Concurrent TNFRSF1A R92Q and pyrin E230K mutations in a child with multiple sclerosis

We report a 16-year-old female patient with a severe course of multiple sclerosis and concomitant symptoms suggestive of a hereditary autoinflammatory disease. Genetic analyses revealed that she inherited a TNFRSF1A R92Q mutation from her mother and a pyrin E230K mutation from her father. To our knowledge, this is the first report of a patient with severe childhood multiple sclerosis and mutations in two genes which predispose to hereditary autoinflammatory disorders. We speculate that these mutations contribute to early multiple sclerosis manifestation and enhance the inflammatory damage inflicted by the autoimmune response

First generation of optical fiber phase reference distribution system for TESLA

This report describes the design of a phase stable Fiber Optic (FO) link for the TESLA technology based projects. The concept of this long optical link, with a feedback system suppressing long term drifts of the RF signal phase is described. Stability requirements are given and most important design issues affecting the system performance are discussed. The technical design issues of system components like laser transmitter and optical phase shifter are described in detail. Last sections depict the software developed for system control and experimental results obtained after system was assembled

Research on the properties of binary liquid metal systems with lithium as one component - The electrical resistivity of liquid lithium saturated with cesium Final report

Electrical resistivity of liquid lithium saturated with cesiu

Comment on "Giant absorption cross section of ultracold neutrons in Gadolinium"

Rauch et al (PRL 83, 4955, 1999) have compared their measurements of the Gd cross section for Ultra-cold neutrons with an exptrapolation of the cross section for thermal neutrons and interpreted the discrepancy in terms of coherence properties of the neutron. We show the extrapolation used is based on a misunderstanding and that coherence properties play no role in absorption.Comment: 2 pages, 1 postscript figure, comment on Rauch et al, PRL 83,4955 (1999

Nuclear export factor RBM15 facilitates the access of DBP5 to mRNA

The conserved mRNA export receptor NXF1 (Mex67 in yeast) assembles with messenger ribonucleoproteins (mRNP) in the nucleus and guides them through the nuclear pore complex into the cytoplasm. The DEAD family RNA helicase Dbp5 is essential for nuclear export of mRNA and is thought to dissociate Mex67 from mRNP upon translocation, thereby generating directional passage. However, the molecular mechanism by which Dbp5 recognizes Mex67-containing mRNP is not clear. Here we report that the human NXF1-binding protein RBM15 binds specifically to human DBP5 and facilitates its direct contact with mRNA in vivo. We found that RBM15 is targeted to the nuclear envelope, where it colocalizes extensively with DBP5 and NXF1. Gene silencing of RBM15 leads to cytoplasmic depletion and nuclear accumulation of general mRNA as well as individual endogenous transcripts, indicating that RBM15 is required for efficient mRNA export. We propose a model in which RBM15 acts locally at the nuclear pore complex, by facilitating the recognition of NXF1–mRNP complexes by DBP5 during translocation, thereby contributing to efficient mRNA export

Primary Care Physician Workforce 2020 to 2025 - a cross-sectional study for the Canton of Bern.

