Systematic Protocol for SASW Inversion

Spectral-analysis-of-surface-waves (SASW) is a nondestructive test method for characterization of the variation with depth of the shear modulus of soils. One drawback in SASW is the need for an experienced user to conduct the inversion. Difficulty in SASW inversion arises from lack of constraint of the least squares minimization used on shear wave velocity parameters. For even simple profiles. The inversion algorithm can exhibit instability due to numerical sensitivity of the forward model calculations. The user must provide a reasonable starting profile; and then the parameters must be carefully followed and constrained to reach convergence. The inversion process was explored using a range of dispersion curves ranging from simple to complex layering systems. Three key principles were built into a new protocol to provide necessary constraints on the inversion algorithm. Dispersion data from many test sites have been inverted using the new protocol. Careful adherence to the protocol consistently produces shear wave velocity profiles indicative of site conditions. The protocol provides logic necessary for automation of the inversion process

Distributed Environment for Efficient Virtual Machine Image Management in Federated Cloud Architectures

The use of Virtual Machines (VM) in Cloud computing provides various benefits in the overall software engineering lifecycle. These include efficient elasticity mechanisms resulting in higher resource utilization and lower operational costs. VM as software artifacts are created using provider-specific templates, called VM images (VMI), and are stored in proprietary or public repositories for further use. However, some technology specific choices can limit the interoperability among various Cloud providers and bundle the VMIs with nonessential or redundant software packages, leading to increased storage size, prolonged VMI delivery, stagnant VMI instantiation and ultimately vendor lock-in. To address these challenges, we present a set of novel functionalities and design approaches for efficient operation of distributed VMI repositories, specifically tailored for enabling: (i) simplified creation of lightweight and size optimized VMIs tuned for specific application requirements; (ii) multi-objective VMI repository optimization; and (iii) efficient reasoning mechanism to help optimizing complex VMI operations. The evaluation results confirm that the presented approaches can enable VMI size reduction by up to 55%, while trimming the image creation time by 66%. Furthermore, the repository optimization algorithms, can reduce the VMI delivery time by up to 51% and cut down the storage expenses by 3%. Moreover, by implementing replication strategies, the optimization algorithms can increase the system reliability by 74%

Characterization of two marker chromosomes in a patient with acute nonlymphocytic leukemia by two-color fluorescence in situ hybridization

A patient with acute nonlymphocytic leukemia (ANLL), M5b according to French-American-British (FAB) classification, showed monosomy 16, an extra 1p−, and a 21q+. These derivative chromosomes could not be defined by GTG-banding. For better characterization, we performed two-color fluorescence in situ hybridization (FISH) experiments applying DNA libraries from sorted human chromosomes, chromosome-specific repetitive probes, and a band-specific YAC-clone. With these FISH studies the karyotype could be characterized as 46,XY,+der(1)t(1;21)(p11;?),−16,der(21)t(16;21)(p11.1;q22)

ENTICE VM image analysis and optimised fragmentation

Virtual machine (VM) images (VMIs) often share common parts of significant size as they are stored individually. Using existing de-duplication techniques for such images are non-trivial, impose serious technical challenges, and requires direct access to clouds' proprietary image storages, which is not always feasible. We propose an alternative approach to split images into shared parts, called fragments, which are stored only once. Our solution requires a reasonably small set of base images available in the cloud, and additionally only the increments will be stored without the contents of base images, providing significant storage space savings. Composite images consisting of a base image and one or more fragments are assembled on- demand at VM deployment. Our technique can be used in conjunction with practically any popular cloud solution, and the storage of fragments is independent of the proprietary image storage of the cloud provider

EDGeS: a bridge between desktop grids and service grids

Desktop grids and service grids widely used by their different users communities as efficient solutions for making full use of computing power and achieving loads balances across Intranet or Internet. Nevertheless,little work has been done to combine these two grids technologies together to establish a seamless and vast grid resources pool. In this paper we will present a new European FP7 infrastructure project:EDGeS (enabling desktop grids for e-science), which aim to build technological bridges to facilitate interoperability between desktop grid and service grid. We give also a taxonomy of existing grid systems: desktop grids such as BONIC and XtremWeb, service grids such as EGEE. Then we describe furtherly our solution for identifying translation technologies for porting applications between desktop grids and service grids, and vice versa. There are three themes in our solution, which discuss actual popular bridging technologies, user access issues, and distributed data issues about deployment and application development

Cerebral cavernous malformations associated to meningioma: High penetrance in a novel family mutated in the PDCD10 gene

Multiple familial meningiomas occur in rare genetic syndromes, particularly neurofibromatosis type 2. The association of meningiomas and cerebral cavernous malformations (CCMs) has been reported in few patients in the medical literature. The purpose of our study is to corroborate a preferential association of CCMs and multiple meningiomas in subjects harbouring mutations in the PDCD10 gene (also known as CCM3). Three members of an Italian family affected by seizures underwent conventional brain Magnetic Resonance Imaging (MRI) with gadolinium contrast agent including gradient echo (GRE) imaging. The three CCM-causative genes were sequenced by Sanger method. Literature data reporting patients with coexistence of CCMs and meningiomas were reviewed. MRI demonstrated dural-based meningioma-like lesions associated to multiple parenchymal CCMs in all affected individuals. A disease-causative mutation in the PDCD10 gene (p.Gln112PhefsX13) was identified. Based on neuroradiological and molecular data as well as on literature review, we outline a consistent association between PDCD10 mutations and a syndrome of CCMs with multiple meningiomas. This condition should be considered in the differential diagnosis of multiple/familial meningioma syndromes. In case of multiple/familial meningioma the use of appropriate MRI technique may include GRE and/or susceptibility-weighted imaging (SWI) to rule out CCM. By contrast, proper post-gadolinium scans may aid defining dural lesions in CCM patients and are indicated in PDCD10-mutated individuals

Chromosome 7 gain and DNA hypermethylation at the HOXA10 locus are associated with expression of a stem cell related HOX-signature in glioblastoma.

BACKGROUND: HOX genes are a family of developmental genes that are expressed neither in the developing forebrain nor in the normal brain. Aberrant expression of a HOX-gene dominated stem-cell signature in glioblastoma has been linked with increased resistance to chemo-radiotherapy and sustained proliferation of glioma initiating cells. Here we describe the epigenetic and genetic alterations and their interactions associated with the expression of this signature in glioblastoma. RESULTS: We observe prominent hypermethylation of the HOXA locus 7p15.2 in glioblastoma in contrast to non-tumoral brain. Hypermethylation is associated with a gain of chromosome 7, a hallmark of glioblastoma, and may compensate for tumor-driven enhanced gene dosage as a rescue mechanism by preventing undue gene expression. We identify the CpG island of the HOXA10 alternative promoter that appears to escape hypermethylation in the HOX-high glioblastoma. An additive effect of gene copy gain at 7p15.2 and DNA methylation at key regulatory CpGs in HOXA10 is significantly associated with HOX-signature expression. Additionally, we show concordance between methylation status and presence of active or inactive chromatin marks in glioblastoma-derived spheres that are HOX-high or HOX-low, respectively. CONCLUSIONS: Based on these findings, we propose co-evolution and interaction between gene copy gain, associated with a gain of chromosome 7, and additional epigenetic alterations as key mechanisms triggering a coordinated, but inappropriate, HOX transcriptional program in glioblastoma

Extracellular Vesicle-Associated Aβ Mediates Trans-Neuronal Bioenergetic and Ca\u3csup\u3e2+\u3c/sup\u3e-Handling Deficits in Alzheimer\u27s Disease Models

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca2+ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of Aβ but have an increased Aβ42/ Aβ40 ratio; the majority of Aβ is located on the surface of the EVs. Impairment of lysosome function results in increased generation of EVs with elevated Aβ42 levels. EVs may mediate transcellular spread of pathogenic Aβ species that impair neuronal Ca2+ handling and mitochondrial function, and may thereby render neurons vulnerable to excitotoxicity

The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade glioma treated in EORTC 22033.

The optimal treatment for patients with low-grade glioma (LGG) WHO grade II remains controversial. Overall survival ranges from 2 to over 15 years depending on molecular and clinical factors. Hence, risk-adjusted treatments are required for optimizing outcome and quality of life. We aim at identifying mechanisms and associated molecular markers predictive for benefit from radiotherapy (RT) or temozolomide (TMZ) in LGG patients treated in the randomized phase III trial EORTC 22033. As candidate biomarkers for these genotoxic treatments, we considered the DNA methylome of 410 DNA damage response (DDR) genes. We first identified 62 functionally relevant CpG sites located in the promoters of 24 DDR genes, using the LGG data from The Cancer Genome Atlas. Then we tested their association with outcome [progression-free survival (PFS)] depending on treatment in 120 LGG patients of EORTC 22033, whose tumors were mutant for isocitrate dehydrogenase 1 or 2 (IDHmt), the molecular hallmark of LGG. The results suggested that seven CpGs of four DDR genes may be predictive for longer PFS in one of the treatment arms that comprised MGMT, MLH3, RAD21, and SMC4. Most interestingly, the two CpGs identified for MGMT are the same, previously selected for the MGMT-STP27 score that is used to determine the methylation status of the MGMT gene. This score was higher in the LGG with 1p/19q codeletion, in this and other independent LGG datasets. It was predictive for PFS in the TMZ, but not in the RT arm of EORTC 22033. The results support the hypothesis that a high score predicts benefit from TMZ treatment for patients with IDHmt LGG, regardless of the 1p/19q status. This MGMT methylation score may identify patients who benefit from first-line treatment with TMZ, to defer RT for long-term preservation of cognitive function and quality of life