Silver-Russell syndrome (SRS) is a heterogeneous disorder associated with intrauterine and postnatal growth restriction, body asymmetry, a relative macrocephaly, a characteristic triangular face and ...further dysmorphisms. In about 50% of patients, genetic/epigenetic alterations can be detected: >38% of patients show a hypomethylation of the IGF2/H19 imprinting region in 11p15, whereas the additional 10% carry a maternal uniparental disomy of chromosome 7. In single cases, cytogenetic aberrations can be detected. Nevertheless, there still remain 50% of SRS patients without known genetic/epigenetic alterations. To find out whether submicroscopic imbalances contribute to the aetiology of SRS, 20 idiopathic SRS patients were screened with the Affymetrix GeneChip Human Mapping 500 K array set. Apart from known apathogenic copy number variations, we identified one patient with a 12q14 microdeletion. The 12q14 microdeletion syndrome is characterised by dwarfism but it additionally includes mental retardation and osteopoikilosis. The deletion in our patient is smaller than those in the 12q14 microdeletion carriers but it also affects the LEMD3 and the HMGA2 genes. LEMD3 haploinsufficiency and point mutations have been previously associated with osteopoikilosis but radiographs of our patient at the age of 16 years did not reveal any hint for osteopoikilosis lesions. Haploinsufficiency of HMGA2 is probably responsible for aberrant growth in 12q14 microdeletion syndrome. However, in this study, a general role of HMGA2 mutations for SRS was excluded by sequencing of 20 idiopathic patients. In conclusion, our results exclude a common cryptic chromosomal imbalance in idiopathic SRS patients but show that chromosomal aberrations are relevant in this disease. Thus, molecular karyotyping is indicated in SRS and should be included in the diagnostic algorithm.
Business trends require front-line managers to integrate multiproject concepts with those of traditional single-project management since very rarely can one find major organizations managing just one ...project. A typical situation entails a limited pool of resources which is applied to the management of several projects, with people moving back and forth among different assignments in different projects. Yet, few studies on project management have started to explore the issue of how to manage an organization with multiple inter- or intradepartmental projects. Using a case study method, our exploratory research investigates the specific problems associated with the management of multiple engineering projects in a manufacturing support environment, with the intent to identify common factors of success. Knowing the factors of success is but the first step toward improving multi-project management. Our findings provide insight into how the most important multiple-project success factors in this environment differ from factors of success in traditional single-project management, and are consistent with other emerging research in product development environments. The differences center on resource allocation and flexibility. Some factors, such as ownership, staff experience, and communication, take on additional dimensions when considered in a multiple-versus a single-project environment. Division and assignment of resources, prioritization, and customized management style, which have little relevance in relation to single projects, are shown to play a major role in the success of multiproject management.
Congenital primary hypothyroidism (CH) occurs in 1 of 4000 births. The majority of the cases are due to agenesis or dysgenesis of the thyroid gland, which can be caused by mutations in genes encoding ...for transcriptional factors that are responsible for the development of the thyroid gland. It is also known that the thyrotropin receptor (TSHR), a G-protein coupled receptor, is involved in late stages of thyroid organogenesis. Thus, mutations in the TSHR gene can cause congenital hypothyroidism. However, the clinical spectrum of thyroid abnormalities due to mutant TSHRs is wide and ranges from severe hypoplasia to an almost normal sized and structured thyroid gland. So far, 23 distinct loss-of-function mutations in the TSHR gene have been reported, occurring in families of different ethnic backgrounds and geographical areas. Here we report on a Turkish kindred in which two children were diagnosed to have very mild congenital primary hypothyroidism and one child had subclinical hypothyroidism. A novel homozygous missense mutation in codon 593 (A593 V) of the TSHR gene was identified in the affected individuals as the underlying molecular defect. This mutation substitutes a non-polar amino acid (alanine) with a non-polar amino acid (valine), so that only a minimal impairment of the TSHR function is expected. Indeed, the molecular finding is in agreement with the observed mild phenotype of the affected individuals. Our conclusion is that in mild primary hypothyroidism or subclinical hypothyroidism, mutations in the TSHR gene have to be considered as the molecular cause, especially in patients who have no detectable thyroid autoantibodies and have thyroid glands of normal size and in normal location.
