Control of vibration using compliant actuators

This work proposes a method for controlling vibration using compliant-based actuators. The compliant actuator combines a conventional actuator with elastic elements in a series configuration. The benefits of compliant actuators for vibration control applications, demonstrated in this work, are twofold: (i) vibration reduction over a wide frequency bandwidth by passive control means; (ii) improvement of vibration control performance when active control is applied using the compliant actuator. The vibration control performance is compared with the control performance achieved using the well-known vibration absorber and conventional rigid actuator systems. The performance comparison showed that the compliant actuator provided a better flexibility in achieving vibration control over a certain frequency bandwidth. The passive and active control characteristics of the compliant actuator are investigated, which shows that the control performance is highly dependent on the compliant stiffness parameter. The active control characteristics are analyzed by using the Proportional and Derivative (PD) control strategy which demonstrated the capability of effectively changing the respective effective stiffness and damping of the system. These attractive dual passive-active control characteristics are therefore advantageous for achieving an effective vibration control system, particularly for controlling the vibration over a specific wide frequency bandwidth

Testing the greenhouse gas emissions reduction potential of alternative strategies for the english housing stock

Buildings account for around a third of global energy and process emissions, but have been delivering much smaller emissions savings than other sectors. Although clear standards of new building construction and retrofitting options have been developed and are able to reduce building emissions, there is need for a clear prioritisation of policy options capable of delivering the greatest reduction in emissions at minimal costs. This requires an assessment of the trade-offs between new construction and retrofitting in terms of the pace of adoption of improved building standards and the emissions savings achieved to meet current climate targets. In this paper, a dynamic material flow analysis is used to explore the impact of combined mitigation strategies on both new and existing buildings capable of reducing embodied and operational emissions in the English domestic housing stock. The results show that progress in the use of low carbon materials in construction and the deployment of zero-carbon buildings at scale would not be enough to deliver a reduction of building emissions of the scale required nationally (–66% from current levels by 2050). Improvement in building standards for both new and pre-existing construction is essential to meet targets, but its costs are likely to be unreasonable without a reduction in the demand for floor area per capita by promoting flexible design of buildings, house sharing or telecommuting, which are likely to produce far-reaching implications in social organisation and urban planning.EPSR

National-Scale Rainfall-Triggered Landslide Susceptibility and Exposure in Nepal

Nepal is one of the most landslide-prone countries in the world, with year-on-year impacts resulting in loss of life and imposing a chronic impediment to sustainable livelihoods. Living with landslides is a daily reality for an increasing number of people, so establishing the nature of landslide hazard and risk is essential. Here we develop a model of landslide susceptibility for Nepal and use this to generate a nationwide geographical profile of exposure to rainfall-triggered landslides. We model landslide susceptibility using a fuzzy overlay approach based on freely-available topographic data, trained on an inventory of mapped landslides, and combine this with high resolution population and building data to describe the spatial distribution of exposure to landslides. We find that whilst landslide susceptibility is highest in the High Himalaya, exposure is highest within the Middle Hills, but this is highly spatially variable and skewed to on average relatively low values. Around 4 × 106 Nepalis (∼15\% of the population) live in areas considered to be at moderate or higher degree of exposure to landsliding (>0.25 of the maximum), and critically this number is highly sensitive to even small variations in landslide susceptibility. Our results show a complex relationship between landslides and buildings, that implies wider complexity in the association between physical exposure to landslides and poverty. This analysis for the first time brings into focus the geography of the landslide exposure and risk case load in Nepal, and demonstrates limitations of assessing future risk based on limited records of previous events

CDK6 levels regulate quiescence exit in human hematopoietic stem cells.

