Parity effect and single-electron injection for Josephson-junction chains deep in the insulating state

We have made a systematic investigation of charge transport in 1D chains of Josephson junctions where the characteristic Josephson energy is much less than the single-island Cooper-pair charging energy, $E_\mathrm{J}\ll E_{CP}$. Such chains are deep in the insulating state, where superconducting phase coherence across the chain is absent, and a voltage threshold for conduction is observed at the lowest temperatures. We find that Cooper-pair tunneling in such chains is completely suppressed. Instead, charge transport is dominated by tunneling of single electrons, which is very sensitive to the presence of BCS quasiparticles on the superconducting islands of the chain. Consequently we observe a strong parity effect, where the threshold voltage vanishes sharply at a characteristic parity temperature $T^*$, which is significantly lower than the the critical temperature, $T_c$. A measurable and thermally-activated zero-bias conductance appears above $T^*$, with an activation energy equal to the superconducting gap, confirming the role of thermally-excited quasiparticles. Conduction below $T^*$ and above the voltage threshold occurs via injection of single electrons/holes into the Cooper-pair insulator, forming a non-equilibrium steady state with a significantly enhanced effective temperature. Our results explicitly show that single-electron transport dominates deep in the insulating state of Josephson-junction arrays. This conduction process has mostly been ignored in previous studies of both superconducting junction arrays and granular superconducting films below the superconductor-insulator quantum phase transition.Comment: 8 pages, 6 figure

Predicting Geometrical Variation in Fabricated Assemblies Using a Digital Twin Approach Including a Novel Non-Nominal Welding Simulation

The aerospace industry faces constantly increasing demands on performance and reliability, especially within the vital area of engine development. New technologies are needed in order to push the limits of high precision manufacturing processes for the next generation of aircraft engines. An increased use of in-line data collection in manufacturing is creating an opportunity to individualize each assembly operation rather than treating them identically. Welding is common in this context, and the interaction between welding distortion and variation in part geometries is difficult to predict and manage in products with tight tolerances. This paper proposes an approach based on the Digital Twin paradigm, aiming to increase geometrical quality by combining the novel SCV (Steady-state Convex hull Volumetric shrinkage) method for non-nominal welding simulation with geometrical data collected from 3D scanning of parts. A case study is presented where two parts are scanned and then welded together into an assembly. The scan data is used as input for a non-nominal welding simulation, and the result of the simulation is compared directly to scan data from the real welded assembly. Three different welding simulation methods are used and assessed based on simulation speed and ability to predict the real welding result. The segmented SCV method for welding simulation shows promising potential for this implementation, delivering good prediction accuracy and high simulation speed

Refined structure of Cu-substituted alcohol dehydrogenase at 2.1 Å resolution

Liver alcohol dehydrogenase (LADH) is a ZnII-dependent dimeric enzyme. LADH with the active-site ZnII substituted by CuII resembles blue (type I) copper proteins by its spectroscopic characteristics. In this work we present the X-ray structure of the active site CuII-substituted LADH complex with NADH and dimethyl sulfoxide (DMSO). The structure was solved by molecular replacement. The space group is P21 with cell dimensions a = 44.4, b = 180.6, c = 50.8 Å and [beta] = 108°. There is one dimer of the enzyme in the asymmetric unit. The refinement was carried out to a crystallographic R-factor of 16.1% for 41 119 unique reflections in the resolution range 12.0 to 2.1 Å. The coordination geometry of CuII in LADH is compared with the active-site metal coordination in the Zn-LADH-NADH-DMSO complex and blue-copper proteins. The distances from the metal to the protein ligands (Cys46, His67 and Cys174) are similar for the ZnII and CuII ions. The distances of the O atom of the inhibitor DMSO to the CuII ion in the two subunits of the dimer are 3.19 and 3.45 Å. These are considerably longer than the corresponding distances for the ZnII enzyme, 2.19 and 2.15 Å. The CuII ion is positioned nearly in the plane of the three protein ligands (NS2) with a geometry similar to the trigonal arrangement of the three strongly bound ligands (N2S) in blue-copper proteins. This coordination probably accounts for the similarity of the spectral characteristics of CuII-LADH and type I copper proteins

Effect of Body Mass Index on pregnancy outcomes in nulliparous women delivering singleton babies

Peer reviewedPublisher PD

Assumptions behind grammatical approaches to code-switching: when the blueprint is a red herring

Many of the so-called ‘grammars’ of code-switching are based on various underlying assumptions, e.g. that informal speech can be adequately or appropriately described in terms of ‘‘grammar’’; that deep, rather than surface, structures are involved in code-switching; that one ‘language’ is the ‘base’ or ‘matrix’; and that constraints derived from existing data are universal and predictive. We question these assumptions on several grounds. First, ‘grammar’ is arguably distinct from the processes driving speech production. Second, the role of grammar is mediated by the variable, poly-idiolectal repertoires of bilingual speakers. Third, in many instances of CS the notion of a ‘base’ system is either irrelevant, or fails to explain the facts. Fourth, sociolinguistic factors frequently override ‘grammatical’ factors, as evidence from the same language pairs in different settings has shown. No principles proposed to date account for all the facts, and it seems unlikely that ‘grammar’, as conventionally conceived, can provide definitive answers. We conclude that rather than seeking universal, predictive grammatical rules, research on CS should focus on the variability of bilingual grammars

Trends in caesarean section and instrumental deliveries in relation to Body Mass Index: a clinical survey during 1978 - 2001

<p>Abstract</p> <p>Background</p> <p>During the last 20 years the rate of CS has increased in Sweden as it has in many other countries. The proportion of pregnant women suffering from a high BMI has also increased rapidly during the same time period. It would therefore be of interest to study both how and if these two observations are related to each other. The aim was therefore to study trends in mode of caesarean section (CS) and instrumental deliveries among women in three BMI groups over a time span of almost 25 years with special focus on the observed body weight of pregnant women.</p> <p>Method</p> <p>The design is a retrospective cohort study using medical records of consecutively delivered women at two delivery wards in South East Sweden during the years 1978, 1986, 1992, 1997 and 2001.</p> <p>Results</p> <p>No significant time-trends were found for CS and instrumental delivery within each BMI-group for the time period studied. The proportion of women with BMI ≥ 25 delivered by means of CS or instrumental delivery increased quite dramatically from 1978 to 2001 (χ²test for trend; p < 0.001 for both CS and instrumental deliveries). The mean birth weight in relation to BMI and year of study among women delivered by means of CS decreased, a trend that was most evident between 1997 and 2001 (F-test; p = 0.005, p = 0.004, and p = 0.003 for BMI < 20, 20-24.9, and ≥ 25, respectively).</p> <p>Conclusion</p> <p>Overweight and obese pregnant women constitute a rapidly growing proportion of the total number of CS and instrumental deliveries. Planning and allocation of health resources must be adjusted to this fact and its implications.</p

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial

Extent: 5p.Background: Obesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes. The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes. Methods/Design: Design: Multicentred randomised, controlled trial. Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies. Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice. Outcome assessors will be blinded to the allocated treatment group. Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age). Sample Size: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed). Discussion This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines.Jodie M Dodd, Deborah A Turnbull, Andrew J McPhee, Gary Wittert, Caroline A Crowther and Jeffrey S Robinso