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The increasing availability of high-throughput datasets allows amalgamating research information across a large body of genome regulation studies. Given the recent success of meta-analyses on transcriptional regulators, epigenetic marks, and enhancer:gene associations, we expect that such surveys will continue to provide novel and reproducible insights. However, meta-analyses are severely hampered by the diversity of available data, concurring protocols, an eclectic amount of bioinformatics tools, and myriads of conceivable parameter combinations. Such factors can easily bar life scientists from synthesizing omics data and substantially curb their interpretability. Despite statistical challenges of the method, we would like to emphasize the advantages of joining data from different sources through vote-counting and showcase examples that achieve a simple but highly intuitive data integration.

Cell cycle-dependent gene transcription is tightly controlled by the retinoblastoma (RB):E2F and DREAM complexes, which repress all cell cycle genes during quiescence. Cyclin-dependent kinase (CDK) phosphorylation of RB and DREAM allows for the expression of two gene sets. The first set of genes, with peak expression in G1/S, is activated by E2F transcription factors (TFs) and is required for DNA synthesis. The second set, with maximum expression during G2/M, is required for mitosis and is coordinated by the MuvB complex, together with B-MYB and Forkhead box M1 (FOXM1). In this review, we summarize the key findings that established the distinct control mechanisms regulating G1/S and G2/M gene expression in mammals and discuss recent advances in the understanding of the temporal control of these genes.

Objectives In the microbiological diagnosis of periprosthetic joint infection (PJI), there is much discussion about the methodology of obtaining proper specimens, the processing technique, and suitable culture media. This retrospective study was conducted to analyse the accuracy of our culture techniques. Methods Tissue samples and components from 258 patients after revision arthroplasty of the hip, knee, and shoulder were investigated, and the results of tissue cultures (TC) were compared to those of sonicate fluid cultures (SFC). Furthermore, an evaluation was performed of the influence of different culture media on the detection rate. Results PJI was confirmed in 186 patients. The overall sensitivity of TC was no different to that of SFC (91.3% vs 90.8%, P = 1). In 153 cases (82.3%), TC and SFC showed concordant positive results. Results were discordant in 33 cases (17.7%). When differentiated according to the type of infection, TC showed significantly better results than SFC in detecting polymicrobial infections (97.0% vs 67.0%, P = 0.004). There were also significant differences between the culture media regarding the yield of microorganisms. Conclusions TC was more effective in detecting co-infections. The best results were obtained using both TC and SFC. The choice of culture media has a significant influence on the quality of results.

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7(−/−) mice. Although palmitoylation of barttin in kidneys of Zdhhc7(−/−) animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7(−/−) mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.

Summary Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent an attractive model to investigate CM function and disease mechanisms. One characteristic marker of ventricular specificity of human CMs is expression of the ventricular, slow β-myosin heavy chain (MyHC), as opposed to the atrial, fast α-MyHC. The main aim of this study was to investigate at the single-cell level whether contraction kinetics and electrical activity of hESC-CMs are influenced by the relative expression of α-MyHC versus β-MyHC. For effective assignment of functional parameters to the expression of both MyHC isoforms at protein and mRNA levels in the very same hESC-CMs, we developed a single-cell mapping technique. Surprisingly, α- versus β-MyHC was not related to specific contractile or electrophysiological properties of the same cells. The multiparametric cell-by-cell analysis suggests that in hESC-CMs the expression of genes associated with electrical activity, contraction, calcium handling, and MyHCs is independently regulated., Highlights • Single-cell mapping technique allows multiparametric characterization of hESC-CMs • Twitch and action potential kinetics are independent of MyHC isoform in hESC-CMs • Myosin-mRNA levels are only weakly correlated with respective protein levels, In this article, Natalie Weber and colleagues developed a single-cell mapping technique for multiparametric analysis of hESC cardiomyocytes (hESC-CMs). Characterization of function (twitch and action potential) in direct relation to the expressed myosin heavy chain isoform by multiparametric analysis suggests that in hESC-CMs the expression of genes associated with electrical activity, contraction, calcium handling, and myosin heavy chains is independently regulated.

Summary Background & aims Bariatric surgery has been well established and considered the treatment of choice in morbid obesity. However, some patients refuse surgery because long-term effects have not been fully elucidated, quality of life might change and lifelong supplementation with vitamins and trace elements may be required. Our aim was to exhaust non-surgical treatment modalities and to evaluate such an intensified treatment alternative. Methods A total of 206 patients (mean age = 46 years; BMI = 49 kg/m2) enrolled since 2013 into a non-surgical multimodality obesity treatment program covered by major health insurances were prospectively evaluated over a three year period. The 12-month treatment course comprised 57 h cognitive-behavioral therapy, 53.5 h physical exercise training, and 43.5 h nutritional therapy offered in small groups. Weight loss was induced by a formula-based, very low-calorie diet for 12 weeks in combination with a gastric balloon. The primary outcome was relative weight loss (RWL). Secondary outcome measures were waist-to-hip ratio, blood pressure, antihypertensive drug treatment, anti-diabetic medication, HbA1c, and quality of life. Results 166 Patients (81%) completed treatment. Mean (±SD) weight loss after 12 months for women and men were 28.8 kg (±14.7) and 33.7 kg (±19.5), respectively, among completers. RWL was 21.9% (±10.0) and excess weight loss (EWL) was 46.9% (±22.2), whereas intention-to-treat analysis revealed a RWL of 20.0% (±10.4) and an EWL of 42.9% (±22.9). Weight loss was accompanied by improved quality of life, lowered HbA1c values, and a significantly reduced need of antihypertensive and diabetes medications over the study period. Three year follow-up data from the first 78 patients (76% follow-up rate) revealed a RWL of 13% (±13.1) and an EWL of 27.2% (±28.8). The majority of patients (51%) maintained a RWL of 10% or more, and 44% had an EWL > 30%. Conclusions In patients with morbid obesity, an intensified non-surgical multimodality treatment program may achieve significant and sustained weight loss accompanied by improvement of disease markers as well as quality of life for at least three years.