The focus of this study is on the effect of form deviations of a partial journal bearing's sliding surface on the friction force in mixed lubrication conditions. The measured friction varied ...considerably when the bearing was rotated in the opposite direction at the same speed and normal load. This unexpected observation motivated the presented simulation study. The overall form deviations of the surface of the test bearing were measured with white light interferometry and used as simulation input. The two-scale simulation approach considers the effect of the surface roughness on a microscopic and the global bearing geometry with the surface form deviations on a macroscopic scale. Simulation results show that the surface form deviations can have a noticeable effect on the pressure distribution of the lubricant and hence on the size of the asperity contact area which leads to the differences in friction. The influence of the lubricant viscosity, the clearance gap and the surface roughness were analysed in a parametric simulation study. Results show that the clearance and the surface roughness control the impact of the surface form deviations on the friction force. All in all, the results show the necessity to include all scales of surface form deviations in the simulation of journal bearings in a mixed lubrication regime.
Congenital hypothyroidism occurs with a prevalence of approximately 1:3 500. Defects in thyroid hormone synthesis which lead to goitrous hypothyroidism account for 10-15% of these cases. Several ...genetic defects have been characterized and mutations in the thyroid peroxidase (TPO) gene are the most common cause for dyshormonogenesis.So far, more than 80 mutations in the TPO gene have been described, resulting in a variable decrease in TPO bioactivity. Clinically TPO defects manifest with congenital primary goitrous hypothyroidism.We here present 2 children with congenital primary hypothyroidism, who were identified to have compound heterozygous TPO mutations. They both shared the same novel mutation in the TPO gene (C756R) in exon 13. One case presented with an apparently dominant inheritance of thyroid dyshormonogenesis.
Doppler tracking data of three orbiting spacecraft have been reanalyzed to develop a new gravitational field model for the planet Mars, Goddard Mars Model 1 (GMM-1). This model employs nearly all ...available data, consisting of approximately 1100 days of S band tracking data collected by NASA's Deep Space Network from the Mariner 9 and Viking 1 and Viking 2 spacecraft, in seven different orbits, between 1971 and 1979. GMM-1 is complete to spherical harmonic degree and order 50, which corresponds to a half-wavelength spatial resolution of 200-300 km where the data permit. GMM-1 represents satellite orbits with considerably better accuracy than previous Mars gravity models and shows greater resolution of identifiable geological structures. The notable improvement in GMM-1 over previous models is a consequence of several factors: improved computational capabilities, the use of otpimum weighting and least squares collocation solution techniques which stabilized the behavior of the solution at high degree and order, and the use of longer satellite arcs than employed in previous solutions that were made possible by improved force and measurement models. The inclusion of X band tracking data from the 379-km altitude, nnear-polar orbiting Mars Observer spacecraft should provide a significant improvement over GMM-1, particularly at high latitudes where current data poorly resolve the gravitational signature of the planet.
The German study group for quality assurance in pediatric endocrinology and the University of Ulm have established a software ("Hypo Dok") for the documentation of longitudinal data of patients with ...congenital primary hypothyroidism (CH). Aim of this study was to analyse the long-term follow-up of patients with CH and to compare treatment with current guidelines.
Anonymised data of 1,080 patients from 46 centres were statistically analysed.
Newborn screening result was available at a mean age of 7.3 days. Confirmation of the diagnosis was established at 8.4 days and therapy was started at 11 days. The average screening TSH was 180.0 mIU/L. During the first 3 months mean levothyroxine (LT4) dose was 10.7 µg/kg/day or 186.0 µg/m²/day. Weight-, BMI- and height-SDS did not differ significantly from the normal population. Only 25% of the patients (n=262) underwent formal EQ/IQ-testing. Their average IQ was 98.8 ± 13.2 points.
In Germany screening, confirmation and start of treatment of CH are within the recommended time frame of 14 days. Initial LT4-doses are adequate. The auxological longterm outcome of young CH patients is normal. The implementation of standardized IQ testing has to be improved in routine patient care.
Longitudinal data of patients with CH was analysed and compared to current guidelines. Confirmation and start of treatment are according to the recommendations. However standardised IQ testing requires improvement.
This paper describes the setup of a sampling-based ratio bridge for calibrating voltage transformers. The advantage of this ratio method is that voltage transformers with different transformer ratios ...can be easily compared. Initial measurements of the components of the bridge indicate low systematic errors, negligible voltage dependency and low phase errors around 50 / 60 Hz. This indicates an attainable uncertainty of below 2 ppm for the ratio error and \pmb{0.5\ \mu} \mathbf{rad} for the phase displacement of voltage transformers.
All mice were housed, treated and handled under permission and in accordance with the guidelines of the Animal Care Committee of the University of Leipzig and the Regional Board of Animal Care for ...the district of Leipzig (Landesdirektion Sachsen, Leipzig, approval number TVV 55/11). The Animal Care Committee of the University of Leipzig and the Regional Board of Animal Care for the district of Leipzig specifically approved this study. 1.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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