Investigation of bone resorption within a cortical basic multicellular unit using a lattice-based computational model

In this paper we develop a lattice-based computational model focused on bone resorption by osteoclasts in a single cortical basic multicellular unit (BMU). Our model takes into account the interaction of osteoclasts with the bone matrix, the interaction of osteoclasts with each other, the generation of osteoclasts from a growing blood vessel, and the renewal of osteoclast nuclei by cell fusion. All these features are shown to strongly influence the geometrical properties of the developing resorption cavity including its size, shape and progression rate, and are also shown to influence the distribution, resorption pattern and trajectories of individual osteoclasts within the BMU. We demonstrate that for certain parameter combinations, resorption cavity shapes can be recovered from the computational model that closely resemble resorption cavity shapes observed from microCT imaging of human cortical bone.Comment: 17 pages, 11 figures, 1 table. Revised version: paper entirely rewritten for a more biology-oriented readership. Technical points of model description now in Appendix. Addition of two new figures (Fig. 5 and Fig. 9) and removal of former Fig.

Monitoring impacts from Council Regulation (EU) No 333/2011: End-of-waste criteria for Al/Fe scrap

On 9 October 2011, Council Regulation 333/2011 came into force establishing criteria by which scrap from iron and steel, aluminium and aluminium alloys could cease to be regulated as waste. This study examines the impacts of the Regulation on scrap availability, trade flows, prices, administrative requirements and environment or human health incidents. Because no data currently distinguishes between waste and end-of-waste compliant scrap, information was collected from the EU Competent Authorities and industry using detailed surveys. Across Europe, approximately 250 companies provided responses to the industry survey (representing approximately one quarter of the membership of the scrap industry associations), with a further 15 submissions from industry associations and 25 from Competent Authorities, although the survey responses were notably skewed towards Italy. The results of the study show that more than 1,100 scrap industry companies are already using the end-of-waste criteria across Europe. Uptake is most pronounced in Italy, where over 1,000 scrap companies generate end-of-waste compliant scrap. This rapid uptake in Italy is due in part to a specific legal framework on secondary raw materials already in place before the introduction of the end-of-waste criteria. In the rest of Europe there are a further 100 scrap companies active in end-of-waste scrap. In terms of the quantity of end-of-waste compliant scrap available on the market, this study estimates that, as a lower bound, at least 15% of EU scrap steel and 10% of EU scrap aluminium is compliant. Importantly, this study has found almost no evidence that end-of-waste has caused any negative impacts on the market, whether that be to scrap quality, availability/trade or on the environment. On the contrary, quite a number of the survey participants, both from industry and Competent Authorities highlighted the perceived benefits of the introduction of end-of-waste for metal scrap. These perceived benefits include: creating a simplified regulatory framework and offering companies greater flexibility and legal certainty. Some companies identified improved scrap quality and increased sales prices. At the expert workshop participants debated several ideas for a future monitoring system. One key conclusion was that there is no urgent need to revisit monitoring in the near future, due to the relatively modest rate of uptake outside Italy and the very few, if any, negative impacts observed so far. A repeat of the industry and authorities’ surveys in 2-3 years times was deemed to be the most appropriate way to monitor end-of-waste for scrap metal, and copper scrap could be added to the scope of that exercise.JRC.J.5-Sustainable Production and Consumptio

Mobile crowdsensing for road sustainability: exploitability of publicly-sourced data

ABSTRACTThis paper examines the opportunities and the economic benefits of exploiting publicly-sourced datasets of road surface quality. Crowdsourcing and crowdsensing initiatives channel the parti..

FluxSat: measuring the ocean-atmosphere turbulent exchange of heat and moisture from space

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gentemann, C. L., Clayson, C. A., Brown, S., Lee, T., Parfitt, R., Farrar, J. T., Bourassa, M., Minnett, P. J., Seo, H., Gille, S. T., & Zlotnicki, V. FluxSat: measuring the ocean-atmosphere turbulent exchange of heat and moisture from space. Remote Sensing, 12(11), (2020): 1796, doi:10.3390/rs12111796.Recent results using wind and sea surface temperature data from satellites and high-resolution coupled models suggest that mesoscale ocean–atmosphere interactions affect the locations and evolution of storms and seasonal precipitation over continental regions such as the western US and Europe. The processes responsible for this coupling are difficult to verify due to the paucity of accurate air–sea turbulent heat and moisture flux data. These fluxes are currently derived by combining satellite measurements that are not coincident and have differing and relatively low spatial resolutions, introducing sampling errors that are largest in regions with high spatial and temporal variability. Observational errors related to sensor design also contribute to increased uncertainty. Leveraging recent advances in sensor technology, we here describe a satellite mission concept, FluxSat, that aims to simultaneously measure all variables necessary for accurate estimation of ocean–atmosphere turbulent heat and moisture fluxes and capture the effect of oceanic mesoscale forcing. Sensor design is expected to reduce observational errors of the latent and sensible heat fluxes by almost 50%. FluxSat will improve the accuracy of the fluxes at spatial scales critical to understanding the coupled ocean–atmosphere boundary layer system, providing measurements needed to improve weather forecasts and climate model simulations.C.L.G. was funded by NASA grant 80NSSC18K0837. C.A.C. was funded by NASA grants 80NSSC18K0778 and 80NSSC20K0662. J.T.F. was funded by NASA grants NNX17AH54G, NNX16AH76G, and 80NSSC19K1256. S.T.G. was funded by the National Science Foundation grant PLR-1425989 and by the NASA Ocean Vector Winds Science Team grant 80NSSC19K0059. M.B. was funded in part by the Ocean Observing and Monitoring Division, Climate Program Office (FundRef number 100007298), National Oceanic and Atmospheric Administration, U.S. Department of Commerce, and by the NASA Ocean Vector Winds Science Team grant through NASA/JPL. H.S. was funded by National Oceanic and Atmospheric Administration (NOAA) grant NA19OAR4310376 and the Andrew W. Mellon Foundation Endowed Fund for Innovative Research at Woods Hole Oceanographic Institution

