Multiple hypothesis testing and clustering with mixtures of non-central t-distributions applied in microarray data analysis

Multiple testing analysis, based on clustering methodologies, is usually applied in Microarray Data Analysis for comparisons between pair of groups. In this paper, we generalize this methodology to deal with multiple comparisons among more than two groups obtained from microarray expressions of genes. Assuming normal data, we define a statistic which depends on sample means and sample variances, distributed as a non-central t-distribution. As we consider multiple comparisons among groups, a mixture of non-central t-distributions is derived. The estimation of the components of mixtures is obtained via a Bayesian approach, and the model is applied in a multiple comparison problem from a microarray experiment obtained from gorilla, bonobo and human cultured fibroblasts.Clustering, MCMC computation, Microarray analysis, Mixture distributions, Multiple hypothesis testing, Non-central t-distribution

STT-RAM memory hierarchy designs aimed to performance, reliability and energy consumption

Current applications demand larger on-chip memory capacity since off-chip memory accesses be-come a bottleneck. However, if we want to achieve this by scaling down the transistor size of SRAM-based Last-Level Caches (LLCs) it may become prohibitive in terms of cost, area and en-ergy. Therefore, other technologies such as STT-RAM are becoming real alternatives to build the LLC in multicore systems. Although STT-RAM bitcells feature high density and low static power, they suffer from other trade-offs. On the one hand, STT-RAM writes are more expensive than STT-RAM reads and SRAM writes. In order to address this asymmetry, we will propose microarchitectural techniques to minimize the number of write operations on STT-RAM cells. On the other hand, reliability also plays an important role. STT-RAM cells suffer from three types of errors: write, read disturbance, and retention errors. Regarding this, we will suggest tech-niques to manage redundant information allowing error detection and information recovery.Postprint (published version

ReD: A reuse detector for content selection in exclusive shared last-level caches

The reference stream reaching a chip multiprocessor Shared Last-Level Cache (SLLC) shows poor temporal locality, making conventional cache management policies inefficient. Few proposals address this problem for exclusive caches. In this paper, we propose the Reuse Detector (ReD), a new content selection mechanism for exclusive hierarchies that leverages reuse locality at the SLLC, a property that states that blocks referenced more than once are more likely to be accessed in the near future. Being placed between each L2 private cache and the SLLC, ReD prevents the insertion of blocks without reuse into the SLLC. It is designed to overcome problems affecting similar recent mechanisms (low accuracy, reduced visibility window and detector thrashing). ReD improves performance over other state-of-the-art proposals (CHAR, Reuse Cache and EAF cache). Compared with the baseline system with no content selection, it reduces the SLLC miss rate (MPI) by 10.1% and increases harmonic IPC by 9.5%.Peer ReviewedPostprint (author's final draft

Near-optimal replacement policies for shared caches in multicore processors

An optimal replacement policy that minimizes the miss rate in a private cache was proposed several decades ago. It requires knowing the future access sequence the cache will receive. There is no equivalent for shared caches because replacement decisions alter this future sequence. We present a novel near-optimal policy for minimizing the miss rate in a shared cache that approaches the optimal execution iteratively. During each iteration, the future access sequence is reconstructed on every miss interleaving the future per-core sequences, taken from the previous iteration. This single sequence feeds a classical private-cache optimum replacement policy. Our evaluation on a shared last-level cache shows that our proposal iteratively converges to a near-optimal miss rate that is independent of the initial conditions, within a margin of 0.1%. The best state-of-the-art online policies achieve around 65% of the miss rate reduction obtained by our near-optimal proposal. In a shared cache, miss rate optimization does not imply the optimization of other metrics. Therefore, we also propose a new near-optimal policy to maximize fairness between cores. The best state-of-the-art online policy achieves 60% of the improvement in fairness seen with our near-optimal policy. Our proposals are useful both for setting upper performance bounds and inspiring implementable mechanisms for shared caches.The authors acknowledge support from grants (1) PID2019-105660RB-C21 and PID2019-107255GB-C22 from Agencia Estatal de Investigación (AEI) from Spain and European Regional Development Fund (ERDF); (2) gaZ: T58_20R research group from Aragón Government and European Social Fund (ESF); and (3) 2014-2020 "Construyendo Europa desde Aragón" from European Regional Development Fund (ERDF).Peer ReviewedPostprint (author's final draft

