A Laboratory Test Setup for in Situ Measurements of the Dielectric Properties of Catalyst Powder Samples under Reaction Conditions by Microwave Cavity Perturbation : Set up and Initial Tests

The catalytic behavior of zeolite catalysts for the ammonia-based selective catalytic reduction (SCR) of nitrogen oxides (NOX) depends strongly on the type of zeolite material. An essential precondition for SCR is a previous ammonia gas adsorption that occurs on acidic sites of the zeolite. In order to understand and develop SCR active materials, it is crucial to know the amount of sorbed ammonia under reaction conditions. To support classical temperature-programmed desorption (TPD) experiments, a correlation of the dielectric properties with the catalytic properties and the ammonia sorption under reaction conditions appears promising. In this work, a laboratory test setup, which enables direct measurements of the dielectric properties of catalytic powder samples under a defined gas atmosphere and temperature by microwave cavity perturbation, has been developed. Based on previous investigations and computational simulations, a resonator cavity and a heating system were designed, installed and characterized. The resonator cavity is designed to operate in its TM010 mode at 1.2 GHz. The first measurement of the ammonia loading of an H-ZSM-5 zeolite confirmed the operating performance of the test setup at constant temperatures of up to 300 °C. It showed how both real and imaginary parts of the relative complex permittivity are strongly correlated with the mass of stored ammonia

Analysis of the Proteolytic Processing of ABCA3: Identification of Cleavage Site and Involved Proteases

Rationale ABCA3 is a lipid transporter in the limiting membrane of lamellar bodies in alveolar type II cells. Mutations in the ABCA3 gene cause respiratory distress syndrome in new-borns and childhood interstitial lung disease. ABCA3 is N-terminally cleaved by an as yet unknown protease, a process believed to regulate ABCA3 activity. Methods The exact site where ABCA3 is cleaved was localized using mass spectrometry (MS). Proteases involved in ABCA3 processing were identified using small molecule inhibitors and siRNA mediated gene knockdown. Results were verified by in vitro digestion of a synthetic peptide substrate mimicking ABCA3's cleavage region, followed by MS analysis. Results We found that cleavage of ABCA3 occurs after Lys174 which is located in the proteins' first luminal loop. Inhibition of cathepsin L and, to a lesser extent, cathepsin B resulted in attenuation of ABCA3 cleavage. Both enzymes showed activity against the ABCA3 peptide in vitro with cathepsin L being more active. Conclusion We show here that, like some other proteins of the lysosomal membrane, ABCA3 is a substrate of cathepsin L. Therefore, cathepsin L may represent a potential target to therapeutically influence ABCA3 activity in ABCA3-associated lung disease

The Health Initiative Program for Kids (HIP Kids): Effects of a 1-Year Multidisciplinary Lifestyle Intervention on Adiposity and Quality of Life in Obese Children and Adolescents -- A Longitudinal Pilot Intervention Study

BACKGROUND: Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents. METHODS: Obese children and adolescents 8-17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted of fifteen 90-minute educational sessions led by a dietitian, exercise specialist, and social worker. Anthropometric measures, body composition, and QoL (Pediatric Quality of Life Inventory 4.0), were assessed at baseline, 3 months, and 12 months. Laboratory values were measured at baseline and 12 months. The primary outcome measures were change in BMI and BMI z-score, secondary outcome measures included change in QoL and body composition. A paired sample t-test was used to assess within-group differences and 95% confidence intervals were reported for the mean differences. RESULTS: 42 obese children and adolescents (21 girls) completed the 1-year intervention (mean age 12.8 ± 3.14 years). Mean baseline BMI was 31.96 ± 5.94 kg/m(2) and BMI z-score was +2.19 ± 0.34. Baseline QoL (self-assessments and parental assessments) was impaired: mean baseline scores were 74.5 ± 16.5 and 63.7 ± 19.4 for physical functioning and 69.0 ± 14.9 and 64.0 ± 18.3 for emotional functioning, respectively. At 12 months, BMI z-score had decreased (-0.07 ± 0.11, 95% CI: -0.11 to -0.04). BMI (0.80 ± 1.57 kg/m(2), 95% CI 0.31 to 1.29) and fat-free mass (4.02 ± 6.27 kg, 95% CI 1.90 to 6.14) increased, but % body fat and waist circumference did not. Both the parent-reported physical (11.3 ± 19.2, 95% CI 4.7 to 17.9) and emotional (7.7 ± 15.7, 95% CI 2.3 to 13.0) functioning QoL scores and the children\u27s self-reported physical (5.3 ± 17.1, 95% CI 0.5 to 11.1) and emotional (7.9 ± 14.3, 95% CI 3.2 to 12.7) functioning scores significantly improved. CONCLUSIONS: Following a 1-year intervention, the participants\u27 BMI z-scores and QoL improved, while other adiposity-related measures of body composition remained unchanged. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000015622

