Correctors Rescue CFTR Mutations in Nucleotide‐Binding Domain 1 (NBD1) by Modulating Proteostasis

We evaluated whether small molecule correctors could rescue four nucleotide‐binding domain 1 (NBD1) mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (A455E, S492F, ΔI507, and R560T). We first transfected Cos‐7 cells (green monkey kidney cells) with A455E, S492F, ΔI507, or R560T and created HEK‐293 (human embryonic kidney cells) cell lines stably expressing these CFTR mutations. The mutants showed lowered protein expression, instability at physiological temperature, and rapid degradation. After treatment with correctors CFFT‐002, CFFT‐003, C3, C4, and/or C18, the combination of C18+C4 showed the most correction and resulted in increased CFTR residing in the plasma membrane. We found a profound decrease in binding of CFTR to histone deacetylases (HDAC) 6 and 7 and heat shock proteins (Hsps) 27 and 40. Silencing Hsp27 or 40 rescued the mutants, but no additional amount of CFTR was rescued when both proteins were knocked down simultaneously. Thus, CFTR mutations in NBD1 can be rescued by a combination of correctors, and the treatment alters the interaction between mutated CFTR and the endoplasmic reticulum machinery.     

N‐acetylcysteine may improve residual renal function in hemodialysis patients: A pilot study

Clinical outcomes in chronic dialysis patients are highly dependent on preservation of residual renal function (RRF). N‐acetylcysteine (NAC) may have a positive effect on renal function in the setting of nephrotoxic contrast media administration. In our recent study, we showed that NAC may improve RRF in peritoneal dialysis patients. The aim of the present study was to investigate the effect of NAC on RRF in patients treated with chronic hemodialysis. Prevalent chronic hemodialysis patients with a residual urine output of at least 100 mL/24 hours were included. The patients were administered oral NAC 1200 mg twice daily for 2 weeks. Residual renal function was assessed at baseline and at the end of treatment using a midweek interdialytic urine collection for measurement of urine output and calculation of residual renal Kt/V and glomerular filtration rate (GFR). Residual GFR was measured as the mean of urea and creatinine residual renal clearance. Each patient served as his own control. Twenty patients were prospectively enrolled in the study. Administration of NAC 1200 mg twice daily for 2 weeks resulted in significant improvement in RRF: urine volume increased from 320 ± 199 to 430 ± 232 mL/24 hours (P < 0.01), residual renal Kt/V increased from 0.19 ± 0.12 to 0.29 ± 0.14 (P < 0.01), and residual GFR increased from 1.6 ± 1.6 to 2.4 ± 2.3 mL/minute/1.73 m² (P < 0.01). N‐acetylcysteine may improve RRF in patients treated with chronic hemodialysis.     

Flux crystal growth of Ba2[(UO2)2Ti2O8]: Structures,spectroscopies and implications

We report a flux crystal growth of Ba₂[(UO₂)₂Ti₂O₈] and subsequent structural and spectroscopic studies using multiple techniques. The layered crystal structure, built up with sheets of edge-sharing dimeric uranyl pentagonal bipyramids and dimeric TiO₅ square pyramids with interlayer Ba(II) ions, was revealed by synchrotron single crystal x-ray diffraction and confirmed with electron diffraction using a transmission electron microscope. The presence of only hexavalent uranium was confirmed by both diffuse reflectance and x-ray absorption near-edge structure spectroscopies, consistent with the bond valence sum calculations. Its vibrational modes were revealed by Raman spectroscopy. In addition, its implications as a potential hexavalent uranium waste form for the immobilization of uranium-rich radioactive wastes were discussed.     

Spatially resolved recording of transient fluorescence‐lifetime effects by line‐scanning TCSPC

We present a technique that records transient changes in the fluorescence lifetime of a sample with spatial resolution along a one‐dimensional scan. The technique is based on scanning the sample with a high‐frequency pulsed laser beam, detecting single photons of the fluorescence light, and building up a photon distribution over the distance along the scan, the arrival times of the photons after the excitation pulses and the time after a stimulation of the sample. The maximum resolution at which lifetime changes can be recorded is given by the line scan period. Transient lifetime effects can thus be resolved at a resolution of about one millisecond. We demonstrate the technique for recording photochemical and nonphotochemical chlorophyll transients in plants and transient changes in free Ca²⁺ in cultured neurons. Microsc. Res. Tech. 77:216–224, 2014. © 2014 Wiley Periodicals, Inc.     

