1,345 research outputs found

    Higher order contributions to Rashba and Dresselhaus effects

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    We have developed a method to systematically compute the form of Rashba- and Dresselhaus-like contributions to the spin Hamiltonian of heterostructures to an arbitrary order in the wavevector k. This is achieved by using the double group representations to construct general symmetry-allowed Hamiltonians with full spin-orbit effects within the tight-binding formalism. We have computed full-zone spin Hamiltonians for [001]-, [110]- and [111]-grown zinc blende heterostructures (D_{2d},C_{4v},C_{2v},C_{3v} point group symmetries), which are commonly used in spintronics. After an expansion of the Hamiltonian up to third order in k, we are able to obtain additional terms not found previously. The present method also provides the matrix elements for bulk zinc blendes (T_d) in the anion/cation and effective bond orbital model (EBOM) basis sets with full spin-orbit effects.Comment: v1: 11 pages, 3 figures, 8 table

    Modeling Phenotypic Heterogeneity of Glycogen Storage Disease Type 1a Liver Disease in Mice by Somatic CRISPR/CRISPR-associated protein 9-Mediated Gene Editing

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    BACKGROUND AND AIMS: Patients with glycogen storage disease type 1a (GSD‐1a) primarily present with life‐threatening hypoglycemia and display severe liver disease characterized by hepatomegaly. Despite strict dietary management, long‐term complications still occur, such as liver tumor development. Variations in residual glucose‐6‐phosphatase (G6PC1) activity likely contribute to phenotypic heterogeneity in biochemical symptoms and complications between patients. However, lack of insight into the relationship between G6PC1 activity and symptoms/complications and poor understanding of the underlying disease mechanisms pose major challenges to provide optimal health care and quality of life for GSD‐1a patients. Currently available GSD‐1a animal models are not suitable to systematically investigate the relationship between hepatic G6PC activity and phenotypic heterogeneity or the contribution of gene‐gene interactions (GGIs) in the liver. APPROACH AND RESULTS: To meet these needs, we generated and characterized a hepatocyte‐specific GSD‐1a mouse model using somatic CRISPR/CRISPR‐associated protein 9 (Cas9)–mediated gene editing. Hepatic G6pc editing reduced hepatic G6PC activity up to 98% and resulted in failure to thrive, fasting hypoglycemia, hypertriglyceridemia, hepatomegaly, hepatic steatosis (HS), and increased liver tumor incidence. This approach was furthermore successful in simultaneously modulating hepatic G6PC and carbohydrate response element‐binding protein, a transcription factor that is activated in GSD‐1a and protects against HS under these conditions. Importantly, it also allowed for the modeling of a spectrum of GSD‐1a phenotypes in terms of hepatic G6PC activity, fasting hypoglycemia, hypertriglyceridemia, hepatomegaly and HS. CONCLUSIONS: In conclusion, we show that somatic CRISPR/Cas9‐mediated gene editing allows for the modeling of a spectrum of hepatocyte‐borne GSD‐1a disease symptoms in mice and to efficiently study GGIs in the liver. This approach opens perspectives for translational research and will likely contribute to personalized treatments for GSD‐1a and other genetic liver diseases

    A Two-Phase Approach for an Integrated Order Batching and Picker Routing Problem

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    International audienceThis article addresses an integrated warehouse order picking problem. The company HappyChic is specialized in men’s ready-to-wear. A central warehouse is dedicated to supplying, every day, the shops of one brand. We focus on the picking area of this warehouse which relies on human picking system. For each picking wave (period of a working day), a set of customer orders has to be prepared. An order is a set of product references, with quantities, i.e., the numbers of items required. The problem consists in jointly deciding: (1) the division of orders into several boxes,respecting weight and size constraints; (2) the batching of boxes into trolleys, that implicitly defines the routing into the picking area. The objective function aims to minimize the total distance. To deal with the large size instances of HappyChic in short computation times, we design a heuristic method based on the split and dynamic programming paradigms. The results are very convincing: the total covered distance decreases by more than 20%. Moreover, we propose an adaptation of the algorithm to prepare homogeneous boxes with respect to classes of products. Thelogistic department of HappyChic is convinced by results obtained in this research work, and the warehouse management system is currently being updated in order to integrate the proposed algorithm

