A novel function for the Caenorhabditis elegans torsin OOC-5 in nucleoporin localization and nuclear import.

Torsin proteins are AAA+ ATPases that localize to the endoplasmic reticular/nuclear envelope (ER/NE) lumen. A mutation that markedly impairs torsinA function causes the CNS disorder DYT1 dystonia. Abnormalities of NE membranes have been linked to torsinA loss of function and the pathogenesis of DYT1 dystonia, leading us to investigate the role of the Caenorhabditis elegans torsinA homologue OOC-5 at the NE. We report a novel role for torsin in nuclear pore biology. In ooc-5-mutant germ cell nuclei, nucleoporins (Nups) were mislocalized in large plaques beginning at meiotic entry and persisted throughout meiosis. Moreover, the KASH protein ZYG-12 was mislocalized in ooc-5 gonads. Nups were mislocalized in adult intestinal nuclei and in embryos from mutant mothers. EM analysis revealed vesicle-like structures in the perinuclear space of intestinal and germ cell nuclei, similar to defects reported in torsin-mutant flies and mice. Consistent with a functional disruption of Nups, ooc-5-mutant embryos displayed impaired nuclear import kinetics, although the nuclear pore-size exclusion barrier was maintained. Our data are the first to demonstrate a requirement for a torsin for normal Nup localization and function and suggest that these functions are likely conserved

Barrier height change in very thin SiO2 films caused by charge injection

In this paper, we report an investigation of barrier height change in gate oxide caused by charge injection. By analyzing the small change in the post-stress Fowler-Nordheim (FN) tunneling current through the oxide layer, the change of the oxide barrier height due to charge injection is determined quantitatively. The barrier height changes associated with different charge-injection directions and measurement polarities for n-channel metal oxide semiconductor field-effect transistors (MOSFETs) are presented. For comparison a measurement on a p-channel MOSFET is also carried out. For all the cases, the barrier height changes always exhibit a power law dependence on injected charge.published_or_final_versio

Influence of nitrogen on tunneling barrier heights and effective masses of electrons and holes at lightly-nitrided SiO2/Si interface

We have determined both the effective masses and the barrier heights for electrons and holes in pure SiO2 and lightly nitrided oxides with various nitrogen concentrations up to 4.5 at %. In contrast to previous studies which were usually carried out by assuming a value for either the effective mass or the barrier height, this study does not make such an assumption. The approach is proven to be reliable by examining the result for the well-studied pure SiO2 thin films. It is observed that with the increase of the nitrogen concentration the effective masses increase while both the barrier heights and the energy gap decrease. © 2004 American Institute of Physics.published_or_final_versio

Evidence for antigenic seniority in influenza A (H3N2) antibody responses in southern China

A key observation about the human immune response to repeated exposure to influenza A is that the first strain infecting an individual apparently produces the strongest adaptive immune response. Although antibody titers measure that response, the interpretation of titers to multiple strains - from the same sera - in terms of infection history is clouded by age effects, cross reactivity and immune waning. From July to September 2009, we collected serum samples from 151 residents of Guangdong Province, China, 7 to 81 years of age. Neutralization tests were performed against strains representing six antigenic clusters of H3N2 influenza circulating between 1968 and 2008, and three recent locally circulating strains. Patterns of neutralization titers were compared based on age at time of testing and age at time of the first isolation of each virus. Neutralization titers were highest for H3N2 strains that circulated in an individual's first decade of life (peaking at 7 years). Further, across strains and ages at testing, statistical models strongly supported a pattern of titers declining smoothly with age at the time a strain was first isolated. Those born 10 or more years after a strain emerged generally had undetectable neutralization titers to that strain (<1:10). Among those over 60 at time of testing, titers tended to increase with age. The observed pattern in H3N2 neutralization titers can be characterized as one of antigenic seniority: repeated exposure and the immune response combine to produce antibody titers that are higher to more 'senior' strains encountered earlier in life. © 2012 Lessler et al.published_or_final_versio

Design optimization considering variable thermal mass, insulation, absorptance of solar radiation, and glazing ratio using a prediction model and genetic algorithm

This paper presents the optimization of building envelope design to minimize thermal load and improve thermal comfort for a two-star green building in Wuhan, China. The thermal load of the building before optimization is 36% lower than a typical energy-efficient building of the same size. A total of 19 continuous design variables, including different concrete thicknesses, insulation thicknesses, absorbance of solar radiation for each exterior wall/roof and different window-to-wall ratios for each façade, are considered for optimization. The thermal load and annual discomfort degree hours are selected as the objective functions for optimization. Two prediction models, multi-linear regression (MLR) model and an artificial neural network (ANN) model, are developed to predict the building thermal performance and adopted as fitness functions for a multi-objective genetic algorithm (GA) to find the optimal design solutions. As compared to the original design, the optimal design generated by the MLRGA approach helps to reduce the thermal load and discomfort level by 18.2% and 22.4%, while the reductions are 17.0% and 22.2% respectively, using the ANNGA approach. Finally, four objective functions using cooling load, heating load, summer discomfort degree hours, and winter discomfort degree hours for optimization are conducted, but the results are no better than the two-objective-function optimization approach

‘Advocacy groups are the connectors’: Experiences and contributions of rare disease patient organization leaders in advanced neurotherapeutics

