Understanding microarchitectural effects on the performance of parallel applications

International audienceSince several years, classical multiprocessor systems have evolved to multicores, which tightly integrate multiple CPU cores on a single die or package. This technological shift leads to sharing of microarchitectural resources between the individual cores, which has direct implications on the performance of parallel applications. It consequently makes understanding and tuning these significantly harder, besides the already complex issues of parallel programming. In this work, we empirically analyze various microarchitectural effects on the performance of parallel applications, through repeatable experiments. We show their importance, besides the effects described by Amdahl's law and synchronization or communication considerations. In addition to the classification of shared resources into storage and bandwidth resources of Abel et al. [1], we view the physical temperature and power budget also as a shared resource. Dynamic Voltage and Frequency Scaling (DVFS) over a wide range is needed to meet these constraints in multicores, thus it is a very important factor for performance nowadays. Our work aims to gain a better understanding of performance-limiting factors in high performance multicores, it shall serve as a basis to avoid them and to find solutions to tune parallel applications

A structurally versatile nickel phosphite acting as a robust bifunctional electrocatalyst for overall water splitting

The design and development of economical and highly efficient electrocatalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) under alkaline conditions are vital in lowering the overall energy losses in alkaline water electrolysis. Here we present a nickel phosphite, Ni11(HPO3)8(OH)6, belonging to the unique class of phosphorus-based inorganic materials with striking structural features that have been explored for the first time in the reaction of electrocatalytic overall water splitting with a profound understanding of the system using in situ and ex situ techniques. When electrophoretically deposited, the nickel phosphite exhibited remarkable electrocatalytic activity, yielding considerably low overpotentials for both the OER and HER with extreme structural stability and enhanced durability in alkaline media. Apart from the attractive structural merits, the higher activity of nickel phosphite is mainly attributed to the formation of oxidized nickel species in the catalytic OER process, while subtle experimental evidence of the participation of phosphite anions for the acceleration of the HER with the support of Ni2+ cations as catalytically active sites is identified, which is highly compelling and has never been previously discovered. Finally, the bifunctionality of nickel phosphite was demonstrated by constructing an alkaline water electrolyzer with a low cell voltage and over 4 days of undiminishing stability. This work offers an appealing cost-effective system based on earth-abundant metals for water electrolysis and can be extended to other transition metal based homo- or hetero-bimetallic phosphites

Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity

AbstractCCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis. Herein, we show that colonic CCL25 expression is not only upregulated in patients with active colitis, but strongly correlates with endoscopic Mayo score and mucosal TNFα expression. Moreover, approximately 90% (CD4+) and 30% (CD8+) of tissue-infiltrating T-cells in colitis were identified as CCR9+ effector lymphocytes, compared to <10% of T-cells being CCR9+ in normal colon. Sorted CCR9+ lymphocytes also demonstrated enhanced cellular adhesion to stimulated hepatic sinusoidal endothelium compared with their CCR9– counterparts when under flow. Collectively, these results suggest that CCR9/CCL25 interactions are not only involved in colitis pathogenesis but also correlate with colonic inflammatory burden; further supporting the existence of overlapping mucosal lymphocyte recruitment pathways between the inflamed colon and liver

CAPS1 Regulates Catecholamine Loading of Large Dense-Core Vesicles

SummaryCAPS1 is thought to play an essential role in mediating exocytosis from large dense-core vesicles (LDCVs). We generated CAPS1-deficient (KO) mice and studied exocytosis in a model system for Ca2+-dependent LDCV secretion, the adrenal chromaffin cell. Adult heterozygous CAPS1 KO cells display a gene dosage-dependent decrease of CAPS1 expression and a concomitant reduction in the number of docked vesicles and secretion. Embryonic homozygous CAPS1 KO cells show a strong reduction in the frequency of amperometrically detectable release events of transmitter-filled vesicles, while the total number of fusing vesicles, as judged by capacitance recordings or total internal reflection microscopy, remains unchanged. We conclude that CAPS1 is required for an essential step in the uptake or storage of catecholamines in LDCVs

Glycemic Variability Promotes Both Local Invasion and Metastatic Colonization by Pancreatic Ductal Adenocarcinoma

Background & Aims: Although nearly half of pancreatic ductal adenocarcinoma (PDAC) patients have diabetes mellitus with episodes of hyperglycemia, its tumor microenvironment is hypoglycemic. Thus, it is crucial for PDAC cells to develop adaptive mechanisms dealing with oscillating glucose levels. So far, the biological impact of such glycemic variability on PDAC biology remains unknown. Methods: Murine PDAC cells were cultured in low- and high-glucose medium to investigate the molecular, biochemical, and metabolic influence of glycemic variability on tumor behavior. A set of in vivo functional assays including orthotopic implantation and portal and tail vein injection were used. Results were further confirmed on tissues from PDAC patients. Results: Glycemic variability has no significant effect on PDAC cell proliferation. Hypoglycemia is associated with local invasion and angiogenesis, whereas hyperglycemia promotes metastatic colonization. Increased metastatic colonization under hyperglycemia is due to increased expression of runt related transcription factor 3 (Runx3), which further activates expression of collagen, type VI, alpha 1 (Col6a1), forming a glycemic pro-metastatic pathway. Through epigenetic machinery, retinoic acid receptor beta (Rarb) expression fluctuates according to glycemic variability, acting as a critical sensor relaying the glycemic signal to Runx3/Col6a1. Moreover, the signal axis of Rarb/Runx3/Col6a1 is pharmaceutically accessible to a widely used antidiabetic substance, metformin, and Rar modulator. Finally, PDAC tissues from patients with diabetes show an increased expression of COL6A1. Conclusions: Glycemic variability promotes both local invasion and metastatic colonization of PDAC. A pro-metastatic signal axis Rarb/Runx3/Col6a1 whose activity is controlled by glycemic variability is identified. The therapeutic relevance of this pathway needs to be explored in PDAC patients, especially in those with diabetes

Modification of LTE Firmwares on Smartphones

Every mobile phone contains a modem subsystem responsible for communication with mobile networks. In contrast to the well known main system of smartphones, running for example an Android operating system, the modem hardware details and its software are secrets of the manufacturer, leaving the modem as a black box to us. Hence, this work analyzes recent Qualcomm modems supporting the latest deployed communication standard LTE. We then use the gained knowledge to implement a patching framework allowing easy modification of the modem’s firmware binary in a high level programming language. To demonstrate its usability, we realize applications ranging from debugging tools up to LTE MAC layer sniffing, security key extraction and access to channel estimates of the physical layer. These also show that malicious code in the modem subsystem imposes a severe and realistic threat. Furthermore, this work opens the modem as a research platform for recent mobile network technologies, removing the need for expensive special equipment in many research projects

