we leverage the relationship between mutational and pathway-level effects to predict phenotypic effects beyond craniofacial shape in specific mutants. We also introduce an online application that provides users the means to customize their own process-centered craniofacial shape analyses in the DO. The process-centered approach is generally applicable to any continuously varying phenotype and thus has wide-reaching implications for complex trait genetics

Introduction to special section: Balancing, restoration, and palinspastic reconstruction

Methods to quantify deformation and reverse the process of strain as a mode to illustrate geologic evolution through time have been previously used for a number of decades. Early efforts on the quantification of bed reconstruction were completed either by manually weighing the sections on delicate balances and obtaining the average height and thickness of strata to be reconstructed by applying a scale factor (Chamberlin, 1910), or by hand-drafting sections with conserved bed length between the folded and faulted sedimentary layers, mainly in a 2D cross section (Bally et al., 1966; Dahlstrom, 1969) or map framework (Dennison and Woodward, 1963). Cross-section techniques initially applied to contractional thrust and fold belts and have proven useful in other structural settings, such as extensional and inverted domains. Development of 3D techniques enabled the analysis of strike-slip and salt tectonics where out-of-plane changes of rock volume could be addressed. Through the years, the widespread application of these techniques to predict fault and horizon geometry at depth has generated newer approaches and more sophisticated algorithms, and it has also demonstrated the potential of structural modeling techniques (e.g., construction of balanced sections, palinspastic reconstruction, kinematic and geomechanical restoration, and forward modeling) in reducing the risk and uncertainty associated with the interpretation of geophysical/geological dat

Application of Multi-core and GPU Architectures on Signal Processing: Case Studies

In this article part of the techniques and developments we are carrying out within the INCO2 group are reported. Results follow the interdisciplinary approach with which we tackle signal processing applications. Chosen case studies show different stages of development: We present algorithms already completed which are being used in practical applications as well as new ideas that may represent a starting point, and which are expected to deliver good results in a short and medium term

SHARDS: A global view of the star formation activity at z~0.84 and z~1.23

In this paper, we present a comprehensive analysis of star-forming galaxies (SFGs) at intermediate redshifts (z~1). We combine the ultra-deep optical spectro-photometric data from the Survey for High-z Absorption Red and Dead Sources (SHARDS) with deep UV-to-FIR observations in the GOODS-N field. Exploiting two of the 25 SHARDS medium-band filters, F687W17 and F823W17, we select [OII] emission line galaxies at z~0.84 and z~1.23 and characterize their physical properties. Their rest-frame equivalent widths (EW$_{\mathrm{rf}}$([OII])), line fluxes, luminosities, star formation rates (SFRs) and dust attenuation properties are investigated. The evolution of the EW$_{\mathrm{rf}}$([OII]) closely follows the SFR density evolution of the universe, with a trend of EW$_{\mathrm{rf}}$([OII])$\propto$(1+z)$^3$ up to redshift z~1, followed by a possible flattening. The SF properties of the galaxies selected on the basis of their [OII] emission are compared with complementary samples of SFGs selected by their MIR and FIR emission, and also with a general mass-selected sample of galaxies at the same redshifts. We demonstrate observationally that the UVJ diagram (or, similarly, a cut in the specific SFR) is only partially able to distinguish the quiescent galaxies from the SFGs. The SFR-M$_*$ relation is investigated for the different samples, yelding a logarithmic slope ~1, in good agreement with previous results. The dust attenuations derived from different SFR indicators (UV(1600), UV(2800), [OII], IR) are compared and show clear trends with respect to both the stellar mass and total SFR, with more massive and highly star-forming galaxies being affected by stronger dust attenuation.Comment: Replaced to match the accepted version (24 pages, 1 table, 17 figures). Published in ApJ, 812, 155 (2015): http://stacks.iop.org/0004-637X/812/15

Plasma proteomic profiling identifies CD33 as a marker of HIV control in natural infection and after therapeutic vaccination

Altres ajuts: National Institutes of Health (NIH), P01-AI131568Biomarkers predicting the outcome of HIV-1 virus control in natural infection and after therapeutic interventions in HIV-1 cure trials remain poorly defined. The BCN02 trial (NCT02616874), combined a T-cell vaccine with romidepsin (RMD), a cancer-drug that was used to promote HIV-1 latency reversal and which has also been shown to have beneficial effects on neurofunction. We conducted longitudinal plasma proteomics analyses in trial participants to define biomarkers associated with virus control during monitored antiretroviral pause (MAP) and to identify novel therapeutic targets that can improve future cure strategies. BCN02 was a phase I, open-label, single-arm clinical trial in early-treated, HIV infected individuals. Longitudinal plasma proteomes were analyzed in 11 BCN02 participants, including 8 participants that showed a rapid HIV-1 plasma rebound during a monitored antiretroviral pause (MAP-NC, 'non-controllers') and 3 that remained off ART with sustained plasma viremia <2000 copies/ml (MAP-C, 'controllers'). Inflammatory and neurological proteomes in plasma were evaluated and integration data analysis (viral and neurocognitive parameters) was performed. Validation studies were conducted in a cohort of untreated HIV-1+ individuals (n = 96) and in vitro viral replication assays using an anti-CD33 antibody were used for functional validation

