Balancing Energy and Performance in Dense Linear System Solvers for Hybrid ARM+GPU platforms

The high performance computing community has traditionally focused uniquely on the reduction of execution time, though in the last years, the optimization of energy consumption has become a main issue. A reduction of energy usage without a degradation of performance requires the adoption of energy-efficient hardware platforms accompanied by the development of energy-aware algorithms and computational kernels. The solution of linear systems is a key operation for many scientific and engineering problems. Its relevance has motivated an important amount of work, and consequently, it is possible to find high performance solvers for a wide variety of hardware platforms. In this work, we aim to develop a high performance and energy-efficient linear system solver. In particular, we develop two solvers for a low-power CPU-GPU platform, the NVIDIA Jetson TK1. These solvers implement the Gauss-Huard algorithm yielding an efficient usage of the target hardware as well as an efficient memory access. The experimental evaluation shows that the novel proposal reports important savings in both time and energy-consumption when compared with the state-of-the-art solvers of the platform.

Operating infrastructure for an FPGA and ARM system

Advances in FPGA technology and higher processing capabilities requirements have pushed to the emerge of All Programmable Systems-on-Chip, which incorporate a hard designed processing system and a programmable logic that enable the development of specialized computer systems for a wide range of practical applications, including data and signal processing, high performance computing, embedded systems, among many others. To give place to an infrastructure that is capable of using the benefits of such a reconfigurable system, the main goal of the thesis is to implement an infrastructure composed of hardware, software and network resources, that incorporates the necessary services for the operation, management and interface of peripherals, that coompose the basic building blocks for the execution of applications. The project will be developed using a chip from the Zynq-7000 All Programmable Systems-on-Chip family.

De impacto : en milo a go go se armó la grande : sesenta revoluciones por segundo 12

Fondo Margaritainés Restrepo

NUMERICAL SIMULATION STUDY OF VIBRATION MITIGATION EFFECTIVENESS OF TUNED MASS DAMPERS FOR TRAFFIC SIGNAL MAST ARM STRUCTURES

Fatigue damage in the connections of single mast arm signal support structures is one of the primary safety concerns because collapse could result from fatigue induced cracking. This type of cantilever signal support structures typically has very light damping and excessively large wind-induced vibration have been observed. Major changes related to fatigue design were made in the 2001 AASHTO LRFD Specification for Structural Supports for Highway Signs, Luminaries, and Traffic Signals and supplemental damping devices have been shown to be promising in reducing the vibration response and thus fatigue load demand on mast arm signal support structures. The primary objective of this study is to investigate the effectiveness and optimal use of one type of damping devices termed tuned mass damper (TMD) in vibration response mitigation. Three prototype single mast arm signal support structures with 50-ft, 60-ft, and 70-ft respectively are selected for this numerical simulation study. In order to validate the finite element models for subsequent simulation study, analytical modeling of static deflection response of mast arm of the signal support structures was performed and found to be close to the numerical simulation results from beam element based finite element model. A 3-DOF dynamic model was then built using analytically derived stiffness matrix for modal analysis and time history analysis. The free vibration response and forced (harmonic) vibration response of the mast arm structures from the finite element model are observed to be in good agreement with the finite element analysis results. Furthermore, experimental test result from recent free vibration test of a full-scale 50-ft mast arm specimen in the lab is used to verify the prototype structure’s fundamental frequency and viscous damping ratio. After validating the finite element models, a series of parametric study were conducted to examine the trend and determine optimal use of tuned mass damper on the prototype single mast arm signal support structures by varying the following parameters: mass, frequency, viscous damping ratio, and location of TMD. The numerical simulation study results reveal that two parameters that influence most the vibration mitigation effectiveness of TMD on the single mast arm signal pole structures are the TMD frequency and its viscous damping ratio.

Studio e realizzazione dell’emulatore μARM e del progetto JaeOS per la didattica dei Sistemi Operativi

La maggior parte degli strumenti per la didattica dei sistemi operativi sono basati sull'architettura MIPS, che è ampiamente superata. Questo lavoro introduce μARM, un emulatore, basato su architettura ARM7TDMI adeguato all'insegnamento a livello universitario. Inoltre viene presentato JaeOS, un manuale di specifiche per un sistema operativo multi-strato che supporti esecuzione multi-processo, memoria virtuale, sincronizzazione dei thread, gestione di dispositivi esterni ed un file system. I progetti tradizionali, come OSP2 o OS/161, forniscono un buon quantitativo di codice già sviluppato agli studenti, i quali devono modificare i moduli del sistema già implementati ed aggiungerne di nuovi. Con μARM/JaeOS gli studenti sono sottoposti ad un'esperienza pedagogicamente differente, partendo dal solo emulatore hardware e finendo con un sistema operativo, interamente sviluppato da loro, in grado di eseguire programmi sviluppati dagli studenti stessi.