Experimental Analysis of Hydraulic Solver Convergence with Genetic Algorithms

A procedure for the experimental convergence evaluation of a hydraulic-network solver is proposed, based on using genetic algorithms to search for network parameter values that maximize the number of iterations of the hydraulic-network solver under test. The efficiency of the method is demonstrated by the example of convergence evaluation for the EPANET hydraulic simulator. Examples of a pipe network and of combinations of parameter values for which the static solver of the simulator fails to converge in a reasonable number of iterations are given. The features of the EPANET 2.00.12 solver responsible for loss of convergence are discussed. New criteria for the automatic start of solution damping aimed at improving the convergence of the solver are proposed. The better convergence of the EPANET solver modified in accordance with these criteria is confirmed by the random and the proposed search-based testing method.     

Micro-Mechanical Parameters in Short Fibre Composite

The aim of this paper is to analyse the contribution of micro-mechanical parameters, on the macroscopic behaviour of a short fibre reinforced thermoplastic composites (SFRTC). By developing an algorithm to provide a representative random micro-structure, a comparative analysis of different micro-mechanical parameters, such as aspect ratio (AR) and fibre orientation (FO), was conducted and compared with the existing analytical models. A study of different aspect ratios and different fibre orientations has been carried out in order to examine their effect on the linear elastic properties of SFRTC. Aspect ratios from one to ten have been analysed for the cases of fully oriented 0° fibres, miss-oriented fibres and randomly oriented fibres. A representative volume element (RVE) was used to investigate the effect of the representative size. Results were analysed statistically through X ² test, and the subsequent representative realisations were compared with the theoretical predictions.     

The Representative Volume Size in Static and Dynamic Micro-Macro Transitions

Two homogenisation schemes (first-order or local, and second-order or non-local) are employed in this paper. In case second-order homogenisation is applied, it turns out that elastic behaviour at the micro-scale implies the appearance of second-order space and time derivatives of macroscopic strain in an otherwise elastic constitutive equation for the macroscopic stress. The coefficients of the second-order terms scale with the size of the Representative Volume Element (RVE) employed in the homogenisation scheme.     

Construct validity of an attention rating scale for traumatic brain injury.

Attention deficits are nearly ubiquitous after traumatic brain injury (TBI). In the subacute phase of moderate to severe TBI, these deficits may be difficult to measure with the precision needed to predict outcomes, assess degree of recovery, and monitor treatment response. This article reports the findings of four studies, three observational and one a randomized, controlled treatment trial of methylphenidate (MP), designed to provide construct validation of the Moss Attention Rating Scale (MARS), an observational measure of attention dysfunction following TBI. One hundred seven participants with moderate to severe TBI were enrolled during treatment on an inpatient rehabilitation unit. MARS scores were provided independently by four rehabilitation disciplines (Physical, Occupational and Speech Therapies and Nursing). Results indicated that the MARS: (1) is more strongly related to concurrent measures of cognitive versus physical disability, supporting its validity as a measure of cognition, (2) is more strongly related to concurrent psychometric measures of attention versus measures thought to rely less on attention, supporting its validity as a measure of attention; and (3) predicts 1-year outcomes of TBI better than psychometric measures of attention. However, the MARS (4) was not differentially affected by MP versus placebo treatment. Results support the construct validity and utility of the MARS, with further research needed to clarify its role in treatment outcome assessment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Skim Milk Whey Cryoconcentration and Impact on the Composition of the Concentrated and Ice Fractions

The present work is a continuation of our previous study on the cryoconcentration of whole milk whey. The aim of the present work was to study a cryoconcentration procedure of skim milk whey and to compare the results with those obtained using whole milk whey. In the present study, skim whey was cryoconcentrated at four stages. It was found that by increasing the cryoconcentration stage, total dry matter content of the concentrated fraction increased, while it decreased in the ice fraction only until the third stage. Total dry matter content in the concentrated fraction reached an average value of 35% (w/v) at the fourth stage. The ratio of total protein to total dry matter remained constant in both fractions independently of the cryoconcentration stage. Results showed that the fat matter is an important factor for protein and lactose distribution between the concentrated and the ice fractions. Mathematical equations were developed to help the optimization of the process. Results showed that three cryoconcentration stages are optimal.