Leveraging data compression for performance-efficient and long-lasting NVM-based last-level cache

Non-volatile memory (NVM) technologies are interesting alternatives for building on-chip Last-Level Caches (LLCs). Their advantages, compared to SRAM memory, are higher density and lower static power, but each write operation slightly wears out the bitcell, to the point of losing its storage capacity. In this context, this paper summarizes three contributions to the state-of-the-art NVM-based LLCs. Data compression reduces the size of the blocks and, together with wear-leveling mechanisms, can defer the wear out NVMs. Moreover, as capacity is reduced by write wear, data compression enables degraded cache frames to allocate blocks whose compressed size is adequate. Our first contribution is a microarchitecture design that leverages data compression and an intra-frame wear-leveling to gracefully deal with NVM-LLCs capacity degradation. The second contribution leverages this microarchitecture design to propose new insertion policies for hybrid LLCs using Set Dueling and taking into account the compression capabilities of the blocks. From a methodological point of view, although different approaches are used in the literature to analyze the degradation of a NV-LLC, none of them allows to study in detail its temporal evolution. In this sense, the third contribution is a forecasting procedure that combines detailed simulation and prediction, enabling an accurate analysis of different cache content mechanisms (replacement, wear leveling, compression, etc.) on the temporal evolution of the performance of multiprocessor systems employing such NVM-LLCs. Using this forecasting procedure we show that the proposed NVM-LLCs organizations and the insertion policies for hybrid LLCs significantly outperform the state-of-the-art in both performance and lifetime metrics.Peer ReviewedPostprint (published version

MRI and CFS oligoclonal bands after autologus hematopoietic stem cell transplantation in MS

To analyze the MRI and CSF oligoclonal bands (OB) changes in patients with MS who underwent an autologous hematopoietic stem cell transplantation (AHSCT). Background: AHSCT is evaluated as an alternative therapy in severe MS. In previous series of AHSCT for MS, data on MRI or OB outcome were limited or not provided. Methods: five patients with a median Kurtzke's EDSS score of 6.5, more than two attacks, and confirmed worsening of the EDSS in the previous year received an AHSCT. Hematopoietic stem cells were mobilized with cyclophosphamide (3 g/m2) and granulocyte colony-stimulating factor (5 microg/kg/d). The graft was T cell depleted by positive CD 34+ selection. Conditioning regimen included BCNU (300 mg/m(2)), cyclophosphamide (150 mg/kg in 3 days), and antithymocyte globulin (60 mg/kg in 4 days). MRI scans were scheduled at baseline and 1, 3, 6, and 12 months and OB analysis at baseline and 3 and 12 months post-AHSCT. Results: four patients had a stable or improved EDSS after a median follow-up of 18 months (range, 12 to 24 months). The fifth patient's condition deteriorated during AHSCT. She partially improved and remained stable after month 3 after AHSCT. The baseline CSF OB persisted 1 year after AHSCT. MRI studies after AHSCT showed no enhanced T1 lesions and no new or enlarging T2 lesions. The median percentage change of T2 lesion load was -11.8% (range, -26.6 to -4.0%). All patients had a decrease of corpus callosum area at 1 year (median, 12.4%; range, 7.8% to 20.5%) that did not progress in the two patients evaluated at 2 years after AHSCT. Conclusions: although the persistence of CSF OB suggests the lymphocytes were not eliminated from the CNS, the follow-up MRI studies showed no enhanced T1 brain lesions and a reduction in the T2 lesion load that correlated with the clinical stabilization of MS after AHSCT

One Health Approach : Invasive California Kingsnake (Lampropeltis californiae) as an Important Source of Antimicrobial Drug-Resistant Salmonella Clones on Gran Canaria Island

