87 research outputs found

    On the Benefits of Transparent Compression for Cost-Effective Cloud Data Storage

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    International audienceInfrastructure-as-a-Service (IaaS) cloud computing has revolutionized the way we think of acquiring computational resources: it allows users to deploy virtual machines (VMs) at large scale and pay only for the resources that were actually used throughout the runtime of the VMs. This new model raises new challenges in the design and development of IaaS middleware: excessive storage costs associated with both user data and VM images might make the cloud less attractive, especially for users that need to manipulate huge data sets and a large number of VM images. Storage costs result not only from storage space utilization, but also from bandwidth consumption: in typical deployments, a large number of data transfers between the VMs and the persistent storage are performed, all under high performance requirements. This paper evaluates the trade-off resulting from transparently applying data compression to conserve storage space and bandwidth at the cost of slight computational overhead. We aim at reducing the storage space and bandwidth needs with minimal impact on data access performance. Our solution builds on BlobSeer, a distributed data management service specifically designed to sustain a high throughput for concurrent accesses to huge data sequences that are distributed at large scale. Extensive experiments demonstrate that our approach achieves large reductions (at least 40%) of bandwidth and storage space utilization, while still attaining high performance levels that even surpass the original (no compression) performance levels in several data-intensive scenarios

    Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome.

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    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.BACKGROUND: Down syndrome (DS) may be considered a genetic form of Alzheimer's disease (AD) due to universal development of AD neuropathology, but diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. A potential biomarker is neurofilament light (NF-L), due to its association with axonal damage in neurodegenerative conditions. METHODS: We measured blood NF-L concentrations in 100 adults with DS using Simoa NF-light® assays, and we examined relationships with age as well as cross-sectional and longitudinal dementia diagnosis. RESULTS: NF-L concentrations increased with age (Spearman's rho = 0.789, p < 0.001), with a steep increase after age 40, and they were predictive of dementia status (p = 0.022 adjusting for age, sex, and APOE4), but they showed no relationship with long-standing epilepsy or premorbid ability. Baseline NF-L concentrations were associated with longitudinal dementia status. CONCLUSIONS: NF-L is a biomarker for neurodegeneration in DS with potential for use in future clinical trials to prevent or delay dementia.This work was funded by a Wellcome Trust Strategic Award (grant number 098330/Z/12/Z) conferred upon The London Down Syndrome (LonDownS) Consortium (Chief Investigator, Andre Strydom)

    A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

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    Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

    Ecological Thresholds in the Savanna Landscape: Developing a Protocol for Monitoring the Change in Composition and Utilisation of Large Trees

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    BACKGROUND: Acquiring greater understanding of the factors causing changes in vegetation structure -- particularly with the potential to cause regime shifts -- is important in adaptively managed conservation areas. Large trees (> or =5 m in height) play an important ecosystem function, and are associated with a stable ecological state in the African savanna. There is concern that large tree densities are declining in a number of protected areas, including the Kruger National Park, South Africa. In this paper the results of a field study designed to monitor change in a savanna system are presented and discussed. METHODOLOGY/PRINCIPAL FINDINGS: Developing the first phase of a monitoring protocol to measure the change in tree species composition, density and size distribution, whilst also identifying factors driving change. A central issue is the discrete spatial distribution of large trees in the landscape, making point sampling approaches relatively ineffective. Accordingly, fourteen 10 m wide transects were aligned perpendicular to large rivers (3.0-6.6 km in length) and eight transects were located at fixed-point photographic locations (1.0-1.6 km in length). Using accumulation curves, we established that the majority of tree species were sampled within 3 km. Furthermore, the key ecological drivers (e.g. fire, herbivory, drought and disease) which influence large tree use and impact were also recorded within 3 km. CONCLUSIONS/SIGNIFICANCE: The technique presented provides an effective method for monitoring changes in large tree abundance, size distribution and use by the main ecological drivers across the savanna landscape. However, the monitoring of rare tree species would require individual marking approaches due to their low densities and specific habitat requirements. Repeat sampling intervals would vary depending on the factor of concern and proposed management mitigation. Once a monitoring protocol has been identified and evaluated, the next stage is to integrate that protocol into a decision-making system, which highlights potential leading indicators of change. Frequent monitoring would be required to establish the rate and direction of change. This approach may be useful in generating monitoring protocols for other dynamic systems

    Cell Cycle Arrest by the Isoprenoids Perillyl Alcohol, Geraniol, and Farnesol Is Mediated by p21Cip1 and p27Kip1 in Human Pancreatic Adenocarcinoma Cells

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    Pancreatic cancer, the fourth leading cause of cancer-associated mortality in the United States, usually presents in an advanced stage and is generally refractory to chemotherapy. As such, there is a great need for novel therapies for this disease. The naturally derived isoprenoids perillyl alcohol, farnesol, and geraniol have chemotherapeutic potential in pancreatic and other tumor types. However, their mechanisms of action in these systems are not completely defined. In this study, we investigated isoprenoid effects on the cell cycle and observed a similar antiproliferative mechanism of action among the three compounds. First, when given in combination, the isoprenoids exhibited an additive antiproliferative effect against MIA PaCa-2 human pancreatic cancer cells. Furthermore, all three compounds induced a G0/G1 cell cycle arrest that coincided with an increase in the expression of the cyclin kinase inhibitor proteins p21Cip1 and p27Kip1 and a reduction in cyclin A, cyclin B1, and cyclin-dependent kinase (Cdk) 2 protein levels. Immunoprecipitation studies demonstrated increased association of both p21Cip1 and p27Kip1 with Cdk2 as well as diminished Cdk2 kinase activity after isoprenoid exposure, indicating a cell cycle-inhibitory role for p21Cip1 and p27Kip1 in pancreatic adenocarcinoma cells. When siRNA was used to inhibit expression of p21Cip1 and p27Kip1 proteins in MIA PaCa-2 cells, conditional resistance to all three isoprenoid compounds was evident. Given similar findings in this cell line and in BxPC-3 human pancreatic adenocarcinoma cells, we conclude that the chemotherapeutic isoprenoid compounds perillyl alcohol, farnesol, and geraniol invoke a p21Cip1- and p27Kip1-dependent antiproliferative mechanism in human pancreatic adenocarcinoma cells
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