Lithospheric structure along wide-angle seismic profile GEORIFT 2013 in Pripyat–Dnieper–Donets Basin (Belarus and Ukraine)

The GEORIFT 2013 (GR'13) WARR (wide-angle reflection and refraction) experiment was carried out in 2013 in the territory of Belarus and Ukraine with broad international co-operation. The aim of the work is to study basin architecture and deep structure of the Pripyat-Dnieper-Donets Basin (PDDB), which is the deepest and best studied Palaeozoic rift basin in Europe. The PDDB is located in the southern part of the East European Craton (EEC) and crosses Sarmatia-one of the three segments of the EEC. The PDDB was formed by Late Devonian rifting associated with domal basement uplift and magmatism. The GR'13 extends in NW SE direction along the PDDB strike and crosses the Pripyat Trough (PT) and Dnieper Graben (DG) separated by the Bragin Uplift (BU) of the basement. The field acquisition along the GR'13 (of 670 km total length) involved 14 shots and recorders deployed every similar to 2.2 km for several shot points. The good quality of the data, with first arrivals visible up to 670 km for several shot points, allowed for construction of a velocity model extending to 80 km depth using ray-tracing modelling. The thickness of the sediments (Vp <6.0 km s(-1)) varies from 1-4 km in the PT, to 5 km in the NW part of the DG, to 10-13 km in the SE part of the profile. Below the DG, at similar to 330-530 km distance, we observed an upwarping of the lower crust (with Vp of similar to 7.1 km s(-1)) to 25 km depth that represents a rift pillow or mantle underplate. The Moho shallows southeastwards from similar to 47 km in the PT to 40-38 km in the DG with mantle velocities of 8.35 and similar to 8.25 km s(-1) in the PT and DG, respectively. A near-horizontal mantle discontinuity was found beneath BU (a transition zone from the PT to the DG) at the depth of 50-47 km. It dips to the depth of similar to 60 km at distances of 360-405 km, similar to the intersecting EUROBRIDGE'97 profile. The crust and upper mantle structure on the GR'13 may reflect varying intensity of rifting in the PDDB from a passive stage in the PT to active rifting in the DG. The absence of Moho uplift and relatively thick crystalline crust under the PT is explained by its tectonic position as a closing unit of the PDDB, with a gradual attenuation of rifting from the southeast to the northwest. The most active stage of rifting is evidenced in the DG by a shallower Moho and by a presence of a rift pillow caused by mafic and ultramafic intrusions during the active phase. The junction of the PT and the DG (the BU) locates just at its intersection with the NS regional tectonic zone Odessa-Gomel. Most likely, the 'blocking' effect of this zone did not allow for further propagation of active rifting to the NW.Peer reviewe

Crustal and Upper Mantle Velocity Model along the DOBRE-4 Profile from North Dobruja to the Central Region of the Ukrainian Shield : 2. Geotectonic Interpretation

Peer reviewe

Crustal and Upper Mantle Velocity Model along the DOBRE-4 Profile from North Dobruja to the Central Region of the Ukrainian Shield : 1. Seismic Data

For studying the structure of the lithosphere in southern Ukraine, wide-angle seismic studies that recorded the reflected and refracted waves were carried out under the DOBRE-4 project. The field works were conducted in October 2009. Thirteen chemical shot points spaced 35-50 km apart from each other were implemented with a charge weight varying from 600 to 1000 kg. Overall 230 recording stations with an interval of 2.5 km between them were used. The high quality of the obtained data allowed us to model the velocity section along the profile for P-and S-waves. Seismic modeling was carried out by two methods. Initially, trial-and-error ray tracing using the arrival times of the main reflected and refracted P-and S-phases was conducted. Next, the amplitudes of the recorded phases were analyzed by the finite-difference full waveform method. The resulting velocity model demonstrates a fairly homogeneous structure from the middle to lower crust both in the vertical and horizontal directions. A drastically different situation is observed in the upper crust, where the Vp velocities decrease upwards along the section from 6.35 km/s at a depth of 15-20 km to 5.9-5.8 km/s on the surface of the crystalline basement; in the Neoproterozoic and Paleozoic deposits, it diminishes from 5.15 to 3.80 km/s, and in the Mesozoic layers, it decreases from 2.70 to 2.30 km/s. The sub-crustal Vp gradually increases downwards from 6.50 to 6.7-6.8 km/s at the crustal base, which complicates the problem of separating the middle and lower crust. The Vp velocities above 6.80 km/s have not been revealed even in the lowermost part of the crust, in contrast to the similar profiles in the East European Platform. The Moho is clearly delineated by the velocity contrast of 1.3-1.7 km/s. The alternating pattern of the changes in the Moho depths corresponding to Moho undulations with a wavelength of about 150 km and the amplitude reaching 8 to 17 km is a peculiarity of the velocity model.Peer reviewe

A Model-Based Methodology for Spray-Drying Process Development

Solid amorphous dispersions are frequently used to improve the solubility and, thus, the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Spray-drying, a well-characterized pharmaceutical unit operation, is ideally suited to producing solid amorphous dispersions due to its rapid drying kinetics. This paper describes a novel flowchart methodology based on fundamental engineering models and state-of-the-art process characterization techniques that ensure that spray-drying process development and scale-up are efficient and require minimal time and API. This methodology offers substantive advantages over traditional process-development methods, which are often empirical and require large quantities of API and long development times. This approach is also in alignment with the current guidance on Pharmaceutical Development Q8(R1). The methodology is used from early formulation-screening activities (involving milligrams of API) through process development and scale-up for early clinical supplies (involving kilograms of API) to commercial manufacturing (involving metric tons of API). It has been used to progress numerous spray-dried dispersion formulations, increasing bioavailability of formulations at preclinical through commercial scales

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

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