Enhancing pantograph-catenary dynamic performance using an inertance-integrated damping system

For modern electrical rail systems, the pantograph-catenary dynamic performance is one of the most critical challenges. Too much fluctuation in contact forces leads to either accelerated wear of the contacting components or losses of contact and, consequently, arcing. In this work, inertance-integrated pantograph damping systems are investigated with the objective of reducing the contact force standard deviation. Firstly, a multibody pantograph model is developed with its accuracy compared with experimental data. The model is improved through the calibration of the pantograph head suspension parameters and the introduction of both non-ideal joint and flexibility effects. Using the calibrated model, beneficial inertance-integrated damping systems are identified for the pantograph suspension. The results show that the configuration with one inerter provides the best performance among other candidate layouts and contends a 40% reduction of the maximum standard deviation of the contact force over the whole operating speed range in the numerical modelling scenario analysed. Considering the identified configuration, time-domain analysis and modal analysis are investigated. It has been shown that the achieved improvement is due to the fact that with the beneficial inertance-integrated damping system, the first resonance frequency of the pantograph system coincides with the natural frequency of the catenary system.info:eu-repo/semantics/publishedVersio

COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal

The COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI binds K63-linked polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through the endocytic pathway to the Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a β’-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts Snc1 recycling causing aberrant accumulation in internal compartments. Moreover, replacement of the β’-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles in a non-degradative pathway

Moss valley – collaboration on and in the edgeland

Edgelands are those spaces that are neither urban nor rural, that seem to be unplanned or unmanaged, and that exist in a patchy between. This article argues that collaborative artistic responses to these spaces are particularly appropriate using a collaboration between the author and visual artist Abi Goodman as an example. This collaboration aims to respond to the tensions that the term edgeland sometimes allows writers to ignore by exploring the term’s history as it morphs from rurban fringe, to rural, urban interface, to postindustrial land, to unmanaged space. It aims to allow the recognition of edgeland as a paradoxical space based upon the writer’s experience in one place, Moss Valley

The Inadequate Treatment of Pain: Collateral Damage from the War on Drugs

Jason Nickerson and Amir Attaran examine the vast inequities in medical pain relief around the world and argue that the global control of licit narcotics be shifted from the International Narcotic Control Board to WHO

Comparative Field Evaluation of Combinations of Long-Lasting Insecticide Treated Nets and Indoor Residual Spraying, Relative to Either Method Alone, for Malaria Prevention in an Area where the main Vector is Anopheles Arabiensis.

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In contrast, adding intact bednets onto IRS enhances protection by preventing mosquito blood-feeding (even if the nets are non-insecticidal) and by slightly increasing mosquito mortality (in case of LLINs). The primary mode of action of intact LLINs against An. arabiensis is clearly bite prevention rather than insecticidal activity. Therefore, where resources are limited, priority should be to ensure that everyone at risk consistently uses LLINs and that the nets are regularly replaced before being excessively torn. Measures that maximize bite prevention (e.g. proper net sizes to effectively cover sleeping spaces, stronger net fibres that resist tears and burns and net use practices that preserve net longevity), should be emphasized

Ocean ecosystem-based management mandates and implementation in the North Atlantic

Ecosystem-based management (EBM) necessarily requires a degree of coordination across countries that share ocean ecosystems, and among national agencies and departments that have responsibilities relating to ocean health and marine resource utilization. This requires political direction, legal input, stakeholder consultation and engagement, and complex negotiations. Currently there is a common perception that within and across national jurisdictions there is excessive legislative complexity, a relatively low level of policy coherence or alignment with regards to ocean and coastal EBM, and that more aligned legislation is needed to accelerate EBM adoption. Our Atlantic Ocean Research Alliance (AORA) task group was comprised of a small, focused and interdisciplinary mix of lawyers, social scientists, and natural scientists from Canada, the USA, and the EU. We characterized, compared, and synthesized the mandates that govern marine activities and ocean stressors relative to facilitating EBM in national and international waters of the North Atlantic, and identified formal mandates across jurisdictions and, where possible, policy and other non-regulatory mandates. We found that irrespective of the detailed requirements of legislation or policy across AORA jurisdictions, or the efficacy of their actual implementation, most of the major ocean pressures and uses posing threats to ocean sustainability have some form of coverage by national or regional legislation. The coverage is, in fact, rather comprehensive. Still, numerous impediments to effective EBM implementation arise, potentially relating to the lack of integration between agencies and departments, a lack of adequate policy alignment, and a variety of other socio-political factors. We note with concern that if challenges regarding EBM implementation exist in the North Atlantic, we can expect that in less developed regions where financial and governance capacity may be lower, that implementation of EBM could be even more challenging

High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington\u27s disease CAG knock-in mice across multiple genetic backgrounds.

Huntington\u27s disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, molecular and cellular phenotypes in the striatum of six distinct knock-in mouse models of the HD mutation. We studied the effects of the HttQ111 allele on the C57BL/6J, CD-1, FVB/NCr1, and 129S2/SvPasCrl genetic backgrounds, and of two additional alleles, HttQ92 and HttQ50, on the C57BL/6J background. We describe the emergence of a transcriptomic signature in HttQ111/+  mice involving hundreds of differentially expressed genes and changes in diverse molecular pathways. We also show that this time course spanned the onset of mutant huntingtin nuclear localization phenotypes and somatic CAG-length instability in the striatum. Genetic background strongly influenced the magnitude and age at onset of these effects. This work provides a foundation for understanding the earliest transcriptional and molecular changes contributing to HD pathogenesis