Introduction: Biomedical progress has facilitated breakthrough advanced neurotherapeutic interventions, whose potential to improve outcomes in rare neurological diseases has increased hope among people with lived experiences and their carers. Nevertheless, gene, somatic cell and other advanced neurotherapeutic interventions carry significant risks. Rare disease patient organizations (RDPOs) may enhance patient experiences, inform expectations and promote health literacy. However, their perspectives are understudied in paediatric neurology. If advanced neurotherapeutics is to optimize RDPO contributions, it demands further insights into their roles, interactions and support needs. Methods: We used a mixed-methodology approach, interviewing 20 RDPO leaders representing paediatric rare neurological diseases and following them up with two online surveys featuring closed and open-ended questions on advanced neurotherapeutics (19/20) and negative mood states (17/20). Qualitative and quantitative data were analysed using thematic discourse analysis and basic descriptive statistics, respectively. Results: Leaders perceived their roles to be targeted at educational provision (20/20), community preparation for advanced neurotherapeutic clinical trials (19/20), information simplification (19/20) and focused research pursuits (20/20). Although most leaders perceived the benefits of collaboration between stakeholders, some cited challenges around collaborative engagement under the following subthemes: conflicts of interest, competition and logistical difficulties. Regarding neurotherapeutics, RDPO leaders identified support needs centred on information provision, valuing access to clinician experts and highlighting a demand for co-developed, centralized, high-level and understandable, resources that may improve information exchange. Leaders perceived a need for psychosocial support within themselves and their communities, proposing that this would facilitate informed decision-making, reduce associated psychological vulnerabilities and maintain hope throughout neurotherapeutic development. Conclusion: This study provides insights into RDPO research activities, interactions and resource needs. It reveals a demand for collaboration guidelines, central information resources and psychosocial supports that may address unmet needs and assist RDPOs in their advocacy. Patient or Public Contribution: In this study, RDPO leaders were interviewed and surveyed to examine their perspectives and roles in advanced neurotherapeutic development. Some participants sent researchers postinterview clarification emails regarding their responses to questions

Ca isotope constraints on chemical weathering processes: Evidence from headwater in the Changjiang River, China

This study aims to clarify the relationship between chemical weathering of rocks and the carbon budget of rivers and better understand the weathering mechanisms of plateau watersheds. We chose to study the Jinsha River, which originates from the Tibetan Plateau and also is in the upper reaches of the Changjiang River. Analysis of hydrochemistry, radiogenic strontium isotope and stable calcium isotopes were conducted of the Jinsha River water samples, which were collected along its mainstream and main tributaries in the summer. The results show that the water chemistry of the mainstream waters is dominated by evaporite weathering, which have low 87Sr/86Sr values (0.7098–0.7108) and wide range of Sr contents (2.70–9.35 μmol/L). In contrast, tributaries of the Jinsha River have higher 87Sr/86Sr (0.7090–0.7157) and lower Sr contents (∼1 μmol/L). Moreover, the Ca isotopic compositions in the mainstream (0.87–1.11‰) are heavier than the tributaries (0.68–0.88‰) and could not be fully explained by the conventional mixing of different sources. We suggest that secondary carbonate precipitation fractionates Ca isotopes in the Jinsha River, and fractionation factors are between 0.99935 and 0.99963. At least 66% of Ca was removed in the mainstream of the Jinsha River through secondary mineral precipitation, and the average value is ∼35% in the tributaries. The results highlight that evaporite weathering results in more carbonate precipitation influencing Ca transportation and cycling in the riverine system constrained by stable Ca isotopic compositions and water chemistry

Estimating Traffic Disruption Patterns with Volunteered Geographic Information

This is the final version. Available from Nature Research via the DOI in this record. Data are available from Zenodo at https://zenodo.org/record/3383443.Accurate understanding and forecasting of traffic is a key contemporary problem for policymakers. Road networks are increasingly congested, yet traffic data is often expensive to obtain, making informed policy-making harder. This paper explores the extent to which traffic disruption can be estimated using features from the volunteered geographic information site OpenStreetMap (OSM). We use OSM features as predictors for linear regressions of counts of traffic disruptions and traffic volume at 6,500 points in the road network within 112 regions of Oxfordshire, UK. We show that more than half the variation in traffic volume and disruptions can be explained with OSM features alone, and use cross-validation and recursive feature elimination to evaluate the predictive power and importance of different land use categories. Finally, we show that using OSM’s granular point of interest data allows for better predictions than the broader categories typically used in studies of transportation and land use.Natural Environment Research Council (NERC)Innovate UKEngineering and Physical Sciences Research Council (EPSRC

Development of Building Thermal Load and Discomfort Degree Hour Prediction Models Using Data Mining Approaches

Thermal load and indoor comfort level are two important building performance indicators, rapid predictions of which can help significantly reduce the computation time during design optimization. In this paper, a three-step approach is used to develop and evaluate prediction models. Firstly, the Latin Hypercube Sampling Method (LHSM) is used to generate a representative 19-dimensional design database and DesignBuilder is then used to obtain the thermal load and discomfort degree hours through simulation. Secondly, samples from the database are used to develop and validate seven prediction models, using data mining approaches including multilinear regression (MLR), chi-square automatic interaction detector (CHAID), exhaustive CHAID (ECHAID), back-propagation neural network (BPNN), radial basis function network (RBFN), classification and regression trees (CART), and support vector machines (SVM). It is found that the MLR and BPNN models outperform the others in the prediction of thermal load with average absolute error of less than 1.19%, and the BPNN model is the best at predicting discomfort degree hour with 0.62% average absolute error. Finally, two hybrid models&mdash;MLR (MLR + BPNN) and MLR-BPNN&mdash;are developed. The MLR-BPNN models are found to be the best prediction models, with average absolute error of 0.82% in thermal load and 0.59% in discomfort degree hour