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Chassefiere E.,University Pierre and Marie Curie | Maria J.-L.,University Pierre and Marie Curie | Goutail J.-P.,University Pierre and Marie Curie | Quemerais E.,University Pierre and Marie Curie | And 49 more authors.
Planetary and Space Science | Year: 2010

Probing of Hermean exosphere by ultraviolet spectroscopy (PHEBUS) is a double spectrometer for the Extreme Ultraviolet range (55-155 nm) and the Far Ultraviolet range (145-315 nm) devoted to the characterization of Mercury's exosphere composition and dynamics, and surface-exosphere connections. This French-led instrument is implemented in a cooperative scheme involving Japan (detectors), Russia (scanner) and Italy (ground calibration). PHEBUS will address the following main scientific objectives relative to Mercury's exosphere: determination of the composition and the vertical structure of the exosphere; characterization of the exospheric dynamics: day to night circulation, transport between active and inactive regions; study of surface release processes; identification and characterization of the sources of exospheric constituents; detection and characterization of ionized species and their relation with the neutral atmosphere; space and time monitoring of exosphere/magnetosphere exchange and transport processes; study and quantification of escape, global scale source/sink balance and geochemical cycles synergistically with other experiments of BepiColombo (Mercury Sodium Atmospheric Spectral Imager (MSASI), Mercury Plasma Particle Experiment (MPPE) on Mercury Magnetospheric Orbiter (MMO); Mercury imaging X-ray spectrometer (MIXS), Search for exosphere refilling and emitted neutral abundance (SERENA) on Mercury Planetary Orbiter (MPO)). Two gratings and two detectors are used according to a specific, compact design. The spectrum detection is based on the photon counting method and is realized using micro-channel plate (MCP) detectors with Resistive Anode Encoder (RAE). Typical photocathodes are CsI or KBr for the extreme ultra-violet (EUV) range, CsTe for the far ultra-violet (FUV) range. Extra visible lines are monitored using a photo-multiplier (PM) that is also used in photon counting mode. In order to prevent sensitivity losses which are critical in UV ranges, a minimum of reflections is achieved inside the instrument using only an off-axis parabola and a set of holographic gratings. A one degree-of-freedom scanning system allows to probe, at the highest possible signal-to-noise ratio, selected regions and altitude ranges of interest. Different modes of observation will be used sequentially (vertical scans, along-orbit scans, grazing observations at twilight, etc.). During the mission, the instrument will be regularly calibrated on well chosen stars, in such a way to quantitatively estimate the overall degradation of the sensitivity of the instrument. © 2008 Elsevier Ltd. All rights reserved.

News Article | February 15, 2017
Site: www.businesswire.com

NEW YORK--(BUSINESS WIRE)--In its latest Cardiology Report, BioPharm Insight (BPI) reported that Amgen’s Repatha Phase III FOURIER trial will be deemed successful by experts if it shows a 35% reduction in major cardiovascular events (MACE). The report from BPI, the most comprehensive life science news and analytical solution, highlights recent editorial coverage of cardiology therapies in development that have potentially market-moving clinical events expected in the next few months. It also provides analysis of sales forecasts and licensing deals. “Amgen’s announcement at the start of February that it met its primary and key secondary composite endpoints was a hugely anticipated event for a drug predicted to have peak sales in excess of $7 billion,” said Peter Murphy, BPI senior editorial analyst. Amgen management has reiterated the cardiovascular outcomes trial (CVOT) trial is powered to show a 15% risk reduction but did not provide further details on FOURIER outcomes, which the market widely expects could be a game-changer for the lipid-lowering treatment space. While equity analysts think a 20% reduction has been hit, experts BPI spoke to said that anything lower than a 35% MACE reduction may mean that the cost outweighs the treatment benefit. “Although Amgen’s news has significant implications for the entire PCSK9-inhibitor class, experts expect to see similar results between Repatha and its competitor Praluent,” said BPI reporter Alexandra Thompson. Amgen’s (NASDAQ:AMGN) Repatha and Praluent, from Sanofi (EPA:SAN) and Regeneron Pharmaceuticals (NASDAQ:REGN), were approved within one month of each other in 2015 and are currently the only two anti-PCSK9s on the market. BPI reports, though, that so far physicians and payers alike are not satisfied that PCSK9 inhibitors successfully lower LDL-c (bad cholesterol) levels. The market is looking for evidence that the reduction in LDL also drives a reduction in the likelihood of patients suffering potentially catastrophic cardiovascular events. Praluent’s Phase III CVOT is due in late 2017, and Alnylam Therapeutics (NASDAQ:ALNY)/The Medicines Company’s (NASDAQ:MDCO)/inclisiran is due to start its own Phase III trials soon. BPI’s Cardiology Report also highlights articles covering experts’ dubious expectations for Merck’s (NYSE:MRK) hypercholesterolemia drug anacetrapib’s Phase III CV trial following termination of three drugs of the same CETP inhibitor class. Pfizer’s (NYSE:PFE) torcetrapib, Roche’s (VTX:ROG) dalcetrapib and Eli Lilly’s (NYSE:LLY) evacetrapib all suffered high-profile clinical trial failures over the past decade. Additionally, the report offers insights on several ongoing therapies under development to prevent heart failure (HF), including Novartis’ (VTX:NOVN) Entresto (sacubitril/valsartan) and Mesoblast’s (ASX:MSB) MPC-150-IM. The perforation risk of MPC-150-IM’s transendocardial delivery could possibly limit its administration to specialized cardiology cell injection centers or warrant cardiologist training, but the significant positive outcomes of the earlier Phase II trial have analysts optimistic, forecasting peak sales of the HF therapy to be $5.2 billion if successful. Learn more about expected market catalyst events in Cardiology Indications with BioPharm Insight’s full report: BioPharm Insight is the most comprehensive life science market intelligence and analytics solution, featuring a team of investigative journalists writing exclusive news and thousands of healthcare data points, aggregated into one centralized source. In addition to the proprietary articles, BioPharm Insight is currently tracking 250,000 management and R&D contacts, 7,500 biopharma companies with full pipeline data, 120,000 investigational and approved drug profiles, 28,000 M&A and licensing deals, 10,000 extended sales forecasts and epidemiology profiles for hundreds of indications.