Due to the inherent uncertainties of rock mass properties, construction planners of hard rock tunnels have difficulty achieving on-time completion within budget. Despite the potential benefits of adapting stochastic programming and feedback control approaches for decision-making for excavation schedules, the lack of formal representations of the planners' rationales required to estimate the costs and durations of excavation schedules makes the implementation of these approaches extremely challenging. To address these limitations, the authors developed an ontology that represents the estimation rationales (e.g., transition costs and durations among excavation methods, multiple sets of rock mass properties, and schedule adjustment policies). This ontology enables planners to explicitly describe more the comprehensive information required to consistently estimate the costs and durations of excavation schedules for both preconstruction and construction compared to the current practices and the existing studies. Further research that accounts for learning effects resulting from transitions among excavation methods would make cost and duration estimations for excavation schedules more realistic.

Uncertain product characteristics in construction projects make it difficult for planners to develop schedules that reduce expected costs, durations, and associated risks. To overcome these challenges in hard rock tunnel projects, this research introduces a methodology that adapts stochastic programming and feedback control approaches for their excavation. Such approaches require rapid and consistent implementation using up-to-date information provided in a probabilistic manner throughout the entire excavation; therefore, the authors tailored dynamic programming and tunneling risk analysis methods for the methodology to address multiple sets of rock mass properties (RMPs), transitions among excavation methods at the excavation method level, decision-making times, and schedule adjustment policies (SAPs). In preconstruction and construction, the methodology allows construction planners of hard rock tunnels to generate a total-cost-optimal excavation schedule for each set of RMPs and evaluate the excavation costs and durations of schedules for multiple sets of RMPs in a timely and consistent manner by considering SAPs. Further research is required to take into account multiple advances of excavation methods for schedule generation and evaluation. Database subject headings Automated schedule generation, hard rock tunnel, uncertainties in rock mass properties, feedback control, stochastic programming, earthwork risk analysis.

For many years, the practice of implementing a design stage building energy performance simulation (BEPS) model has been overshadowed by a perceived lack of accurate results, when predicted model figures are compared with actual usage, post-occupancy. With the worldwide push for more efficient buildings, this perception of lack of accuracy is becoming an important issue. Research has primarily focussed on the examination of post-occupancy calibrated models. In the construction industry, most BEPS models are built to show compliance with national standards and/or regulations, such as ASHRAE or the UK's Part L, or a voluntary code such as LEED™. This is done at the design stage, before construction has commenced, as compliance usually must be shown as part of the regulatory planning and early design process. Examining two very different buildings, a methodology has been devised to identify the groups of influential parameters within a design stage BEPS model and determine quantitatively, how influential these groups might be on the predicted energy usage. The study finds that many similar issues exist in both building's design models, even though the buildings are in different countries, of different operational characteristics and had design models built at differing levels of complexity. The process of developing the most accurate design stage BEPS model is broken down into nine possible model stages and each of the nine is quantitatively assessed. The study gives pertinent guidance to an energy modeller as to the likely accuracy of their model, depending on what data has been used in the model's creation.

Buildings made of additively manufactured (AM) components are likely to have higher energy efficiency and environmental sustainability than conventionally manufactured (CM) buildings. AM building components can be highly customizable, produced with less material, and installed rapidly due to simplified or eliminated connections. Given the continued development of AM and CM technologies and the many market and use scenarios of buildings that prioritize different performance criteria, building components will likely be produced with a mix of AM and CM technologies for the foreseeable future. However, since building professionals are not informed about the value of AM through transparent metrics like cost and environmental impact they are unable to make well-informed decisions about the application of AM in the building sector. Case studies of two AM metallic building components, a large window frame and a bracket, carried out by the authors in collaboration with a global building facade contractor demonstrated that AM for building components is technologically feasible and can lower environmental impact by up to 87%, but is cost-prohibitive given the number of components in a building and the time available to fabricate and install them (in some cases, the manufacturing cost and schedule were about 90% higher and 91% longer respectively). Based on the case studies, a 19-step assessment method was developed with the aim to allow building professionals to rapidly and consistently assess the applicability (A), schedule (S), environmental impact (E), and cost (C) of producing building components with AM vs. CM. The formal, partially automated application of the method showed that it reduces the effort required for the ASEC analyses by 97% and improves the consistency of the A, S, and C analyses. However, the inconsistencies of the environmental impact (E) analysis remained due to the inherent flexibility of the life cycle assessment (LCA) method standardized by ISO14040. Future work includes fuller automation of the method, generality tests and extension of this approach to other industry sectors.