Test of a Smock System on CPR Primary Emergency Measures and Medical Errors During Simulated Emergencies

Rates of survival of victims of sudden cardiac arrest (SCA) using cardio pulmonary resuscitation (CPR) have shown little improvement over the past three decades. Since registered nurses (RNs) comprise the largest group of healthcare providers in U.S. hospitals, it is essential that they are competent in performing the four primary measures (compression, ventilation, medication administration, and defibrillation) of CPR in order to improve survival rates of SCA patients. The purpose of this experimental study was to test a color-coded SMOCK system on:1) time to implement emergency patient care measures 2) technical skills performance 3) number of medical errors, and 4) team performance during simulated CPR exercises. The study sample was 260 RNs (M 40 years, SD=11.6) with work experience as an RN (M 7.25 years, SD=9.42).Nurses were allocated to a control or intervention arm consisting of 20 groups of 5-8 RNs per arm for a total of 130 RNs in each arm. Nurses in each study arm were given clinical scenarios requiring emergency CPR. Nurses in the intervention group wore different color labeled aprons (smocks) indicating their role assignment (medications, ventilation, compression, defibrillation, etc) on the code team during CPR. Findings indicated that the intervention using color-labeled smocks for pre-assigned roles had a significant effect on the time nurses started compressions (t=3.03, p=0.005), ventilations (t=2.86, p=0.004) and defibrillations (t=2.00, p=.05) when compared to the controls using the standard of care. In performing technical skills, nurses in the intervention groups performed compressions and ventilations significantly better than those in the control groups. The control groups made significantly (t=-2.61, p=0.013) more total errors (7.55 SD 1.54) than the intervention group (5.60, SD 1.90). There were no significant differences in team performance measures between the groups. Study findings indicate use of colored labeled smocks during CPR emergencies resulted in: shorter times to start emergency CPR; reduced errors; more technical skills completed successfully; and no differences in team performance.

Fitness cost and interference of Arm/Rmt aminoglycoside resistance with the RsmF housekeeping methyltransferases

Arm/Rmt methyltransferases have emerged recently in pathogenic bacteria as enzymes that confer high-level resistance to 4,6-disubstituted aminoglycosides through methylation of the G1405 residue in the 16S rRNA (like ArmA and RmtA to -E). In prokaryotes, nucleotide methylations are the most common type of rRNA modification, and they are introduced posttranscriptionally by a variety of site-specific housekeeping enzymes to optimize ribosomal function. Here we show that while the aminoglycoside resistance methyltransferase RmtC methylates G1405, it impedes methylation of the housekeeping methyltransferase RsmF at position C1407, a nucleotide that, like G1405, forms part of the aminoglycoside binding pocket of the 16S rRNA. To understand the origin and consequences of this phenomenon, we constructed a series of in-frame knockout and knock-in mutants of Escherichia coli, corresponding to the genotypes rsmF(+), ΔrsmF, rsmF(+) rmtC(+), and ΔrsmF rmtC(+). When analyzed for the antimicrobial resistance pattern, the ΔrsmF bacteria had a decreased susceptibility to aminoglycosides, including 4,6- and 4,5-deoxystreptamine aminoglycosides, showing that the housekeeping methylation at C1407 is involved in intrinsic aminoglycoside susceptibility in E. coli. Competition experiments between the isogenic E. coli strains showed that, contrary to expectation, acquisition of rmtC does not entail a fitness cost for the bacterium. Finally, matrix-assisted laser desorption ionization (MALDI) mass spectrometry allowed us to determine that RmtC methylates the G1405 residue not only in presence but also in the absence of aminoglycoside antibiotics. Thus, the coupling between housekeeping and acquired methyltransferases subverts the methylation architecture of the 16S rRNA but elicits Arm/Rmt methyltransferases to be selected and retained, posing an important threat to the usefulness of aminoglycosides worldwide.