News Article | February 21, 2017
Site: www.forbes.com

TestPlant, a leader in digital service assurance and software test automation, that received investment last year from a €657 million (c.$696m) Carlyle Group fund focused on European technology, media and telecoms (TMT) companies, has announced software industry veteran Dr John Bates who sees “incredibly disruptive forces at work” in the testing arena is to become its new Chief Executive Officer. A dynamic business leader and tech visionary a with a robust track record in enterprise software who gained a Ph.D at Cambridge University in the UK and has worked in the US over the past 12 years, Dr Bates will lead the British-headquartered company into its next phase of growth and global expansion. While he will still be based in the San Francisco Bay area for the time being and where he was previously CEO of PLAT.One, a company with an enterprise-grade Internet of Things (IoT) platform acquired by SAP last September, he will move between TestPlant’s London HQ and their office in Boulder, Colorado. Building on his time at PLAT.One, with its IoT platform, which enables the rapid development and scalable management of enterprise IoT environments - including connected products, smart cities, connected transport and smart manufacturing, Bates, who has been listed as one of the ‘Tech 50’ most influential technologists by Institutional Investor five years running (2011-2015), will continue to be in the US regularly and visit TestPlant’s customers around the globe. As an international software business based in London, TestPlant has in addition to development centers in the US and the UK - sales and support centers located in China, Germany, India and Japan. Their products - through the eggPlant range - are used in over 40 countries by well over 350 enterprise customers in sectors, which includes automotive, financial services, healthcare and life Sciences, media and entertainment, retail as wells as defense and aerospace industries. TestPlant’s eggPlant range comprises a set of tools, which support the design, development, test and management of software applications for mainframe, desktop and mobile use in any technology platform environment, can be deployed to improve and report on the quality and responsiveness of software systems. Relevant in agile, mobile, web and DevOps deployments, the tools are touted as helping technology driven organizations deliver “customer value faster and at higher quality” by automating the testing process, including functional testing, performance testing, load testing - even network emulation. Agnostic, they can function on their own, with test tools from other vendors or together in a unified environment. The Englishman, who has founded and grown a number of cutting-edge businesses and served in a range of ‘C-level’ roles at public software companies, joins TestPlant at a time when he noted incredibly disruptive forces bearing down on industries and “morphing testing into one of the most critical business imperatives.” And, a high-quality digital experience - without friction - he cited as key to businesses right across a range of industries in order to operate efficiently and at top gear. Commenting on the testing landscape on the cusp of fully taking up his new role, Bates said: “A frictionless, high-quality digital experience is essential for any successful business from financial services to retail and  to automotive. And, the update speed of DevOps and Continuous Delivery means that automation is essential to deliver customer value with speed and quality.” He added: “Meanwhile, new software models around mobile, augmented reality, robots, drones, AI algorithms and the Internet-of-Things, are driving new testing requirements.” As such TestPlant’s solutions, which are at work at some of the largest enterprises around the globe and backed by an experienced team are “well placed to power these business imperatives, delivering true test automation” according to Bates. In the world of agile, DevOps and continuous integration, software development could be likened to the ‘Big Apple’ - New York - the city never sleeps. As Bates put it: “In the age of Millennials - the two-second attention span and instant social media retaliation at anything less than full performance, connectivity and outstanding user experience - it’s a tough day to be building software. Combine this with the fact that in the digital era, every company is a software company - and you have the perfect storm.” That, he contended, can only be “calmed” by a testing approach designed for the rigors of continuous automation." And, that hits on not just function but also performance, user experience, security and other critical dimensions,” he stressed. So, can we break this down this concept? Well, let’s consider here a bank rolling out mobile user applications. The apps must run on a wide variety of different devices and be updated continuously with new features and user feedback. Add to that they must work seamlessly each time. As such firms either need the equivalent of an army of testers working on it, testing thousands of dimensions on every device and a wide variety of parameter permutations. Or, they require the ability to algorithmically simulate those users and user cases. That’s where the attributes of a software vendor like TestPlant comes in, which is the recipient of two Queen's Awards for Enterprise and rated an EMEA 500 business. One could also take as an example a major aerospace company rolling out an unmanned air vehicle. In the era of the industrial IoT, this is collecting user feedback and sensor data all the time and must be updated with tweaks continuously. It’s a tough job but somebody has got to do it. “How do we test such a vehicle and ensure it behaves as it should? The whole testing cycle, including how the user interface performs, must be automated,” as Bates asked. Other examples from healthcare to retail and media as well as sectors beyond that abound according to the TestPlant’s new CEO, especially when one considers every business is in the software business. Bates revealed to Forbes that his experience over the last twelve years in the US has enabled him to understand the “pain points now and coming in a number of industries”, and understand the pressure businesses are under in competing in a disruptive environment.  This goes a long way to explaining his decision to join TestPlant. Michael Wand, managing director of The Carlyle Group, which had $158 billion of assets under management across 281 investment vehicles as of December 31, 2016, said in relation to the new CEO’s appointment: “Having backed John Bates and his first business Apama with a previous Carlyle fund and remained in close contact throughout the years, we are pleased that we can re-engage with such a seasoned executive who brings a tremendous amount of unique and highly applicable talent and experience.” It was in January 2016 that TestPlant received investment from Carlyle Europe Technology Partners III, the €657m Carlyle fund focused on European TMT companies and other companies offering growth opportunities through ground breaking and innovative technologies. In so doing the alternative asset manager, which was advised on the transaction by Travers Smith, KPMG and CIL, became TestPlant’s majority shareholder. Wand, who is also TestPlant Director, anticipated that Bates “will positively impact the shaping of TestPlant’s vision and product direction and supercharge the go-to-market strategy.” George Mackintosh, who founded the business in 2008 with chairman Jon Richards and backed initially by VC firm Seraphim Capital, now assumes a new position as a non-executive director on TestPlant’s Board. Carlyle Group, which closed its CETP III fund in May 2015, had at that time half the capital in the new fund consisting of commitments from investors in CETP II, the €522m 2008 vintage fund, with the majority of the fund's investors based in Europe and the US. For the past 15 years Carlyle Europe Technology Partners has been investing in small-cap buy-outs in the European technology sector for the past 15 years or through various industry cycles. In July 2014, CETP III made two investments in the technology sector with a majority investment in Expereo, a global managed networks operator based in The Netherlands, followed in May 2015 by an investment in Telvent Global Services, a Spanish provider of IT infrastructure management and cloud-based services.

Kasaba Y.,Tohoku University | Bougeret J.-L.,University of Paris Descartes | Blomberg L.G.,KTH Royal Institute of Technology | Kojima H.,Kyoto University | And 10 more authors.
Planetary and Space Science | Year: 2010

The BepiColombo Mercury Magnetospheric Orbiter (MMO) spacecraft includes the plasma and radio wave observation system called Plasma Wave Investigation (PWI). Since the receivers for electric field, plasma waves, and radio waves are not installed in any of the preceding spacecraft to Mercury, the PWI will provide the first opportunity for conducting in-situ and remote-sensing observations of electric fields, plasma waves, and radio waves in the Hermean magnetosphere and exosphere. These observations are valuable in studying structure, dynamics, and energy exchange processes in the unique magnetosphere of Mercury. They are characterized by the key words of the non-MHD environment and the peculiar interaction between the relatively large planet without ionosphere and the solar wind with high dynamic pressure. The PWI consists of three sets of receivers (EWO, SORBET, and AM2P), connected to two sets of electric field sensors (MEFISTO and WPT) and two kinds of magnetic field sensors (LF-SC and DB-SC). The PWI will observe both waveforms and frequency spectra in the frequency range from DC to 10 MHz for the electric field and from 0.3 Hz to 640 kHz for the magnetic field. From 2008, we will start the development of the engineering model, which is conceptually consistent with the flight model design. The present paper discusses the significance and objectives of plasma/radio wave observations in the Hermean magnetosphere, and describes the PWI sensors, receivers and their performance as well as the onboard data processing. © 2008 Elsevier Ltd. All rights reserved.

