A Recessive Mutation Resulting in a Disabling Amino Acid Substitution (T194R) in the LHX3 Homeodomain Causes Combined Pituitary Hormone Deficiency

Background/Aims: Recessive mutations in the LHX3 homeodomain transcription factor gene are associated with developmental disorders affecting the pituitary and nervous system. We describe pediatric patients with combined pituitary hormone deficiency (CPHD) who harbor a novel mutation in LHX3. Methods: Two female siblings from related parents were examined. Both patients had neonatal complications. The index patient had CPHD featuring deficiencies of GH, LH, FSH, PRL, and TSH, with later onset of ACTH deficiency. She also had a hypoplastic anterior pituitary, respiratory distress, hearing impairment, and limited neck rotation. The LHX3 gene was sequenced and the biochemical properties of the predicted altered proteins were characterized. Results: A novel homozygous mutation predicted to change amino acid 194 from threonine to arginine (T194R) was detected in both patients. This amino acid is conserved in the DNA-binding homeodomain. Computer modeling predicted that the T194R change would alter the homeodomain structure. The T194R protein did not bind tested LHX3 DNA recognition sites and did not activate the a-glycoprotein and PRL target genes. Conclusion: The T194R mutation affects a critical residue in the LHX3 protein. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in the LHX3 gene. copyright (C) 2012 S. Karger AG, Base

Assessing streams in Germany with benthic invertebrates: development of a practical standardised protocol for macroinvertebrate sampling and sorting

AbstractIn the past, no single standardised method for sampling and sorting benthic macroinvertebrates has been implemented in Germany. Therefore, we tested the suitability of two common sorting protocols, RIVPACS and AQEM/STAR, by taking samples with each protocol at 44 sampling sites. Our results reveal that different methods deliver slightly different assessment results. Moreover these two methods differ in costs. Although the AQEM/STAR protocol takes longer than the RIVPACS protocol, we favoured the AQEM/STAR protocol because of its higher level of standardisation. In order to limit costs to an acceptable level, a modification of the AQEM/STAR protocol (MAS method) is developed. This method is highly standardised, gives stable assessment results and is relatively inexpensive (€ 224.00 for processing of an average sample). A detailed protocol of the newly developed method is given

Comparison of computational codes for direct numerical simulations of turbulent Rayleigh-B\'enard convection

Computational codes for direct numerical simulations of Rayleigh-B\'enard (RB) convection are compared in terms of computational cost and quality of the solution. As a benchmark case, RB convection at $Ra=10^8$ and $Pr=1$ in a periodic domain, in cubic and cylindrical containers is considered. A dedicated second-order finite-difference code (AFID/RBflow) and a specialized fourth-order finite-volume code (Goldfish) are compared with a general purpose finite-volume approach (OpenFOAM) and a general purpose spectral-element code (Nek5000). Reassuringly, all codes provide predictions of the average heat transfer that converge to the same values. The computational costs, however, are found to differ considerably. The specialized codes AFID/RBflow and Goldfish are found to excel in efficiency, outperforming the general purpose flow solvers Nek5000 and OpenFOAM by an order of magnitude with an error on the Nusselt number $Nu$ below $5\%$. However, we find that $Nu$ alone is not sufficient to assess the quality of the numerical results: in fact, instantaneous snapshots of the temperature field from a near wall region obtained for deliberately under-resolved simulations using Nek5000 clearly indicate inadequate flow resolution even when $Nu$ is converged. Overall, dedicated special purpose codes for RB convection are found to be more efficient than general purpose codes.Comment: 12 pages, 5 figure

MRP8 and MRP14, phagocyte-specific danger signals, are sensitive biomarkers of disease activity in cryopyrin-associated periodic syndromes

To assess the sensitivity of the phagocyte-specific molecules myeloid-related protein (MRP) 8 and MRP14 (calprotectin) for monitoring disease activity during anti-interleukin (IL)-1 therapies in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular (CINCA) syndrome

Influence of Solder Pads to PERC Solar Cells for Module Integration

AbstractThe majority of screen printed solar cells has silver pads at the rear side to enable soldering for the module manufacturing. The pads increase the recombination at the silicon/metal interface due to the absence of a back surface field (BSF) at the solder pads. This reduces the efficiency of full-area Al-BSF solar cells. For passivated emitter and rear cells (PERC), a large area fraction of the rear side is covered with the passivation layer. When using specially designed Ag pastes for the rear side of PERC cells, the passivation of this layer is maintained, and the rear recombination is reduced.A comparison of solar cells with and without solder pads confirms that there is no loss in solar cell performance, both cell types achieve an efficiency of 19.6%. We investigate the influence of solder pads to PERC solar cells by calculating the effective rear surface recombination. The calculations confirm that there is a loss in open circuit voltage of less than 2mV due to the solder pads.A 54-cell PERC PV module is manufactured. The cell-to-module loss reveals that the module process is still to be optimized. Comparable modules made from 9 solar cells lost less than 1% relative in all J-V parameters after a 1000h damp-heat test

