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Background Long‐QT syndrome (LQTS) is a cardiac repolarization abnormality that can lead to sudden cardiac death. The most common causes are rare coding variants in the genes KCNQ1, KCNH2, and SCN5A. The data on LQTS epidemiology are limited, and information on expressivity and penetrance of pathogenic variants is sparse. Methods and Results We screened for rare coding variants associated with the corrected QT (QTc) interval in Iceland. We explored the frequency of the identified variants, their penetrance, and their association with severe events. Twelve variants were associated with the QTc interval. Five in KCNQ1, 3 in KCNH2, 2 in cardiomyopathy genes MYBPC3 and PKP2, and 2 in genes where coding variants have not been associated with the QTc interval, ISOC1 and MYOM2. The combined carrier frequency of the 8 variants in the previously known LQTS genes was 530 per 100 000 individuals (1:190). p.Tyr315Cys and p.Leu273Phe in KCNQ1 were associated with having a mean QTc interval longer than 500 ms (P=4.2×10−7; odds ratio [OR], 38.6; P=8.4×10−10, OR, 26.5; respectively), and p.Leu273Phe was associated with sudden cardiac death (P=0.0034; OR, 2.99). p.Val215Met in KCNQ1 was carried by 1 in 280 Icelanders, had a smaller effect on the QTc interval (P=1.8×10−44; effect, 22.8 ms), and did not associate with severe clinical events. Conclusions The carrier frequency of associating variants in LQTS genes was higher than previous estimates of the prevalence of LQTS. The variants have variable effects on the QTc interval, and carriers of p.Tyr315Cys and p.Leu273Phe have a more severe disease than carriers of p.Val215Met. These data could lead to improved identification, risk stratification, and a more precise clinical approach to those with QTc prolongation.

The expansion of semi-infinite plasma into vacuum is analyzed with a hydrodynamic model for cold ions assuming electrons modelled by a kappa-type distribution. Similarly to Mora study of a plasma expansion into vacuum [P. Mora, Phys. Rev. Lett. 90, 185002 (2003)], we formulated empirical expressions for the electric field strength, velocity, and position of the ion front in onedimensional nonrelativistic, collisionless isothermally expanding plasma. Analytic expressions for the maximum ion energy and the spectrum of the accelerated ions in the plasma were derived and discussed to highlight the electron nonthermal effects on enhancing the ion acceleration in plasma expansion into vacuum. [ABSTRACT FROM AUTHOR]

The objective of the present research is to evaluate directly compressible chitosan-based tableting materials for the formulation of mucoadhesive matrix tablets intended for targeted drug release to distal segments of the GIT. The influence of sodium alginate, hypromellose, and silicified microcrystalline cellulose (P90) on compressibility, compactability and lubricant sensitivity ratio was tested. Furthermore, the rheological properties of the hydrated surface layer of the matrix tablets and the mucoadhesion to a mucin substrate were analysed. Compressibility was evaluated using the energy profile of the compression process, compactability by means of the tensile strength of tablets, and lubricant sensitivity ratio was calculated to assess the sensitivity to lubricant. Addition of P90 to chitosan improved compressibility, which is demonstrated by the increase in the energy of plastic deformation and the higher tensile strength of tablets. P90 also significantly reduced the high lubricant sensitivity of chitosan. Presence of retarding components led to a decrease in Emax. All tested matrix tablets revealed a good mucoadhesion without a negative effect of P90 content. The viscosity of a gel layer on the surface of matrix tablets containing hypromellose was higher compared to those with sodium alginate. This was not reflected in the adhesive strength of the tablets. The formulated tableting materials combining chitosan and P90 are a suitable matrix for incorporation of an active ingredient, whose delayed release in the intestine can be achieved by the functionality of the chitosan-sodium alginate complex.

