Pragmatic approach to the development of robust real-time protocols

This research is concerned with the development of distributed real-time systems, in which software is used for the control of concurrent physical processes. These distributed control systems are required to periodically coordinate the operation of several autonomous physical processes, with the property of an atomic action. The implementation of this coordination must be fault-tolerant if the integrity of the system is to be maintained in the presence of processor or communication failures. Commit protocols have been widely used to provide this type of atomicity and ensure consistency in distributed computer systems. The objective of this research is the development of a class of robust commit protocols, applicable to the coordination of distributed real-time control systems. Extended forms of the standard two phase commit protocol, that provides fault-tolerant and real-time behaviour, were developed. Petri nets are used for the design of the distributed controllers, and to embed the commit protocol models within these controller designs. This composition of controller and protocol model allows the analysis of the complete system in a unified manner. A common problem for Petri net based techniques is that of state space explosion, a modular approach to both the design and analysis would help cope with this problem. Although extensions to Petri nets that allow module construction exist, generally the modularisation is restricted to the specification, and analysis must be performed on the (flat) detailed net. The Petri net designs for the type of distributed systems considered in this research are both large and complex. The top down, bottom up and hybrid synthesis techniques that are used to model large systems in Petri nets are considered. A hybrid approach to Petri net design for a restricted class of communicating processes is developed. Designs produced using this hybrid approach are modular and allow re-use of verified modules. In order to use this form of modular analysis, it is necessary to project an equivalent but reduced behaviour on the modules used. These projections conceal events local to modules that are not essential for the purpose of analysis. To generate the external behaviour, each firing sequence of the subnet is replaced by an atomic transition internal to the module, and the firing of these transitions transforms the input and output markings of the module. Thus local events are concealed through the projection of the external behaviour of modules. This hybrid design approach preserves properties of interest, such as boundedness and liveness, while the systematic concealment of local events allows the management of state space. The approach presented in this research is particularly suited to distributed systems, as the underlying communication model is used as the basis for the interconnection of modules in the design procedure. This hybrid approach is applied to Petri net based design and analysis of distributed controllers for two industrial applications that incorporate the robust, real-time commit protocols developed. Temporal Petri nets, which combine Petri nets and temporal logic, are used to capture and verify causal and temporal aspects of the designs in a unified manner

The influence of barefoot and barefoot inspired footwear on the kinetics and kinematics of running in comparison to conventional running shoes.

Barefoot running has experienced a resurgence in footwear biomechanics literature, based on the supposition that it serves to reduce the occurrence of overuse injuries in comparison to conventional shoe models. This consensus has lead footwear manufacturers to develop shoes which aim to mimic the mechanics of barefoot locomotion. This study compared the impact kinetics and 3-D joint angular kinematics observed whilst running: barefoot, in conventional cushioned running shoes and in shoes designed to integrate the perceived benefits of barefoot locomotion. The aim of the current investigation was therefore to determine whether differences in impact kinetics exist between the footwear conditions and whether shoes which aim to simulate barefoot movement patterns can closely mimic the 3-D kinematics of barefoot running. Twelve participants ran at 4.0 m.s-1±5% in each footwear condition. Angular joint kinematics from the hip, knee and ankle in the sagittal, coronal and transverse planes were measured using an eight camera motion analysis system. In addition simultaneous tibial acceleration and ground reaction forces were obtained. Impact parameters and joint kinematics were subsequently compared using repeated measures ANOVAs. The kinematic analysis indicates that in comparison to the conventional and barefoot inspired shoes that running barefoot was associated significantly greater plantar-flexion at footstrike and range of motion to peak dorsiflexion. Furthermore, the kinetic analysis revealed that compared to the conventional footwear impact parameters were significantly greater in the barefoot condition. Therefore this study suggests that barefoot running is associated with impact kinetics linked to an increased risk of overuse injury, when compared to conventional shod running. Furthermore, the mechanics of the shoes which aim to simulate barefoot movement patterns do not appear to closely mimic the kinematics of barefoot locomotion

Efficacy of Two Licensed Avian Influenza H5 Vaccines Against Challenge with a 2015 U.S. H5N2 clade 2.3.4.4 Highly Pathogenic Avian Influenza Virus in Domestic Ducks