News Article | February 22, 2017
Site: www.nature.com

No statistical methods were used to predetermine sample size. The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment. Animal experiments were neither randomized nor blinded. All animals used in this study (ADicerKO, Dicerlox/lox, or C57BL/6) were males and 6 months of age unless specifically indicated otherwise. All animal experiments were conducted in accordance with IRB protocols with respect to live vertebrate experimentation. Human serum was obtained from human subjects after obtaining IRB approval and patients were given informed consent. Mouse and human sera were centrifuged at 1,000g for 5 min and then at 10,000g for 10 min to remove whole cells, cell debris and aggregates. The serum was subjected to 0.1-μm filtration and ultracentrifuged at 100,000g for 1 h. Pelleted vesicles were suspended in 1× PBS, ultracentrifuged again at 100,000g for washing, resuspended in 1× PBS and prepared for electron microscopy and immune-electron microscopy or miRNA extraction. All in vitro experiments were carried out using exosome-free FBS. AML-12 cells were acquired from ATCC (cat no. CRL-2254) and were tested for mycoplasma contamination. Dicerfl/fl brown preadipocytes were generated as previously described16. For exosome loading, exosome preparations were isolated and diluted with PBS to final volume of 100 μl. Exosome electroporation was carried out by using a variation of a previously described technique45. Exosome preparations were mixed with 200 μl phosphate-buffered sucrose (272 mM sucrose 7 mM, K HPO ) with 10 nΜ of a miRNA mimic, and the mixture was pulsed at 500 mV with 250 μF capacitance using a Bio-Rad Gene Pulser (Bio-Rad). Electroporated exosomes were resuspended in a total volume of 500 μl PBS and added to the target cells. Isolated exosomes were subjected to immune-electron microscopy using standard techniques7. In brief, exosome suspensions were fixed with 2% glutaraldehyde supplemented with 0.15 M sodium cacodylate and post-fixed with 1% OsO . They were then dehydrated with ethanol and embedded in Epon 812. Samples were sectioned, post-stained with uranyl acetate and lead citrate, and examined with an electron microscope. For immune-electron microscopy, cells were fixed with a solution of 4% paraformaldehyde, 2% glutaraldehyde and 0.15 M sodium cacodylate and processed as above. Sections were probed with anti-CD63 (Santa Cruz Biotechnology, sc15363) or anti-CD9 (Abcam, ab92726) antibodies (or rabbit IgG as a control) and visualized with immunogold-labelled secondary antibodies. Immuno-electron microscopy analysis revealed that the isolated exosomes were 50–200 nM in diameter and stained positively for the tetraspanin exosome markers CD63 and CD9 (ref. 46). Exosomal concentration was assessed using the EXOCET ELISA assay (System Biosciences), which measured the esterase activity of cholesteryl ester transfer protein (CETP) activity. CETP is known to be enriched in exosomal membranes. The assay was calibrated using a known isolated exosome preparation (System Biosciences). Additionally, exosome preparations were subjected to the qNano system employing tunable resistive pulse sensing technology (IZON technologies) to measure the number and size distribution of exosomes. For total serum miRNA isolation, 100 μl of serum was obtained from ADicerKO mice or Lox littermates and miRNAs were isolated using an Exiqon miRCURY Biofluid RNA isolation kit following the manufacturer’s protocol. RNA was isolated from exosomal preparations using TRIzol, following the manufacturer’s protocol (Life Sciences). Subsequently, 50 ng of exosomal RNA was subjected to reverse transcription into cDNA by using a mouse miRNome profiler kit (System Biosciences). qPCR was then performed in 6-μl reaction volumes containing cDNA along with universal primers for each miRNA and SYBR Green PCR master mix (Bio-Rad). In line with previous research, for all serum and exosomal miRNA quantitative PCR reactions the C values were normalized using U6 snRNA as an internal control. To estimate miRNA abundance in fat tissue, data were normalized using the global average of expressed C values per sample47, as the snRNA U6 was differentially expressed between depots. For all quantitative PCR reactions involving gene expression calculations for FGF21, normalization was carried out by using the TATA-binding protein as an internal control. Differential expression analysis of the high-throughput −ΔC values was done using the Bioconductor limma package48 in R (www.r-project.org). Fold differences in comparisons were expressed as 2−ΔΔC . Ct Principal component analysis plots were created using R with the ggplot2 package. A detection threshold was set to C  = 34 for all mouse miRNA PCR reactions; no threshold was used for human miRNA PCR, according to the manufacturer’s recommendation (System Biosciences). An miRNA was plotted only if its raw C value was ≤34 in at least three samples, except for the brown pre-adipocyte and 4-week-old mouse experiments, in which the raw C only had to be ≤34 twice. miRNA −ΔC values were Z scored and heatmaps were created by Cluster 3.0 and TreeView programs as previously described49. Fat tissue transplantation was carried out as previously described50. In brief, 10-week-old male Lox donor mice (C57BL/6 males) were killed, and their inguinal, epididymal, and BAT fat depots were isolated, cut into several 20-mg pieces and transplanted into 10-week-old male ADicerKO mice (n = 5 male mice per group). Each recipient ADicerKO mice received the equivalent