Structural health monitoring relies on mechanical and thermal measurements of the component. Whereas for a strain gauge on the surface of a component a structural model is needed to gain knowledge of the internal state at the point of interest, integrated sensors can measure strain and temperature directly inside the component without the influence of adhesives required to mount the sensor on the surface. Integrating sensors in gravity die casting leads to certain requirements. The Sensors have to withstand the harsh conditions of the casting process at temperatures around 750 °C and a shrinkage of 1.1 % during solidification of the melt. The yield of embedded sensors can be increased, if the sensor-substrate is based on the same coefficient of thermal expansion, which reduces stress during the cooling phase and at the solidification point of the melt through shrinkage. Aluminum as substrate keeps the amount of foreign matter in the casting good at a minimum. In this paper we present the first approach to integrate sensors on aluminum substrates during gravity die casting. The design, fabrication and embedding of screen printed thick-film sensors is shown. The embedded sensors are examined before and after their integration into gravity die-cast aluminum in terms of thermal behavior and diffusion.

This paper presents a new method to quickly and accurately estimate the material, fabrication, and erection cost of steel frames based on early-design information. To use the proposed Integrated Steel Design (ISD) method, engineers first upload a structural model consisting of a frame layout with preliminary member sizes and connection types specified. The frame connections are then automatically detailed to produce a bill of quantities suitable for fabrication. Next, the total installed cost is estimated based on unit rates maintained by suppliers on a secure web portal. Finally, the cost feedback is provided in the context of the 3-D model in near real-time. We apply the proposed analytical method to several moment frames to illustrate its advantages compared to more approximate approaches. These initial results demonstrate the potential of the ISD method to improve early stage design decision-making through better vertical integration of project information in the AEC industry.

This paper introduces an autonomous payment administration solution, integrating blockchain-enabled smart contracts and robotic reality capture technologies. The construction progress is captured, analyzed, and documented respectively using sensing, machine intelligence, and as-built building information models (BIM). The progress data is stored in a distributed manner using content addressable file sharing; it is then broadcasted to a smart contract which administers payments and transfers lien rights respectively using crypto currencies/tokens and non-fungible tokens (NFT). The method was successfully implemented for payments to 7 subcontractors in two real-world commercial construction projects in Canada and United States where progress was captured using a camera-equipped unmanned aerial vehicle (UAV) and an unmanned ground vehicle (UGV) equipped with a laser scanner. The method eliminates reliance on today's heavily intermediated payment applications and showed promise for achieving accurate, efficient, and timely payment administration. Future work should further explore the connections between off- and on-chain realities.

This work assesses the impact of blockchain and smart contracts on the visibility of construction supply chain and in the context of payments (intersection of cash and product flows). It uses comparative empirical experiments (Charrette Test Method) to draw comparisons between the visibility of state-of-practice and blockchain-enabled payment systems in a commercial construction project. Comparisons were drawn across four levels of granularity. The findings are threefold: 1) blockchain improved information completeness and information accuracy compared with the digital state-of-practice solution; 2) the improvements were significantly more pronounced for information queries that had higher product, trade, and temporal granularity; and 3) blockchain-enabled solution was robust when faced with more granular information queries, while the conventional solution experienced 50% and 66.7% decline respectively in completeness and accuracy of information. The paper concludes with a discussion of mechanisms contributing to visibility and the implications for the construction industry.

Background: Education is related to dementia risk. Researchers in public health often treat education as a modifiable risk factor, implying that prolonging education may reduce dementia incidence. This reasoning rests on the largely untested assumption that education has causal effects on dementia risk. Methods: We used variance in education induced by a compulsory schooling reform, which extended Swedish primary school (Folkskola) from 6 to 7 years as a tool for studying direct causal effects of education on dementia risk. The reform was implemented gradually in school districts and had minor spillover effects. We studied 18 birth cohorts (1920-1937), excluding individuals with unknown reform status, those who died, emigrated, or received dementia diagnosis prior to 65 years of age. The outcome was dementia diagnosis in the National Inpatient and Cause of Death Registers. The reform allowed us to study direct effects of prolonged education with high validity and statistical precision. In the main analyses, we employed sex-stratified Cox survival models with stratified baseline hazards at the school-district level, used chronological age as the time scale, and dummy-coded cohort effects. Findings: 1,341,842 individuals were included. The reform did not affect the risk of dementia diagnosis in a statistically significant way. The estimates and associated confidence intervals (women: HR = 1.01; 95% CI = 0.97-1.04; men: HR = 1.02; 95% CI = 0.99-1.06; all: HR = 1.01; 95% CI = 0.98-1.04) indicate that any direct effect is likely of a negligible or very small magnitude. Sensitivity analyses targeting pre-post changes, differences in healthcare-seeking behavior, and impact of exposure misclassification left results essentially unaltered. Interpretation: Longer education, at least in the absence of sizable spillover effects to adult socio-economic factors, cannot be uncritically assumed to substantially reduce the risk of moderate to severe dementia. Funding Statement: FORTE (2013-2277) and Swedish Research Council (446-2013-7189) to ML. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was approved by the Regional Ethical Review Board in Stockholm (Case number: 2010/1185-31/5).

To apply prefabricated wall panels to construction projects in a cost-effective manner, it is important to reduce logistics costs for stacking, transportation, and installation processes. However, currently stacking planners often generate stacking plans that incur unnecessary logistics costs. For example, generated plans often result in stacks that require panel reshuffling work or unstable stacks that require additional braces. To enable the planners to generate stacking plans rapidly and systematically considering not only the constraints of reshuffling effort and panel stability but also the objective of using the minimal number of trailers, the authors developed a methodology based on the first fit algorithm. By applying the methodology to two case projects, the authors found that it generates stacking plans with lower reshuffling effort and higher panel stability while using the same number of trailers and in a fraction of the time compared to the conventional practice.

