AllenRV: an Extensible Monitor for Multiple Complex Specifications with High Reactivity

International audienceAllenRV is a tool for monitoring temporal specifications, designed for ensuring good scalability in terms of size and number of formulae, and high reactivity. Its features reflect this design goal. For ensuring scalability in the number of formulae, it can simultaneously monitor a set of formulae written in past and future, next-free LTL, with some metric extensions; their efficient simultaneous monitoring is supported by a let construct allowing to share computations between formulae. For ensuring scalability in the size of formulae, it allows defining new abstractions as user-defined operators, which take discrete time boolean signals as arguments, but also constant parameters such as delays. For ensuring high reactivity, its monitoring algorithm does not require clock tick events, unlike many other tools. This is achieved by recomputing output signals both upon input signals changes and upon internally generated timeout events relative to such changes. As a consequence, monitoring remains efficient on arbitrarily fine-grained time domains. AllenRV is implemented by extending the existing Allen language and compiler, initially targeting ubiquitous applications using binary sensors, with temporal logic operators and a comprehensive library of user-defined operators on top of them. The most complex of these operators, including a complete adaptation of Allen-logic relations as selection operators, are proven correct with respect to their defined semantics. Thus, AllenRV offers an open platform for cooperatively developing increasingly complex libraries of high level, general or domain-specific, temporal operators and abstractions, without compromising correctness

Re-branding Abu Dhabi: From oil giant to energy titan

This article presents a case study of Abu Dhabi\u27s \u27energy re-branding\u27 since 2005 when it declared its intention to transform itself from an oil exporter to a total energy giant that also embraces alternative (renewable and nuclear) energy. The first part of the article identifies the benefits of this policy for Abu Dhabi\u27s external diplomacy but argues that the real driver is the emirate\u27s domestic gas shortage and its effects on economic diversification and political legitimacy. The second part of the article discusses the motivations and interactions of local and foreign agents by focusing on the implementation of alternative energy platforms. It therefore provides a rare glimpse of the policy-making process in Abu Dhabi. The final part of the article examines the extent to which energy re-branding may be linked to a process by the government to reiterate, reinterpret and repudiate Emirati identity in order to enhance regime legitimacy in the twenty-first century. © 2012 Macmillan Publishers Ltd

Kinematic analysis validation and calibration of a haptic interface

Initial calibration tests of a novel hybrid-structured kinesthetic haptic device based on an R-CUBE mechanism is presented in this paper. Experimental validation of the kinematics along with the experimental test set-up description is provided for the manufactured R-CUBE mechanism

Low Oxygen Modulates Multiple Signaling Pathways, Increasing Self-Renewal, While Decreasing Differentiation, Senescence, and Apoptosis in Stromal MIAMI Cells

Human bone marrow multipotent mesenchymal stromal cell (hMSC) number decreases with aging. Subpopulations of hMSCs can differentiate into cells found in bone, vasculature, cartilage, gut, and other tissues and participate in their repair. Maintaining throughout adult life such cell subpopulations should help prevent or delay the onset of age-related degenerative conditions. Low oxygen tension, the physiological environment in progenitor cell-rich regions of the bone marrow microarchitecture, stimulates the self-renewal of marrow-isolated adult multilineage inducible (MIAMI) cells and expression of Sox2, Nanog, Oct4a nuclear accumulation, Notch intracellular domain, notch target genes, neuronal transcriptional repressor element 1 (RE1)-silencing transcription factor (REST), and hypoxia-inducible factor-1 alpha (HIF-1α), and additionally, by decreasing the expression of (i) the proapoptotic proteins, apoptosis-inducing factor (AIF) and Bak, and (ii) senescence-associated p53 expression and β-galactosidase activity. Furthermore, low oxygen increases canonical Wnt pathway signaling coreceptor Lrp5 expression, and PI3K/Akt pathway activation. Lrp5 inhibition decreases self-renewal marker Sox2 mRNA, Oct4a nuclear accumulation, and cell numbers. Wortmannin-mediated PI3K/Akt pathway inhibition leads to increased osteoblastic differentiation at both low and high oxygen tension. We demonstrate that low oxygen stimulates a complex signaling network involving PI3K/Akt, Notch, and canonical Wnt pathways, which mediate the observed increase in nuclear Oct4a and REST, with simultaneous decrease in p53, AIF, and Bak. Collectively, these pathway activations contribute to increased self-renewal with concomitant decreased differentiation, cell cycle arrest, apoptosis, and/or senescence in MIAMI cells. Importantly, the PI3K/Akt pathway plays a central mechanistic role in the oxygen tension-regulated self-renewal versus osteoblastic differentiation of progenitor cells