Evaluation of mammographic density patterns: reproducibility and concordance among scales

<p>Abstract</p> <p>Background</p> <p>Increased mammographic breast density is a moderate risk factor for breast cancer. Different scales have been proposed for classifying mammographic density. This study sought to assess intra-rater agreement for the most widely used scales (Wolfe, Tabár, BI-RADS and Boyd) and compare them in terms of classifying mammograms as high- or low-density.</p> <p>Methods</p> <p>The study covered 3572 mammograms drawn from women included in the DDM-Spain study, carried-out in seven Spanish Autonomous Regions. Each mammogram was read by an expert radiologist and classified using the Wolfe, Tabár, BI-RADS and Boyd scales. In addition, 375 mammograms randomly selected were read a second time to estimate intra-rater agreement for each scale using the kappa statistic. Owing to the ordinal nature of the scales, weighted kappa was computed. The entire set of mammograms (3572) was used to calculate agreement among the different scales in classifying high/low-density patterns, with the kappa statistic being computed on a pair-wise basis. High density was defined as follows: percentage of dense tissue greater than 50% for the Boyd, "heterogeneously dense and extremely dense" categories for the BI-RADS, categories P2 and DY for the Wolfe, and categories IV and V for the Tabár scales.</p> <p>Results</p> <p>There was good agreement between the first and second reading, with weighted kappa values of 0.84 for Wolfe, 0.71 for Tabár, 0.90 for BI-RADS, and 0.92 for Boyd scale. Furthermore, there was substantial agreement among the different scales in classifying high- versus low-density patterns. Agreement was almost perfect between the quantitative scales, Boyd and BI-RADS, and good for those based on the observed pattern, i.e., Tabár and Wolfe (kappa 0.81). Agreement was lower when comparing a pattern-based (Wolfe or Tabár) versus a quantitative-based (BI-RADS or Boyd) scale. Moreover, the Wolfe and Tabár scales classified more mammograms in the high-risk group, 46.61 and 37.32% respectively, while this percentage was lower for the quantitative scales (21.89% for BI-RADS and 21.86% for Boyd).</p> <p>Conclusions</p> <p>Visual scales of mammographic density show a high reproducibility when appropriate training is provided. Their ability to distinguish between high and low risk render them useful for routine use by breast cancer screening programs. Quantitative-based scales are more specific than pattern-based scales in classifying populations in the high-risk group.</p

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry

Objectives. This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. Methods. RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. Results. Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. Conclusion. Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies

The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase

Purpose: ABTL0812 is a novel first-in-class, small molecule which showed antiproliferative effect on tumor cells in phenotypic assays. Here we describe the mechanism of action of this antitumor drug, which is currently in clinical development. Experimental design: We investigated the effect of ABTL0812 on cancer cell death, proliferation, and modulation of intracellular signaling pathways, using human lung (A549) and pancreatic (MiaPaCa-2) cancer cells and tumor xenografts. To identify cellular targets, we performed in silico high-throughput screening comparing ABTL0812 chemical structure against ChEMBL15 database. Results: ABTL0812 inhibited Akt/mTORC1 axis, resulting in impaired cancer cell proliferation and autophagy-mediated cell death. In silico screening led us to identify PPARs, PPARα and PPARγ as the cellular targets of ABTL0812. We showed that ABTL0812 activates both PPAR receptors, resulting in upregulation of Tribbles-3 pseudokinase (TRIB3) gene expression. Upregulated TRIB3 binds cellular Akt, preventing its activation by upstream kinases, resulting in Akt inhibition and suppression of the Akt/mTORC1 axis. Pharmacologic inhibition of PPARα/γ or TRIB3 silencing prevented ABTL0812-induced cell death. ABTL0812 treatment induced Akt inhibition in cancer cells, tumor xenografts, and peripheral blood mononuclear cells from patients enrolled in phase I/Ib first-in-human clinical trial. Conclusions: ABTL0812 has a unique and novel mechanism of action, that defines a new and drugable cellular route that links PPARs to Akt/mTORC1 axis, where TRIB3 pseudokinase plays a central role. Activation of this route (PPARα/γ-TRIB3-Akt-mTORC1) leads to autophagy-mediated cancer cell death. Given the low toxicity and high tolerability of ABTL0812, our results support further development of ABTL0812 as a promising anticancer therapy

Determination of essential biomarkers in lung cancer : a real-world data study in Spain with demographic, clinical, epidemiological and pathological characteristics

Background The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. Patients and methods The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. Results Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. Conclusions Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer