Cerebrovascular atherosclerosis in type III hyperlipidemia is modulated by variation in the Apolipoprotein A5 gene

<p>Abstract</p> <p>Objective</p> <p>Type III Hyperlipoproteinemia is a rare lipid disorder with a frequency of 1-5 in 5000. It is characterized by the accumulation of triglyceride rich lipoproteins and patients are at increased risk of developping atherosclerosis. Type III HLP is strongly associated with the homozygous presence of the ε2 allele of the <it>APOE </it>gene.</p> <p>However only about 10% of subjects with APOE2/2 genotype develop hyperlipidemia and it is therefore assumed that further genetic and environmental factors are necessary for the expression of disease. It has recently been shown that variation in the <it>APOA5 </it>gene is one of these co-factors. The aim of this study is to investigate the development of cerebrovascular atherosclerosis in patients with Type III hyperlipoproteinemia (Type III HLP) and the role of variation in the APOA5 gene as a risk factor.</p> <p>Methods</p> <p>60 patients with type III hyperlipidemia and ApoE2/2 genotype were included in the study after informed consent. The presence of cerebrovascular atherosclerosis was investigated using B-mode ultra-sonography of the carotid artery. Serum lipid levels were measured by standard procedures. The APOE genotype and the 1131T > C and S19W SNPs in the APOA5 gene and the APOC3 sstI SNP were determined by restriction isotyping Allele frequencies were determined by gene counting and compared using Fisher's exact test. Continuous variables were compared using the Mann Whitney test. A p value of 0.05 or below was considered statistically significant. Analysis was performed using Statistica 7 software.</p> <p>Results</p> <p>The incidence of the APOA5 SNPs, -1131T > C and S19W and the APOC3 sstI SNP were determined as a potential risk modifier. After correction for conventional risk factors, the C allele of the 1131T > C SNP in the APOA5 gene was associated with an increased risk for the development of carotid plaque in patients with Type III HLP with an odds ratio of 3.69. Evaluation of the genotype distribution was compatible with an independent effect of APOA5.</p> <p>Conclusions</p> <p>The development of atherosclerosis in patients with Type III HLP is modulated by variation in the <it>APOA5 </it>gene.</p

From Teamchef Arminius to Hermann Junior: glocalised discourse about a national foundation myth

If for much of the nineteenth and twentieth centuries, the ‘Battle of the Teutoburg Forest’, fought in 9 CE between Roman armies and Germanic tribes, was predominantly a reference point for nationalist and chauvinist discourses in Germany, the first decade of the twenty-first century has seen attempts to link public remembrance with local/regional identities on the one hand and international/intercultural contact on the other. In the run up to and during the ‘anniversary year’ of 2009, German media, sports institutions and various other official institutions articulating tourist, economic and political interests attempted to create a new ‘glocalised’ version of the public memory of the Teutoburg battle. Combining methods of Cognitive Linguistics and Critical Discourse Analysis, the paper analyses the narrative and argumentative topoi employed in this re-orientation of public memory, with a special emphasis on hybrid, post-national identity-construction. Das zweitausendjährige Gedenkjahr der „Schlacht im Teutoburger Wald“ im Jahr 2009 bot eine günstige Gelegenheit, die bis in die zweite Hälfte des 20. Jahrhunderts dominante Tradition nationalistisch–chauvinistischer Deutungen des Sieges von germanischen Stämmen über drei römische Legionen zu korrigieren und zu überwinden. Der Aufsatz analysiert mit Hilfe diskurslinguistischer Methoden die Anstrengungen regionaler Institutionen und Medien, die nationale Vereinnahmung des historischen Gedenkens kritisch zu thematisieren sowie neue, zum eine lokal situierte, zum andern international orientierte Identifikationsangebote anzubieten. Die Analyse zeigt, dass solche „de-nationalisierten“ Identifikationsangebote zwar teilweise auch früher verwendet wurden, aber heutzutage rekontextualisiert und auf innovative Weise in den Vordergrund gestellt werden

Integrated Circuit Design in US High-Energy Physics

This whitepaper summarizes the status, plans, and challenges in the area of integrated circuit design in the United States for future High Energy Physics (HEP) experiments. It has been submitted to CPAD (Coordinating Panel for Advanced Detectors) and the HEP Community Summer Study 2013(Snowmass on the Mississippi) held in Minnesota July 29 to August 6, 2013. A workshop titled: US Workshop on IC Design for High Energy Physics, HEPIC2013 was held May 30 to June 1, 2013 at Lawrence Berkeley National Laboratory (LBNL). A draft of the whitepaper was distributed to the attendees before the workshop, the content was discussed at the meeting, and this document is the resulting final product. The scope of the whitepaper includes the following topics: Needs for IC technologies to enable future experiments in the three HEP frontiers Energy, Cosmic and Intensity Frontiers; Challenges in the different technology and circuit design areas and the related R&D needs; Motivation for using different fabrication technologies; Outlook of future technologies including 2.5D and 3D; Survey of ICs used in current experiments and ICs targeted for approved or proposed experiments; IC design at US institutes and recommendations for collaboration in the future

Dynamic reconfiguration of human brain networks during learning

Human learning is a complex phenomenon requiring flexibility to adapt existing brain function and precision in selecting new neurophysiological activities to drive desired behavior. These two attributes -- flexibility and selection -- must operate over multiple temporal scales as performance of a skill changes from being slow and challenging to being fast and automatic. Such selective adaptability is naturally provided by modular structure, which plays a critical role in evolution, development, and optimal network function. Using functional connectivity measurements of brain activity acquired from initial training through mastery of a simple motor skill, we explore the role of modularity in human learning by identifying dynamic changes of modular organization spanning multiple temporal scales. Our results indicate that flexibility, which we measure by the allegiance of nodes to modules, in one experimental session predicts the relative amount of learning in a future session. We also develop a general statistical framework for the identification of modular architectures in evolving systems, which is broadly applicable to disciplines where network adaptability is crucial to the understanding of system performance.Comment: Main Text: 19 pages, 4 figures Supplementary Materials: 34 pages, 4 figures, 3 table

F-ATPase ofDrosophila melanogasterForms 53-Picosiemen (53-pS) Channels Responsible for Mitochondrial Ca2+-induced Ca2+Release

Mitochondria of Drosophila melanogaster undergo Ca2+-induced Ca2+ release through a putative channel (mCrC) that has several regulatory features of the permeability transition pore (PTP). The PTP is an inner membrane channel that forms from F-ATPase, possessing a conductance of 500 picosiemens (pS) in mammals and of 300 pS in yeast. In contrast to the PTP, the mCrC of Drosophila is not permeable to sucrose and appears to be selective for Ca2+ and H+. We show (i) that like the PTP, the mCrC is affected by the sense of rotation of F-ATPase, by Bz-423, and by Mg2+/ADP; (ii) that expression of human cyclophilin D in mitochondria of Drosophila S2R+ cells sensitizes the mCrC to Ca2+ but does not increase its apparent size; and (iii) that purified dimers of D. melanogaster F-ATPase reconstituted into lipid bilayers form 53-pS channels activated by Ca2+ and thiol oxidants and inhibited byMg(2+)/gamma-imino ATP. These findings indicate that the mCrC is the PTP of D. melanogaster and that the signature conductance of F-ATPase channels depends on unique structural features that may underscore specific roles in different species

Weak Lensing from Space I: Instrumentation and Survey Strategy

A wide field space-based imaging telescope is necessary to fully exploit the technique of observing dark matter via weak gravitational lensing. This first paper in a three part series outlines the survey strategies and relevant instrumental parameters for such a mission. As a concrete example of hardware design, we consider the proposed Supernova/Acceleration Probe (SNAP). Using SNAP engineering models, we quantify the major contributions to this telescope's Point Spread Function (PSF). These PSF contributions are relevant to any similar wide field space telescope. We further show that the PSF of SNAP or a similar telescope will be smaller than current ground-based PSFs, and more isotropic and stable over time than the PSF of the Hubble Space Telescope. We outline survey strategies for two different regimes - a ``wide'' 300 square degree survey and a ``deep'' 15 square degree survey that will accomplish various weak lensing goals including statistical studies and dark matter mapping.Comment: 25 pages, 8 figures, 1 table, replaced with Published Versio

Supernova / Acceleration Probe: A Satellite Experiment to Study the Nature of the Dark Energy

The Supernova / Acceleration Probe (SNAP) is a proposed space-based experiment designed to study the dark energy and alternative explanations of the acceleration of the Universe's expansion by performing a series of complementary systematics-controlled measurements. We describe a self-consistent reference mission design for building a Type Ia supernova Hubble diagram and for performing a wide-area weak gravitational lensing study. A 2-m wide-field telescope feeds a focal plane consisting of a 0.7 square-degree imager tiled with equal areas of optical CCDs and near infrared sensors, and a high-efficiency low-resolution integral field spectrograph. The SNAP mission will obtain high-signal-to-noise calibrated light-curves and spectra for several thousand supernovae at redshifts between z=0.1 and 1.7. A wide-field survey covering one thousand square degrees resolves ~100 galaxies per square arcminute. If we assume we live in a cosmological-constant-dominated Universe, the matter density, dark energy density, and flatness of space can all be measured with SNAP supernova and weak-lensing measurements to a systematics-limited accuracy of 1%. For a flat universe, the density-to-pressure ratio of dark energy can be similarly measured to 5% for the present value w0 and ~0.1 for the time variation w'. The large survey area, depth, spatial resolution, time-sampling, and nine-band optical to NIR photometry will support additional independent and/or complementary dark-energy measurement approaches as well as a broad range of auxiliary science programs. (Abridged)Comment: 40 pages, 18 figures, submitted to PASP, http://snap.lbl.go

ESR, raman and conductivity studies on fractionated poly(2-methoxyaniline-5-sulfonic acid)

Synthesis methods used to produce poly(2-methoxyaniline-5-sulfonic acid) (PMAS), a water soluble, self-doped conducting polymer, have been shown to form two distinctly different polymer fractions with molecular weights of approximately 2 kDa and 8 -10 kDa. The low molecular weight (LMWT) PMAS fraction is redox inactive and non-conducting while the high molecular weight (HMWT) PMAS is electro-active with electrical conductivities of 0.94 0.05 S cm-1. Previous investigations have illustrated the different photochemical and electrochemical properties of these fractions, but have not correlated these properties with the structural and electronic interactions that drive them. Incomplete purification of the PMAS mixture, typically via bag dialysis, has been shown to result in a mixture of approximately 50:50 HMWT:LMWT PMAS with electrical conductivity significantly lower at approximately 0.10 to 0.26 S cm-1. The difference between the electrical conductivities of these fractions has been investigated by the controlled addition of the non-conducting LMWT PMAS fraction into the HMWT PMAS composite film with the subsequent electronic properties investigated by solid-state ESR and Raman spectroscopies. These studies illustrate strong electronic intereactions of the insulating LMWT PMAS with the emeraldine salt HMWT PMAS to substantially alter the population of the electronic charge carriers in the conducting polymer. ESR studies on these mixtures, when compared to HMWT PMAS, exhibited a lower level of electron spin in the presence of LMWT PMAS indicative of the the formation of low spin bipolarons without a change the oxidation state of the conducting HMWT fraction

Environmental and financial implications of ethanol as a bioethylene feedstock versus as a transportation fuel

Bulk chemicals production from biomass may compete with biofuels for low-cost and sustainable biomass sources. Understanding how alternative uses of biomass compare in terms of financial and environmental parameters is therefore necessary to help ensure that efficient uses of resources are encouraged by policy and undertaken by industry. In this paper, we compare the environmental and financial performance of using ethanol as a feedstock for bioethylene production or as a transport fuel in the US life cycle-based models are developed to isolate the relative impacts of these two ethanol uses and generate results that are applicable irrespective of ethanol production pathway. Ethanol use as a feedstock for bioethylene production or as a transport fuel leads to comparable greenhouse gas (GHG) emissions and fossil energy consumption reductions relative to their counterparts produced from fossil sources. By displacing gasoline use in vehicles, use of ethanol as a transport fuel is six times more effective in reducing petroleum energy use on a life cycle basis. In contrast, bioethylene predominately avoids consumption of natural gas. Considering 2013 US ethanol and ethylene market prices, our analysis shows that bioethylene is financially viable only if significant price premiums are realized over conventional ethylene, from 35% to 65% depending on the scale of bioethylene production considered (80 000 t yr−1 to 240 000 t yr−1). Ethanol use as a transportation fuel is therefore the preferred pathway considering financial,GHGemissions, and petroleum energy use metrics, although bioethylene production could have strategic value if demand-side limitations of ethanol transport fuel markets are reached