Herstellung und Analyse einer ddRAD-Bibliothek von Gampsocleis glabra

In dieser Bachelorarbeit wurde eine ddRAD-Bibliothek (double digest reactions-site associated DNA) hergestellt, um die Heideschrecke Gampsocleis glabra populationsgenetisch zu analysieren. Das Ziel ist es, eine Aussage zu treffen, ob sich der Genotyp, der isoliert vorkommenden Heideschrecke verändert hat, so dass sich neue Populationen gebildet haben. Dafür wurden Proben aus Deutschland (Klietz, Munster, Rheinmetall), Niederlande, Slowakei und Ungarn untersucht. Das Protokoll für die Herstellung der ddRAD-Bibliothek wurde neu zusammengestellt, deswegen ist ein weiteres Ziel dieser Arbeit das Protokoll qualitativ zu untersuchen, ob es für die Analyse in der Populationsgenetik eingesetzt werden kann und um es weiter zu verbessern. Eine ddRAD-Bibliothek ist eine DNA-Bibliothek, die es ermöglicht, mehrere DNA-Fragmente von Proben, die durch eine Digestion mit zwei Restriktionsenzymen entstehen, mit unterscheidbarem Adapter und Primer (Barcode, Index) und einer NGS-Sequenzierung populationsgenetisch zu untersuchen. Es wird eine ddRAD-Bibliothek eingesetzt, weil sie kostengünstiger, effizienter und mehr genetische Informationen bzw. Polymorphismen erzeugt als anderen Methoden z.B. „SNP-Chips“. Für die Beantwortung der Fragen wurden zwei ddRad-Bibliotheken hergestellt, jeweils mit 24 Proben aus unterschiedlichen Fundorten. Für die Herstellung wurde die Restriktionsenzyme SbfI und MseI für die Digestion eingesetzt. Die Unterscheidung der Proben wurde mit den spezifischen Adaptern und Primern für die Illumina-NGS-Sequenzierung gewährleistet. Die Fragmentierung erfolgte mit magnetischen Beads und BluePippin. Jeder Schritt der Herstellung wurde mit dem Elektrophorese-System Tapestation kontrolliert. Die Sequenzierung wurde mit eine Illumina MiSeq durchgeführt. Die bioinformatische Bearbeitung und Vorbereitung der Reads erfolgte mit den Programmen STACKS und CUTADAPT. Anschließend wurde mit STRUCTURE und STRUCTURE HARVESTER die Populationsstruktur bestimmt. Dabei wurden jeweils die beiden einzelnen Bibliotheken und eine Zusammenführung der Daten der beiden Bibliothek analysiert. Die Analyse der Qualität wurde mit dem Programm FASTQC und MULTIQC durchgeführt. Die Einstellungen des Programms wurde so konzipiert, dass sie eine Schnellanalyse möglich macht. Die beiden Bibliotheken sind nach dem Phred-Qualität-Wert, der für die meisten Sequenzen zwischen 30 und 35 liegt, für die Populationsgenetik einsetzbar. Die einzelnen Bibliotheken haben Anteile von drei Populationen, die zusammengeführten Daten habe Anteile von vier Populationen im Genotyp. Es hat sich gezeigt, dass die Aussagen der drei Populationsstrukturen nicht einheitlich sind und durch die stochastische Bearbeitung (MCMC, Ad-hoc-Statistik) nicht vergleichbar sind. Für eine bessere Aussage über eine Populationsstruktur müsste die ddRAD-Bibliothek um mehrere Proben aus verschiedenen Fundorten vergrößert werden, die pro Ort die gleiche Anzahl haben

Empirical study of Amdahl’s law on multicore processors

Since many years, we observe a shift from classical multiprocessor systems tomulticores, which tightly integrate multiple CPU cores on a single die or package. This shift doesnot modify the fundamentals of parallel programming, but makes harder the understanding andthe tuning of the performances of parallel applications. Multicores technology leads to sharing ofmicroarchitectural resources between the individual cores, which Abel et al. [1] classified in storageand bandwidth resources. In this work, we empirically analyze the effects of such sharing onprogram performance, through repeatable experiments. We show that they can dominate scalingbehavior, besides the effects described by Amdahl’s law and synchronization or communicationconsiderations. In addition to the classification of [1], we view the physical temperature and powerbudget also as a shared resource. It is a very important factor for performance nowadays, sinceDVFS over a wide range is needed to meet these constraints in multicores. Furthermore, wedemonstrate that resource sharing not just leads a flat speedup curve with increasing thread countbut can even cause slowdowns. Last, we propose a formal modeling of the performances to allowdeeper analysis. Our work aims to gain a better understanding of performance limiting factors inhigh performance multicores, it shall serve as basis to avoid them and to find solutions to tune theparallel applications.Cela fait plusieurs années que les systèmes multi-processeurs ont évolué vers des systèmesmulti-cœurs. Cette évolution ne bouleverse pas les fondements de la programmation parallèle, mais rendplus difficile l’analyse et l’optimisation des performances des codes. La technologie multi-cœurs engendreun partage de ressources micro-architecturales entre les cœurs individuels, classifiées en ressources destockage ou de bande passante d’après les travaux d’Abel et al [1]. Dans ce document, nous effectuonsune analyse fine et empirique des effets de ce partage de ressources sur les performances. Nous montronsqu’ils dominent la scalabilité des temps d’exécution, au delà des considérations de synchronisation etde communication modélisées dans la loi d’Amdahl. En plus de la classification étudiée dans [1], nousregardons la température physique et la puissance électrique comme des ressources partagées. Ellesdeviennent des facteurs très importants pour les performances actuellement; la modulation de fréquence(DVFS) est utilisée dans presque tous les systèmes multi-cœeurs à hautes performances. Aussi, nousmontrons que le partage de ressources micro-architecturales engendre non seulement une stagnationdes accélérations (lespeedupde l’application en fonction du nombre de threads parallèles sur cœursphysiques), mais parfois une dégradation (slowdown). En dernier, nous proposons une modélisationformelle des performances d’applications parallèles permettant une analyse plus fine. Notre travailpermet une meilleure compréhension des facteurs limitants les performances des applications parallèlessur systèmes multi-cœurs, servant de base ensuite pour l’analyse et l’optimisation de ces performances

