Hidden symmetry and nonlinear paraxial atom optics

A hidden symmetry of the nonlinear wave equation is exploited to analyse the propagation of paraxial and uniform atom-laser beams in time-independent, quadratic and cylindrical potentials varying smoothly along the propagation axis. The quality factor and the paraxial ABCD formalism are generalized to account exactly for mean-field interaction effects in such beams. Using an approach based on moments, these theoretical tools provide a very simple and yet exact picture of the interacting beam profile evolution. Guided atom laser experiments are discussed. This treatment addresses simultaneously optical and atomic beams in a unified manner, exploiting the formal analogy between nonlinear optics and nonlinear paraxial atom optics.Comment: Final Version. Changes in the abstract and minor changes in the text with respect to the version published in PR

Precision atomic gravimeter based on Bragg diffraction

We present a precision gravimeter based on coherent Bragg diffraction of freely falling cold atoms. Traditionally, atomic gravimeters have used stimulated Raman transitions to separate clouds in momentum space by driving transitions between two internal atomic states. Bragg interferometers utilize only a single internal state, and can therefore be less susceptible to environmental perturbations. Here we show that atoms extracted from a magneto-optical trap using an accelerating optical lattice are a suitable source for a Bragg atom interferometer, allowing efficient beamsplitting and subsequent separation of momentum states for detection. Despite the inherently multi-state nature of atom diffraction, we are able to build a Mach-Zehnder interferometer using Bragg scattering which achieves a sensitivity to the gravitational acceleration of $\Delta g/g = 2.7\times10^{-9}$ with an integration time of 1000s. The device can also be converted to a gravity gradiometer by a simple modification of the light pulse sequence.Comment: 13 pages, 11 figure

Marine radioecology after the Fukushima Dai-ichi nuclear accident : are we better positioned to understand the impact of radionuclides in marine ecosystems?

© The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Science of The Total Environment 618 (2017): 80-92, doi:10.1016/j.scitotenv.2017.11.005.This paper focuses on how a community of researchers under the COMET (CO-ordination and iMplementation of a pan European projecT for radioecology) project has improved the capacity of marine radioecology to understand at the process level the behaviour of radionuclides in the marine environment, uptake by organisms and the resulting doses after the Fukushima Dai-ichi nuclear accident occurred in 2011. We present new radioecological understanding of the processes involved, such as the interaction of waterborne radionuclides with suspended particles and sediments or the biological uptake and turnover of radionuclides, which have been better quantified and mathematically described. We demonstrate that biokinetic models can better represent radionuclide transfer to biota in non-equilibrium situations, bringing more realism to predictions, especially when combining physical, chemical and biological interactions that occur in such an open and dynamic environment as the ocean. As a result, we are readier now than we were before the FDNPP accident in terms of having models that can be applied to dynamic situations. The paper concludes with our vision for marine radioecology as a fundamental research discipline and we present a strategy for our discipline at the European and international levels. The lessons learned are presented along with their possible applicability to assess/reduce the environmental consequences of future accidents to the marine environment and guidance for future research, as well as to assure sustainability of marine radioecology in Europe and globally. This guidance necessarily reflects on why and where further research funding is needed, signalling the way for future investigations.The research leading to this paper has received funding from the European Union's seventh Framework programme (FP7/2007-2013) under grant agreement No. is 604974 (Projects within COMET: Marine Initial Research Activity and The impact of recent releases from the Fukushima nucleaR Accident on the Marine Environment - FRAME). Sampling off Japan has been supported by the Gordon and Betty Moore Foundation, the Deerbrook Charitable Trust and contributions to the WHOI Centre for Marine and Environmental Radioactivity. We acknowledge the JSPS KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas Grant No. 24110005 for supporting in part the activities during the research cruises to the FDNPP area

PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome

The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that ablation in mouse causes a necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice with conditional PARL deficiency in the nervous system, but not in muscle, develop a similar phenotype as germline KOs, demonstrating the vital role of PARL in neurological homeostasis. Genetic modification of two major PARL substrates, PINK1 and PGAM5, do not modify this severe neurological phenotype. brain mitochondria are affected by progressive ultrastructural changes and by defects in Complex III (CIII) activity, coenzyme Q (CoQ) biosynthesis, and mitochondrial calcium metabolism. PARL is necessary for the stable expression of TTC19, which is required for CIII activity, and of COQ4, which is essential in CoQ biosynthesis. Thus, PARL plays a previously overlooked constitutive role in the maintenance of the respiratory chain in the nervous system, and its deficiency causes progressive mitochondrial dysfunction and structural abnormalities leading to neuronal necrosis and Leigh-like syndrome

