86 research outputs found
Molecular, Biochemical and Genetic Characteristics of BSE in Canada
The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE) have recently been recognized to be heterogeneous. In particular, three types [classical (C) and two atypical (H, L)] have been identified, largely on the basis of characteristics of the proteinase K (PK)-resistant core of the misfolded prion protein associated with the disease (PrPres). The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrPres, including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity. Two cases exhibited molecular weight and glycoform profiles similar to those of previously reported atypical cases, one corresponding to H-type BSE (case 6) and the other to L-type BSE (case 11). All other cases were classified as C-type. PK digestion under mild and stringent conditions revealed a reduced protease resistance in both of these cases compared to the C-type cases. With Western immunoblotting, N-terminal-specific antibodies bound to PrPres from case 6 but not to that from case 11 or C-type cases. C-terminal-specific antibodies revealed a shift in the glycoform profile and detected a fourth protein fragment in case 6, indicative of two PrPres subpopulations in H-type BSE. No mutations suggesting a genetic etiology were found in any of the 17 animals by sequencing the full PrP-coding sequence in exon 3 of the PRNP gene. Thus, each of the three known BSE types have been confirmed in Canadian cattle and show molecular characteristics highly similar to those of classical and atypical BSE cases described from Europe, Japan and the USA. The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide
Glucokinase (GCK) Mutations and Their Characterization in MODY2 Children of Southern Italy
Type 2 Maturity Onset Diabetes of the Young (MODY2) is a monogenic autosomal disease characterized by a primary defect in insulin secretion and hyperglycemia. It results from GCK gene mutations that impair enzyme activity. Between 2006 and 2010, we investigated GCK mutations in 66 diabetic children from southern Italy with suspected MODY2. Denaturing High Performance Liquid Chromatography (DHPLC) and sequence analysis revealed 19 GCK mutations in 28 children, six of which were novel: p.Glu40Asp, p.Val154Leu, p.Arg447Glyfs, p.Lys458_Cys461del, p.Glu395_Arg397del and c.580-2A>T. We evaluated the effect of these 19 mutations using bioinformatic tools such as Polymorphism Phenotyping (Polyphen), Sorting Intolerant From Tolerant (SIFT) and in silico modelling. We also conducted a functional study to evaluate the pathogenic significance of seven mutations that are among the most severe mutations found in our population, and have never been characterized: p.Glu70Asp, p.His137Asp, p.Phe150Tyr, p.Val154Leu, p.Gly162Asp, p.Arg303Trp and p.Arg392Ser. These seven mutations, by altering one or more kinetic parameters, reduced enzyme catalytic activity by >40%. All mutations except p.Glu70Asp displayed thermal-instability, indeed >50% of enzyme activity was lost at 50°C/30 min. Thus, these seven mutations play a pathogenic role in MODY2 insurgence. In conclusion, this report revealed six novel GCK mutations and sheds some light on the structure-function relationship of human GCK mutations and MODY2
Exploring the Solar Wind from Its Source on the Corona into the Inner Heliosphere during the First Solar Orbiter-Parker Solar Probe Quadrature
This Letter addresses the first Solar Orbiter (SO)–Parker Solar Probe (PSP) quadrature, occurring on 2021 January 18 to investigate the evolution of solar wind from the extended corona to the inner heliosphere. Assuming ballistic propagation, the same plasma volume observed remotely in the corona at altitudes between 3.5 and 6.3 solar radii above the solar limb with the Metis coronagraph on SO can be tracked to PSP, orbiting at 0.1 au, thus allowing the local properties of the solar wind to be linked to the coronal source region from where it originated. Thanks to the close approach of PSP to the Sun and the simultaneous Metis observation of the solar corona, the flow-aligned magnetic field and the bulk kinetic energy flux density can be empirically inferred along the coronal current sheet with an unprecedented accuracy, allowing in particular estimation of the Alfvén radius at 8.7 solar radii during the time of this event. This is thus the very first study of the same solar wind plasma as it expands from the sub-Alfvénic solar corona to just above the Alfvén surface
Dynamical Evolution of Planetary Systems
Planetary systems can evolve dynamically even after the full growth of the
planets themselves. There is actually circumstantial evidence that most
planetary systems become unstable after the disappearance of gas from the
protoplanetary disk. These instabilities can be due to the original system
being too crowded and too closely packed or to external perturbations such as
tides, planetesimal scattering, or torques from distant stellar companions. The
Solar System was not exceptional in this sense. In its inner part, a crowded
system of planetary embryos became unstable, leading to a series of mutual
impacts that built the terrestrial planets on a timescale of ~100 My. In its
outer part, the giant planets became temporarily unstable and their orbital
configuration expanded under the effect of mutual encounters. A planet might
have been ejected in this phase. Thus, the orbital distributions of planetary
systems that we observe today, both solar and extrasolar ones, can be different
from the those emerging from the formation process and it is important to
consider possible long-term evolutionary effects to connect the two.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H.
