DAMOV: A New Methodology and Benchmark Suite for Evaluating Data Movement Bottlenecks

Data movement between the CPU and main memory is a first-order obstacle against improving performance, scalability, and energy efficiency in modern systems. Computer systems employ a range of techniques to reduce overheads tied to data movement, spanning from traditional mechanisms (e.g., deep multi-level cache hierarchies, aggressive hardware prefetchers) to emerging techniques such as Near-Data Processing (NDP), where some computation is moved close to memory. Our goal is to methodically identify potential sources of data movement over a broad set of applications and to comprehensively compare traditional compute-centric data movement mitigation techniques to more memory-centric techniques, thereby developing a rigorous understanding of the best techniques to mitigate each source of data movement. With this goal in mind, we perform the first large-scale characterization of a wide variety of applications, across a wide range of application domains, to identify fundamental program properties that lead to data movement to/from main memory. We develop the first systematic methodology to classify applications based on the sources contributing to data movement bottlenecks. From our large-scale characterization of 77K functions across 345 applications, we select 144 functions to form the first open-source benchmark suite (DAMOV) for main memory data movement studies. We select a diverse range of functions that (1) represent different types of data movement bottlenecks, and (2) come from a wide range of application domains. Using NDP as a case study, we identify new insights about the different data movement bottlenecks and use these insights to determine the most suitable data movement mitigation mechanism for a particular application. We open-source DAMOV and the complete source code for our new characterization methodology at https://github.com/CMU-SAFARI/DAMOV.Comment: Our open source software is available at https://github.com/CMU-SAFARI/DAMO

Neoliberalismo, políticas públicas e desigualdade: Uma análise principalmente do Brasil

In this paper, we intend to identify the main aspects and interests of neoliberal politics and its effort to use the State as an instrument to benefit financial capital, equipping it and equating it with the private company. Our objective is to show that capitalism, with its cyclical economic and social crises, does not offer alternatives to overcome unemployment, as well as the inequality that spreads in all countries. In the financial sector and in large companies, there was an unprecedented policy of opening borders with the reduction of labor and social rights. However, this policy must be analyzed and considered.Pretendemos identificar os principais aspectos e interesses da política Neoliberal e seu esforço em utilizar o Estado como um instrumento para beneficiar o capital financeiro, o aparelhando e o equiparado à Empresa privada. Nosso objetivo é mostrar que o capitalismo, com suas crises econômicas e sociais cíclicas, não oferece alternativas para superar o desemprego, assim como, a desigualdade que se espalha em todos os países. No setor financeiro e nas grandes empresas houve uma política sem precedentes de abertura de fronteiras com a redução dos direitos trabalhistas e sociais. Entretanto, essa política deve ser analisada e ponderada

SynCron: Efficient Synchronization Support for Near-Data-Processing Architectures

Near-Data-Processing (NDP) architectures present a promising way to alleviate data movement costs and can provide significant performance and energy benefits to parallel applications. Typically, NDP architectures support several NDP units, each including multiple simple cores placed close to memory. To fully leverage the benefits of NDP and achieve high performance for parallel workloads, efficient synchronization among the NDP cores of a system is necessary. However, supporting synchronization in many NDP systems is challenging because they lack shared caches and hardware cache coherence support, which are commonly used for synchronization in multicore systems, and communication across different NDP units can be expensive. This paper comprehensively examines the synchronization problem in NDP systems, and proposes SynCron, an end-to-end synchronization solution for NDP systems. SynCron adds low-cost hardware support near memory for synchronization acceleration, and avoids the need for hardware cache coherence support. SynCron has three components: 1) a specialized cache memory structure to avoid memory accesses for synchronization and minimize latency overheads, 2) a hierarchical message-passing communication protocol to minimize expensive communication across NDP units of the system, and 3) a hardware-only overflow management scheme to avoid performance degradation when hardware resources for synchronization tracking are exceeded. We evaluate SynCron using a variety of parallel workloads, covering various contention scenarios. SynCron improves performance by 1.27$\times$ on average (up to 1.78$\times$) under high-contention scenarios, and by 1.35$\times$ on average (up to 2.29$\times$) under low-contention real applications, compared to state-of-the-art approaches. SynCron reduces system energy consumption by 2.08$\times$ on average (up to 4.25$\times$).Comment: To appear in the 27th IEEE International Symposium on High-Performance Computer Architecture (HPCA-27