Climate adaptation for coastal infrastructure projects raises unique challenges because global-scale environmental changes may require similar projects to be completed in many locations over the same time frame. Existing methods to forecast resource demand and capacity do not consider this phenomenon of a global change affecting many localities and the resulting increased demand for resources. Current methods do not relate to the most up-to-date climate science information, and they are too costly or too imprecise to generate global, regional, and local forecasts of “climate-critical resources” that will be required for infrastructure protection. They either require too much effort to create the many localized designs or are too coarse to consider information sources about local conditions and structure-specific engineering knowledge. We formalized the concept of a “minimum assumption credible design” (MACD) to leverage available local information (topography/bathymetry and existing infrastructure) and the essential engineering knowledge and required construction materials (i.e., a design cross-section template). The aggregation of the resources required for individual local structures then forecasts the resource demand for global adaptation projects. We illustrate the application of the MACD method to estimate the demand for construction materials critical to protect seaports from sea-level-rise-enhanced storm surges. We examined 221 of the world’s 3,300+ seaports to calculate the resource requirements for a coastal storm surge protection structure suited to current upper-bound projections of two meters of sea level rise by 2100. We found that a project of this scale would require approximately 436 million cubic meters of construction materials, including cement, sand, aggregate, steel rebar, and riprap. For cement alone, ∼49 million metric tons would be required. The deployment of the MACD method would make resource forecasts for adaptation projects more transparent and widely accessible and would highlight areas where current engineering knowledge or material, engineering workforce, and equipment capacity fall short of meeting the demands of adaptation projects.

Threading dislocations in heteroepitaxial diamond films deposited on Ir/YSZ/Si(001) substrates with an off-axis angle of 4° towards [100] have been studied by cross-section transmission electron microscopy using the weak-beam dark-field (WBDF) technique for Burgers vector identification and large-angle convergent beam electron diffraction (LACBED) in order to facilitate a precise crystallographic determination of the local growth surface. Close to the diamond/iridium interface the films contain a high density of dislocations of both 90° and 45° types. Within the first micron of film growth their density decreases drastically by annihilation or mutual interaction resulting in a preference for 45° type dislocations. Vicinal growth surfaces cause a tilt of the dislocation line vector away from the crystallographic [001] axis in the step-flow direction. Tilting is influenced by gas phase impurities. With 100 ppm nitrogen in the feed gas, step bunching produces a structured surface consisting of an alternating sequence of terraces with reduced off-axis angle crystallographically close to (001) and risers with increased off angle. The dislocations with lines close to [001] during terrace growth abruptly tilt by more than 20° at the transition to riser growth. The appearance of several discrete tilt angles during nitrogen free growth without pronounced step bunching is attributed to the corresponding Burgers vectors which cause either effective climb for the lower angles or effective glide for the higher ones. The present observations are of high relevance for improved strategies towards a further dislocation density reduction and an efficient control of intrinsic stress formation.

Virtual-work methods on simplified models can rapidly provide the optimal distribution of material within a frame structure with computational efficiency that is only weakly dependent on the problem size. The drawbacks to these methods are that they require simplified objective and constraint functions, and the results do not always translate to a near-optimal solution from the simplified model to the exact model. The main contribution of this paper is a new method that expands the applicability of traditional virtual-work methods by using the Pareto set of sizing variables related to any objective and constraint functions, to include their exact stiffness contribution and a detailed monetary-cost function. Using the Pareto set enables frame-sizing solutions with optimal or near-optimal cost, complying with any number of global compliance constraints, and all typical local constraints. This method is compared to several metaheuristic methods. Metaheuristic optimization methods are the typical choice for problems with complex objective and constraint functions, as they have no restrictions on the types of variables or the functions they are suited to. The proposed method consistently achieves improved solution quality, and orders-of-magnitude improved computational efficiency over the sampled metaheuristic methods. These improvements facilitate optimization of an expanded set of sizing problems that are currently impractical, and with better results.

We describe a method that allows an easy separation of a single crystal diamond layer grown by homoepitaxy in a chemical vapour deposition (CVD) process from the growth substrate. In a first step a thin SiO2 layer is deposited on top of the seed crystal. This layer is patterned by photolithography and reactive ion etching (RIE) to obtain a mask with open windows and covered areas. In an epitaxial lateral overgrowth (ELO) process diamond is grown homoepitaxially through the free window areas and laterally across the covered areas until the mask is completely covered by diamond. During cool down from deposition temperature tensile stress σzz perpendicular to the growth surface is formed in the diamond bridges grown in the window areas. The absolute value of the stress depends on growth temperature, difference in coefficients of thermal expansion (CTE) between diamond and the specific mask material and finally on the fill factor (FF). The stress amplitude can reach more than +2 GPa and stress intensity factors in the range of typical fracture toughness values reported for single crystal diamond. Our experiments demonstrate that an immediate crack formation can be achieved which facilitates an easy separation between the CVD grown diamond layer and the seed crystal. The described concept develops its highest potential with increasing lateral dimensions of the seed wafers.