Deeg & J.A. Belmont
Euclid: Covariance of weak lensing pseudo-C_ell estimates. Calculation, comparison to simulations, and dependence on survey geometry
An accurate covariance matrix is essential for obtaining reliable
cosmological results when using a Gaussian likelihood. In this paper we study
the covariance of pseudo-C_ estimates of tomographic cosmic shear power
spectra. Using two existing publicly available codes in combination, we
calculate the full covariance matrix, including mode-coupling contributions
arising from both partial sky coverage and non-linear structure growth. For
three different sky masks, we compare the theoretical covariance matrix to that
estimated from publicly available N-body weak lensing simulations, finding good
agreement. We find that as a more extreme sky cut is applied, a corresponding
increase in both Gaussian off-diagonal covariance and non-Gaussian super-sample
covariance is observed in both theory and simulations, in accordance with
expectations. Studying the different contributions to the covariance in detail,
we find that the Gaussian covariance dominates along the main diagonal and the
closest off-diagonals, but further away from the main diagonal the super-sample
covariance is dominant. Forming mock constraints in parameters describing
matter clustering and dark energy, we find that neglecting non-Gaussian
contributions to the covariance can lead to underestimating the true size of
confidence regions by up to 70 per cent. The dominant non-Gaussian covariance
component is the super-sample covariance, but neglecting the smaller connected
non-Gaussian covariance can still lead to the underestimation of uncertainties
by 10--20 per cent. A real cosmological analysis will require marginalisation
over many nuisance parameters, which will decrease the relative importance of
all cosmological contributions to the covariance, so these values should be
taken as upper limits on the importance of each component
Non-canonical amino acids bearing thiophene and bithiophene: synthesis by an Ugi multicomponent reaction and studies on ion recognition ability
Novel thienyl and bithienyl amino acids with different substituents were obtained by a multicomponent Ugi reaction between a heterocyclic aldehyde, an amine, an acid and an isocyanide. Due to the presence of the sulphur heterocycle at the side chain, these unnatural amino acids are highly emissive and bear extra electron donating atoms so they were tested for their ability to act as fluorescent probes and chemosensors in the recognition of biomedically relevant ions in acetonitrile and acetonitrile/water solutions. The results obtained from spectrophotometric/spectrofluorimetric titrations in the presence of organic and inorganic anions, and alkaline; alkaline-earth and transition metal cations indicated that the bithienyl amino acid bearing a methoxy group is a selective colorimetric chemosensor for Cu2+, while the other (bi)thienyl amino acids act as fluorimetric chemosensors with high sensitivity towards Fe3+ and Cu2+ in a metal-ligand complex with 1:2 stoichiometry. The photophysical and ion sensing properties of these amino acids confirm their potential as fluorescent probes suitable for incorporation into peptidic frameworks with chemosensory ability.Thanks are due to Fundação para a Ciência e Tecnologia (FCT-Portugal) and FEDER-COMPETE for financial support through Centro de QuÃmica [PEst-C/QUI/UI0686/2013 (F-COMP-01-0124-FEDER-037302)] and a PhD grant to C.I.C. Esteves (SFRH/BD/68360/2010). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased with funds from FCT and FEDER.info:eu-repo/semantics/publishedVersio
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Design of the ECCE Detector for the Electron Ion Collider
Preprint submitted to Nuclear Instruments and Methods A. The file archived on this institutional repository has not been certified by peer review.32 pages, 29 figures, 9 tablesThe EIC Comprehensive Chromodynamics Experiment (ECCE) detector has been designed to address the full scope of the proposed Electron Ion Collider (EIC) physics program as presented by the National Academy of Science and provide a deeper understanding of the quark-gluon structure of matter. To accomplish this, the ECCE detector offers nearly acceptance and energy coverage along with excellent tracking and particle identification. The ECCE detector was designed to be built within the budget envelope set out by the EIC project while simultaneously managing cost and schedule risks. This detector concept has been selected to be the basis for the EIC project detector.Office of Science in the Department of Energy, the National Science Foundation, and the Los Alamos National
Laboratory Laboratory Directed Research and Development (LDRD) 20200022DR; This research used resources of the Compute and Data Environment for Science (CADES) at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC05-
00OR22725. The work of AANL group are supported by the Science Committee of RA, in the frames of the research project # 21AG-1C028. And we gratefully acknowledge that support of Brookhaven National Lab and the Thomas Jefferson National Accelerator Facility which are operated under contracts DESC0012704 and DE-AC05-06OR23177 respectivel
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AI-assisted optimization of the ECCE tracking system at the Electron Ion Collider
arXiv preprint [v2] Fri, 20 May 2022 03:23:44 UTC (2,296 KB) made available under a Creative Commons (CC BY) Attribution Licence, now in press, published by Elsevier: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, available online 17 November 2022 at: https://doi.org/10.1016/j.nima.2022.167748The Electron-Ion Collider (EIC) is a cutting-edge accelerator facility that will study the nature of the "glue" that binds the building blocks of the visible matter in the universe. The proposed experiment will be realized at Brookhaven National Laboratory in approximately 10 years from now, with detector design and R&D currently ongoing. Notably, EIC is one of the first large-scale facilities to leverage Artificial Intelligence (AI) already starting from the design and R&D phases. The EIC Comprehensive Chromodynamics Experiment (ECCE) is a consortium that proposed a detector design based on a 1.5T solenoid. The EIC detector proposal review concluded that the ECCE design will serve as the reference design for an EIC detector. Herein we describe a comprehensive optimization of the ECCE tracker using AI. The work required a complex parametrization of the simulated detector system. Our approach dealt with an optimization problem in a multidimensional design space driven by multiple objectives that encode the detector performance, while satisfying several mechanical constraints. We describe our strategy and show results obtained for the ECCE tracking system. The AI-assisted design is agnostic to the simulation framework and can be extended to other sub-detectors or to a system of sub-detectors to further optimize the performance of the EIC detector.Office of Nuclear Physics in the Office of Science in the Department of Energy; National Science Foundation, and the Los Alamos National Laboratory Laboratory Directed Research and Development (LDRD) 20200022DR
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