A robust design methodology suitable for application to one-off products

Robust design is an activity of fundamental importance when designing large, complex, one-off engineering products. Work is described which is concerned with the application of the theory of design of experiments and stochastic optimization methods to explore and optimize at the concept design stage. The discussion begins with a description of state-of-the-art stochastic techniques and their application to robust design. The content then focuses on a generic methodology which is capable of manipulating design algorithms that can be used to describe a design concept. An example is presented, demonstrating the use of the system for the robust design of a catamaran with respect to seakeeping

The status of the interaction region design and machine detector interface of the FCC-ee

We present the latest development for the FCC-ee interaction region. It represents a major challenge for the FCC-ee collider, which has to achieve extremely high luminosity over a wide range of centre-of-mass energies. The FCC-ee will host two or four high-precision experiments. The machine parameters have to be well controlled and the design of the machine-detector-interface has to be carefully optimized. In particular, the complex final focus hosted in the detector region has to be carefully designed, and the impact of beam losses and of any type of radiation generated in the interaction region, including beamstrahlung, have to be simulated in detail. We discuss mitigation measures and the expected impact of beam losses and radiation on the detector background. We also report the progress of the mechanical model of the interaction region layout, including the engineering design of the central beampipe, and other MDI components

Cystatins as calpain inhibitors: Engineered chicken cystatin- and stefin B-kininogen domain 2 hybrids support a cystatin-like mode of interaction with the catalytic subunit of μ-calpain

Within the cystatin superfamily, only kininogen domain 2 (KD2) is able to inhibit μ- and m-calpain. In an attempt to elucidate the structural requirements of cystatins for calpain inhibition, we constructed recombinant hybrids of human stefin B (an intracellular family 1 cystatin) with KD2 and Delta L110 deletion mutants of chicken cystatin-KD2 hybrids. Substitution of the N-terminal contact region of stefin B by the corresponding KD2 sequence resulted in a calpain inhibitor of K-i = 188 nM. Deletion of L110, which forms a beta -bulge in family 1 and 2 cystatins but is lacking in KD2, improved inhibition of mu -calpain 4- to 8-fold. All engineered cystatins were temporary inhibitors of calpain due to slow substrate-like cleavage of a single peptide bond corresponding to Gly9-Ala10 in chicken cystatin. Biomolecular interaction analysis revealed that, unlike calpastatin, the cystatin-type inhibitors do not bind to the calmodulin-like domain of the small subunit of calpain, and their interaction with the mu -calpain heterodimer is completely prevented by a synthetic peptide comprising subdomain B of calpastatin domain 1. Based on these results we propose that (i) cystatin-type calpain inhibitors interact with the active site of the catalytic domain of calpain in a similar cystatin-like mode as with papain and (ii) the potential for calpain inhibition is due to specific subsites within the papain-binding regions of the general cystatin fold

Does regular antenatal exercise promote exclusive breastfeeding during the first 3 months of life? Secondary analyses of a randomized controlled trial

INTRODUCTION Exclusive breastfeeding (EBF) and antenatal exercise are independently ssociated with positive short- and long-term health effects for women and their children. The aims of the study were to investigate whether antenatal exercise promotes EBF three months postpartum and further to explore factors associated with EBF at three months postpartum. METHODS This study was a follow-up of a Norwegian two-center randomized controlled trial to assess the effect of an antenatal exercise protocol. The recruited pregnant women were randomized to either a 12-week standardized antenatal exercise program with one weekly group training led by a physiotherapist and two weekly home training sessions or standard antenatal care. Women reported breastfeeding status in a questionnaire at three months postpartum. RESULTS Of the 726 women, 88% were EBF at three months postpartum. There was no significant difference in EBF rates between the intervention group (87%) and the control group (89%). EBF was positively associated with maternal education (AOR=3.4; 95% CI: 1.7–6.7) and EBF at discharge from the hospital (AOR=22.2; 95% CI: 10–49). Admission to neonatal intensive care unit was identified as a significant barrier to EBF (AOR=0.2; 95% CI: 0.1–0.4). Significantly more women in the non-EBF group had sought professional help compared to women in the EBF group (p≤0.001). CONCLUSIONS Regular physical exercise during pregnancy did not influence the exclusive breastfeeding rates at three months postpartum. Considering the health effects of exclusive breastfeeding and antenatal physical exercise, studies with follow-up periods beyond three months postpartum are warranted.publishedVersio

How does the removal of federal subsidies affect investment in coastal protection infrastructure?

Shoreline armoring, which involves the installation of hardened structures to protect coastal property, dramatically alters shoreline composition and resulting ecological functions. Accelerating hazard threats to growing coastal communities compounds this problem, creating demand for more armoring. We examine whether designation by the U.S. Coastal Barrier Resources Act (CBRA) – enacted to disincentivize urban development on hazardous coastal barriers – is associated with lower propensities to armor shorelines. In designated areas, CBRA removes access to federally-subsidized flood insurance, infrastructure subsidies, and disaster assistance. Using logistic regression modeling, we examine armoring at the parcel scale across the State of Florida (USA), controlling for CBRA designation, land use, and local population density. Our findings reveal a significant negative relationship between CBRA designation and the odds of armoring, particularly for residential and vacant properties. As coastal areas grapple with increasing impacts from coastal hazards, removal of public subsidies may be an effective non-regulatory method for maintaining the ecological and protective benefits of natural shorelines