transplanted fat mass of two donor Lox control mice. Transplanted mice received post-surgical analgesic intraperitoneal injections (buprenorphine, 50 mg/kg) for 7 days. At day 12, a glucose tolerance test was performed after a 16-h fast by intraperitoneal injection of 2 g/kg glucose. All mice were killed after 14 days. All procedures were conducted in accordance with Institutional Animal Care and Use Committee regulations. An adenoviral Fgf21 3′ UTR reporter was created by cloning the 3′ UTR of Fgf21 into the pMir-Report vector. Subsequently, the luciferase-tagged 3′ UTR fragment was cloned into the adenoviral vector pacAd5-CMV-IRES-GFP, creating an adenovirus bearing the Fgf21 3′UTR reporter. Hsa-miR-302f-3′-UTR was created by cloning the synthesized Luc-miR-302f-3′-UTR fragment (Genescript) into the Viral Power Adenoviral Expression System (Invitrogen). In vitro bioluminescence was measured using a dual luciferase kit (Promega). Eight-week-old male ADicerKO or wild-type mice were injected intravenously with adenovirus bearing the 3′-UTR of Fgf21 fused to the luciferase gene to create two groups of liver-reporter mice—one with a ADicerKO background and one with a wild-type background. One day later, a third group of ADicerKO mice, which had also been injected intravenously with an adenovirus bearing the 3′-UTR of Fgf21 fused to the luciferase gene, were injected intravenously with exosomes isolated from the serum of wild-type mice. After 24 h, in vivo luminescence of the Fgf21 3′ UTR was measured using the IVIS imaging system (Perkin Elmer) by administering d-luciferin (20 mg/kg) according to the manufacturer’s protocol (Perkin Elmer). For the second group, 8-week-old male ADicerKO or wild-type mice were also transfected with adenovirus bearing the 3′ UTR of Fgf21 fused to the luciferase gene by intravenous injection. After 1 day, mice received an intravenous injection of exosomes isolated from the serum of either ADicerKO mice or ADicerKO mice reconstituted in vitro with 10 nM miR-99b by electroporation. Twenty-four hours later, in vivo luminescence was measured using the IVIS imaging system by administering d-luciferin (20 mg/kg) according to the manufacturer’s protocol (Perkin Elmer). Protocol 1. On day 0, adenovirus bearing either pre-hsa_miR-302f or lacZ mRNA (as a control) was injected directly into the BAT of 8-week-old male C57BL/6 mice. Hsa_miR-302f is human-specific and does not have a mouse homologue. This procedure was conducted under ketamine-induced anaesthesia. Four days later, the same mice were injected intravenously with an adenovirus bearing the 3′ UTR of miR-302f in-frame with the luciferase gene, thereby transducing the liver tissue of the mouse with this human 3′ UTR miRNA reporter. Suppression of the 3′ UTR miR-302f reporter would occur only if there was communication between the BAT-produced miRNA and the liver. In vivo luminescence was measured on day 6 using the IVIS imaging system as described above. Protocol 2. To assess specifically the role of exosomal miR-302f in the regulation of its target reporter in the liver, two separate cohorts of 8-week-old male C57BL/6 mice were generated. One cohort was injected with adenovirus bearing pre-miR-302f or lacZ directly into the BAT (the donor cohort); the second cohort was transfected with an adenovirus bearing the 3′ UTR reporter of this miR-302f in the liver, as described for Protocol 1 (the acceptor cohort). Serum was obtained on days 3 and 6 from the donor cohorts; the exosomes were isolated and then injected intravenously into the acceptor mice the next day (days 4 and 7). On day 8, in vivo luminescence was measured in the acceptor mice using the IVIS imaging system as described above. To test for the presence of adenovirus in the liver and BAT of C57BL/6 mice, 100 mg tissue was homogenized in 1 ml sterile 1× PBS. The homogenate was spun down and 150 μl cleared supernatant was used to isolate adenoviral DNA using the Nucleospin RNA and DNA Virus kit, following the manufacturer’s protocol (Takara). PCR was performed on 2 μl isolated adenoviral DNA using SYBR green to detect lacZ or miR-302f amplicons. For all PCR data obtained in the fat-tissue-transplantation experiment, an miRNA was considered to be present only if its mean C in the wild-type group was <34. We then identified those miRNAs that were significantly decreased in ADicerKO serum. For an miRNA to be considered restored after transplantation by a particular depot it had to be significantly increased from ADicerKO serum with a mean C  < 34 and its C had to be more than 50% of the way from ADicerKO to the wild type on the C scale. ANOVA tests were followed by two-tailed Dunn’s post-hoc analysis or Tukey’s multiple comparisons test to identify statistically significant comparisons. All t-tests and Mann–Whitney U-tests were two-tailed. P values less than 0.05 were considered significant. All ANOVA, t-tests, and area-under-the-curve calculations were carried out in GraphPad Prism 5.0. For miRDB analysis (http://www.mirdb.org), a search by target gene was performed against the mouse database. A target score of 85 was set to exclude potential false-positive interacting miRNAs. All high-throughput qRT–PCR data (raw C values), the code used to analyse them (in the free statistical software R), and its output (including supplementary tables, tables used to generate heatmaps, and statements in the text) can be freely downloaded and reproduced from https://github.com/jdreyf/fat-exosome-microrna. All other data are available from the corresponding author upon reasonable request.