Highly pathogenic avian influenza (HPAI) clade 2.3.4.4 viruses from the H5 goose/Guangdong lineage caused a major outbreak in poultry in the United States in 2015. Although the outbreak was controlled, vaccines were considered as an alternative control method, and new vaccines were approved and purchased by the U.S. Department of Agriculture National Veterinary Stockpile for emergency use. In this study, we evaluated the efficacy of two of these vaccines in protecting Pekin ducks (Anas platyrhynchos var. domestica) against challenge with a H5N2 HPAI poultry isolate. A recombinant alphavirus-based vaccine and an inactivated adjuvanted reverse genetics vaccine, both expressing the hemagglutinin gene of a U.S. H5 clade 2.3.4.4 isolate (A/Gyrfalcon/Washington/41088-6/2014 H5N8), were used to immunize the ducks. The vaccines were given either as single vaccination at 2 days of age or in a prime-boost strategy at 2 and 15 days of age. At 32 days of age, all ducks were challenged with A/turkey/Minnesota/12582/15 H5N2 HPAI virus clade 2.3.4.4. All ducks from the nonvaccinated challenge control group became infected and shed virus; one duck in this group presented mild ataxia, and a second duck died. No mortality or clinical signs were observed in vaccinated and challenged ducks, with the exception of one duck presenting with mild ataxia. Both vaccines, regardless of the vaccination strategy used, were immunogenic in ducks and reduced or prevented virus shedding after challenge. In conclusion, good protection against H5Nx infection was achieved in ducks vaccinated with the vaccines examined, which were homologous to the challenge virus, with prime-boost strategies conferring the best protection against infection.info:eu-repo/semantics/publishedVersio

Eden Vision: Analysis and Insight:An independent review of the evidence gathered during the Autumn 2018 Eden District Council public engagement exercise

The creation of a 2050 Penrith Strategic Masterplan (‘PSM’), in conjunction with a 2050 Vision for Eden, was a significant attempt by Eden District Council (‘EDC’) to take a stronger role in shaping every aspect of the environment, economy and society of the region in future years. The PSM, produced over the spring and summer of 2018 aims to address a pressing need for Eden and Cumbria to tackle the demographic challenge of a rapidly ageing population, by shaping thinking and action in ways that extend far beyond the statutory duties of a District Council. This approach to long range policy making places the council as a central place-shaping organisation, bringing together diverse voices in order to think through and plan out the development path of the region. This is an ambitious goal for EDC to pursue. Such an approach is fraught with risk, and certainly there will be experiments, some mistakes, opportunities won and ideas lost, as the organisation learns new ways of thinking and working. We believe that any attempt to build a sustainable, healthy and prosperous future for the region needs to engage with long term, far reaching issues and that external engagement is critical, and needs to be supported by business, academia and the wider community of Eden. That is why Lancaster University and the University of Cumbria are supporting EDC with the analysis in this report

De novoframeshift mutation in ASXL3 in a patient with global developmental delay, microcephaly, and craniofacial anomalies

BACKGROUND: Currently, diagnosis of affected individuals with rare genetic disorders can be lengthy and costly, resulting in a diagnostic odyssey and in many patients a definitive molecular diagnosis is never achieved despite extensive clinical investigation. The recent advent and use of genomic medicine has resulted in a paradigm shift in the clinical molecular genetics of rare diseases and has provided insight into the causes of numerous rare genetic conditions. In particular, whole exome and genome sequencing of families has been particularly useful in discovering de novo germline mutations as the cause of both rare diseases and complex disorders. CASE PRESENTATION: We present a six year old, nonverbal African American female with microcephaly, autism, global developmental delay, and metopic craniosynostosis. Exome sequencing of the patient and her two parents revealed a heterozygous two base pair de novo deletion, c.1897_1898delCA, p.Gln633ValfsX13 in ASXL3, predicted to result in a frameshift at codon 633 with substitution of a valine for a glutamine and introduction of a premature stop codon. CONCLUSIONS: We provide additional evidence that, truncating and frameshifting mutations in the ASXL3 gene are the cause of a newly recognized disorder characterized by severe global developmental delay, short stature, microcephaly, and craniofacial anomalies. Furthermore, we expand the knowledge about disease causing mutations and the genotype-phenotype relationships in ASXL3 and provide evidence that rare, nonsynonymous, damaging mutations are not associated with developmental delay or microcephaly

Phosphorylation of p66Shc and forkhead proteins mediates Aβ toxicity

Excessive accumulation of amyloid β-peptide (Aβ) plays an early and critical role in synapse and neuronal loss in Alzheimer's Disease (AD). Increased oxidative stress is one of the mechanisms whereby Aβ induces neuronal death. Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66Shc, we investigated the role of p66Shc in Aβ toxicity. Treatment of cells and primary neuronal cultures with Aβ caused apoptotic death and induced p66Shc phosphorylation at Ser36. Ectopic expression of a dominant-negative SEK1 mutant or chemical JNK inhibition reduced Aβ-induced JNK activation and p66Shc phosphorylation (Ser36), suggesting that JNK phosphorylates p66Shc. Aβ induced the phosphorylation and hence inactivation of forkhead transcription factors in a p66Shc-dependent manner. Ectopic expression of p66ShcS36A or antioxidant treatment protected cells against Aβ-induced death and reduced forkhead phosphorylation, suggesting that p66Shc phosphorylation critically influences the redox regulation of forkhead proteins and underlies Aβ toxicity. These findings underscore the potential usefulness of JNK, p66Shc, and forkhead proteins as therapeutic targets for AD