Linking Spatial and Temporal Dynamic of Bacterioplankton Communities With Ecological Strategies Across a Coastal Frontal Area

Ocean frontal systems are widespread hydrological features defining the transition zone between distinct water masses. They are generally of high biological importance as they are often associated with locally enhanced primary production by phytoplankton. However, the composition of bacterial communities in the frontal zone remains poorly understood. In this study, we investigate how a coastal tidal front in Brittany (France) structures the free-living bacterioplankton communities in a spatio-temporal survey across four cruises, five stations and three depths. We used 16S rRNA gene surveys to compare bacterial community structures across 134 seawater samples and defined groups of co-varying taxa (modules) exhibiting coherent ecological patterns across space and time. We found that bacterial communities composition was strongly associated with the biogeochemical characteristics of the different water masses and that the front act as an ecological boundary for free-living bacteria. Seasonal variations in primary producers and their distribution in the water column appeared as the most salient parameters controlling heterotrophic bacteria which dominated the free-living community. Different dynamics of modules observed in this environment were strongly consistent with a partitioning of heterotrophic bacterioplankton in oligotroph and copiotroph ecological strategies. Oligotroph taxa, dominated by SAR11 Clade members, were relatively more abundant in low phytoplankton, high inorganic nutrients water masses, while copiotrophs and particularly opportunist taxa such as Tenacibaculum sp. or Pseudoalteromonas sp. reached their highest abundances during the more productive period. Overall, this study shows a remarkable coupling between bacterioplankton communities dynamics, trophic strategies, and seasonal cycles in a complex coastal environment

Transgenic neuronal overexpression reveals that stringently regulated p23 expression is critical for coordinated movement in mice

<p>Abstract</p> <p>Background</p> <p>p23 belongs to the highly conserved p24 family of type I transmembrane proteins, which participate in the bidirectional protein transport between the endoplasmic reticulum and Golgi apparatus. Mammalian p23 has been shown to interact with γ-secretase complex, and modulate secretory trafficking as well as intramembranous processing of amyloid precursor protein in cultured cells. Negative modulation of β-amyloid production by p23 in cultured cell lines suggested that elevation of p23 expression in neurons might mitigate cerebral amyloid burden.</p> <p>Results</p> <p>We generated several lines of transgenic mice expressing human p23 in neurons under the control of <it>Thy-1.2 </it>promoter. We found that even a 50% increase in p23 levels in the central nervous system of mice causes post-natal growth retardation, severe neurological problems characterized by tremors, seizure, ataxia, and uncoordinated movements, and premature death. The severity of the phenotype closely correlated with the level of p23 overexpression in multiple transgenic lines. While the number and general morphology of neurons in Hup23 mice appeared to be normal throughout the brain, abnormal non-Golgi p23 localization was observed in a subset of neurons with high transgene expression in brainstem. Moreover, detailed immunofluorescence analysis revealed marked proliferation of astrocytes, activation of microglia, and thinning of myelinated bundles in brainstem of Hup23 mice.</p> <p>Conclusions</p> <p>These results demonstrate that proper level of p23 expression is critical for neuronal function, and perturbing p23 function by overexpression initiates a cascade of cellular reactions in brainstem that leads to severe motor deficits and other neurological problems, which culminate in premature death. The neurological phenotype observed in Hup23 mice highlights significant adverse effects associated with manipulating neuronal expression of p23, a previously described negative modulator of γ-secretase activity and β-amyloid production. Moreover, our report has broader relevance to molecular mechanisms in several neurodegenerative diseases as it highlights the inherent vulnerability of the early secretory pathway mechanisms that ensure proteostasis in neurons.</p

Pennsylvania Folklife Vol. 45, No. 3

• Folklife at the Margins: Cultural Conservation for the Schuylkill Heritage Corridor • The Goschenhoppen Historians: Preserving and Celebrating Pennsylvania German Folk Culture • The African American Festival of Odunde: Twenty Years on South Street • Joanna Furnace: Then and Now • Port Clinton: A Peek Into the Pasthttps://digitalcommons.ursinus.edu/pafolklifemag/1146/thumbnail.jp

Structural and Mutational Analysis of Functional Differentiation between Synaptotagmins-1 and -7