Evaluation system of adaptive lighting systems indynamic situations at night-time

In the recent years, one of the key areas of research on automotive lighting has been focused on developing adaptive lighting systems. The performance of such systems depends not only on their photometric characteristics but also due to driving situation, roadway geometry and vehicle kinematics. Hence, objective evaluation and characterization of adaptive lighting systems require driving test under usual road conditions. An evaluation system, that provides accurate and reliable measurement results in various environments, presents multifaceted technological challenges. The system is intended to provide a simple software adaptation in case of additional or new hardware components offering versatile test procedures. Additional challenges are imposed by the need of synchronization of several measurement systems. All these various aspects have been taken into account in the developed system

Impact of Silibinin A on bioenergetics in PC12APPsw cells and mitochondrial membrane properties in murine brain mitochondria

Age-related multifactorial diseases, such as the neurodegenerative Alzheimer’s disease (AD), still remain a challenge to today’s society. One mechanism associated with AD and aging in general is mitochondrial dysfunction (MD). Increasing MD is suggested to trigger other pathological processes commonly associated with neurodegenerative diseases. Silibinin A (SIL) is the main bioactive compound of the Silymarin extract from the Mediterranean plant Silybum marianum (L.) (GAERTN/Compositae). It is readily available as a herbal drug and well established in the treatment of liver diseases as a potent radical scavenger reducing lipid peroxidation and stabilize membrane properties. Recent data suggest that SIL might also act on neurological changes related to MD. PC12APPsw cells produce low levels of human Aβ and thus act as a cellular model of early AD showing changed mitochondrial function. We investigated whether SIL could affect mitochondrial function by measuring ATP, MMP, as well as respiration, mitochondrial mass, cellular ROS and lactate/pyruvate concentrations. Furthermore, we investigated its effects on the mitochondrial membrane parameters of swelling and fluidity in mitochondria isolated from the brains of mice. In PC12APPsw cells, SIL exhibits strong protective effects by rescuing MMP and ATP levels from SNP-induced mitochondrial damage and improving basal ATP levels. However, SIL did not affect mitochondrial respiration and mitochondrial content. SIL significantly reduced cellular ROS and pyruvate concentrations. Incubation of murine brain mitochondria with SIL significantly reduces Ca2+ induced swelling and improves membrane fluidity. Although OXPHOS activity was unaffected at this early stage of a developing mitochondrial dysfunction, SIL showed protective effects on MMP, ATP- after SNP-insult and ROS-levels in APPsw-transfected PC12 cells. Results from experiments with isolated mitochondria imply that positive effects possibly result from an interaction of SIL with mitochondrial membranes and/or its antioxidant activity. Thus, SIL might be a promising compound to improve cellular health when changes to mitochondrial function occur