The development of large-scale projects has comprehensive effects on economic, social, and environmental sustainability. These effects are closely related to the time of the development. The evaluation of various time-dependent metrics for multiple development scenarios supports stakeholders in making informed decisions for their master plans. However, current practice lacks an integrated methodology that enables automatic evaluation of the metrics and visualization of the evaluation results, making the master planning process arduous. The existing Building Information Model (BIM)-based decision-support methods have been used to create alternatives rapidly, evaluate multiple metrics, and visualize alternative plans prior to actual construction; however, those methods have primarily focused on building design and construction. Therefore, they are limited in their ability to provide an appropriate methodology for master planning of large-scale development projects. This paper introduces the Development Strategy Formulation and Evaluation Methodology (DSFEM), which is tailored for the master plans of large-scale developments. Based on this methodology, we developed the Development Strategy Simulator (DSS), an automated and integrated decision-support system. We applied the DSFEM and DSS to the Qatar Economic Zone (QEZ) project as a case study. The application results demonstrate that the DSFEM and DSS allow for automatic and integrated evaluation and visualization of development scenarios and their metrics, supporting multiple stakeholders in making timely and informed decisions.

A growing body of research indicates that climate change is having and will continue to have a range of negative impacts on social–environmental systems. Reducing the vulnerability and increasing the resilience of these systems has thus becomes a focus of research, disaster planning, and policy-making. Seaports, located in environmentally sensitive, high-risk locations, are particularly vulnerable to severe storms and the increased sea levels resulting from such climate changes. Planning and policy making for seaports must therefore consider the human factor, that is the population potentially vulnerable to climate change induced events and also the complex network of stakeholders that depend on their functionality. An increasing body of literature suggests that, for planners to be effective in increasing resiliency of social-environmental systems to climate change-related events and other hazards, they must understand and incorporate the perceptions and concerns of the stakeholders in their assessment and planning processes. This study uses empirical evidence collected through case studies of two particularly exposed ports in the US: Gulfport (Mississippi) and Providence (Rhode Island), in order to examine how port stakeholders such as port operators, municipal planners, port tenants, and coastal managers, perceive storm impacts and the seaport's vulnerability, and how their planning and policy making address these perceived concerns. Results suggest the following: (1) Port stakeholders of Gulfport (MS) and Providence (RI) identified a wide range of direct damages, indirect costs, and intangible consequences of a hurricane hitting the port; (2) these impacts would result in costs that would be borne by all port stakeholders as well as society as a whole; and (3) in Providence and Gulfport, plans and policies that address storm resilience for the ports did not include the concerns of many stakeholders.

This paper offers a novel method to rank residential appliance energy efficiency utilizing energy efficiency frontiers. The method is validated using a real-world case study of 4231 buildings in Ireland. Our results show that structural factors have the largest impact on energy efficiency, followed by socioeconomic factors and behavioral factors. For example, households with high penetration of efficient lightbulbs and double-glazed windows were on average 4 and 3.5% more efficient than others. Households with the head of household having higher education are on average 1.3% more efficient than their peers. Finally, households that track their energy savings are on average 0.4% more efficient than others. Furthermore, installing heater timers, wall insulation, and living in owned residences were correlated with higher efficiency. Generally, families with kids who have full-time employment and are highly-educated are more efficient compared to families with no kids, or families with retirees or unemployed members. This result has important implications for both targeting and messaging of energy efficiency programs. Some behavioral factors demonstrated significant impact on appliance energy efficiency. For instance, households that expressed interest in making major energy-saving lifestyle changes scored higher efficiency ranks on average. Conversely, households that expressed doubt about their motivation to save energy ranked lower in efficiency. This finding validates the role of educational programs to increase awareness about energy efficiency and its importance. In short, our results show that a data-driven analysis of a population is needed to develop a balanced view of the drivers of energy efficiency, and to devise a targeted approach to improve homes’ energy efficiency.

Summary To harness the potential of human pluripotent stem cells (hPSCs), an abundant supply of their progenies is required. Here, hPSC expansion as matrix-independent aggregates in suspension culture was combined with cardiomyogenic differentiation using chemical Wnt pathway modulators. A multiwell screen was scaled up to stirred Erlenmeyer flasks and subsequently to tank bioreactors, applying controlled feeding strategies (batch and cyclic perfusion). Cardiomyogenesis was sensitive to the GSK3 inhibitor CHIR99021 concentration, whereas the aggregate size was no prevailing factor across culture platforms. However, in bioreactors, the pattern of aggregate formation in the expansion phase dominated subsequent differentiation. Global profiling revealed a culture-dependent expression of BMP agonists/antagonists, suggesting their decisive role in cell-fate determination. Furthermore, metallothionein was discovered as a potentially stress-related marker in hPSCs. In 100 ml bioreactors, the production of 40 million predominantly ventricular-like cardiomyocytes (up to 85% purity) was enabled that were directly applicable to bioartificial cardiac tissue formation., Graphical Abstract, Highlights • Efficient cardiac differentiation protocol in suspension by chemical Wnt modulators • Differentiation is CHIR concentration dependent, but aggregate size independent • Bioreactor-controlled hPSC expansion dictates subsequent lineage differentiation • Metallothionein is a potentially stress-induced marker of hPSC culture, In this article, Zweigerdt and colleagues show hPSC expansion as matrix-independent aggregates in suspension culture combined with efficient and scalable cardiac differentiation in stirred tank bioreactors. The strategy enables the generation of 40 million cardiomyocytes (up to 85% purity) of predominantly ventricular-like phenotype per run that were directly applicable to bioartificial cardiac tissue formation.