Does removal of federal subsidies discourage urban development? An evaluation of the US Coastal Barrier Resources Act

Urban development relies on many factors to remain viable, including infrastructure, services, and government provisions and subsidies. However, in situations involving federal or state level policy, development responds not just to one regulatory signal, but also to multiple signals from overlapping and competing jurisdictions. The 1982 U.S. Coastal Barrier Resources Act (CoBRA) offers an opportunity to study when and how development restrictions and economic disincentives protect natural resources by stopping or slowing urban development in management regimes with distributed authority and responsibility. CoBRA prohibits federal financial assistance for infrastructure, post-storm disaster relief, and flood insurance in designated sections (CoBRA units) of coastal barriers. How has CoBRA's removal of these subsidies affected rates and types of urban development Using building footprint and real estate data (n = 1,385,552 parcels), we compare density of built structures, land use types, residential house size, and land values within and outside of CoBRA units in eight Southeast and Gulf Coast states. We show that CoBRA is associated with reduced development rates in designated coastal barriers. We also demonstrate how local responses may counteract withdrawal of federal subsidies. As attention increases towards improving urban resilience in high hazard areas, this work contributes to understanding how limitations on infrastructure and insurance subsidies can affect outcomes where overlapping jurisdictions have competing goals

Global wave loads on a damaged ship

A computational tool was applied based on a two dimensional linear method to predict the hydrodynamic loads for damaged ships. Experimental tests on a ship model have also been carried out to predict the hydrodynamic loads in various design conditions. The results of the theoretical method and experimental tests are compared to validate the theoretical method. The extreme wave induced loads have been calculated by short term prediction. For the loads in intact condition, the prediction with duration of 20 years at sea state 5 is used, while for loads in damaged conditions the prediction in 96 hours exposure time at sea 3 is used. The maximum values of the most probable extreme amplitudes of dynamic wave induced loads in damaged conditions are much less than those in intact condition because of the reduced time. An opening could change the distribution of not only stillwater bending moment but also wave-induced bending moment. It is observed that although some cross sections are not structurally damaged, the total loads acting on these cross sections after damage may be increased dramatically compared to the original design load in intact condition

Maternal vitamin D status in pregnancy and molar incisor hypomineralisation and hypomineralised second primary molars in the offspring at 7–9 years of age:a longitudinal study

Purpose: The study aimed to investigate associations between maternal vitamin D status during pregnancy and molar incisor hypomineralisation (MIH) and hypomineralised second primary molars (HSPM) among children. Methods: The study had a longitudinal design using prospectively collected data from 176 mother and child pairs. Mothers were initially recruited in a randomised controlled trial to assess a pregnancy exercise programme. Along with the 7-year follow-up, we invited the children to a dental examination. The exposure variable was maternal serum 25-hydroxyvitamin D in gestational weeks 18–22 and 32–36, categorised as insufficient (< 50 nmol/l) and sufficient (≥ 50 nmol/l). Negative binomial hurdle models were used to analyse potential associations between the exposure variables and MIH or HSPM. The models were adjusted for potential confounders. Results: Among the children (7–9 years old), 32% and 22% had at least one tooth with MIH or HSPM, respectively. A significant association was found between insufficient maternal vitamin D measured in gestational weeks 18–22 and the number of affected teeth among those with MIH at 7–9 years (adjusted RR = 1.82, 95% CI 1.13–2.93). Conclusion: Considering any limitations of the present study, it has been shown that insufficient maternal serum vitamin D at mid-pregnancy was associated with a higher number of affected teeth among the offspring with MIH at 7–9 years of age. Further prospective studies are needed to investigate whether this finding is replicable and to clarify the role of maternal vitamin D status during pregnancy and MIH, as well as HSPM, in children

Basic Apoptotic Mechanisms of Lead Toxicity in Human Leukemia (Hl-60) Cells

Lead exposure represents a medical and public health emergency, especially in children consuming high amounts of lead-contaminated flake paints. It may also cause hematological effects to people of all ages. Recent studies in our laboratory have indicated that apoptosis may be associated with the lead-induced oxidative stress and DNA damage. However, the mechanisms underlying its effect on lymphocytes are still largely unknown. Therefore, the aim of the present study was to investigate the apoptotic mechanisms of lead nitrate [Pb(NO3)2] using HL-60 cells as a test model. HL-60 cells were treated with different concentrations of Pb(NO3)2 for 24 h prior to cell viability assay and flow cytometry assessment. The results obtained from the trypan blue exclusion test indicated that at very low concentration, Pb(NO3)2 has no effect on the viability of HL-60 cells. A significant (p < 0.05) decrease in cell viability was observed when exposed to high level of Pb(NO3)2. Data generated from the flow cytometric assessment indicated that Pb(NO3)2 exposure significantly (p < 0.05) increased the proportion of annexin V positive cells (apoptotic cells) compared to the control. Pb(NO3)2 induced apoptosis of HL-60 cells was associated with the activation of caspase-3. In summary, these studies demonstrated that Pb(NO3)2 represents an apoptosis-inducing agent in HL-60 promyelocytic leukemia cells and its apoptotic mechanism functions, at least in part via, induction of phosphatidylserine externalization and caspase-3 activation