Effects of low-fat diets differing in protein and carbohydrate content on cardiometabolic risk factors during weight loss and weight maintenance in obese adults with type 2 diabetes

Despite evidence for the benefits of higher-protein (HP) diets in weight loss, their role in type 2 diabetes mellitus (T2DM) management and weight maintenance is not clear. This randomised study compared the effects of a HP diet (38% carbohydrate, 30% protein, 29% fat) to a isocaloric higher-carbohydrate diet (HC: 53%:21%:23%) on cardiometabolic risk factors for 12 weeks in energy restriction (~30% reduction) followed by 12 weeks of energy balance whilst performing regular exercise. Outcomes were measured at baseline and the end of each phase. Sixty-one overweight/obese adults (BMI (body mass index) 34.3 ± 5.1 kg/m2, aged 55 ± 8 years) with T2DM who commenced the study were included in the intention-to-treat analysis including the 17 participants (HP n = 9, HC n = 8) who withdrew. Following weight loss (M ± SEM: -7.8 ± 0.6 kg), there were significant reductions in HbA1c (–1.4% ± 0.1%, p < 0.001) and several cardiometabolic health risk factors. Improvements were sustained for 12 weeks when weight was stabilised and weight loss maintained. Both the HP and HC dietary patterns with concurrent exercise may be effective strategies for weight loss and weight maintenance in T2DM although further studies are needed to determine the longer term effects of weight maintenance

Human occupation of northern Europe in MIS 13: Happisburgh Site 1 (Norfolk, UK) and its European context

The timing, environmental setting and archaeological signatures of an early human presence in northernEurope have been longstanding themes of Palaeolithic research. In the space of 20 years, the earliestrecord of human occupation in Britain has been pushed back from 500 ka (Boxgrove) to 700 ka (Pakefield)and then to >800 ka (Happisburgh Site 3). Other sites also contribute to this record of humanoccupation; a second locality at Happisburgh, referred to as Site 1, attests to human presence at around500 ka (MIS 13). This paper provides the first comprehensive account of research undertaken at HappisburghSite 1 since 2000. The early human landscape and depositional environment was that of a riverfloodplain, where an active river channel, in which a grey sand was deposited, was abandoned, forming afloodplain lake, with marginal marsh/swamp environments, which was infilled with organic mud. Thissuccession is sealed by Middle Pleistocene glacial deposits. An assemblage of 199 flint flakes, flake toolsand cores was recovered from the grey sand and organic mud. The evidence from Happisburgh Site 1 isplaced in the context of the wider British and European MIS 13 record. The growing evidence for asignificant dispersal of humans into northern Europe around 500 ka raises critical questions concerningthe environmental conditions under which this took place. We also consider the evolutionary andbehavioural changes in human populations that might have enabled the more widespread and persistentperiod of human presence in northern Europe at this time.</p

Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models.

Leber congenital amaurosis type 10 (LCA10) is a severe inherited retinal dystrophy associated with mutations in CEP290. The deep intronic c.2991+1655A>G mutation in CEP290 is the most common mutation in LCA10 individuals and represents an ideal target for oligonucleotide therapeutics. Here, a panel of antisense oligonucleotides was designed to correct the splicing defect associated with the mutation and screened for efficacy and safety. This identified QR-110 as the best-performing molecule. QR-110 restored wild-type CEP290 mRNA and protein expression levels in CEP290 c.2991+1655A>G homozygous and compound heterozygous LCA10 primary fibroblasts. Furthermore, in homozygous three-dimensional iPSC-derived retinal organoids, QR-110 showed a dose-dependent restoration of mRNA and protein function, as measured by percentage and length of photoreceptor cilia, without off-target effects. Localization studies in wild-type mice and rabbits showed that QR-110 readily reached all retinal layers, with an estimated half-life of 58 days. It was well tolerated following intravitreal injection in monkeys. In conclusion, the pharmacodynamic, pharmacokinetic, and safety properties make QR-110 a promising candidate for treating LCA10, and clinical development is currently ongoing.This study was funded by ProQR. iPSC work in the Cheetham lab is also supported by the Wellcome Trust, Fight for Sight, RP Fighting Blindness, and Moorfields Eye Charity