AIM OF THIS STUDY The Swiss primary care sector faces a lack in its workforce and the Canton of Bern - the second largest canton (i.e. federal state) - is believed to be more affected than others. To be able to predict a shortage in the overall workforce, reliable numbers for the workforce of all general practitioners (GPs) and paediatricians (primary care physicians, PCPs) actively working in the Canton of Bern are needed. Switzerland has no registry of active PCPs; therefore, our goal was to (1) define the number and characteristics of all PCPs in the Canton of Bern, (2) to establish the workforce density for the whole canton and its administrative districts, and (3) to forecast the next five years with respect to the PCP workforce development. METHODS In this cross-sectional study, we contacted all potential PCPs of the Canton of Bern. We included all board-certified physicians in general internal medicine, paediatrics and physicians with the title "Praktischer Arzt (practical doctor)" with a professional license from the available registers (MedReg and the FMH register). All potential PCPs received a questionnaire to assess their involvement in the primary care setting, their personal characteristics including workload (current and in 5 years to allow us to estimate the projected workforce per projected population size in 2025), type of practice, administrative district, and additional questions on their acceptance of new patients and their perception of a shortage in their region. The data from non-responders were collected via follow-up letters, emails and phone calls. The density was calculated as full-time equivalent PCPs per 1000 inhabitants in total and per district. RESULTS From all potential PCPs (n = 2217), we identified 972  working in the Canton of Bern, 851 as GPs (88%) and 121 as paediatricians (12%). From these physicians, we had a response rate of 95%. The mean age was 53 years for GPs and 50 years for paediatricians. Thirteen percent of all PCPs were aged 65 or older. The average workload was 7.6 half-days (GPs) and 6.9 half-days (paediatricians). We found a density of 0.75 (95% confidence interval [CI] 0.69-0.81) full-time equivalents per 1000 inhabitants for the total of the Canton of Bern, and a regional variability with densities between 0.59 to 0.93. Without new PCPs, the workforce density of PCPs will drop to 0.56 (95% CI 0.49-0.62) within the next 5years. CONCLUSION This is the first study in which 95% of active PCPs participated and it demonstrated that within the next 5 years there will be a shortage in the workforce of PCPs that can only be improved by higher numbers of new domestic PCPs - even after accounting for the current inflow of foreign PCPs

Identification and characterization of the mouse nuclear export factor (Nxf) family members

TAP/hNXF1 is a key factor that mediates general cellular mRNA export from the nucleus, and its orthologs are structurally and functionally conserved from yeast to humans. Metazoans encode additional proteins that share homology and domain organization with TAP/hNXF1, suggesting their participation in mRNA metabolism; however, the precise role(s) of these proteins is not well understood. Here, we found that the human mRNA export factor hNXF2 is specifically expressed in the brain, suggesting a brain-specific role in mRNA metabolism. To address the roles of additional NXF factors, we have identified and characterized the two Nxf genes, Nxf2 and Nxf7, which together with the TAP/hNXF1's ortholog Nxf1 comprise the murine Nxf family. Both mNXF2 and mNXF7 have a domain structure typical of the NXF family. We found that mNXF2 protein is expressed during mouse brain development. Similar to TAP/hNXF1, the mNXF2 protein is found in the nucleus, the nuclear envelope and cytoplasm, and is an active mRNA export receptor. In contrast, mNXF7 localizes exclusively to cytoplasmic granules and, despite its overall conserved sequence, lacks mRNA export activity. We concluded that mNXF2 is an active mRNA export receptor similar to the prototype TAP/hNXF1, whereas mNXF7 may have a more specialized role in the cytoplasm

Comparison of carbohydrate utilization in man using indirect calorimetry and mass spectrometry after an oral load of 100 g naturally-labelled [13C]glucose

1. Carbohydrate (CHO) oxidation was measured simultaneously in a group of five normal subjects after an oral load of 100 g naturally-labelled [13C]glucose, using indirect calorimetry and mass spectrometry. 2. CHO utilization, calculated from the results of indirect calorimetry, increased 30 min after the glucose load to reach a peak at 90 min. It then decreased to reach basal values at 380 min. Cumulative total CHO oxidation at 480 min was 83±8g, and CHO oxidized above basal levels, 37±3 g. 3. Enrichment of expired carbon dioxide with 13C began at 60 min and maximum values were observed at 270 min. At 480 min, cumulative CHO oxidation measured by use of [13C]glucose was 29 g. The difference from calorimetric values can be attributed in part to the slow isotopic dilution in the glucose and bicarbonate pools. 4. Thus, approximately 30% of the glucose load was oxidized during the 8 h after its ingestion and this accounts for a significant part of the increased CHO oxidation (37 g), as measured by indirect calorimetr