E6-Associated Protein Dependent Estrogen Receptor Regulation of Protein Kinase A Regulatory Subunit R2A Expression in Neuroblastoma

E6ap is a known transcriptional coregulator for estrogen receptor alpha (Er, Erα) in the presence of estrogen. Protein kinase A (PKA) contains two regulatory subunits derived from four genes. Recent evidence demonstrates that PKA regulates E6ap activity. Data generated in our lab indicated estrogen dependent regulation of Pkar2a levels. Our project sets to investigate a possible feedback mechanism constituting of Erα and E6ap transcriptional regulation of Pkar2a expression. Western blot evaluated protein regulation correlations with E2 in mouse neuroblastoma lines. Bioinformatics detected estrogen response element (ERE) sequences. quantitative polymerase chain reaction (qPCR) validated the western blot results. ERE oligonucleotides were synthesized. Reporter gene transcriptional activity was evaluated via Luciferase assay output. Electromobility shift assay (EMSA) assessed direct binding between Erα relevant sequences. Chromatin immunoprecipitation (ChIP) and Re-ChIP were conducted in quantifying protein complex recruitment levels. Pkar2a protein expression directly correlated with E2, and four putative ERE sequences were identified. Pkar2a mRNA expression reverted to baseline with either E2 or E6ap absent. In the presence of E2, ERE-1 and ERE-4 possessed Luciferase reporter gene transcriptional capabilities. ERE-1 portrayed band shifts, representing direct binding to Erα with E2 supplementation. With E2, ERE-1 significantly enhanced Erα and E6ap recruitment levels to the Pkar2a promoter. Pkar2a is directly regulated by Erα and E6ap in the presence of estrogen stimulus. This work indicates a feedback mechanism in the interplay between PKA and E6ap, which may prove crucial for the role of both proteins in cancers and neurogenetic diseases like Angelman syndrome

Label-Free Quantitative LC–MS Proteomics of Alzheimer’s Disease and Normally Aged Human Brains

Quantitative proteomics analysis of cortical samples of 10 Alzheimer’s disease (AD) brains versus 10 normally aged brains was performed by following the accurate mass and time tag (AMT) approach with the high resolution LTQ Orbitrap mass spectrometer. More than 1400 proteins were identified and quantitated. A conservative approach of selecting only the consensus results of four normalization methods was suggested and used. A total of 197 proteins were shown to be significantly differentially abundant (<i>p</i>-values <0.05, corrected for multiplicity of testing) in AD versus control brain samples. Thirty-seven of these proteins were reported as differentially abundant or modified in AD in previous proteomics and transcriptomics publications. The rest to the best of our knowledge are new. Mapping of the discovered proteins with bioinformatic tools revealed significant enrichment with differentially abundant proteins of pathways and processes known to be important in AD, including signal transduction, regulation of protein phosphorylation, immune response, cytoskeleton organization, lipid metabolism, energy production, and cell death

Label-Free Quantitative LC–MS Proteomics of Alzheimer’s Disease and Normally Aged Human Brains

Quantitative proteomics analysis of cortical samples of 10 Alzheimer’s disease (AD) brains versus 10 normally aged brains was performed by following the accurate mass and time tag (AMT) approach with the high resolution LTQ Orbitrap mass spectrometer. More than 1400 proteins were identified and quantitated. A conservative approach of selecting only the consensus results of four normalization methods was suggested and used. A total of 197 proteins were shown to be significantly differentially abundant (<i>p</i>-values <0.05, corrected for multiplicity of testing) in AD versus control brain samples. Thirty-seven of these proteins were reported as differentially abundant or modified in AD in previous proteomics and transcriptomics publications. The rest to the best of our knowledge are new. Mapping of the discovered proteins with bioinformatic tools revealed significant enrichment with differentially abundant proteins of pathways and processes known to be important in AD, including signal transduction, regulation of protein phosphorylation, immune response, cytoskeleton organization, lipid metabolism, energy production, and cell death