The aim of this study was to investigate the invasive species Lampropeltis californiae (California kingsnake) as a reservoir of Salmonella and its ability to spread different clones of the bacterium with zoonotic potential into the environment, as well as study its antimicrobial resistance patterns in Gran Canaria (Spain). The main results showed that a high diversity of Salmonella subsp. salamae strains circulate in Gran Canaria with a high prevalence of resistance shown for antimicrobials of public health importance, as summarised in the European Decision 2013/652/EU. The increase in the reptile population has led to a rise in the number of zoonotic infections due to close contact with reptiles, with reptile-associated salmonellosis being particularly relevant. California kingsnake invasion not only threatens the endemic reptile population of the island of Gran Canaria (Spain) but also poses serious public health problems by spreading zoonotic pathogens and their antimicrobial resistance (AMR) to the environment. Thus, the aim of this study was to assess the occurrence, genetic diversity, and AMR among Salmonella spp. strains isolated from California kingsnakes in Gran Canaria Island (Spain). Of 73 invasive individuals captured, 20.5% carried Salmonella spp., belonging to different subspecies and serovars, with subsp. salamae as the most abundant. Pulsed-field electrophoresis showed high genetic diversity among subsp. salamae isolates, and among these, 73.3% showed resistance to at least one of the antimicrobials tested. In conclusion, the present study revealed the importance of wild invasive California kingsnakes as reservoirs of drug-resistant Salmonella spp. that could pose a direct threat to livestock and humans. Identification of drug-resistant Salmonella strains in wildlife provides valuable information on potential routes of transmission that involve risks to public and animal health

La perspectiva de género en la docencia universitaria de Economía e Historia

La perspectiva de gènere en la docència universitària implica sotmetre a reflexió els conceptes i anàlisi de les corrents acadèmiques dominants, identificar els biaixos de gènere, promoure una interpretació més àmplia i completa de la realitat i afavorir la sensibilització i conscienciació de les i els estudiants. Vol dir, essencialment, una reorganització de continguts, una reflexió sobre els conceptes, models, teories i perspectiva d'anàlisi, així com la introducció de nous casos, exemples pràctics, fonts de referència, etc. Aquest estudi mostra els resultats d'un projecte d'innovació docent que pretén donar les primeres passes per aconseguir la incorporació transversal de la perspectiva de gènere en la docència. L'aplicació del mateix s'ha efectuat en el grau d'Administració i Direcció d'Empreses i el grau de Ciències Polítiques de la Universitat de Barcelona.  Es van estudiar els plans docents, es va identificar el biaix sistemàtic en la majoria de les assignatures, es van dissenyar activitats de reflexió i sensibilització i es va proposar un qüestionari de validació de l'aprenentatge. En conjunt es va comptar amb la participació de 480 estudiants. Els resultats mostren que, tot i els avenços aconseguits en termes legals i administratius, la posició i el paper de la dona en l'economia i la història contínua, en general, invisibilitzat. S'aprecia, també, que les dones són més conscients de l'existència de desigualtats i més permeables a les actuacions docents que incorporen reflexions i anàlisi d'aquesta índole. Finalment, s'observa que les accions docents que incorporen la perspectiva de gènere contribueixen a canviar les percepcions de les / us estudiants i tenen efectes positius sobre la seva conscienciació i sensibilització.The introduction of a gender perspective into university teaching needs a deep rethinking about the concepts and analysis of the academic mainstream, identifying gender biases, promoting a broader and more complete interpretation of reality and easing gender awareness among students. It means, essentially, a reorganization of contents, a critical review on the concepts, models, theories and approaches of analysis, as well as the introduction of new cases, practical examples, reference sources, etc. This article shows the results of a teaching innovation project that aims to take the first steps into that direction. It has been implemented in the degree of Business Administration and Management and the degree of Political Science of the University of Barcelona. The main action consisted on a study of the teaching plans where a systematic bias was identified in most of the subjects, reflexion and sensitization activities in class and a validation of learning questionnaires. Altogether, 480 students participated. The results show that, despite the progress made in legal and administrative terms, the position and role of women in the economy and history continues, in general, to be invisible. It is also apparent that women are more aware of the existence of inequalities and more permeable to teaching activities that incorporate gender as an issue. Finally, it is stated that the teaching actions that incorporate the gender perspective do contribute to change the perceptions of the students and have positive effects on their awareness on it.Introducir la perspectiva de género en la docencia universitaria implica someter a reflexión los conceptos y análisis de las corrientes académicas dominantes, identificar los sesgos de género, promover una interpretación más amplia y completa de la realidad y favorecer la sensibilización y concienciación de las y los estudiantes. Significa, esencialmente, una reorganización de contenidos, una reflexión sobre los conceptos, modelos, teorías y perspectiva de análisis, así como la introducción de nuevos casos, ejemplos prácticos, fuentes de referencia, etc. Este estudio muestra los resultados de un proyecto de innovación docente que pretende dar los primeros pasos para lograr la incorporación transversal de la perspectiva de género en la docencia. La aplicación del mismo se ha efectuado en el grado de Administración y Dirección de Empresas y el grado de Ciencias Políticas de la Universidad de Barcelona. Se estudiaron los planes docentes, se identificó el sesgo sistemático en la mayoría de las asignaturas, se diseñaron actividades de reflexión y sensibilización y se propuso un cuestionario de validación del aprendizaje. En conjunto se contó con la participación de 480 estudiantes. Los resultados muestran que, pese a los avances conseguidos en términos legales y administrativos, la posición y el papel de la mujer en la economía y la historia continua, en general, invisibilizado. Se aprecia, también, que las mujeres son más conscientes de la existencia de desigualdades y más permeables a las actuaciones docentes que incorporan reflexiones y análisis de esta índole. Finalmente, se observa que las acciones docentes que incorporan la perspectiva de género contribuyen a cambiar las percepciones de las/os estudiantes y tienen efectos positivos sobre su concienciación y sensibilización

Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells.

Protein kinase C (PKC) comprises a family of highly related serine/threonine protein kinases involved in multiple signaling pathways, which control cell proliferation, survival, and differentiation. The role of PKCα in cancer has been studied for many years. However, it has been impossible to establish whether PKCα acts as an oncogene or a tumor suppressor. Here, we analyzed the importance of PKCα in cellular processes such as proliferation, migration, or apoptosis by inhibiting its gene expression in a luminal A breast cancer cell line (MCF-7). Differential expression analysis and phospho-kinase arrays of PKCα-KD vs. PKCα-WT MCF-7 cells identified an essential set of proteins and oncogenic kinases of the JAK/STAT and PI3K/AKT pathways that were down-regulated, whereas IGF1R, ERK1/2, and p53 were up-regulated. In addition, unexpected genes related to the interferon pathway appeared down-regulated, while PLC, ERBB4, or PDGFA displayed up-regulated. The integration of this information clearly showed us the usefulness of inhibiting a multifunctional kinase-like PKCα in the first step to control the tumor phenotype. Then allowing us to design a possible selection of specific inhibitors for the unexpected up-regulated pathways to further provide a second step of treatment to inhibit the proliferation and migration of MCF-7 cells. The results of this study suggest that PKCα plays an oncogenic role in this type of breast cancer model. In addition, it reveals the signaling mode of PKCα at both gene expression and kinase activation. In this way, a wide range of proteins can implement a new strategy to fine-tune the control of crucial functions in these cells and pave the way for designing targeted cancer therapies.Work in Murcia was supported by grants BFU2017-87222-P (MICINN, Spain-FEDER) to S.C.-G. and J.C.G.-F. and Fundación Séneca Region de Murcia 20885/PI/18 to S.C.-G.S

ReD: A policy based on reuse detection for demanding block selection in last-level Caches

In this paper, we propose a new block selection policy for Last-Level Caches (LLCs) that decides, based on Reuse Detection, whether a block coming from main memory is inserted, or not, in the LLC. The proposed policy, called ReD, is demanding in the sense that blocks bypass the LLC unless their expected reuse behavior matches specific requirements, related either to their recent reuse history or to the behavior of associated instructions. Generally, blocks are only stored in the LLC the second time they are requested in a limited time window. Secondarily, some blocks enter the LLC on the first request if their associated requesting instruction has shown to request highly-reused blocks in the past. ReD includes two table structures that allow tracking, measuring and correlating reuse for specific block addresses and requesting program counters within a constrained storage budget. It can be implemented on top of any other base replacement algorithm. Other parts of the base replacement policy, such as promotion or victim selection, can remain unchanged, enabling our policy to work along with many state-of-the-art replacement algorithms.Peer ReviewedPostprint (published version