175 research outputs found

    Fatty acid-related modulations of membrane fluidity in cells: detection and implications

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    Metabolic homeostasis of fatty acids is complex and well-regulated in all organisms. The biosynthesis of saturated fatty acids (SFA) in mammals provides substrates for ?-oxidation and ATP production. Monounsaturated fatty acids (MUFA) are products of desaturases that introduce a methylene group in cis geometry in SFA. Polyunsaturated fatty acids (n-6 and n-3 PUFA) are products of elongation and desaturation of the essential linoleic acid and ?-linolenic acid, respectively. The liver processes dietary fatty acids and exports them in lipoproteins for distribution and storage in peripheral tissues. The three types of fatty acids are integrated in membrane phospholipids and determine their biophysical properties and functions. This study was aimed at investigating effects of fatty acids on membrane biophysical properties under varying nutritional and pathological conditions, by integrating lipidomic analysis of membrane phospholipids with functional two-photon microscopy (fTPM) of cellular membranes. This approach was applied to two case studies: first, pancreatic beta-cells, to investigate hormetic and detrimental effects of lipids. Second, red blood cells extracted from a genetic mouse model defective in lipoproteins, to understand the role of lipids in hepatic diseases and metabolic syndrome and their effect on circulating cells

    Computational integrity with a public random string from quasi-linear PCPs

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    A party running a computation remotely may benefit from misreporting its output, say, to lower its tax. Cryptographic protocols that detect and prevent such falsities hold the promise to enhance the security of decentralized systems with stringent computational integrity requirements, like Bitcoin [Nak09]. To gain public trust it is imperative to use publicly verifiable protocols that have no “backdoors” and which can be set up using only a short public random string. Probabilistically Checkable Proof (PCP) systems [BFL90, BFLS91, AS98, ALM + 98] can be used to construct astonishingly efficient protocols [Kil92, Mic00] of this nature but some of the main components of such systems — proof composition [AS98] and low-degree testing via PCPs of Proximity (PCPPs) [BGH + 05, DR06] — have been considered efficient only asymptotically, for unrealistically large computations; recent cryptographic alternatives [PGHR13, BCG + 13a] suffer from a non-public setup phase. This work introduces SCI, the first implementation of a scalable PCP system (that uses both PCPPs and proof composition). We used SCI to prove correctness of executions of up to 2202^{20} cycles of a simple processor (Figure 1) and calculated (Figure 2) its break-even point [SVP + 12, SMBW12]. The significance of our findings is two-fold: (i) it marks the transition of core PCP techniques (like proof composition and PCPs of Proximity) from mathematical theory to practical system engineering, and (ii) the thresholds obtained are nearly achievable and hence show that PCP-supported computational integrity is closer to reality than previously assumed

    The Soreq Applied Research Accelerator Facility (SARAF) - Overview, Research Programs and Future Plans

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    The Soreq Applied Research Accelerator Facility (SARAF) is under construction in the Soreq Nuclear Research Center at Yavne, Israel. When completed at the beginning of the next decade, SARAF will be a user facility for basic and applied nuclear physics, based on a 40 MeV, 5 mA CW proton/deuteron superconducting linear accelerator. Phase I of SARAF (SARAF-I, 4 MeV, 2 mA CW protons, 5 MeV 1 mA CW deuterons) is already in operation, generating scientific results in several fields of interest. The main ongoing program at SARAF-I is the production of 30 keV neutrons and measurement of Maxwellian Averaged Cross Sections (MACS), important for the astrophysical s-process. The world leading Maxwellian epithermal neutron yield at SARAF-I (5×10105\times 10^{10} epithermal neutrons/sec), generated by a novel Liquid-Lithium Target (LiLiT), enables improved precision of known MACSs, and new measurements of low-abundance and radioactive isotopes. Research plans for SARAF-II span several disciplines: Precision studies of beyond-Standard-Model effects by trapping light exotic radioisotopes, such as 6^6He, 8^8Li and 18,19,23^{18,19,23}Ne, in unprecedented amounts (including meaningful studies already at SARAF-I); extended nuclear astrophysics research with higher energy neutrons, including generation and studies of exotic neutron-rich isotopes relevant to the rapid (r-) process; nuclear structure of exotic isotopes; high energy neutron cross sections for basic nuclear physics and material science research, including neutron induced radiation damage; neutron based imaging and therapy; and novel radiopharmaceuticals development and production. In this paper we present a technical overview of SARAF-I and II, including a description of the accelerator and its irradiation targets; a survey of existing research programs at SARAF-I; and the research potential at the completed facility (SARAF-II).Comment: 32 pages, 31 figures, 10 tables, submitted as an invited review to European Physics Journal

