An Experiment on Bare-Metal BigData Provisioning

Many BigData customers use on-demand platforms in the cloud, where they can get a dedicated virtual cluster in a couple of minutes and pay only for the time they use. Increasingly, there is a demand for bare-metal bigdata solutions for applications that cannot tolerate the unpredictability and performance degradation of virtualized systems. Existing bare-metal solutions can introduce delays of 10s of minutes to provision a cluster by installing operating systems and applications on the local disks of servers. This has motivated recent research developing sophisticated mechanisms to optimize this installation. These approaches assume that using network mounted boot disks incur unacceptable run-time overhead. Our analysis suggest that while this assumption is true for application data, it is incorrect for operating systems and applications, and network mounting the boot disk and applications result in negligible run-time impact while leading to faster provisioning time.This research was supported in part by the MassTech Collaborative Research Matching Grant Program, NSF awards 1347525 and 1414119 and several commercial partners of the Massachusetts Open Cloud who may be found at http://www.massopencloud.or

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

International audienceRelevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2R gamma(null)(c) mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies

Effect of base–acid properties of the mixtures of water with methanol on the solution enthalpy of selected cyclic ethers in this mixture at 298.15 K

The enthalpies of solution of cyclic ethers: 1,4- dioxane, 12-crown-4 and 18-crown-6 in the mixture of water and methanol have been measured within the whole mole fraction range at T = 298.15 K. Based on the obtained data, the effect of base–acid properties of water– methanol mixtures on the solution enthalpy of cyclic ethers in these mixtures has been analyzed. The solution enthalpy of cyclic ethers depends on acid properties of water– methanol mixtures in the range of high and medium water contents in the mixture. Based on the analysis performed, it can be assumed that in the mixtures of high methanol contents, cyclic ethe

Aortic valvuloplasty of calcific aortic stenosis with monofoil and trefoil balloon catheters: practical considerations

In order to evaluate the relation between balloon design (monofoil, trefoil) and valvular configuration, experimental aortic valvuloplasty was performed in four post-mortem hearts with calcific aortic sten

M2: Malleable Metal as a Service

Existing bare-metal cloud services that provide users with physical nodes have a number of serious disadvantage over their virtual alternatives, including slow provisioning times, difficulty for users to release nodes and then reuse them to handle changes in demand, and poor tolerance to failures. We introduce M2, a bare-metal cloud service that uses network-mounted boot drives to overcome these disadvantages. We describe the architecture and implementation of M2 and compare its agility, scalability, and performance to existing systems. We show that M2 can reduce provisioning time by over 50% while offering richer functionality, and comparable run-time performance with respect to tools that provision images into local disks. M2 is open source and available at https://github.com/CCI-MOC/ims.Comment: IEEE International Conference on Cloud Engineering 201

Feasibility, effectiveness, and acceptability of an afternoon-evening sleep schedule in older nightshift workers

Study Objectives: To explore the feasibility, effectiveness, and acceptability of an afternoon-evening sleep schedule in older (age 50–65 years) nightshift workers. Methods: We used a three-part strategy: a screening survey to identify individuals who said they could adopt an 8-hour afternoon-evening sleep schedule; a field study where daily diary and actigraphy data were collected during a baseline week and intervention week, with randomization to self-selected sleep, 8-hour afternoon-evening time in bed (TIB), or 8-hour self-selected TIB; and follow-up focus groups to understand the acceptability of the intervention. Results: Gender (p &lt; 0.001), Hispanic ethnicity (p = 0.023), the care of children (p = 0.014), and chronotype (p = 0.012), predicted the reported ability to spend 8 hours in bed in the afternoon-evening. Participants assigned to the 8-hour self-selected and 8-hour afternoon-evening groups significantly increased their TIB and sleep duration compared to baseline (p &lt; 0.05), while the control group did not. Although spending 8 hours in bed was feasible for the participants during the study, focus group discussions indicated participants would not continue an 8-hour TIB schedule after the study due to family responsibilities and other activities of daily living. Conclusions: Spending 8 hours in bed between successive night shifts, initiated at both a self-selected time and in the afternoon-evening, increased the sleep duration of older shiftworkers, but most would not continue such a schedule on their own. Additional research is needed to find countermeasures for the reduced sleep duration experienced by most shiftworkers that are not only effective, but also compatible with shiftworkers’ lifestyles.</p

Reducing data movement costs using energy-efficient, active computation on ssd

ABSTRACT Modern scientific discovery often involves running complex application simulations on supercomputers, followed by a sequence of data analysis tasks on smaller clusters. This offline approach suffers from significant data movement costs such as redundant I/O, storage bandwidth bottleneck, and wasted CPU cycles, all of which contribute to increased energy consumption and delayed end-toend performance. Technology projections for an exascale machine indicate that energy-efficiency will become the primary design metric. It is estimated that the energy cost of data movement will soon rival the cost of computation. Consequently, we can no longer ignore the data movement costs in data analysis. To address these challenges, we advocate executing data analysis tasks on emerging storage devices, such as SSDs. Typically, in extreme-scale systems, SSDs serve only as a temporary storage system for the simulation output data. In our approach, Active Flash, we propose to conduct in-situ data analysis on the SSD controller without degrading the performance of the simulation job. By migrating analysis tasks closer to where the data resides, it helps reduce the data movement cost. We present detailed energy and performance models for both active flash and offline strategies, and study them using extreme-scale application simulations, commonly used data analytics kernels, and supercomputer system configurations. Our evaluation suggests that active flash is a promising approach to alleviate the storage bandwidth bottleneck, reduce the data movement cost, and improve the overall energy efficiency

Targeting FGFR4 Inhibits Hepatocellular Carcinoma in Preclinical Mouse Models

The fibroblast growth factor (FGF)-FGF receptor (FGFR) signaling system plays critical roles in a variety of normal developmental and physiological processes. It is also well documented that dysregulation of FGF-FGFR signaling may have important roles in tumor development and progression. The FGFR4–FGF19 signaling axis has been implicated in the development of hepatocellular carcinomas (HCCs) in mice, and potentially in humans. In this study, we demonstrate that FGFR4 is required for hepatocarcinogenesis; the progeny of FGF19 transgenic mice, which have previously been shown to develop HCCs, bred with FGFR4 knockout mice fail to develop liver tumors. To further test the importance of FGFR4 in HCC, we developed a blocking anti-FGFR4 monoclonal antibody (LD1). LD1 inhibited: 1) FGF1 and FGF19 binding to FGFR4, 2) FGFR4–mediated signaling, colony formation, and proliferation in vitro, and 3) tumor growth in a preclinical model of liver cancer in vivo. Finally, we show that FGFR4 expression is elevated in several types of cancer, including liver cancer, as compared to normal tissues. These findings suggest a modulatory role for FGFR4 in the development and progression of hepatocellular carcinoma and that FGFR4 may be an important and novel therapeutic target in treating this disease