Cryogenic pellet launcher adapted for controlling of tokamak plasma edge instabilities.

One of the main challenges posed recently on pellet launcher systems in fusion-oriented plasma physics is the control of the plasma edge region. Strong energy bursts ejected from the plasma due to edge localized modes (ELMs) can form a severe threat for in-vessel components but can be mitigated by sufficiently frequent triggering of the underlying instabilities using hydrogen isotope pellet injection. However, pellet injection systems developed mainly for the task of ELM control, keeping the unwanted pellet fueling minimized, are still missing. Here, we report on a novel system developed under the premise of its suitability for control and mitigation of plasma edge instabilities. The system is based on the blower gun principle and is capable of combining high repetition rates up to 143 Hz with low pellet velocities. Thus, the flexibility of the accessible injection geometry can be maximized and the pellet size kept low. As a result the new system allows for an enhancement in the tokamak operation as well as for more sophisticated experiments investigating the underlying physics of the plasma edge instabilities. This article reports on the design of the new system, its main operational characteristics as determined in extensive test bed runs, and also its first test at the tokamak experiment ASDEX Upgrade.

Reduction of motion sickness in prehospital trauma care.

Motion sickness adds to the discomfort of many patients being transported by ambulance. Recent research has demonstrated the effectiveness of oxygen therapy in reducing motion sickness during transport to hospital. However, patients reported negative reactions to wearing a facemask, which produced feelings of claustrophobia and anxiety. We therefore tested the hypothesis that supplemental oxygen inhaled from a new oxygen delivery device OxyArm, which avoids direct contact with the patient's skin, may reduce the incidence of motion sickness and increase patient satisfaction. Forty patients suffering from minor trauma were included in a prospective, randomised trial. Twenty patients received oxygen administered using a conventional Venturi mask (group 1), and 20 patients received oxygen using the new OxyArm device (group 2). Measurements made included oxygen saturation (SaO2), heart rate, systolic and diastolic blood pressures, and patients' subjective score of satisfaction with smell of the device, claustrophobia, inconvenience produced by the oxygen inhalation device and nausea were scored using a visual analogue scale. All patients were haemodynamically stable and comparable between the two groups. Peripheral SaO2 increased in both groups. The scores of nausea and claustrophobia were significantly lower in the OxyArm group, in addition, satisfaction with the OxyArm device was significantly higher. In conclusion, the use of OxyArm device produced a lower incidence of motion sickness combined with the additional benefit of greater patient satisfaction, when compared with a conventional facemask, during prehospital transfer of trauma patients.

The kinesin-like motor protein KIF1C occurs in intact cells as a dimer and associates with proteins of the 14-3-3 family.

Proteins of the kinesin superfamily are regulated in their motor activity as well as in their ability to bind to their cargo by carboxyl-terminal associating proteins and phosphorylation. KIF1C, a recently identified member of the KIF1/Unc104 family, was shown to be involved in the retrograde vesicle transport from the Golgi-apparatus to the endoplasmic reticulum. In a yeast two-hybrid screen using the carboxyl-terminal 350 amino acids of KIF1C as a bait, we identified as binding proteins 14-3-3 beta, gamma, epsilon, and zeta. In addition, a clone encoding the carboxyl-terminal 290 amino acids of KIF1C was found, indicating a potential for KIF1C to dimerize. Subsequent transient overexpression experiments showed that KIF1C can dimerize efficiently. However, in untransfected cells, only a small portion of KIF1C was detected as a dimer. The association of 14-3-3 proteins with KIF1C could be confirmed in transient expression systems and in untransfected cells and was dependent on the phosphorylation of serine 1092 located in a consensus binding sequence for 14-3-3 ligands. Serine 1092 was a substrate for the protein kinase casein kinase II in vitro, and inhibition of casein kinase II in cells diminished the association of KIF1C with 14-3-3gamma. Our data thus suggest that KIF1C can form dimers and is associated with proteins of the 14-3-3 family.

Characterization of KIF1C, a new kinesin-like protein involved in vesicle transport from the Golgi apparatus to the endoplasmic reticulum.

Kinesins comprise a large family of microtubule-based motor proteins, of which individual members mediate specific types of motile processes. Using the ezrin domain of the protein-tyrosine phosphatase PTPD1 as a bait in a yeast two-hybrid screen, we identified a new kinesin-like protein, KIF1C. KIF1C represents a member of the Unc104 subfamily of kinesin-like proteins that are involved in the transport of mitochondria or synaptic vesicles in axons. Like its homologues, the 1103-amino acid protein KIF1C consists of an amino-terminal motor domain followed by a U104 domain and probably binds to target membranes through carboxyl-terminal sequences. Interestingly, KIF1C was tyrosine-phosphorylated after peroxovanadate stimulation when overexpressed in 293 or NIH3T3 fibroblasts or in native C2C12 cells. Using immunofluorescence, we found that KIF1C is localized primarily at the Golgi apparatus. In brefeldin A-treated cells, the Golgi membranes and KIF1C redistributed to the endoplasmic reticulum (ER). This brefeldin A-induced flow of Golgi membranes into the ER was inhibited in cells transiently overexpressing catalytically inactive KIF1C. In conclusion, our data suggest an involvement of tyrosine phosphorylation in the regulation of the Golgi to ER membrane flow and describe a new kinesin-like motor protein responsible for this transport.