News Article | March 11, 2016
Site: news.yahoo.com

LONDON (Reuters) - So-called "good" cholesterol may actually increase heart attack risks in some people, researchers said on Thursday, a discovery that casts fresh doubt on drugs designed to raise it. High density lipoprotein (HDL) cholesterol is generally associated with reduced heart risks, since it usually offsets the artery-clogging effects of the low density (LDL) form. But some people have a rare genetic mutation that causes the body to have high levels of HDL and this group, paradoxically, has a higher heart risk, scientists reported in the journal Science. "Our results indicate that some causes of raised HDL actually increase risk for heart disease," said lead researcher Daniel Rader of the University of Pennsylvania. "This is the first demonstration of a genetic mutation that raises HDL but increases risk of heart disease." The scientists found that people with the mutation had an increased relative risk of coronary heart disease almost equivalent to the risk caused by smoking. Normally, HDL is an important helper in the smooth running of the cardiovascular system by ferrying cholesterol to the liver, where it is eliminated. But this process is disrupted in people with a faulty version of a gene known as SCARB1, leading to high levels of HDL that fails to do its job, Rader and colleagues found. The mutation appears to be specific to people of Ashkenazi Jewish descent. The finding could help explain why drugs that boost HDL have so far failed to deliver expected benefits in clinical trials. Over the past decade, three experimental drugs known as CETP inhibitors from Pfizer, Roche and Eli Lilly have flopped in tests, leaving Merck's anacetrapib as the only one remaining in late-stage studies. Peter Weissberg, medical director at the British Heart Foundation, which supported the research, said the new research had shed light on a major puzzle and could open up new medical avenues in the longer term. "These unexpected findings pave the way for further research into the SCARB1 pathway to identify new treatments to reduce heart attacks in the future," he said in a statement.