Coiled armrings: an Hiberno-Viking silver arm-ring type

The purpose of this paper is to isolate and discuss a distinctive type of Hiberno-Viking silver armring. Here termed the 'coiled armring', it is dated to the late ninth/early tenth centuries. The methods of manufacture, ornamentation, date and origins of the type are discussed and the objects are assessed against the background of hoard-associated material and related types of silver armrings. A descriptive catalogue of the material is provided.

Évaluation de l’état des dalles en béton armé enterrées

Dans le souci d’améliorer le réseau de distribution de l'énergie électrique, tout en maintenant l'intégrité de certains sites urbains protégés, plusieurs municipalités du Québec ont choisi d’enfouir leurs fils électriques. Ce type d’installation requiert des chambres de raccordement souterraines afin de réaliser l’entretien du réseau et le câblage. Ces chambres sont typiquement placées à tous les 300 mètres du réseau et sont généralement recouvertes d’épaisseurs de remblai allant de 0,6 m à 1m. L’un des principaux problèmes affectant l’état structural de ces chambres est la dégradation du béton de la surface externe de celles-ci. Dans certains cas, la dégradation peut atteindre une portion non négligeable de l’épaisseur de la dalle, jusqu’à en causer l’effondrement. En plus de présenter un danger pour la population, ces effondrements entraînent des coûts d’entretien élevés pour les propriétaires d’ouvrages. En outre, ces chambres sont difficiles à inspecter par l’intérieur. Cette problématique est d’autant plus importante étant donné la grande quantité de chambres de raccordement souterraines construites par le passé. Dans ce contexte, Hydro-Québec a lancé un programme de recherche visant à faire l'évaluation par des techniques de contrôle non destructif de l’état du béton du toit des chambres de raccordement souterraines. C'est dans ce cadre que s'inscrit cette étude. Le but de notre projet est d'évaluer les capacités de la technique du Géoradar à détecter l’endommagement du béton et, si possible, déterminer l’étendue en profondeur des dégradations dans le béton de ces dalles en béton armé enterrées. Ce mémoire de maîtrise présente la méthode proposée pour atteindre cet objectif. Des simulations numériques ont été réalisées, dans un premier temps, pour établir les limites de l'application Géoradar dans le cadre de notre problématique. Les résultats obtenus ont ensuite été confrontés à des essais réalisés sur des dalles réelles enterrées. Les travaux ont permis de montrer sans équivoque qu'avec le Géoradar, il est possible de déceler la dégradation au niveau des dalles enterrées, lorsque celles-ci se situaient à une profondeur maximale de 75 cm sous un sol de type sableux. Mais, il est encore difficile de pouvoir estimer l’étendue en profondeur de la dégradation, sans connaître l'état initial des dalles.

Quantification de l'amortissement visqueux élastique des piles en béton armé des ponts routiers québécois

Le dimensionnement des ponts et viaducs au Canada se base sur la norme CAN/CSA S6-14. Pour le calcul de ces structures sous des charges extrêmes, des cartes d'aléa sismique sont produites par la Commission géologique du Canada selon un taux d'amortissement de 5 %. La norme propose des taux d'amortissement visqueux élastique de 2 % pour le béton et de 1 % pour l'acier. Un nouveau facteur de correction selon l'amortissement est mentionné dans cette norme pour modifier les spectres de réponse provenant des cartes sismiques. Plusieurs études sur des ouvrages d'art quantifient les taux d'amortissement visqueux élastique entre 1 % et 2 %, confirmant ainsi qu'il est nécessaire d'utiliser un facteur de correction des spectres pour éviter une sous-évaluation des déplacements au niveau du tablier. Le projet de recherche consiste à quantifier le taux d'amortissement visqueux élastique des ponts routiers grâce à des essais in situ sur des ouvrages du Québec. Les essais débutent avec l'acquisition de données à l'aide d'accéléromètres alors que le pont est sous vibrations ambiantes. Une fois les propriétés modales extraites, un essai sous vibrations forcées par balayage des fréquences est effectué, en ciblant les fréquences propres. L'interprétation de la réponse de la structure à ce dernier essai permet de trouver précisément l'amortissement. Une étude paramétrique sur le logiciel OpenSees est aussi effectuée pour évaluer l'impact de la variation du taux d'amortissement utilisé sur les déplacements du tablier lors d'un séisme. Les résultats démontrent que le taux d'amortissement visqueux élastique peut être aussi bas que 1 %, ce qui peut doubler la réponse en déplacements aux joints d'un pont par rapport à une analyse avec 5 % d'amortissement. Le mémoire cherche à clarifier l'utilisation de la norme S6-14, à démontrer l'importance d'utiliser un bon taux d'amortissement et à encourager l'utilisation d'un facteur de correction des spectres adéquat pour calculer la réponse sismique des ponts routiers québécois et canadiens. Des recommandations sont proposées dans ce sens.