Fully Constrained Design (FCD) is a new method for discrete sizing optimization of steel structures that balances computational efficiency with solution quality for application to large-scale problems. The proposed method is based on optimality criteria, but does not require gradient information and handles discrete variables. Based on benchmarking studies, FCD produces superior quality solutions to optimality criteria (>4%), but inferior to heuristic methods (

Sharing temporary structures minimizes the risks and costs associated with their set-up and break-down. Yet sharing makes temporary structure planning and re-planning more complex, as construction engineers need to understand the conditions of activities to determine the accessibility and sharing possibilities. BIM (building information modeling) technology can extract and process geometric and action data in 3D models. Using BIM can increase consistency and speed in identification of sharing solutions for temporary structures. At present, the construction industry does not leverage advances in BIM for planning temporary structures because it lacks formalization that defines key properties and relationship variables for sharing. In this paper, the geometric and action conditions affecting temporary structure sharing are examined to put forth a formalization for a computer application (a proprietary tool developed by the primary author) called the Temporary Structure-Planning Generator (TSPG). The formalization for the TSPG allows construction engineers to rapidly generate multiple temporary structure-sharing options with a selection consistency not yet seen in current construction practice.

Combined sewer overflows (CSO) often present complex geometries and variable hydraulic conditions that do not fit any standards and make it tough to measure their discharge. A CFD-based methodology to assess the overflow discharge and the related uncertainties using measurements of the water depth in sewage networks, and especially in non-standard CSOs, has therefore been developed. This methodology presents several advantages: it includes the optimization of the sensor location, integrates the boundary conditions variability and calculates the global uncertainty related to the chosen height-discharge relationship. Moreover, the final instrumentation requires little maintenance and can be secured. This particular study focuses on a one-site validation of this methodology through the example of “Herbet” CSO, one of the biggest of Clermont-Ferrand's sewer network, FRANCE (up to 4 m 3 /s). This article also aims learning by feedback from the on-site measurements and defining a method to validate the acquired data. It is particularly interesting to secure the measurement and detect a possible drift in a sensor in real-time.

This paper describes a new bi-level hierarchical method for optimizing the shape and member sizes of both determinate and indeterminate truss structures. The method utilizes a unique combination of algorithms that are organized hierarchically: the Fully Constrained Design (FCD) method for discrete sizing optimization is nested within SEQOPT, a gradient-based optimization method that operates on continuous shape variables. We benchmarked the method against several existing techniques using numerical examples and found that it compared favorably in terms of solution quality and computational efficiency. We also present a successful industry application of the method to demonstrate its practical benefits.

Look-ahead schedules (LASs) in the finishing phase of complex projects produced with sufficient detail can help prevent conflict, ensure correct work sequence, and facilitate a fluent workflow for a crew, preventing rework. Unfortunately, such LASs are rarely used in these projects because of the time-consuming schedule generation process, the high probability of introducing errors into the LASs and the inability to find the close-to-optimum LAS from the vast number of feasible alternatives. This paper proposes an automated LAS generation (ALASG) method addressing these challenges. A software prototype developed based on the ALASG method is presented and a simulation-based approach is introduced to find close-to-optimum LASs quickly in terms of construction duration or cost for a case study. The proposed method contributes to the field of automated project scheduling, particularly automated look-ahead scheduling, through the quick generation of error-free, close-to-optimum LASs for the finishing phase of complex projects.

The beams extracted from thermal neutron sources such as nuclear reactors are monochromatised by Bragg diffraction using imperfect single crystals with an angular mosaic spread of typically 0.2–0.8°. For neutron wavelengths below 1.5 A, the highest reflectivity of all crystalline materials is expected for diamond. Nowadays diamond single crystals with an appropriate mosaic spread exceeding a thickness of 1 mm can be grown by heteroepitaxy on an Ir/yttria-stabilised zirconia bilayer deposited on a Si(001) single crystal. To explain the observed neutron reflectivity being below the theoretically expected value, we have studied the spatial distribution of the mosaic structure of two crystals by high resolution X-ray diffraction using a laboratory X-ray source and synchrotron radiation. The first sample (A) showed a uniform mosaic spread of 0.18° ± 0.02° across the 1 cm wide sample. The peak shift of the X-ray rocking curves of 0.08° indicated a weak curvature of the crystal lattice. The measured absolute neutron peak reflectivity of 34% corresponded to 90% of the value predicted by theory. The peak width of the neutron rocking curve for the second sample (B) was twice as big, but here the peak reflectivity of 13% corresponded to only half of the theoretical value. This unfavourable behaviour could be assigned to a substantial spatial variation of the mosaic spread deduced from the synchrotron X-ray studies. X-ray diffraction with high spatial resolution indicated a mosaic block size below 50 μm for sample A. This was consistent with chemical etching experiments on the surface of a comparable sample which showed both randomly distributed dislocations and others that are arranged in boundaries of several 10 μm large domains.

Space-use can only be effectively determined when space, user, and activity perspectives are taken into account simultaneously. We develop a knowledge-based framework for automated space-use analysis to enable analyzers to predict and update space utilization simultaneously considering these three perspectives with computational assistance. The framework includes the formalization of the concepts for space-use analysis such as users, user activities, spaces, equipment, and space utilization, the ontological relationships among the concepts, and the automated space-use analysis process. We demonstrate the effectiveness of the proposed framework through a trial run on select areas in an academic building at Stanford University. Our results show that the proposed framework can support iterative refinement of the architectural design and its usage by predicting the utilization and visualizing the results automatically. This automation in space-use analysis contributes a consistent, clear, and efficient means of analyzing space-use in support of architects' and clients' decision-making about the design.