    Critical Role of Gap Junction Coupled K(ATP) Channel Activity for Regulated Insulin Secretion

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    Pancreatic β-cells secrete insulin in response to closure of ATP-sensitive K(+) (K(ATP)) channels, which causes membrane depolarization and a concomitant rise in intracellular Ca(2+) (Ca(i)). In intact islets, β-cells are coupled by gap junctions, which are proposed to synchronize electrical activity and Ca(i) oscillations after exposure to stimulatory glucose (>7 mM). To determine the significance of this coupling in regulating insulin secretion, we examined islets and β-cells from transgenic mice that express zero functional K(ATP) channels in approximately 70% of their β-cells, but normal K(ATP) channel density in the remainder. We found that K(ATP) channel activity from approximately 30% of the β-cells is sufficient to maintain strong glucose dependence of metabolism, Ca(i), membrane potential, and insulin secretion from intact islets, but that glucose dependence is lost in isolated transgenic cells. Further, inhibition of gap junctions caused loss of glucose sensitivity specifically in transgenic islets. These data demonstrate a critical role of gap junctional coupling of K(ATP) channel activity in control of membrane potential across the islet. Control via coupling lessens the effects of cell–cell variation and provides resistance to defects in excitability that would otherwise lead to a profound diabetic state, such as occurs in persistent neonatal diabetes mellitus

    Magnetic effects at the interface between nonmagnetic oxides

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    The electronic reconstruction at the interface between two insulating oxides can give rise to a highly-conductive interface. In analogy to this remarkable interface-induced conductivity we show how, additionally, magnetism can be induced at the interface between the otherwise nonmagnetic insulating perovskites SrTiO3 and LaAlO3. A large negative magnetoresistance of the interface is found, together with a logarithmic temperature dependence of the sheet resistance. At low temperatures, the sheet resistance reveals magnetic hysteresis. Magnetic ordering is a key issue in solid-state science and its underlying mechanisms are still the subject of intense research. In particular, the interplay between localized magnetic moments and the spin of itinerant conduction electrons in a solid gives rise to intriguing many-body effects such as Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions, the Kondo effect, and carrier-induced ferromagnetism in diluted magnetic semiconductors. The conducting oxide interface now provides a versatile system to induce and manipulate magnetic moments in otherwise nonmagnetic materials.Comment: Nature Materials, July issu

    Land Surface Precipitation and Hydrology in MERRA-2

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    The Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), provides global, 1-hourly estimates of land surface conditions for 1980-present at 50-km resolution. Outside of the high latitudes, MERRA-2 uses observations-based precipitation data products to correct the precipitation falling on the land surface. This paper describes the precipitation correction method and evaluates the MERRA-2 land surface precipitation and hydrology. Compared to monthly GPCPv2.2 observations, the corrected MERRA-2 precipitation (M2CORR) is better than the precipitation generated by the atmospheric models within the cyclingMERRA-2 system and the earlier MERRA reanalysis. Compared to 3-hourlyTRMM observations, the M2CORR diurnal cycle has better amplitude but less realistic phasing than MERRA-2 model-generated precipitation. Because correcting the precipitation within the coupled atmosphere-land modeling system allows the MERRA-2 near-surface air temperature and humidity to respond to the improved precipitation forcing, MERRA-2 provides more self-consistent surface meteorological data than were available from the earlier, offline MERRA-Land reanalysis. Overall, MERRA-2 land hydrology estimates are better than those of MERRA-Land and MERRA. A comparison against GRACE satellite observations of terrestrial water storage demonstrates clear improvements in MERRA-2 over MERRA in South America and Africa but also reflects known errors in the observations used to correct the MERRA-2 precipitation. The MERRA-2 and MERRA-Land surface and root zone soil moisture skill vs. in situ measurements is slightly higher than that of ERA-Interim Land and higher than that of MERRA (significantly for surface soil moisture). Snow amounts from MERRA-2 have lower bias and correlate better against reference data than do those of MERRA-Land and MERRA, with MERRA-2 skill roughly matching that of ERA-Interim Land. Seasonal anomaly R values against naturalized stream flow measurements in the United States are, on balance, highest for MERRA-2 and ERA-Interim Land, somewhat lower for MERRA-Land, and lower still for MERRA

