Project VIMTO: A new system for the vibration and impact monitoring of tram operations

Disturbance to building occupants caused by tram-generated ground-borne noise and vibration presents a significant barrier to the expansion of tram networks in our cities. Furthermore, such disturbance is often an indicator of deteriorating track infrastructure. Monitoring and understanding ground-borne noise and vibration is therefore a key priority for tram operators. Project VIMTO (Vibration and Impact Monitoring of Tram Operations) is concerned with developing a new system for monitoring vibration and impact of trams, whereby the vehicles themselves are used as the primary monitoring instrument. Low-cost vehicle-mounted instrumentation is being used to record axle-box vibration signatures, along with positioning data, to ‘map’ a tram network in terms of its propensity to generate vibration. Such mapping aims to offer near real-time continuous monitoring, enabling the formulation of more efficient, optimised maintenance strategies. This paper describes the current development system and presents some initial results from trials on the Midland Metro, UK.This work was funded by the EPSRC Impact Acceleration Account (Grant No. EP/K503757/1) and by the Cambridge Centre for Smart Infrastructure and Construction (EP/I019308/1)

Understanding the EU's circular economy policies through futures of circularity

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: Data will be made available on request.In April 2022, the European Commission (EC) published a set of policy proposals to foster the European Union's (EU) transition to the circular economy (CE). Despite significant academic debate on the implications of transitioning to the CE, there remains little empirical and theoretical knowledge about what kind of circular future the EC policy proposals prescribe. In this paper, we explore the circular futures underpinning the EC policies and strategies on the CE by conducting a content analysis of the EC's CE policies between 2011 and 2022 using Bauwens et al.’s (2020) theoretical approach of circular futures as an analytical framework. We find that the EC's CE policies result from hybrid combinations of often competing, different circular futures. Despite this hybridity, circular modernism imaginaries that rely on techno-optimism and centralised governance tend to dominate, leading to a weak version of the CE that may be unable to meet the EU's environmental ambitions.European Union Horizon 2020European Research Council (ERC

Minor structural modifications to alchemix influence mechanism of action and pharmacological activity

Alchemix is an exemplar of a class of anthraquinone with efficacy against multidrug resistant tumors. We have explored further the mechanism of action of alchemix and investigated the effect of extending its side arm bearing the alkylating functionality with regard to DNA binding and activity against multidrug resistant cancer cells. Increasing the distance between the intercalating chromophore and the alkylating functionality of ICT2901 (propyl), ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation sites, more potent topoisomerase II inhibition and generated more apoptotic and necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly, alchemix, the compound with the shortest distance between its intercalative chromophore and alkylating functionality (ethyl), did not conform to this SAR. A different toxicity pattern against DNA repair defective CHO cell lines as well as arrest of cells in G1 supports a somewhat distinct mode of action by alchemix compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series has led to significant changes to the stability of DNA-compound complexes and cellular activity. Given that the failure of chemotherapy in the clinic is often associated with MDR, the results of both alchemix and ICT2901 represent important advances towards improved therapies

Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

Landscape of international event-based biosurveillance

Event-based biosurveillance is a scientific discipline in which diverse sources of data, many of which are available from the Internet, are characterized prospectively to provide information on infectious disease events. Biosurveillance complements traditional public health surveillance to provide both early warning of infectious disease events and situational awareness. The Global Health Security Action Group of the Global Health Security Initiative is developing a biosurveillance capability that integrates and leverages component systems from member nations. This work discusses these biosurveillance systems and identifies needed future studies

Similarity solutions for unsteady shear-stress-driven flow of Newtonian and power-law fluids : slender rivulets and dry patches

Unsteady flow of a thin film of a Newtonian fluid or a non-Newtonian power-law fluid with power-law index N driven by a constant shear stress applied at the free surface, on a plane inclined at an angle α to the horizontal, is considered. Unsteady similarity solutions representing flow of slender rivulets and flow around slender dry patches are obtained. Specifically, solutions are obtained for converging sessile rivulets (0 < α < π/2) and converging dry patches in a pendent film (π/2 < α < π), as well as for diverging pendent rivulets and diverging dry patches in a sessile film. These solutions predict that at any time t, the rivulet and dry patch widen or narrow according to |x|3/2, and the film thickens or thins according to |x|, where x denotes distance down the plane, and that at any station x, the rivulet and dry patch widen or narrow like |t|−1, and the film thickens or thins like |t|−1, independent of N

How to increase the potential policy impact of environmental science research

This article highlights eight common issues that limit the policy impact of environmental science research. The article also discusses what environmental scientists can do to resolve these issues, including (1) optimising the directness of their study so that it examines similar processes/populations/environments/ecosystems to that of policy interest; (2) using the most powerful study design possible, to increase confidence in the identified causal mechanisms; (3) selecting a sufficient sample size, to reduce the chance of false positives/negatives and increase policy-makers’ confidence in extrapolation of the findings; (4) minimizing the risk of bias through randomization of study units to treatment and control groups (reducing the risk of selection bias), blinding of study units and investigators (reducing the risk of performance and detection bias), following-up study units from enrolment to study completion (reducing the risk of attrition bias) and prospectively registering the study on a publically-available platform (reducing the risk of reporting and publication bias); (5) proving that statistical analyses meet test assumptions by reporting the results of statistical assumption checks, ideally publishing full datasets online in an open-access format; (6) publishing the research whether statistically significant or not, policy-makers are just as interested in the negative or insignificant results as they are in the positive results; (7) making the study easy to find and use, the title and abstract of an article are of high importance in determining whether articles are examined in detail or not and used to inform policy; (8) contributing towards systematic reviews on environmental topics, to provide policy-makers with comprehensive, reproducible and updateable syntheses of all the evidence on a given topic.</p

Are autistic traits in the general population stable across development?

There is accumulating evidence that autistic traits (AT) are on a continuum in the general population, with clinical autism representing the extreme end of a quantitative distribution. While the nature and severity of symptoms in clinical autism are known to persist over time, no study has examined the long-term stability of AT among typically developing toddlers. The current investigation measured AT in 360 males and 400 males from the general population close to two decades apart, using the Pervasive Developmental Disorder subscale of the Child Behavior Checklist in early childhood (M = 2.14 years; SD = 0.15), and the Autism-Spectrum Quotient in early adulthood (M = 19.50 years; SD = 0.70). Items from each scale were further divided into social (difficulties with social interaction and communication) and non-social (restricted and repetitive behaviours and interests) AT. The association between child and adult measurements of AT as well the influence of potentially confounding sociodemographic, antenatal and obstetric variables were assessed using Pearson's correlations and linear regression. For males, Total AT in early childhood were positively correlated with total AT (r = .16, p = .002) and social AT (r = .16, p = .002) in adulthood. There was also a positive correlation for males between social AT measured in early childhood and Total (r = .17, p = .001) and social AT (r = .16, p = .002) measured in adulthood. Correlations for non-social AT did not achieve significance in males. Furthermore, there was no significant longitudinal association in AT observed for males or females. Despite the constraints of using different measures and different raters at the two ages, this study found modest developmental stability of social AT from early childhood to adulthood in boys

Evidence for different mechanisms of 'unhooking' for melphalan and cisplatin-induced DNA interstrand cross-links in vitro and in clinical acquired resistant tumour samples

DNA interstrand cross-links (ICLs) are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma) and solid tumours (ovarian cancer) that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy. The repair of ICLs is complex but it is assumed that the 'unhooking' step is common to all ICLs