The expansion of semi-infinite laser produced plasma into vacuum is analyzed with a hydrodynamic model for cold ions assuming electrons modeled by a kappa-type distribution. Self-similar analytic expressions for the potential, velocity, and density of the plasma have been derived. It is shown that nonthermal energetic electrons have the role of accelerating the self-similar expansion.

Plasma expansion and soliton formation in laser created plasma are addressed. Nonlinear acoustic waves in plasma where the combined effect of trapped and non-thermal electrons are dealt with, in plasma expansion are studied. Using the perturbation method, a modified Korteweg–de Vries equation (mKdV) that describes how the ion acoustic waves (IAW) are derived. The plasma is modeled by a Cairns distribution function for non-thermal electrons combined with Gurevich distribution function for the trapped electrons. It is found that parameters taken into account have significant effects on the properties of nonlinear waves as well as on plasma expansion into vacuum. We point out, that this work has been motivated by space and laboratory plasma observations of plasmas containing energetic particles, combined with trapped particles. Furthermore, this study is of interest in the context of the investigation of mono-energetic ion beams from intense laser interactions with plasmas. [ABSTRACT FROM AUTHOR]

Modulated self-assembly protocols are used to develop facile, HF-free syntheses of the archetypal flexible PCP, MIL-53(Cr), and novel isoreticular analogues MIL-53(Cr)-Br and MIL-53(Cr)-NO 2 . All three PCPs show good SO 2 uptake (298 K, 1 bar) and high chemical stabilities against dry and wet SO 2 . Solid-state photoluminescence spectroscopy indicates all three PCPs exhibit turn-off sensing of SO 2 , in particular MIL-53(Cr)-Br, which shows a 2.7-fold decrease in emission on exposure to SO 2 at room temperature, indicating potential sensing applications.

Porosity and surface area analysis play a prominent role in modern materials science. At the heart of this sits the Brunauer-Emmett-Teller (BET) theory, which has been a remarkably successful contribution to the field of materials science. The BET method was developed in the 1930s for open surfaces but is now the most widely used metric for the estimation of surface areas of micro- and mesoporous materials. Despite its widespread use, the calculation of BET surface areas causes a spread in reported areas, resulting in reproducibility problems in both academia and industry. To prove this, for this analysis, 18 already-measured raw adsorption isotherms were provided to sixty-one labs, who were asked to calculate the corresponding BET areas. This round-robin exercise resulted in a wide range of values. Here, the reproducibility of BET area determination from identical isotherms is demonstrated to be a largely ignored issue, raising critical concerns over the reliability of reported BET areas. To solve this major issue, a new computational approach to accurately and systematically determine the BET area of nanoporous materials is developed. The software, called "BET surface identification" (BETSI), expands on the well-known Rouquerol criteria and makes an unambiguous BET area assignment possible., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

The synthesis of phase pure metal-organic frameworks (MOFs) - network solids of metal clusters connected by organic linkers - is often complicated by the possibility of forming multiple diverse phases from one metal-ligand combination. For example, there are at least six Fe-terephthalate MOFs reported to date, with many examples in the literature of erroneous assignment of phase based on diffraction data alone. Herein, we show that modulated self-assembly can be used to influence the kinetics of self-assembly of Fe-terephthalate MOFs. We comprehensively assess the effect of addition of both coordinating modulators and pH modulators on the outcome of syntheses, as well as probing the influence of the oxidation state of the Fe precursor (oxidation modulation) and the role of the counteranion on the phase(s) formed. In doing so, we shed light on the thermodynamic landscape of this phase system, uncover mechanistics of modulation, provide robust routes to phase pure materials, often as single crystals, and introduce two new Fe-terephthalate MOFs to an already complex system. The results highlight the potential of modulated self-assembly to bring precision control and new structural diversity to systems that have already received significant study.