Synaptotagmins are known to mediate diverse forms of Ca2+-triggered exocytosis through their C2 domains, but the principles underlying functional differentiation among them are unclear. Synaptotagmin-1 functions as a Ca2+ sensor in neurotransmitter release at central nervous system synapses, but synaptotagmin-7 does not, and yet both isoforms act as Ca2+ sensors in chromaffin cells. To shed light into this apparent paradox, we have performed rescue experiments in neurons from synaptotagmin-1 knockout mice using a chimera that contains the synaptotagmin-1 sequence with its C2B domain replaced by the synaptotagmin-7 C2B domain (Syt1/7). Rescue was not achieved either with the WT Syt1/7 chimera or with nine mutants where residues that are distinct in synaptotagmin-7 were restored to those present in synaptotagmin-1. To investigate whether these results arise because of unique conformational features of the synaptotagmin-7 C2B domain, we determined its crystal structure at 1.44 Å resolution. The synaptotagmin-7 C2B domain structure is very similar to that of the synaptotagmin-1 C2B domain and contains three Ca2+-binding sites. Two of the Ca2+-binding sites of the synaptotagmin-7 C2B domain are also present in the synaptotagmin-1 C2B domain and have analogous ligands to those determined for the latter by NMR spectroscopy, suggesting that a discrepancy observed in a crystal structure of the synaptotagmin-1 C2B domain arose from crystal contacts. Overall, our results suggest that functional differentiation in synaptotagmins arises in part from subtle sequence changes that yield dramatic functional differences

Oncogenic role of EAPII in lung cancer development and its activation of the MAPK–ERK pathway

Cancer progression involves multiple complex and interdependent steps, including progressive proliferation, angiogenesis and metastases. The complexity of these processes requires a comprehensive elucidation of the integrated signaling networks for better understanding. EAPII interacts with multiple cancer-related proteins, but its biological significance in cancer development remains unknown. In this report we identified the elevated level of EAPII protein in non-small-cell lung carcinoma (NSCLC) patients and NSCLC cell lines in culture. The oncogenic role of EAPII in lung cancer development was demonstrated using NSCLC cells with genetic manipulations that influence EAPII expression: EAPII overexpression increases proliferation of NSCLC cells with an accelerated transition of cell cycle and facilitates xenograft tumor growth in vivo; EAPII knockdown results in apoptosis of NSCLC cells and reduces xenograft tumor formation. To further explore the mechanism of EAPII's oncogenic role in lung cancer development and to elucidate the potential signaling pathway(s) that EAPII may impact, we employed antibody array to investigate the alternation of the major signaling pathways in NSCLC cells with altered EAPII level. We found that EAPII overexpression significantly activated Raf1 and ERK1/2, but not c-Jun N-terminal kinase and p38 pathways. Consistently, the protein and mRNA levels of MYC and cyclin D1, which are targets of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK–ERK) pathway, are significantly increased by EAPII overexpression. Taken together, we demonstrated that EAPII is an oncogenic factor and the activation of MAPK–ERK signaling pathway by EAPII may contribute to lung cancer development

Real-Time Imaging Reveals the Dynamics of Leukocyte Behaviour during Experimental Cerebral Malaria Pathogenesis

During experimental cerebral malaria (ECM) mice develop a lethal neuropathological syndrome associated with microcirculatory dysfunction and intravascular leukocyte sequestration. The precise spatio-temporal context in which the intravascular immune response unfolds is incompletely understood. We developed a 2-photon intravital microscopy (2P-IVM)-based brain-imaging model to monitor the real-time behaviour of leukocytes directly within the brain vasculature during ECM. Ly6Chi monocytes, but not neutrophils, started to accumulate in the blood vessels of Plasmodium berghei ANKA (PbA)-infected MacGreen mice, in which myeloid cells express GFP, one to two days prior to the onset of the neurological signs (NS). A decrease in the rolling speed of monocytes, a measure of endothelial cell activation, was associated with progressive worsening of clinical symptoms. Adoptive transfer experiments with defined immune cell subsets in recombinase activating gene (RAG)-1-deficient mice showed that these changes were mediated by Plasmodium-specific CD8+ T lymphocytes. A critical number of CD8+ T effectors was required to induce disease and monocyte adherence to the vasculature. Depletion of monocytes at the onset of disease symptoms resulted in decreased lymphocyte accumulation, suggesting reciprocal effects of monocytes and T cells on their recruitment within the brain. Together, our studies define the real-time kinetics of leukocyte behaviour in the central nervous system during ECM, and reveal a significant role for Plasmodium-specific CD8+ T lymphocytes in regulating vascular pathology in this disease. © 2014 Pai et al