    Local Electronic Structure of Defects in Superconductors

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    The electronic structure near defects (such as impurities) in superconductors is explored using a new, fully self-consistent technique. This technique exploits the short-range nature of the impurity potential and the induced change in the superconducting order parameter to calculate features in the electronic structure down to the atomic scale with unprecedented spectral resolution. Magnetic and non-magnetic static impurity potentials are considered, as well as local alterations in the pairing interaction. Extensions to strong-coupling superconductors and superconductors with anisotropic order parameters are formulated.Comment: RevTex source, 20 pages including 22 figures in text with eps

    Clinical examination, critical care ultrasonography and outcomes in the critically ill : cohort profile of the Simple Intensive Care Studies-I

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    Purpose In the Simple Intensive Care Studies-I (SICS-I), we aim to unravel the value of clinical and haemodynamic variables obtained by physical examination and critical care ultrasound (CCUS) that currently guide daily practice in critically ill patients. We intend to (1) measure all available clinical and haemodynamic variables, (2) train novices in obtaining values for advanced variables based on CCUS in the intensive care unit (ICU) and (3) create an infrastructure for a registry with the flexibility of temporarily incorporating specific (haemodynamic) research questions and variables. The overall purpose is to investigate the diagnostic and prognostic value of clinical and haemodynamic variables. Participants The SICS-I includes all patients acutely admitted to the ICU of a tertiary teaching hospital in the Netherlands with an ICU stay expected to last beyond 24 hours. Inclusion started on 27 March 2015. Findings to date On 31 December 2016, 791 eligible patients fulfilled our inclusion criteria of whom 704 were included. So far 11 substudies with additional variables have been designed, of which six were feasible to implement in the basic study, and two are planned and awaiting initiation. All researchers received focused training for obtaining specific CCUS images. An independent Core laboratory judged that 632 patients had CCUS images of sufficient quality. Future plans We intend to optimise the set of variables for assessment of the haemodynamic status of the critically ill patient used for guiding diagnostics, prognosis and interventions. Repeated evaluations of these sets of variables are needed for continuous improvement of the diagnostic and prognostic models. Future plans include: (1) more advanced imaging; (2) repeated clinical and haemodynamic measurements; (3) expansion of the registry to other departments or centres; and (4) exploring possibilities of integration of a randomised clinical trial superimposed on the registry. Study registration number NCT02912624; Pre-results.Peer reviewe

    Local Electronic Structure of a Single Magnetic Impurity in a Superconductor

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    The electronic structure near a single classical magnetic impurity in a superconductor is determined using a fully self-consistent Koster-Slater algorithm. Localized excited states are found within the energy gap which are half electron and half hole. Within a jellium model we find the new result that the spatial structure of the positive-frequency (electron-like) spectral weight (or local density of states), can differ strongly from that of the negative frequency (hole-like) spectral weight. The effect of the impurity on the continuum states above the energy gap is calculated with good spectral resolution for the first time. This is also the first three-dimensional self-consistent calculation for a strong magnetic impurity potential.Comment: 13 pages, RevTex, change in heuristic picture, no change in numerical result

    Renormalized Path Integral for the Two-Dimensional Delta-Function Interaction

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    A path-integral approach for delta-function potentials is presented. Particular attention is paid to the two-dimensional case, which illustrates the realization of a quantum anomaly for a scale invariant problem in quantum mechanics. Our treatment is based on an infinite summation of perturbation theory that captures the nonperturbative nature of the delta-function bound state. The well-known singular character of the two-dimensional delta-function potential is dealt with by considering the renormalized path integral resulting from a variety of schemes: dimensional, momentum-cutoff, and real-space regularization. Moreover, compatibility of the bound-state and scattering sectors is shown.Comment: 26 pages. The paper was significantly expanded and numerous equations were added for the sake of clarity; the main results and conclusions are unchange
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