Phase control in the self-assembly of metal-organic frameworks (MOFs) is often a case of trial and error; judicious control over a number of synthetic variables is required to select the desired topology and control features such as interpenetration and defectivity. Herein, we present a comprehensive investigation of self-assembly in the Fe-biphenyl-4,4'-dicarboxylate system, demonstrating that coordination modulation can reliably tune between the kinetic product, noninterpenetrated MIL-88D(Fe), and the thermodynamic product, two-fold interpenetrated MIL-126(Fe). Density functional theory simulations reveal that correlated disorder of the terminal anions on the metal clusters results in hydrogen bonding between adjacent nets in the interpenetrated phase and this is the thermodynamic driving force for its formation. Coordination modulation slows self-assembly and therefore selects the thermodynamic product MIL-126(Fe), while offering fine control over defectivity, inducing mesoporosity, but electron microscopy shows MIL-88D(Fe) persists in many samples despite not being evident by diffraction. Interpenetration control is also demonstrated using the 2,2'-bipyridine-5,5'-dicarboxylate linker; it is energetically prohibitive for it to adopt the twisted conformation required to form the interpenetrated phase, although multiple alternative phases are identified due to additional coordination of Fe cations to its N donors. Finally, we introduce oxidation modulation-the use of metal precursors in different oxidation states from that found in the final MOF-to kinetically control self-assembly. Combining coordination and oxidation modulation allows the synthesis of pristine MIL-126(Fe) with BET surface areas close to the predicted maximum for the first time, suggesting that combining the two may be a powerful methodology for the controlled self-assembly of high-valent MOFs.

The pituitaries and adrenals of 30 patients died from extensive fresh myocardial infarction and of 25 patients died from other diseases were studied. In myocardial infarction the mean weight of the above glands was significantly higher than in other diseases. In most cases an increase in number of pituitary ACTH-cells was observed with the immunoperoxidase method. In non-cardiogenic shock (another 9 cases) gland weight was also increased but without a significant increase in the number of ACTH-cells. Hyperactivity of the anterior pituitary-adrenal system is due to a number of known factors. It may be assumed that patients who have infarction are either exposed to an extraordinary amount of stress stimuli or are more susceptible to stress than normal subjects. The findings may indicate the morphological basis of this situation. Of the shock phenomena, incomplete necrosis and haemorrhage of the adrenal cortex are frequent. In the pituitary neural lobe the neurosecretory material, which proved to be vasopressin with the PAP-method, was found to be increased more frequently in myocardial infarction than after other diseases.

In cortex, habenular- or hypothalamic regions of white rats electrocoagulation was carried out. Animals were killed from 6 days to 5 months after the operation. Serial slides of the brain were investigated by the aid of a reaction of SDH, alfa-GPDH, LDH, G6PDH, TPND. Group of neurons around the lesion may show a decreased, normal and increased activity of the enzymes investigated. As for the far effect of the lesion in case of the injury of the postcomissural fornix changes could have to be revealed in the corpus mamillare. Activization of neuroglia is marked by the increase of the reaction of G6PDH, LDH and TPNDH. Enzyme activity of cells of microglial origin at the beginning seems to be significant, later on, when the activity of phagocytes comes to the end it decreases to the minimum. Regeneration of cells of the leptomeninges and their role in demarcation of the process is marked by the increase of enzyme activity.

A single-approximately LD50-dosis of the 3-AP given to white rats following the unilateral ligature of the carotid artery in almost 70 percent of the animals caused hydropic-vacuolic degeneration and cell necrosis in the nucleus ruber. Similar changes were quite infrequent in the mesenphalic nuclei. The regressiv changes can be prevented by nicotinamid. When smaller doses are given they do not occur at all. Electronmicroscopic findings help to explain some aspects of the pathogenesis of these rather selective changes.

Imprints of haematoxilin-eosin and Giemsa-stained, 33 surgically removed different intracranial tumors were examined. In case of sufficient number of cells and adequate clinical data, the cytological examination was suitable to quick intraoperative diagnosis in majority of cases. Its demonstration on GFAP smear facilitates the diagnosing of gliomas.