    Gigantic retroperitoneal hematoma as a complication of anticoagulation therapy with heparin in therapeutic doses: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Spontaneous retroperitoneal hemorrhage is a distinct clinical entity that can present as a rare life-threatening event characterized by sudden onset of bleeding into the retroperitoneal space, occurring in association with bleeding disorders, intratumoral bleeding, or ruptures of any retroperitoneal organ or aneurysm. The spontaneous form is the most infrequent retroperitoneal hemorrhage, causing significant morbidity and representing a diagnostic challenge.</p> <p>Case presentation</p> <p>We report the case of a patient with coronary artery disease who presented with transient ischemic attack, in whom anticoagulant therapy with heparin precipitated a massive spontaneous atraumatic retroperitoneal hemorrhage (with international normalized ratio 2.4), which was treated conservatively.</p> <p>Conclusion</p> <p>Delay in diagnosis is potentially fatal and high clinical suspicion remains crucial. Finally, it is a matter of controversy whether retroperitoneal hematomas should be surgically evacuated or conservatively treated and the final decision should be made after taking into consideration patient's general condition and the possibility of permanent femoral or sciatic neuropathy due to compression syndrome.</p

    Ethnic Identity of Older Chinese in Canada

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    In Canada’s multicultural society, ethnic identity is important to the elderly and can influence areas such as access to services, health promotion and care. Often, the complex nature of ethnic identity is underestimated when looking at cultural groups. This study aims to: (a) validate the factor structure of a Chinese ethnic identity measure for older Chinese in Canada, (b) examine the level of ethnic identity of the participants, and (c) examine the correlates of ethnic identity in these older individuals. Using data from a large, national research project on the elderly Chinese in Canada, this study analyzed the results gathered from a total of 2,272 participants. Principal component analysis, maximum-likelihood confirmatory factor analysis, and multiple regression analysis were performed. The results indicated that ethnic identity of the older Chinese is a multi-dimensional construct made up of three factors: (a) culture related activities, (b) community ties, (c) linkage with country of origin, and (d) cultural identification. The findings have provided a better understanding of how ethnic identity can be measured among the aging Chinese population in Canada

    A Common Ca2+-Driven Interdomain Module Governs Eukaryotic NCX Regulation

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    Na+/Ca2+ exchanger (NCX) proteins mediate Ca2+-fluxes across the cell membrane to maintain Ca2+ homeostasis in many cell types. Eukaryotic NCX contains Ca2+-binding regulatory domains, CBD1 and CBD2. Ca2+ binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, whereas CALX, a Drosophila NCX ortholog, displays an inhibitory response to regulatory Ca2+. To further elucidate the underlying regulatory mechanisms, we determined the 2.7 Å crystal structure of mammalian CBD12-E454K, a two-domain construct that retains wild-type properties. In conjunction with stopped-flow kinetics and SAXS (small-angle X-ray scattering) analyses of CBD12 mutants, we show that Ca2+ binding to Ca3-Ca4 sites tethers the domains via a network of interdomain salt-bridges. This Ca2+-driven interdomain switch controls slow dissociation of “occluded” Ca2+ from the primary sensor and thus dictates Ca2+ sensing dynamics. In the Ca2+-bound conformation, the interdomain angle of CBD12 is very similar in NCX and CALX, meaning that the interdomain distances cannot account for regulatory diversity in NCX and CALX. Since the two-domain interface is nearly identical among eukaryotic NCXs, including CALX, we suggest that the Ca2+-driven interdomain switch described here represents a general mechanism for initial conduction of regulatory signals in NCX variants

    A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol.

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    BACKGROUND: Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies shows the potential of neo-adjuvant chemo-radiotherapy but the relative radio-resistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic radiotherapy achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of clear resection margins and local disease control. METHODS/DESIGN: SPARC is a "rolling-six" design single-arm study to establish the maximum tolerated dose for margin-intensive stereotactic radiotherapy before resection of pancreatic cancer at high risk of positive resection margins. Eligible patients will have histologically or cytologically proven pancreatic cancer defined as borderline-resectable per National Comprehensive Cancer Network criteria or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres and a 'rolling-six' design is utilised to minimise delays and facilitate ongoing recruitment during dose-escalation. Radiotherapy will be delivered in 5 daily fractions and surgery, if appropriate, will take place 5-6 weeks after radiotherapy. The margin-intense radiotherapy concept includes a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration, and up to 4 radiotherapy dose levels will be investigated. Maximum tolerated dose is defined as the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. Secondary endpoints include resection rate, resection margin status, response rate, overall survival and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to stereotactic radiotherapy in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015. DISCUSSION: This prospective multi-centre study aims to establish the maximum tolerated dose of pre-operative margin-intensified stereotactic radiotherapy in pancreatic cancer at high risk of positive resection margins with a view to subsequent definitive comparison with other neoadjuvant treatment options