News Article | December 27, 2016
Site: www.eurekalert.org

The Biophysical Society has announced the winners of its international travel grants to attend the Biophysical Society's 61st Annual Meeting in New Orleans, February 11-15, 2017. The purpose of these awards is to foster and initiate further interaction between American biophysicists and scientists working in countries experiencing financial difficulties. Recipients of this competitive award are chosen based on scientific merit and their proposed presentation at the meeting. They will be honored at a reception on Sunday, February 12 at the Ernest N. Morial Convention Center. The 2017 recipients of the International Travel Award, along with their institutional affiliation and abstract title, are listed below. Ana F. Guedes, Institute of Molecular Medicine, Portugal, ATOMIC FORCE MICROSCOPY AS A TOOL TO EVALUATE THE RISK OF CARDIOVASCULAR DISEASES IN PATIENTS. Karishma Bhasne Mohali, Indian Institute of Science Education and Research (IISER), A TALE OF TWO AMYLOIDOGENIC INTRINSICALLY DISORDERED PROTEINS: INTERPLAY OF TAU AND α-SYNUCLEIN. Chan Cao, East China University of Science and Technology, DIRECT IDENTIFICATION OF ADENINE, THYMINE, CYTOSINE AND GUANINE USING AEROLYSIN NANOPORE. Venkata Reddy Chirasani, Indian Institute of Technology Madras, LIPID TRANSFER MECHANISM OF CETP BETWEEN HDL AND LDL: A COARSEGRAINED SIMULATION STUDY. Assaf Elazar, Weizmann Institute of Science, Israel, DECIPHERING MEMBRANE PROTEIN ENERGETICS USING DEEP SEQUENCING; TOWARDS ROBUST DESIGN AND STRUCTURE PREDICTION OF MEMBRANE PROTEINS. Manuela Gabriel, University of Buenos Aires, Argentina, 3D ORBITAL TRACKING OF SINGLE GOLD NANOPARTICLES: A NEW APPROACH TO STUDY VESICLE TRAFFICKING IN CHROMAFFIN CELLS. Farah Haque National Centre for Biological Sciences, India, A NEW HUMANIZED MOUSE MODEL FOR STUDYING INHERITED CARDIOMYOPATHIC MUTATIONS IN THE MYH7 GENE. Stephanie Heusser, Stockholm University, Switzerland, STRUCTURAL AND FUNCTIONAL EVIDENCE FOR MULTI-SITE ALLOSTERY MEDIATED BY GENERAL ANESTHETICS IN A MODEL LIGAND-GATED ION CHANNEL. Amir Irani, Massey University, New Zealand, HOMOGALACTURONANS ILLUMINATE THE ROLE OF COUNTERION CONDENSATION IN POLYELECTROLYTE TRANSPORT. Olfat Malak, University of Nantes, France, HIV-TAT INDUCES A DECREASE IN IKR AND IKS VIA REDUCTION IN PHOSPHATIDYLINOSITOL-(4,5)-BISPHOSPHATE AVAILABILITY. CONFORMATIONAL TRANSITION AND ASSEMBLY OF E.COLI CYTOLYSIN A PORE FORMING TOXIN BY SINGLE MOLECULE FLUORESCENCE. Sabrina Sharmin, Shizuoka University, Japan, EFFECTS OF LIPID COMPOSITIONS ON THE ENTRY OF CELL PENETRATING PEPTIDE OLIGOARGININE INTO SINGLE VESICLES. Xin Shi, East China University of Science and Technology, DIRECT OBSERVATION OF SINGLE BIOPOLYMER FOLDING AND UNFOLDING PROCESS BY SOLIDSTATE NANOPORE. Omar Alijevic, University of Lausanne, Switzerland, ANALYSIS OF GATING OF ACID-SENSING ION CHANNELS (ASICS) UNDER RAPID AND SLOW PH CHANGES. Swapna Bera, Bose Institute, India, BIOPHYSICAL INSIGHTS INTO THE MEMBRANE INTERACTION OF THE CORE AMYLOID-FORMING Aβ40 FRAGMENT K16-K28 AND ITS ROLE IN THE PATHOGENESIS OF