New directions for patient-centred care in scleroderma : the Scleroderma Patient-centred Intervention Network (SPIN)

Systemic sclerosis (SSc), or scleroderma, is a chronic multisystem autoimmune disorder characterised by thickening and fibrosis of the skin and by the involvement of internal organs such as the lungs, kidneys, gastrointestinal tract, and heart. Because there is no cure, feasibly-implemented and easily accessible evidence-based interventions to improve health-related quality of life (HRQoL) are needed. Due to a lack of evidence, however, specific recommendations have not been made regarding non-pharmacological interventions (e.g. behavioural/psychological, educational, physical/occupational therapy) to improve HRQoL in SSc. The Scleroderma Patient-centred Intervention Network (SPIN) was recently organised to address this gap. SPIN is comprised of patient representatives, clinicians, and researchers from Canada, the USA, and Europe. The goal of SPIN, as described in this article, is to develop, test, and disseminate a set of accessible interventions designed to complement standard care in order to improve HRQoL outcomes in SSc.The initial organisational meeting for SPIN was funded by a Canadian Institutes of Health Research (CIHR) Meetings, Planning, and Dissemination grant to B.D. Thombs (KPE-109130), Sclerodermie Quebec, and the Lady Davis Institute for Medical Research of the Jewish General Hospital, Montreal, Quebec. SPIN receives finding support from the Sclemderma Society of Ontario, the Scleroderma Society of Canada, and Sclerodermie Quebec. B.D. Thombs and M. Hudson are supported by New Investigator awards from the CIHR, and Etablissement de Jeunes Chercheurs awards from the Fonds de la Recherche en Sante Quebec (FRSQ). M. Baron is the director of the Canadian Scleroderma Research Group, which receives grant folding from the CIHR, the Scleroderma Society of Canada and its provincial chapters, Scleroderma Society of Ontario, Sclerodermie Quebec, and the Ontario Arthritis Society, and educational grants from Actelion Pharmaceuticals and Pfizer. M.D. Mayes and S. Assassi are supported by the NIH/NIAMS Scleroderma Center of Research Translation grant no. P50-AR054144. S.J. Motivala is supported by an NIH career development grant (K23 AG027860) and the UCLA Cousins Center for Psychoneuroimmunology. D. Khanna is supported by a NIH/NIAMS K23 AR053858-04) and NIH/NIAMS U01 AR057936A, the National Institutes of Health through the NIH Roadmap for Medical Research Grant (AR052177), and has served as a consultant or on speakers bureau for Actelion, BMS, Gilead, Pfizer, and United Therapeutics

Mechanisms of congenital heart disease caused by NAA15 haploinsufficiency

Rationale: NAA15 is a component of the N-terminal (Nt) acetyltransferase complex, NatA. The mechanism by which NAA15 haploinsufficiency causes congenital heart disease (CHD) remains unknown. To better understand molecular processes by which NAA15 haploinsufficiency perturbs cardiac development, we introduced NAA15 variants into human induced pluripotent stem cells (iPSCs) and assessed the consequences of these mutations on RNA and protein expression. Objective: We aim to understand the role of NAA15 haploinsufficiency in cardiac development by investigating proteomic effects on NatA complex activity, and identifying proteins dependent upon a full amount of NAA15. Methods and Results: We introduced heterozygous LoF, compound heterozygous and missense residues (R276W) in iPS cells using CRISPR/Cas9. Haploinsufficient NAA15 iPS cells differentiate into cardiomyocytes, unlike NAA15-null iPS cells, presumably due to altered composition of NatA. Mass spectrometry (MS) analyses reveal ~80% of identified iPS cell NatA targeted proteins displayed partial or complete Nt-acetylation. Between null and haploinsufficient NAA15 cells Nt-acetylation levels of 32 and 9 NatA-specific targeted proteins were reduced, respectively. Similar acetylation loss in few proteins occurred in NAA15 R276W iPSCs. In addition, steady-state protein levels of 562 proteins were altered in both null and haploinsufficient NAA15 cells; eighteen were ribosomal-associated proteins. At least four proteins were encoded by genes known to cause autosomal dominant CHD. Conclusions: These studies define a set of human proteins that requires a full NAA15 complement for normal synthesis and development. A 50% reduction in the amount of NAA15 alters levels of at least 562 proteins and Nt-acetylation of only 9 proteins. One or more modulated proteins are likely responsible for NAA15-haploinsufficiency mediated CHD. Additionally, genetically engineered iPS cells provide a platform for evaluating the consequences of amino acid sequence variants of unknown significance on NAA15 function