Azacitidine and Lenalidomide Combination Therapy in Myelodysplastic Syndromes: Topography and Translational Relevance of Nuclear Phospholipase C β - dependent Signalling

Nuclear inositide signalling pathways, and particularly those regulated by PI-PLCβ1, are associated with cell proliferation and differentiation. Myelodysplastic syndromes (MDS) are a heterogeneous spectrum of chronic myeloid hemopathies with associated symptomatic cytopenias and substantial potential for evolution to acute myeloid leukemia (AML). MDS patients are currently treated with two main approaches, epigenetic (Azacitidine) and immunomodulatory (Lenalidomide: above all in cell clones bearing a deletion of the long arm of the chromosome 5 [del(5q)]). As Azacitidine and Lenalidomide alone can show adverse effects or patients can be refractory, an experimental current approach is the combination of the two drugs. Clinically, this combination therapy is promising, while its molecular effect has to be clarified. Stemming from these data, in this study the effect of an Azacitidine-Lenalidomide combination therapy was studied, in both MDS patients and hematopoietic cell lines. The specific aims of this study were to evaluate the effect of Azacitidine and Lenalidomide MDS therapy on: cell cycle regulation, hematopoietic differentiation, gene mutation and miR expression. Lenalidomide alone, via PI-PLCβ1/PKC pathway, was able to induce a selective G0/G1 arrest of the cell cycle in del(5q) cells, slowing down their rate proliferation and favouring erythropoiesis activation. In addition, although the mutation profile at baseline was not entirely capable of predicting the clinical effect of Azacitidine and Lenalidomide therapy, the presence of specific point mutations affecting three inositide genes (PI3KCD, AKT3, PLCG2) was correlated to and anticipated a negative clinical outcome. Moreover, the differential miR expression was detectable even from the 4th cycle of therapy in responder patients, as compared to non-responders. In MDS, this is the first evidence that the molecular mutation profiling of inositide genes or a specific mini-cluster of differentially expressed miRs, targeting inositide signaling molecules, can be associated with the clinical response, thus possibly predicting the effect of the therapy.

Design of experiment in drug development: optimal allocations in multi-arm clinical trials and design space for multi-step processes

In this thesis, we deal with the design of experiments in the drug development process, focusing on the design of clinical trials for treatment comparisons (Part I) and the design of preclinical laboratory experiments for proteins development and manufacturing (Part II). In Part I we propose a multi-purpose design methodology for sequential clinical trials. We derived optimal allocations of patients to treatments for testing the efficacy of several experimental groups by also taking into account ethical considerations. We first consider exponential responses for survival trials and we then present a unified framework for heteroscedastic experimental groups that encompasses the general ANOVA set-up. The very good performance of the suggested optimal allocations, in terms of both inferential and ethical characteristics, are illustrated analytically and through several numerical examples, also performing comparisons with other designs proposed in the literature. Part II concerns the planning of experiments for processes composed of multiple steps in the context of preclinical drug development and manufacturing. Following the Quality by Design paradigm, the objective of the multi-step design strategy is the definition of the manufacturing design space of the whole process and, as we consider the interactions among the subsequent steps, our proposal ensures the quality and the safety of the final product, by enabling more flexibility and process robustness in the manufacturing.