Lung disease caused by ABCA3 mutations

Background Knowledge about the clinical spectrum of lung disease caused by variations in the ATP binding cassette subfamily A member 3 (ABCA3) gene is limited. Here we describe genotype-phenotype correlations in a European cohort. Methods We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015. Results Of 22 homozygous (15 male) and 18 compound heterozygous patients (3 male), 37 presented with neonatal respiratory distress syndrome as term babies. At follow-up, two major phenotypes are documented: patients with (1) early lethal mutations subdivided into (1a) dying within the first 6 months or (1b) before the age of 5 years, and (2) patients with prolonged survival into childhood, adolescence or adulthood. Patients with null/null mutations predicting complete ABCA3 deficiency died within the 1st weeks to months of life, while those with null/other or other/other mutations had a more variable presentation and outcome. Treatment with exogenous surfactant, systemic steroids, hydroxychloroquine and whole lung lavages had apparent but many times transient effects in individual subjects. Conclusions Overall long-term (>5 years) survival of subjects with two disease-causing ABCA3 mutations was <20%. Response to therapies needs to be ascertained in randomised controlled trials

Proof of infectivity of hepatitis E virus particles from the ejaculate of chronically infected patients

Recently, hepatitis E virus (HEV, Paslahepevirus balayani) particles were detected for the first time in the ejaculate of two chronically infected patients. Since then, we have been able to detect HEV in ejaculate in five further patients, and thus in a total of seven out of nine (78%) chronically infected men (age 36–67 years, median 56 years). In five patients, the HEV RNA concentration was more than 100-fold higher compared to the serum, while in two patients, the viral load was more than 10-fold lower. However, it has remained unclear whether viral particles shed in the ejaculate were infectious, as a previous cell culture model had failed to demonstrate the infectivity. In the current study, we employed an optimized HEV cell culture system based on overconfluent PLC/PRF/5 cells to investigate the infectivity of HEV particles from ejaculate and other body fluids. With this approach, we were able to show for the first time that HEV particles in the ejaculate from several patients were infectious. HEV replicated to high viral loads of 1e9 HEV RNA copies per ml. This indicates that HEV-positive ejaculate could bear a risk of infection for sexual partners

Prognostic impact of urokinase-type plasminogen activator system components in clear cell renal cell carcinoma patients without distant metastasis

Background Members of the urokinase-type plasminogen activator (uPA) system including uPA, its receptor uPAR and the plasminogen activator inhibitor 1 (PAI-1) play an important role in tumour invasion and progression in a variety of tumour types. Since the majority of clear cell renal cell carcinoma (ccRCC) shows distant metastasis at time of diagnosis or later, the interplay of uPA, uPAR and PAI-1 might be of importance in this process determining the patients’ outcome. Methods Corresponding pairs of malignant and non-malignant renal tissue specimens were obtained from 112 ccRCC patients without distant metastasis who underwent tumour nephrectomy. Tissue extracts prepared from fresh-frozen tissue samples by detergent extraction were used for the determination of antigen levels of uPA, uPAR and PAI-1 by ELISA. Antigen levels were normalised to protein concentrations and expressed as ng per mg of total protein. Results Antigen levels of uPA, uPAR, and PAI-1 correlated with each other in the malignant tissue specimens (rs=0.51-0.65; all P<0.001). Antigen levels of uPA system components were significantly higher in tissue extracts of non-organ confined tumours (pT3+4) compared to organ-confined tumours (pT1+2; all P<0.05). Significantly elevated levels of uPAR and PAI-1 were also observed in high grade ccRCC. When using median antigen levels as cut-off points, all three uPA system factors were significant predictors for disease-specific survival (DSS) in univariate Cox’s regression analyses. High levels of uPA and uPAR remained independent predictors for DSS with HR=2.86 (95% CI 1.07-7.67, P=0.037) and HR=4.70 (95% CI 1.51-14.6, P=0.008), respectively, in multivariate Cox’s regression analyses. A combination of high antigen levels of uPA and/or uPAR further improved the prediction of DSS in multivariate analysis (HR=14.5, 95% CI 1.88-111.1, P=0.010). Moreover, high uPA and/or uPAR levels defined a patient subgroup of high risk for tumour-related death in ccRCC patients with organ-confined disease (pT1+2) (HR=9.83, 95% CI 1.21-79.6, P=0.032). Conclusions High levels of uPA and uPAR in tumour tissue extracts are associated with a significantly shorter DSS of ccRCC patients without distant metastases