ALZHEIMER'S DISEASE. Anais Cassaignau, University College London, United Kingdom, STRUCTURAL INVESTIGATION OF AN IMMUNOGLOBULIN DOMAIN ON THE RIBOSOME USING NMR SPECTROSCOPY. Bappaditya Chandra, Tata Institute of Fundamental Research, India, SECONDARY STRUCTURE FLIPPING CONNECTED TO SALT-BRIDGE FORMATION CONVERTS TOXIC AMYLOID-β40 OLIGOMERS TO FIBRILS. Gayathri Narasimhan, Cinvestav, Mexico, ANTIHYPERTROPHIC EFFECTS OF DIAZOXIDE INVOLVES CHANGES IN MIR-132 EXPRESSION IN ADULT RAT CARDIOMYCYTES. Giulia Paci, European Molecular Biology Laboratory, Germany, FOLLOWING A GIANT'S FOOTSTEPS: SINGLE-PARTICLE AND SUPER-RESOLUTION APPROACHES TO DECIPHER THE NUCLEAR TRANSPORT OF HEPATITIS B VIRUS CAPSIDS. Bizhan Sharopov, Bogomoletz Institute of Physiology National Academy of Sciences of Ukraine, DISSECTING LOCAL AND SYSTEMIC EFFECTS OF TRPV1 ON BLADDER CONTRACTILITY IN DIABETES. Chao Sun, East China Normal University, FUNCTION OF BACTERIORUBERIN IN ARCHAERHODOPSIN 4, FROM EXPRESSION TO CHARACTERIZATION. Matthew Batchelor, University of Leeds, United Kingdom STRUCTURAL DYNAMICS IN THE MYOSIN 7A SINGLE α-HELIX DOMAIN. Daniel Havelka, Czech Academy of Sciences, MICROVOLUME DIELECTRIC SPECTROSCOPY AND MOLECULAR DYNAMICS OF AMINO ACIDS. Ivan Kadurin, University College London, United Kingdom, INVESTIGATION OF THE PROTEOLYTIC CLEAVAGE OF α2δ SUBUNITS: A MECHANISTIC SWITCH FROM NHIBITION TO ACTIVATION OF VOLTAGE-GATED CALCIUM CHANNELS? Linlin Ma, University of Queensland, Australia, NOVEL HUMAN EAG CHANNEL ANTAGONISTS FROM SPIDER VENOMS. Ivana Malvacio, University of Cagliari, Italy, MOLECULAR INSIGHTS ON THE RECOGNITION OF SUBSTRATES BY THE PROMISCUOUS EFFLUX PUMP ACRB. Cristina Moreno Vadillo, Cardiovascular Research Institute Maastricht, Netherlands, RESTORING DEFECTIVE CAMP-DEPENDENT UPREGULATION IN LONG-QT SYNDROME TYPE-1 THROUGH INTERVENTIONS THAT PROMOTE IKS CHANNEL OPENING. Melanie Paillard, Claude Bernard University Lyon 1, France, TISSUE-SPECIFIC MITOCHONDRIAL DECODING OF CYTOPLASMIC CA2+ SIGNALS IS CONTROLLED BY THE STOICHIOMETRY OF MICU1/2 AND MCU. Mohammed Mostafizur Rahman, Institute for Stem Cell Biology and Regenerative Medicine, India, STRESS-INDUCED DIFFERENTIAL REGULATION LEADS TO DECOUPLING OF THE ACTIVITY BETWEEN MPFC AND AMYGDALA. Marcin Wolny, University of Leeds, United Kingdom, DESIGN AND CHARACTERIZATION OF LONG AND STABLE DE NOVO SINGLE α-HELIX DOMAINS. Elvis Pandzic, University of New South Wales, Australia, VELOCITY LANDSCAPES RESOLVE MULTIPLE DYNAMICAL POPULATIONS FROM FLUORESCENCE IMAGE TIME SERIES. The Biophysical Society, founded in 1958, is a professional, scientific Society established to encourage development and dissemination of knowledge in biophysics. The Society promotes growth in this expanding field through its annual meeting, monthly journal, and committee and outreach activities. Its 9000 members are located throughout the U.S. and the world, where they teach and conduct research in colleges, universities, laboratories, government agencies, and industry. For more information on these awards, the Society, or the 2017 Annual Meeting, visit http://www.