We propose a method to examine structural and behavioral determinants of residential electricity consumption, by developing separate models for daily maximum (peak) and minimum (idle) consumption. We apply our method on a data set of 1628 households' electricity consumption. The results show that weather, location and floor area are among the most important determinants of residential electricity consumption. In addition to these variables, number of refrigerators and entertainment devices (e.g., VCRs) are among the most important determinants of daily minimum consumption, while number of occupants and high-consumption appliances such as electric water heaters are the most significant determinants of daily maximum consumption. Installing double-pane windows and energy-efficient lights helped to reduce consumption, as did the energy-conscious use of electric heater. Acknowledging climate change as a motivation to save energy showed correlation with lower electricity consumption. Households with individuals over 55 or between 19 and 35 years old recorded lower electricity consumption, while pet owners showed higher consumption. Contrary to some previous studies, we observed no significant correlation between electricity consumption and income level, home ownership, or building age. Some otherwise energy-efficient features such as energy-efficient appliances, programmable thermostats, and insulation were correlated with slight increase in electricity consumption.

Decisions made during a building's early design stages critically determine its environmental impact. However, designers are faced with many decisions during these stages and typically lack intuition on which decisions are most significant to a building's impact. As a result, designers often defer decisions to later stages of the design process. Life-cycle assessment (LCA) can be used to enable better early stage decision-making by providing feedback on the environmental impacts of building information modeling (BIM) design choices. This paper presents a method for applying LCA to early stage decision-making in order to inform designers of the relative environmental impact importance of building component material and dimensioning choices. Sensitivity analysis is used to generalize the method across a range of building shapes and design parameters. An impact allocation scheme is developed that shows the distribution of embodied impacts among building elements, and an impact reduction scheme shows which material and thickness decisions achieve the greatest embodied impact reductions. A multi-building residential development is used as a case study for introducing the proposed method to industry practice. Results show that the method can assist in the building design process by highlighting those early stage decisions that frequently achieve the most significant reductions in embodied carbon footprint.

Flexible problem formulation is required for product model-based thermal analysis using multidisciplinary design optimization (MDO) environments for speed, accuracy, scalability, and cost-effectiveness in the Architecture, Engineering, and Construction (AEC) industry. The integration of daylighting simulation into an MDO process, however, presents several implementation challenges. In current practice, the process of an architect, engineer, or daylighting consultant to determine how to analyze a given building design for daylighting performance is frequently subjective, time-consuming, and inconsistent. Furthermore, long simulation time requirements for daylighting significantly hinder the realization of many benefits from MDO. The determination of which spaces in a building are sufficiently different to warrant an independent daylighting analysis is based primarily on building physics, building design criteria, and operating schedules (e.g. occupancy schedules). This characteristic of daylighting analysis creates the opportunity to develop intelligent mechanisms to automate the identification of the building spaces for analysis using performance-based methods, simulation of spatial results, and the scaling of spatial simulation results to whole building performance metrics in a fraction of the time it takes in current practice. Such methods would result in improved speed, accuracy, scalability, and cost-effectiveness for MDO- and non-MDO-based daylighting simulation. Currently, no such methods exist in literature or in practice. This paper fills these gaps by presenting a methodology for automated product model decomposition and recomposition for climate-based daylighting simulation using Radiance. The authors validate the research with the method's application to several test cases and a large federal office building industry case study.

Building energy performance is often inadequate given design goals. While different types of assessment methods exist, they either do not consider design goals and/or are not general enough to integrate new and innovative energy concepts. Furthermore, existing assessment methods focus mostly on the building and system level while ignoring more detailed data. With the availability and affordability of more detailed measured data, the increased number of measured data points requires a structure to organize these data. This paper presents the Energy Performance Comparison Methodology (EPCM), which enables the identification of performance problems based on a comparison of measured data and simulated data representing design goals. The EPCM is based on an interlinked building object hierarchy that structures the detailed performance data from a spatial and mechanical perspective. This research is developed and tested on multiple case studies that provide real-life context and more generality compared to single case studies.

Genetic algorithms (GAs) are widely used in finding solutions for resource constrained multi-project scheduling problems (RCMPSP) in construction projects. In the finishing phase of a complex construction project, each room forms a confined space for crews to conduct a series of activities and can thus be considered as an individual sub-project. Generating the look-ahead schedule (LAS) which takes into account the limited resources available at the job site falls in the domain of RCMPSP. Therefore GAs can be used to address this scheduling problem and help construction managers to guide the daily work on site. However, current GAs do not consider three key practical aspects that the project planers and construction managers deal with frequently at the job sites: the engineering priorities of each individual sub-project, the zone constraint and the blocking constraint. By addressing these aspects, this paper proposes a GA-based method that takes them into account in the search process for optimum project duration and/or cost. Two examples are used for the discussion of the effectiveness of this method and to showcase its capability in project scheduling when the scale of a project increases.