Regulated blood production is achieved through the hierarchical organization of dormant hematopoietic stem cell (HSC) subsets that differ in self-renewal potential and division frequency, with long-term (LT)-HSCs dividing the least. The molecular mechanisms underlying this variability in HSC division kinetics are unknown. We report here that quiescence exit kinetics are differentially regulated within human HSC subsets through the expression level of CDK6. LT-HSCs lack CDK6 protein. Short-term (ST)-HSCs are also quiescent but contain high CDK6 protein levels that permit rapid cell cycle entry upon mitogenic stimulation. Enforced CDK6 expression in LT-HSCs shortens quiescence exit and confers competitive advantage without impacting function. Computational modeling suggests that this independent control of quiescence exit kinetics inherently limits LT-HSC divisions and preserves the HSC pool to ensure lifelong hematopoiesis. Thus, differential expression of CDK6 underlies heterogeneity in stem cell quiescence states that functionally regulates this highly regenerative system.This work was supported by the Swiss National Science Foundation (E.L.), Roche (E.L.), the Fondation Suisse pour les Bourses en Me´ decine et Biologie (E.L.), the Swedish Research Council (S.Z.); and a Canadian Institutes of Health Research (CIHR) fellowship in partnership with the Aplastic Anemia and Myelodysplasia Association of Canada (S.Z.). Work in J.E.D.’s laboratory is supported by grants from the CIHR, Canadian Cancer Society, Terry Fox Foundation, Genome Canada through the Ontario Genomics Institute, Ontario Institute for Cancer Research with funds from the province of Ontario, a Canada Research Chair, the Princess Margaret Hospital foundation, and the Ontario Ministry of Health and Long Term Care (OMOHLTC). Research in E.L.’s laboratory is currently supported by a recruitment support from the Wellcome Trust and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute.This is the final published version. It first appeared at http://www.cell.com/cell-stem-cell/abstract/S1934-5909%2815%2900018-1

Numerical benchmark campaign of cost action tu1404 – microstructural modelling

This paper presents the results of the numerical benchmark campaign on modelling of hydration and microstructure development of cementitious materials. This numerical benchmark was performed in the scope of COST Action TU1404 “Towards the next generation of standards for service life of cement-based materials and structures”. Seven modelling groups took part in the campaign applying different models for prediction of mechanical properties (elastic moduli or compressive strength) in cement pastes and mortars. The simulations were based on published experimental data. The experimental data (both input and results used for validation) were open to the participants. The purpose of the benchmark campaign was to identify the needs of different models in terms of input experimental data, verify predictive potential of the models and finally to provide reference cases for new models in the future. The results of the benchmark show that a relatively high scatter in the predictions can arise between different models, in particular at early ages (e.g. elastic Young’s modulus predicted at 1 d in the range 6-20 GPa), while it reduces at later age, providing relatively good agreement with experimental data. Even though the input data was based on a single experimental dataset, the large differences between the results of the different models were found to be caused by distinct assumed properties for the individual phases at the microstructural level, mainly because of the scatter in the nanoindentation-derived properties of the C-S-H phase.</jats:p

Creatine Protects against Excitoxicity in an In Vitro Model of Neurodegeneration

Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common molecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions. Moreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents, mainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly neuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with glutamate or H2O2. In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance, leading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively antagonized the H2O2-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as an antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response, which initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that high-dose creatine supplementation as a health-promoting agent in specific pathological situations or as a primary prophylactic compound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of creatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with reduced glutamate spillover, oxidative stress and subsequent excitotoxicity

Adjuvant chemotherapy for resected early-stage non-small cell lung cancer

BACKGROUND: To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC),we performed two systematic reviews and meta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010. OBJECTIVES: To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival:A. Surgery versus surgery plus adjuvant chemotherapyB. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapyin patients with histologically diagnosed early stage NSCLC.(2)To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival. SEARCH METHODS: We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, handsearching relevant meeting proceedings and by discussion with trialists and organisations. SELECTION CRITERIA: We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment. DATA COLLECTION AND ANALYSIS: We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status. MAIN RESULTS: We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p< 0.0001), with an absolute increase in survival of 4% at five years.We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years.For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup.We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low. AUTHORS' CONCLUSIONS: Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out