Update of variants identified in the pancreatic β-cell K ATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes

The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the β-cell ATP-sensitive potassium channel, a key component of the glucose-stimulated insulin secretion pathway. Mutations in the two genes cause dysregulated insulin secretion; inactivating mutations cause an oversecretion of insulin, leading to congenital hyperinsulinism, whereas activating mutations cause the opposing phenotype, diabetes. This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site.P30 DK020595/NH/NIH HHS/United States K23 DK094866/NH/NIH HHS/United States R03 DK103096/NH/NIH HHS/United States 1-11-CT-41/American Diabetes Association/International R01 DK104942/DK/NIDDK NIH HHS/United States WT_/Wellcome Trust/United Kingdom WT098395/Z/12/Z/WT_/Wellcome Trust/United Kingdom UL1 TR000430/NH/NIH HHS/United States P30 DK020595/DK/NIDDK NIH HHS/United States UL1 TR000430/TR/NCATS NIH HHS/United States 1-17-JDF-008/American Diabetes Association/International 105636/Z/14/Z/WT_/Wellcome Trust/United Kingdom 110675/European Association for the Study of Diabetes-Novo Nordisk/International 16/0005407/DUK_/Diabetes UK/United Kingdom R01 DK104942/NH/NIH HHS/United States R03 DK103096/DK/NIDDK NIH HHS/United States K23 DK094866/DK/NIDDK NIH HHS/United Statespublished version, accepted version (12 month embargo), submitted versio

Non-destructive seed detection in mandarins: comparison of automatic threshold methods FLASH and COMSPIRA MRIs

Here, we review different methods for non-destructive horticultural produce size determination, focusing on electronic technologies capable of measuring fruit volume. The usefulness of produce size estimation is justified and a comprehensive classification system of the existing electronic techniques to determine dimensional size is proposed. The different systems identified are compared in terms of their versatility, precision and throughput. There is general agreement in considering that online measurement of axes, perimeter and projected area has now been achieved. Nevertheless, rapid and accurate volume determination of irregular-shaped produce, as needed for density sorting, has only become available in the past few years. An important application of density measurement is soluble solids content (SSC) sorting. If the range of SSC in the batch is narrow and a large number of classes are desired, accurate volume determination becomes important. A good alternative for fruit three-dimensional surface reconstruction, from which volume and surface area can be computed, is the combination of height profiles from a range sensor with a two-dimensional object image boundary from a solid-state camera (brightness image) or from the range sensor itself (intensity image). However, one of the most promising technologies in this field is 3-D multispectral scanning, which combines multispectral data with 3-D surface reconstruction

Rifting in heterogeneous lithosphere inferences from numerical modeling of the northern North Sea and the Oslo Graben.

Permian rifting and magmatism are widely documented across NW Europe. The different Permian basins often display contrasting structural styles and evolved in lithospheric domains with contrasting past evolution and contrasting thermotectonic ages. In particular, the Oslo Graben and the northern North Sea rift initiated in close areas of northern Europe. The Oslo Graben evolved in the cold and stable Precambrian lithosphere of Fennoscandia, whereas the northern North Sea rift took birth in freshly reworked Caledonian lithosphere. Huge volumes of magmatic rocks characterize the relatively narrow Oslo Graben. In contrast, little magmatism is documented for the wide northern North Sea rift. Differences in timing between both rifts are inferred but still debated. We present numerical thermomechanical models along a lithospheric E-W section that involves both the Oslo Graben and the northern North Sea area. Because the modeled section crosses the boundary between Caledonian and Proterozoic provinces, thermal and compositional heterogeneities are considered. As is suggested by various geophysical data sets, we also consider lithospheric thickness heterogeneities in the Precambrian lithosphere. Modeling results suggest that the northern North Sea was on top of "weak" lithosphere very sensitive to far-field stresses. Consequently, we suggest that rifting in the northern North Sea began as early as regional extension was effective (i.e., Late Carboniferous-Early Permian) and does not postdate the Oslo Graben as it is commonly assumed. Rifting in the "strong" Precambrian lithosphere is unexpected. Modeling results suggest that a pre-existing lithospheric thickness contrast within the Fennoscandian lithosphere favored rifting in the Oslo Graben

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats

Macrophyte abundance in Waquoit Bay : effects of land-derived nitrogen loads on seasonal and multi-year biomass patterns

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Estuaries and Coasts 31 (2008): 532-541, doi:10.1007/s12237-008-9039-6.Anthropogenic inputs of nutrients to coastal waters have rapidly restructured coastal ecosystems. To examine the response of macrophyte communities to land-derived nitrogen loading, we measured macrophyte biomass monthly for six years in three estuaries subject to different nitrogen loads owing to different land uses on the watersheds. The set of estuaries sampled had nitrogen loads over the broad range of 12 to 601 kg N ha-1 y-1. Macrophyte biomass increased as nitrogen loads increased, but the response of individual taxa varied. Specifically, biomass of Cladophora vagabunda and Gracilaria tikvahiae increased significantly as nitrogen loads increased. The biomass of other macroalgal taxa tended to decrease with increasing load, and the relative proportion of these taxa to total macrophyte biomass also decreased. The seagrass, Zostera marina, disappeared from the higher loaded estuaries, but remained abundant in the estuary with the lowest load. Seasonal changes in macroalgal standing stock were also affected by nitrogen load, with larger fluctuations in biomass across the year and higher minimum biomass of macroalgae in the higher loaded estuaries. There were no significant changes in macrophyte biomass over the six years of this study, but there was a slight trend of increasing macroalgal biomass in the latter years. Macroalgal biomass was not related to irradiance or temperature, but Z. marina biomass was highest during the summer months when light and temperatures peak. Irradiance might, however, be a secondary limiting factor controlling macroalgal biomass in the higher loaded estuaries by restricting the depth of the macroalgal canopy. The relationship between the bloom-forming macroalgal species, C. vagabunda and G. tikvahiae, and nitrogen loads suggested a strong connection between development on watersheds and macroalgal blooms and loss of seagrasses. The influence of watershed land uses largely overwhelmed seasonal and inter-annual differences in standing stock of macrophytes in these temperate estuaries.This research was supported by the National Oceanic and Atmospheric Administration (NOAA), Cooperative Institute for Coastal and Estuarine Environmental Technologies (CICEET-UNH#99-304, NOAA NA87OR512), NOAA National Estuarine Research Reserve Graduate Research Fellowship NERRS GRF, #NA77OR0228), and an Environmental Protection Agency (EPA) STAR Fellowship for Graduate Environmental Study (U-915335-01-0) awarded to J. Hauxwell. S. Fox was supported by a NOAA NERRS GRF (#NA03NOS4200132) and an EPA STAR Graduate Research Fellowship. We also thank the Quebec-Labrador Foundation Atlantic Center for the Environment's Sounds Conservancy Program and the Boston University Ablon/Bay Committee for their awarding research funds