The sound pressure level in receiving rooms, caused by taps at the ends of pipe systems, is considered. The structure-borne sound power, from the pipes to the supporting wall, was obtained from intensity measurement of the fluid-borne sound power of the tap. The fluid-borne sound power is combined with a ratio of structure-borne sound power to fluid-borne sound power, obtained from laboratory measurements of similar pipe assemblies. Alternatively, a reception plate method is proposed, which avoids the necessity for intensity measurements. The structure-borne power into walls, to which the pipe work is attached, provides input to the standard building propagation model, which yields the predicted sound pressure level in the adjacent room.

The construction industry will have to find new ways of building to accomplish radical reductions of pollution and waste. Nano and biotechnology along with information technology have the potential to constitute a new building paradigm. The paper describes the concept of nano- to meter-scale building, which is based on this potential. The concept is not focused on the application of nanomaterials like nanosilica or carbon nanotubes, but on a new way of building, which unfolds from the nano into the meter range. It is based on bionanorobots, producing building materials using carbon extracted from CO2 in the air. Criteria and requirements regarding relevant technologies are defined and compared to the current research in the fields of bioengineering, nanorobotics, and characteristics and production of carbon nanotubes. The paper also presents a concept of a new building technology that would enable control and monitoring of construction at the nano level, as well as requirements regarding design methods and tools including the building information model that will become the only human input to the automated nano- to meter-scale building process. The paper concludes with suggestions for further research and development.

Diamond single crystals were recently proposed as monochromators of unprecedented performance [1] (Freund, 2009). In the present paper we describe how diamond crystals with a suitable mosaic spread can be produced using a specific plasma CVD technique. Up to 2 mm thick samples with an average mosaic spread of 0.2° have been produced. We report on X- and gamma-ray characterisation checking the uniformity of the mosaic structure and present the results of a first study regarding the neutron reflection properties of this outstanding material. These promising results show that the diamond diffraction properties are not too far from the theoretical expectations. For example, 34% peak reflectivity has been obtained for a 1 mm thick crystal at 1 A wavelength.

This paper introduces and evaluates a novel heating and cooling concept employing thermo-active building systems and environmental energy, harnessed from two 11-m 3 rainwater cisterns for a 285-m 2 residential building in passive house standard in Germany. The building strives for a significantly reduced primary energy use with carefully coordinated measures, such as high quality building envelope, by means of vacuum insulated panels, supply and exhaust air system with heat recovery, reduced solar heat gains (solar shading), and the integration of thermal solar collectors and photovoltaic in the plant system. On this premise, a comprehensive long-term monitoring in high time-resolution was carried out for the building for two years with an accompanying commissioning of the building performance. Measurements comprise the energy use for heating, cooling, and ventilation, as well as the auxiliary equipment, the performance of the environmental heat source and sink (rainwater cistern), thermal comfort, and local climatic site conditions. The analysis focuses on the performance and the efficiency of rainwater cisterns as natural heat source and sink as well as the heat pump system. The paper discusses the performance of thermo-active building systems, investigates the thermal comfort, determines the efficiency of the heating/cooling system, and evaluates the total end and primary energy use of the building.

BSND encodes barttin, an accessory subunit of renal and inner ear chloride channels. To date, all mutations of BSND have been shown to cause Bartter syndrome type IV, characterized by significant renal abnormalities and deafness. We identified a BSND mutation (p.I12T) in four kindreds segregating nonsyndromic deafness linked to a 4.04-cM interval on chromosome 1p32.3. The functional consequences of p.I12T differ from BSND mutations that cause renal failure and deafness in Bartter syndrome type IV. p.I12T leaves chloride channel function unaffected and only interferes with chaperone function of barttin in intracellular trafficking. This study provides functional data implicating a hypomorphic allele of BSND as a cause of apparent nonsyndromic deafness. We demonstrate that BSND mutations with different functional consequences are the basis for either syndromic or nonsyndromic deafness.

Taps and other valves are major sound sources in piping systems and can cause unacceptable noise levels in buildings. The noise results from the fluid-, structure- and air-borne sound emission. At present the acoustic emission of water appliances is tested according to a European standard, the shortcomings of which are apparent as a result of a round robin test of different European laboratories. As a result, there are currently neither acceptable measurement methods for water appliances available nor input data for prediction models. This paper considers methods of characterizing water appliances as sources of structure-borne sound. The concepts of mobility and free velocity are employed for a source characterisation based on power. Taps are considered alone and also in combination with a basin, where again the mobility and free velocity are used. A reception plate method is assessed as an alternative. The two methods each provide an independent characterisation of a structure-borne sound source as a single value. The values are on a power basis and provide input data suitable for prediction of the installed structure-borne power and thence the resultant sound pressure in adjacent rooms. Measured and predicted values of sound pressure level, caused by a wash-basin installed in an adjacent room, are compared.

Architecture, engineering, and construction (AEC) projects are characterized by a large variation in requirements and work routines. Therefore, it is difficult to develop and implement information systems to support projects. To address these challenges, this paper presents a project-centric research and development methodology that combines ethnographic observation of practitioners working in local project organizations to understand their local requirements and the iterative improvement of information systems directly on projects in small action research implementation cycles. The paper shows the practical feasibility of the theoretical methodology using cases from AEC projects in North America and Europe. The cases provide evidence that ethnographic–action research is well suited to support the development and implementation of information systems. In particular, the paper shows that the method enabled researchers on the cases to identify specific problems on AEC projects and, additionally, helped these researchers to adapt information systems accordingly in close collaboration with the practitioners working on these projects.