Modelling the embodied carbon cost of UK domestic building construction: Today to 2050

The construction of new domestic properties contributes 2% of UK territorial greenhouse gas (GHG) emissions. The UK government aims to increase construction of new homes in England by almost a third, to 300,000 per year by the mid-2020s, whilst simultaneously reducing emissions in line with its net zero 2050 commitment. In this paper, for the first time, the upfront embodied carbon cost of constructing domestic properties in the UK by 2050 is quantified. A bottom-up analysis modelling seven domestic building typologies was used, with the material use for each based on current UK practice. Possible interventions to reduce the embodied carbon cost are then analysed. The results show that maintaining today's levels of construction will use the remaining 2050 carbon budget apportioned to house building (160 MtCO 2e) by 2036, and cause a substantial increase in domestic floor area per capita. However, construction could reduce and cease entirely by 2035 without reducing today's living floor area per capita (37.5 m 2), resulting in a substantially reduced cumulative embodied carbon of 88 MtCO 2e by 2050. Increasing living floor area per capita to the EU average of 40.5 m 2, can be achieved within the carbon budget and with zero emissions by 2050. In contrast, increasing house building to government targets will result in double the cumulative emissions than the budget allows. A number of carbon reduction interventions were then investigated. It was found that of to 75% embodied carbon savings can be achieved by simultaneously changing the typology share, increasing material efficiency, increasing conversion from non-residential buildings and increasing the use of timber for structural purposes.</p

Comparative numerical analysis for cost and embodied carbon optimisation of steel building structures

The study investigates an area of sustainable structural design that is often overlooked in practical engineering applications. Specifically, a novel method to optimise the cost and embodied carbon performance of steel building structures simultaneously is explored in this paper. To achieve this, a parametric design model was developed to rapidly analyse code compliant structural configurations based on project specific constraints and rigorous testing of multiple steel beams (UB sections), floor construction typologies (precast or composite) and column layouts that could not be performed manually by engineering practitioners. Detailed objective functions are embedded in the model to compute the cost and life cycle carbon emissions of different material types used in the structure. Results from a comparative numerical analysis of a real case study illustrate that the proposed optimisation approach could guide structural engineers towards areas of the solution space with realistic design configurations, enabling them to effectively evaluate cost and carbon trade-offs. This significant contribution implies that the optimisation model could reduce the time required for the design and analysis of multiple structural configurations especially during the early stages of a project. Overall, the paper suggests that the deployment of automated design procedures can enhance the quality as well as the efficiency of the optimisation analysis.The research described in this paper was financially supported by Innovate UK through the ‘Innovative engineering approach for material, carbon and cost efficiency of steel buildings’ project with reference number 10247

U7 snRNAs induce correction of mutated dystrophin pre-mRNA by exon skipping.

Most cases of Duchenne muscular dystrophy are caused by dystrophin gene mutations that disrupt the mRNA reading frame. Artificial exclusion (skipping) of a single exon would often restore the reading frame, giving rise to a shorter, but still functional dystrophin protein. Here, we analyzed the ability of antisense U7 small nuclear (sn)RNA derivatives to alter dystrophin pre-mRNA splicing. As a proof of principle, we first targeted the splice sites flanking exon 23 of dystrophin pre-mRNA in the wild-type muscle cell line C2C12 and showed precise exon 23 skipping. The same strategy was then successfully adapted to dystrophic immortalized mdx muscle cells where exon-23-skipped dystrophin mRNA rescued dystrophin protein synthesis. Moreover, we observed a stimulation of antisense U7 snRNA expression by the murine muscle creatine kinase enhancer. These results demonstrate that alteration of dystrophin pre-mRNA splicing could correct dystrophin gene mutations by expression of specific U7 snRNA constructs

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

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

Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable

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