Bettaieb L.,University Pierre and Marie Curie | Kokabi H.,University Pierre and Marie Curie | Poloujadoff M.,University Pierre and Marie Curie | Coillot C.,CETP
Journal of Nondestructive Evaluation | Year: 2011

Electromagnetic Non Destructive Evaluation (E-NDE) is often conducted by inducing eddy currents in the structure to be examined, if this is conducting. Existence of flaws is detected by difference between the response of defect-free structures and damaged ones. In the present paper, we model such processes in order to predict the feasibility of this evaluation and to facilitate the interpretation of the observation. An original method is to represent a crack by a current source producing a magnetic signal. We have applied it to the case of a defect with a standard shape. The experimental evidences for the validity of this method are given. © Springer Science+Business Media, LLC 2009.

Habets F.,Meteo - France | Habets F.,CNRS Transfers and Interactions in Hydrosystems and Soils | Gascoin S.,CNRS Transfers and Interactions in Hydrosystems and Soils | Korkmaz S.,MINES ParisTech | And 11 more authors.
Hydrology and Earth System Sciences | Year: 2010

The Somme River Basin is located above a chalk aquifer and the discharge of the somme River is highly influenced by groundwater inflow (90% of river discharge is baseflow). In 2001, the Somme River Basin suffered from a major flood causing damages estimated to 100 million euro (Deneux and Martin, 2001). The purpose of the present research is to evaluate the ability of four hydrologic models to reproduce flood events in the Somme River Basin over an 18-year period, by comparison with observed river discharge and piezometric level as well as satellite-derived extents of flooded area. The models used differ in their computation of surface water budget and in their representation of saturated and unsaturated zones. One model needed structural modification to be able to accurately simulate the riverflows of the Somme river. The models obtained fair to good simulations of the observed piezometric levels, but they all overestimate the piezometric level after flooding, possibly because of a simplistic representation of deep unsaturated flow. Models differ in their annual partition of the infiltration of water within the root zone (mostly driven by simulated evapotranspiration), but these differences are attenuated by water transfers within the saturated and unsaturated zone. As a consequence, the inter-model dispersion of the computed annual baseflow is reduced. The aquifer overflow areas simulated during flooding compare well with local data and satellite images. The models showed that this overflow occurs almost every year in the same areas (in floodplain), and that the flooding of 2001 was characterized by an increase in the quantity of the overflow and not much by a spreading of the overflow areas. Inconsistencies between river discharge and piezometric levels suggest that further investigation are needed to estimate the relative influence of unsaturated and saturated zones on the hydrodynamics of the Somme River Basin. © 2010 Author(s).

LONDON, Dec. 19, 2016 /PRNewswire/ -- Cholesterol-Lowering Drugs Market Forecast 2015-2025: Opportunities in PCSK9 Inhibitors, CETP Inhibitors, MTTP Inhibitors, ApoB Inhibitors and PPAR AgonistsWhat can be expected from the cholesterol-lowering drugs market? Which areas are going to grow...

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