Predictable and robust performance of a Bi-2223 superconducting coil for compact isochronous cyclotrons

The development of ever smaller medical particle accelerators is motivated by a desire to make proton therapy accessible to more patients. Reducing the footprint of particle accelerators and subsequently proton therapy facilities allows for cheaper and broader usage of proton therapy. By employing superconducting technologies for field shaping, the size of particle accelerators can be reduced further below what is possible with saturated iron. This article discusses experiments on a first-of-its-kind double pancake (DP), and an assembly of six DP coils, designed to be used as a so-called ‘flutter coil’ for a compact isochronous cyclotron for proton therapy, fabricated from high-temperature superconducting (HTS) Bi 2 − x Pbx Sr2Ca2Cu3Oy (Bi-2223) tape. The coils were mounted under pre-stress within a stainless-steel structure to maintain mechanical stability during the experiments. The critical current as a function of the temperature of both coils was measured in a conduction-cooled setup. A model describing the coils, based on tape data, was created and revealed that the measurements were in excellent agreement with the predictions. Additional experiments were performed to study the quench and thermal runaway behaviour of the HTS coils, determining whether such coils can be protected against fault scenarios, using realistic quench-detection levels and discharge extraction-rates. These experiments demonstrate that the coils are very robust and can be well protected against quenches and thermal-runaway events using common quench-protection measures with realistic parameters.</p

EMC testing of electricity meters using real-world and artificial current waveforms

In 2015, the energy measurement of some static electricity meters was found to be sensitive to specific conducted electromagnetic disturbances with very fast current changes caused by highly nonlinear loads, leading to meter errors up to several hundred percent. This article describes new results on the electromagnetic compatibility (EMC) of 16 different meters from all over Europe when exposed to real-world disturbance signals. Those test signals were obtained from household appliances and onsite measurements at metered supply points all over Europe. The results show that also the interference signals recorded onsite can cause measurement errors as large as several hundred percent, even for meters that pass the present EMC standards. This unambiguously demonstrates that the present immunity testing standards do not cover the most disturbing conducted interference occurring in present daily-life situations due to the increased use of nonlinear electronics. Furthermore, to enable the adoption of potential new test waveforms in future standards for electricity meter testing, artificial test waveforms were constructed based on real-world waveforms using a piece-wise linear model. These artificial test waveforms were demonstrated to cause meter errors similar to those caused by the original real-life waveforms they are representing, showing that they are suitable candidates for use in improved standardization of electricity meter testing.Postprint (published version

Laboratory evolution of Pyrococcus furiosus alcohol dehydrogenase to improve the production of (2S,5S)-hexanediol at moderate temperatures

There is considerable interest in the use of enantioselective alcohol dehydrogenases for the production of enantio- and diastereomerically pure diols, which are important building blocks for pharmaceuticals, agrochemicals and fine chemicals. Due to the need for a stable alcohol dehydrogenase with activity at low-temperature process conditions (30°C) for the production of (2S,5S)-hexanediol, we have improved an alcohol dehydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus (AdhA). A stable S-selective alcohol dehydrogenase with increased activity at 30°C on the substrate 2,5-hexanedione was generated by laboratory evolution on the thermostable alcohol dehydrogenase AdhA. One round of error-prone PCR and screening of ∼1,500 mutants was performed. The maximum specific activity of the best performing mutant with 2,5-hexanedione at 30°C was tenfold higher compared to the activity of the wild-type enzyme. A 3D-model of AdhA revealed that this mutant has one mutation in the well-conserved NADP(H)-binding site (R11L), and a second mutation (A180V) near the catalytic and highly conserved threonine at position 183

Structural basis of catalysis in the bacterial monoterpene synthases linalool synthase and 1,8-cineole synthase

Terpenoids form the largest and stereochemically most diverse class of natural products, and there is considerable interest in producing these by biocatalysis with whole cells or purified enzymes, and by metabolic engineering. The monoterpenes are an important class of terpenes and are industrially important as flavors and fragrances. We report here structures for the recently discovered Streptomyces clavuligerus monoterpene synthases linalool synthase (bLinS) and 1,8-cineole synthase (bCinS), and we show that these are active biocatalysts for monoterpene production using biocatalysis and metabolic engineering platforms. In metabolically engineered monoterpene-producing E. coli strains, use of bLinS leads to 300-fold higher linalool production compared with the corresponding plant monoterpene synthase. With bCinS, 1,8-cineole is produced with 96% purity compared to 67% from plant species. Structures of bLinS and bCinS, and their complexes with fluorinated substrate analogues, show that these bacterial monoterpene synthases are similar to previously characterized sesquiterpene synthases. Molecular dynamics simulations suggest that these monoterpene synthases do not undergo large-scale conformational changes during the reaction cycle, making them attractive targets for structured-based protein engineering to expand the catalytic scope of these enzymes toward alternative monoterpene scaffolds. Comparison of the bLinS and bCinS structures indicates how their active sites steer reactive carbocation intermediates to the desired acyclic linalool (bLinS) or bicyclic 1,8-cineole (bCinS) products. The work reported here provides the analysis of structures for this important class of monoterpene synthase. This should now guide exploitation of the bacterial enzymes as gateway biocatalysts for the production of other monoterpenes and monoterpenoids

Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members. In these 57 patients we identified 49 different mutations, including six multiple exon deletions, six known mutations and 37 novel mutations (13 missense, five nonsense, 13 frame shift, four splice site and two translation initiation mutations). Clinical data were retrospectively collected from referring physicians by means of a questionnaire. Three different phenotypes were recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2 years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental retardation and movement disorder, without epilepsy (15%); and (iii) one adult case of glucose transporter-1 deficiency syndrome with minimal symptoms. Recognizing glucose transporter-1 deficiency syndrome is important, since a ketogenic diet was effective in most of the patients with epilepsy (86%) and also reduced movement disorders in 48% of the patients with a classical phenotype and 71% of the patients with a non-classical phenotype. The average delay in diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years (range 1 month-16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range 0.9-2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was below 0.50 in all but one patient (range 0.19-0.52). Cerebrospinal fluid lactate was low to normal in all patients. Our relatively large series of 57 patients with glucose transporter-1 deficiency syndrome allowed us to identify correlations between genotype, phenotype and biochemical data. Type of mutation was related to the severity of mental retardation and the presence of complex movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type of mutation and phenotype. In conclusion, a substantial number of the patients with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study demonstrates that a lumbar puncture provides the diagnostic clue to glucose transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic delay to allow early start of the ketogenic die

Carboxylic ester hydrolases from hyperthermophiles

Carboxylic ester hydrolyzing enzymes constitute a large group of enzymes that are able to catalyze the hydrolysis, synthesis or transesterification of an ester bond. They can be found in all three domains of life, including the group of hyperthermophilic bacteria and archaea. Esterases from the latter group often exhibit a high intrinsic stability, which makes them of interest them for various biotechnological applications. In this review, we aim to give an overview of all characterized carboxylic ester hydrolases from hyperthermophilic microorganisms and provide details on their substrate specificity, kinetics, optimal catalytic conditions, and stability. Approaches for the discovery of new carboxylic ester hydrolases are described. Special attention is given to the currently characterized hyperthermophilic enzymes with respect to their biochemical properties, 3D structure, and classification

Ascorbate Biosynthesis during Early Fruit Development Is the Main Reason for Its Accumulation in Kiwi

Background: Ascorbic acid (AsA) is a unique antioxidant as well as an enzyme cofactor. Although it has multiple roles in plants, it is unclear how its accumulation is controlled at the expression level, especially in sink tissues. Kiwifruit (Actinidia) is well-known for its high ascorbate content. Our objective was to determine whether AsA accumulates in the fruits primarily through biosynthesis or because it is imported from the foliage. Methodology/Principal Findings: We systematically investigated AsA levels, biosynthetic capacity, and mRNA expression of genes involved in AsA biosynthesis in kiwi (A. deliciosa cv. Qinmei). Recycling and AsA localization were also monitored during fruit development and among different tissue types. Over time, the amount of AsA, with its capacity for higher biosynthesis and lower recycling, peaked at 30 days after anthesis (DAA), and then decreased markedly up to 60 DAA before declining more slowly. Expression of key genes showed similar patterns of change, except for L-galactono-1,4-lactone dehydrogenase and L-galactose-1-phosphate phosphatase (GPP). However, GPP had good correlation with the rate of AsA accumulation. The expression of these genes could be detected in phloem of stem as well as petiole of leaf and fruit. Additionally, fruit petioles had greater ascorbate amounts, although that was the site of lowest expression by most genes. Fruit microtubule tissues also had higher AsA. However, exogenous applications of AsA to those petioles did not lead to its transport into fruits, and distribution of ascorbate was cell-specific in the fruits, with more accumulation occurring in large

Diffuse scattering in random-stacking hexagonal close-packed crystals of colloidal hard spheres

Microradian X-ray diffraction from sedimentary colloidal crystals is studied using synchrotron radiation with photon energies of 12.4, 27, and 38 keV. Stacking disorder in these hard-sphere crystals leads to diffuse X-ray scattering along the Bragg scattering rods normal to the randomly stacked layers. We observed the appearance of diffuse scattering, shown to be induced by multiple scattering, along the secondary Bragg rods in between the stacking-independent true Bragg reflections. This effect can be reduced by measuring at higher X-ray energies

Strålande tider, härliga tider? Konsumtion av pilsnerfilmer och äldre svenska komiska filmer i en nutida kontext

In Sweden there has been a surge of interest in the films classified as pilsnerfilms, i.e. comical films produced for little money in the 1930's and containing a more working class and/or rural setting then the so called "champagne comedies" from the same era. The concept "pilsnerfilm" is how ever a little vague and although the main focus of this paper is pilsnerfilms, it will also cover other types of comical films made in Sweden between the 1930's and 1940's. This paper examines the now-existing network of people interested in these types of movies. It will do so by interviewing seven of the most prominent fans of movies made during the 1930's and 1940's. Most of them are living in Stockholm. The paper discuss how through the consumption of these types of films, a nostalgic gaze is created. With a nostalgic gaze the enthusiasts for pilsnerfilms can in the present create a history of a bygone Sweden and they can also try to establish a form of contact with the actors in the movies from the 1930's and 1940's. The contact can be by collecting the movies, but more prominently the contact is even more grounded in a physical world, by having contact with still living actors who were active during that time or the now deceased actors relatives or by visiting the departed actors grave. The paper also discuss questions regarding cultural heritage and how the network thinks about the treatment the pilsnerfilms and other comical films from 1930's and 1940's have received from the owner's of the movies. Particularly the main company the owns the large majority of Swedish films; SF. It evokes questions regarding how to present movies as cultural heritage and which people should have to power to do that. The aspects brings the question of knowledge and feelings to mind. The network of enthusiasts can be viewed as a affective alliance, meaning it exists a emotional connection between cultural expression and individuals. It is the networks affective alliance that the connoisseur can organize it's knowledge. Emotions and knowledge can't be separated. To both have the right knowledge and the right emotions is crucial for the network. And through the networks emotions and knowledge, the fragments that create the story of pilsnerfilm is put together