Neural states in parietal areas during arm reaching

Since the first subdivisions of the brain into macro regions, it has always been thought a priori that, given the heterogeneity of neurons, different areas host specific functions and process unique information in order to generate a behaviour. Moreover, the various sensory inputs coming from different sources (eye, skin, proprioception) flow from one macro area to another, being constantly computed and updated. Therefore, especially for non-contiguous cortical areas, it is not expected to find the same information. From this point of view, it would be inconceivable that the motor and the parietal cortices, diversified by the information encoded and by the anatomical position in the brain, could show very similar neural dynamics. With the present thesis, by analyzing the population activity of parietal areas V6A and PEc with machine learning methods, we argue that a simplified view of the brain organization do not reflect the actual neural processes. We reliably detected a number of neural states that were tightly linked to distinct periods of the task sequence, i.e. the planning and execution of movement and the holding of target as already observed in motor cortices. The states before and after the movement could be further segmented into two states related to different stages of movement planning and arm posture processing. Rather unexpectedly, we found that activity during the movement could be parsed into two states of equal duration temporally linked to the acceleration and deceleration phases of the arm. Our findings suggest that, at least during arm reaching in 3D space, the posterior parietal cortex (PPC) shows low-level population neural dynamics remarkably similar to those found in the motor cortices. In addition, the present findings suggest that computational processes in PPC could be better understood if studied using a dynamical system approach rather than studying a mosaic of single units.

A phase II, single arm study of CarbopLatin plus Etoposide with Bevacizumab and Atezolizumab in patients with exTEnded-disease small-cell lung cancer (SCLC) – CeLEBrATE trial

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor diagnosed at extended disease SCLC (ES-SCLC) stage in about 70% of cases. The new standard of treatment for patients with ES-SCLC is a combination of platinum-etoposide chemotherapy and atezolizumab or durvalumab, two programmed cell death ligand 1 (PD-L1) inhibitory monoclonal antibodies (mAb). However, the benefit derived from the addition of PD-L1 inhibitors to chemotherapy in ES-SCLC was limited and restricted to a subset of patients. The vascular endothelial growth factor (VEGF) is the most important pro-angiogenic factor implicated in cancer angiogenesis, which is abundant in SCLC and associated with poor prognosis. Antiangiogenic agents, such as bevacizumab, a humanized mAb against VEGF, added to platinum-etoposide chemotherapy improved progression-free survival in SCLC in two trials, but it did not translate into a benefit in overall survival. Nevertheless, VEGF has also acts as a mediator of an immunosuppressive microenvironment and its inhibition can revert the immune-suppressive tumor microenvironment and potentially enhance the efficacy of immunotherapies. Based on available preclinical data, we hypothesized that VEGF inhibition by bevacizumab could improve atezolizumab efficacy in a synergistic way and designed a phase II single-arm trial of bevacizumab in combination with carboplatin, etoposide, and atezolizumab as first-line treatment in ES-SCLC. The trial, which is still ongoing, enrolled 53 patients, including those with treated or untreated asymptomatic brain metastases (provided criteria are met), who received atezolizumab, bevacizumab, carboplatin and etoposide for 4-6 cycles (induction phase), followed by maintenance with atezolizumab and bevacizumab for a maximum of 18 total cycles or until disease progression, patient refusal, unacceptable toxicity. The evaluation of efficacy of the experimental combination in terms of 1-year overall survival rate is not yet mature (primary objective of the trial). The combination was feasible and the toxicity profile manageable (secondary objective of the trial).

Relative influence of gaze and static arm position in the Superior Parietal Lobule of the macaque monkey during reaching

The superior parietal lobule (SPL) of macaques is classically described as an associative cortex implicated in visuospatial perception, planning and control of reaching and grasping movements (De Vitis et al., 2019; Galletti et al., 2003, 2018, 2022; Fattori et al., 2017; Hadjidimitrakis et al., 2015). These processes are the result of the integration of signals related to different sensory modalities. During a goal-directed action, eye and limb information are combined to ensure that the hand is transported at the gazed target location and the arm is maintained steady in the final position. The SPL areas V6A, PEc and PE contain cells sensitive to the direction of gaze and limb position but less is known about the degree of independent encoding of these signals. In this thesis, we evaluated the influence of eye and arm position information upon single neuron activity of areas V6A, PEc and PE during the holding period after the execution of arm reaching movement, when the gaze and hand are both still at the reach target. Two male macaques (Macaca fascicularis) performed a reaching task while single unit activity was recorded from areas V6A, PEc and PE. We found that neurons in all these areas were modulated by eye and static arm positions with a joint encoding of gaze and somatosensory signals in V6A and PEc and a mostly separate processing of the two signals in PE. The elaboration of this information reflects the functional gradient found in the SPL with the caudal sector characterized by visuo-somatic properties in comparison to the rostral sector dominated by somatosensory signals. This evidence well agree also with the recent reallocation of areas V6A and PEc in Brodmann’s area 7 depending on their similar structural and functional features with respect to PE belonging to Brodmann’s area 5 (Gamberini et al., 2020).