Limbostomy: Longitudinal Intravital Microendoscopy in Murine Osteotomies

Bone healing involves the interplay of immune cells, mesenchymal cells, and vasculature over the time course of regeneration. Approaches to quantify the spatiotemporal aspects of bone healing at cellular resolution during long bone healing do not yet exist. Here, a novel technique termed Limbostomy is presented, which combines intravital microendoscopy with an osteotomy. This design allows a modular combination of an internal fixator plate with a gradient refractive index (GRIN) lens at various depths in the bone marrow and can be combined with a surgical osteotomy procedure. The field of view (FOV) covers a significant area of the fracture gap and allows monitoring cellular processes in vivo. The GRIN lens causes intrinsic optical aberrations which have to be corrected. The optical system was characterized and a postprocessing algorithm was developed. It corrects for wave front aberration-induced image plane deformation and for background and noise signals, enabling us to observe subcellular processes. Exemplarily, we quantitatively and qualitatively analyze angiogenesis in bone regeneration. We make use of a transgenic reporter mouse strain with nucleargreen fluorescent protein and membrane-bound tdTomato under the Cadherin-5 promoter. We observe two phases of vascularization. First, rapid vessel sprouting pervades the FOV within 3-4 days after osteotomy. Second, the vessel network continues to be dynamically remodeled until the end of our observation time, 14 days after surgery. Limbostomy opens a unique set of opportunities and allows further insight on spatiotemporal aspects of bone marrow biology, for example, hematopoiesis, analysis of cellular niches, immunological memory, and vascularization in the bone marrow during health and disease

HETDEX pilot survey for emission-line galaxies - I. Survey design, performance, and catalog

We present a catalog of emission-line galaxies selected solely by their emission-line fluxes using a wide-field integral field spectrograph. This work is partially motivated as a pilot survey for the upcoming Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). We describe the observations, reductions, detections, redshift classifications, line fluxes, and counterpart information for 397 emission-line galaxies detected over 169 sq.arcmin with a 3500-5800 Ang. bandpass under 5 Ang. full-width-half-maximum (FWHM) spectral resolution. The survey's best sensitivity for unresolved objects under photometric conditions is between 4-20 E-17 erg/s/sq.cm depending on the wavelength, and Ly-alpha luminosities between 3-6 E42 erg/s are detectable. This survey method complements narrowband and color-selection techniques in the search for high redshift galaxies with its different selection properties and large volume probed. The four survey fields within the COSMOS, GOODS-N, MUNICS, and XMM-LSS areas are rich with existing, complementary data. We find 104 galaxies via their high redshift Ly-alpha emission at 1.9<z<3.8, and the majority of the remainder objects are low redshift [OII]3727 emitters at z<0.56. The classification between low and high redshift objects depends on rest frame equivalent width, as well as other indicators, where available. Based on matches to X-ray catalogs, the active galactic nuclei (AGN) fraction amongst the Ly-alpha emitters (LAEs) is 6%. We also analyze the survey's completeness and contamination properties through simulations. We find five high-z, highly-significant, resolved objects with full-width-half-maximum sizes >44 sq.arcsec which appear to be extended Ly-alpha nebulae. We also find three high-z objects with rest frame Ly-alpha equivalent widths above the level believed to be achievable with normal star formation, EW(rest)>240 Ang.Comment: 45 pages, 36 figures, 5 tables, submitted to ApJ

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

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Berufliche Rehabilitation: Fakten - Analysen - Entwicklungstendenzen; Evaluation von Leistungen zur Teilhabe behinderter Menschen am Arbeitsleben; Zwischenbericht

Die Leistungen zur Teilhabe behinderter Menschen am Arbeitsleben in den Bereichen der Arbeitsförderung und der Grundsicherung für Arbeitsuchende sind eine bedeutende Komponente der Arbeitsmarktpolitik. Mit der mehrstufig angelegten Evaluation von Leistungen zur Teilhabe behinderter Menschen am Arbeitsleben sollen Ansatzpunkte für die Optimierung der praktischen Umsetzung und die Fortentwicklung des rechtlichen Rahmens dieser Leistungen ermittelt werden. Bislang wurden drei Forschungsmodule durchgeführt. Deren Ergebnisse werden mit dem hier vorliegenden Bericht veröffentlicht. Inhaltsverzeichnis: Teil A: Basisstudie zur Evaluation von Leistungen zur Teilhabe behinderter Menschen am Arbeitsleben; Zusammenfassender Bericht. Teil B: Implementationsstudie 1 zur Evaluation von Leistungen zur Teilhabe behinderter Menschen am Arbeitsleben; Zusammenfassender Bericht. Teil C: Beratung zu wirkungsanalytischen Ansätzen für die Evaluation von Leistungen zur Teilhabe behinderter Menschen am Arbeitsleben: Zusammenfassender Bericht