Human beta 2-glycoprotein I: molecular analysis of DNA and amino acid polymorphism.

In this study, we describe a two-allelic RsaI restriction fragment length polymorphism identified by Southern blot analysis and by allele-specific polymerase chain reaction amplification for the human beta 2-glycoprotein I (beta 2-I; apolipoprotein H = APOH) gene. This polymorphism, which segregates in a co-dominant fashion, leads to a valine-leucine amino acid exchange at amino acid position 247. The allele frequency has been established in 34 unrelated parents of the Centre d'Etude du Polymorphisme Humain family panel and was found to be 0.76 for valine and 0.23 for leucine. The Val-Leu polymorphism described in this study does not correlate with the four isoelectric focusing alleles previously described, indicating that other variants are responsible for this polymorphism.

Norrie disease is caused by mutations in an extracellular protein resembling C-terminal globular domain of mucins.

A candidate gene for Norrie disease, an X-linked disorder characterized by blindness, deafness and mental disturbances, was recently isolated and found to contain microdeletions in numerous patients. No strong homologies were identified. By studying the number and spacing of cysteine residues, we now detect homologies between the Norrie gene product and a C-terminal domain which is common to a group of proteins including mucins. Three newly-characterized missense mutations, replacing evolutionarily conserved cysteines or creating new cysteine codons, emphasize the functional importance of these sites. These findings and the clinical features of this disorder suggest a possible role for the Norrie gene in neuroectodermal cell-cell interaction.

Clostridium homopropionicum sp. nov., a new strict anaerobe growing with 2-, 3-, or 4-hydroxybutyrate.

From anoxic sewage sludge a new strictly anaerobic, spore-forming bacterium was isolated with 2-hydroxybutyrate as sole substrate. 2-, 3-, and 4-hydroxybutyrate, 4-chlorobutyrate, crotonate, vinylacetate, and pyruvate were fermented to acetate and butyrate. Fructose was converted to acetate, butyrate, butanol, and H2. Lactate and acrylate were fermented to acetate and propionate. Cells pregrown with lactate fermented 2-hydroxybutyrate to butyrate, propionate and acetate. No inorganic electron acceptors were reduced. The DNA base ratio was 32.0 +/- 1.0 mol% and was similar to that of Clostridium propionicum, which was determined to be 35.3 +/- 0.5 mol%. Strain LuHBu1 is described as type strain of a new species, Clostridium homopropionicum sp. nov. Another isolate obtained from marine sediment degraded 2- and 3-hydroxybutyrate to acetate and butyrate and was in some respects similar to the known species Ilyobacter polytropus.

Organization, sequence and expression of the HLA-B27 gene: a molecular approach to analyze HLA and disease associations.

Among the numerous autoimmune diseases associated with various HLA alleles, the one with the highest relative risk so far reported has been ankylosing spondylitis with HLA-B27. To examine this relationship more directly, we have cloned the gene encoding the HLA-B27 antigen and determined its complete DNA sequence. Comparison of the HLA-B27 sequence with that of the allelic HLA-B27 shows a high level of homology. Mutations are distributed evenly between exons and introns. Exon 1 and intron 1 are the most divergent ones, and the degree of divergence distinctly declines towards the 3' end. The HLA-B57 gene when transfected into murine L cells is expressed on the cell surface and reacts with a panel of monoclonal antibodies directed against monomorphic and polymorphic determinants associated with HLA-B27 antigen. The isolation of this gene allows for the first time a search for structural features which make the HLA-B27 antigen a high risk genetic factor for a group of rheumatoid disorders, in particular ankylosing spondylitis.

A longitudinal study of immunological parameters in multiple sclerosis: cell-mediated immunity and complement profiles.

In a 1 year longitudinal study of twenty-two patients with multiple sclerosis (MS) and twenty-one normal control subjects, peripheral blood leucocytes were stimulated with lipoplysaccharide (LPS), a B cell mitogen, and phytohaemagglutinin (PHA) a T cell mitogen. EA- and EAC-rosette formation was also performed to assay null and B cells respectively, and the serum concentration of the C3 component of complement was determined. For ten multiple sclerosis (MS) patients with stationary phases of the disease, percentages of lymphocytes significantly lower than normal were found with normal leucocyte counts in the peripheral blood. Lymphocyte stimulation by PHA was significantly lower than normal in stable MS, while neither LPS stimulation nor EA- and EAC-rosette formation differed significantly from the controls. The C3 serum concentration was found to be significantly higher than normal. For nine out of twelve MS patients with a fluctuating clinical course, the C3 concentration was elevated during remission, but dropped to normal levels during relapse. None of the other parameters studied could be correlated with the clinical course.

A longitudinal study of immunological parameters in multiple sclerosis. Cytotoxic antibodies.

Complement-dependent gliotoxic antibody activity was determined in 22 patients with multiple sclerosis (MS) and 19 normal control persons. Peripheral blood serum was collected from MS patients at about 4-week intervals for one year, and the results of cytotoxicity tests correlated with the course of disease. For 10 MS patients with stable disease, complement-dependent cytotoxic antibodies directed against a noncytocidally infected mouse glial cell line (an as yet unidentified virus) were found in significantly higher than normal titer. For 12 MS patients with fluctuating clinical course, the gliotoxic antibody titer remained relatively constant before relapse. During relapse, the titer remained constant or dropped. With remission initially low titers increased appreciably.