Economics bridge between theory and practice of Sustainable built environment: a case for marginal benefit and marginal cost

Common economic gauges that validate Sustainable Built Environment (SBE) in households may cause for such projects to be shelved especially when the result of commercial feasibility study does not favour the stakeholders. It is a fact that the capital cost of Energy Efficient (EE) equipment and Renewable Energy (RE) system are more expensive than the conventional methods. However, SBE is now necessary and the gap between theory and practical of SBE in relation to economics aspect must be narrowed. The economics of SBE must not only assert the environmental implication but also make tangible its benefit to the household for championing the cause. In Economics, Marginal Cost (MC) and Marginal Benefits (MB) measure additional benefits of every additional costs of investment at a specific level of production and consumption; and Economists suggests that effective gain and loss must be compared to the status quo, i.e., Relative Position (RP). These Economics theories of MC, MB and RP are adapted to measure the progression of SBE with regards to lighting requirements in a living/dining area simulated to represent two types of houses: with and without Passive Architecture (PA) design strategies. Both are applied with conventional incandescent light bulbs and EE light fittings as well as RE in lieu of the mains electricity supply. The comparative approach shows the value of MB and MC at every stage of the SBE progression and this enables the household to make informed decision at a margin. The result suggests that the value of MB is more than MC when both cases use EE light fittings, i.e., approximately RM2 gain for every RM1 cost. It is also found that RE benefits the household more in PA case. This approach makes economic sense in so far encouraging household to opt for SBE

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

The effects of nail rigidity on fracture healing in rats with osteoporosis

Background and purpose Stress shielding from rigid internal fixation may lead to refracture after removal of the osteosynthesis material. We investigated the effect of a low-rigidity (Ti-24Nb-4Zr-7.9Sn) intramedullary nail regarding stress shielding and bone healing of osteoporotic fractures in the rat

Functional classification of proteins based on projection of amino acid sequences: application for prediction of protein kinase substrates

<p>Abstract</p> <p>Background</p> <p>The knowledge about proteins with specific interaction capacity to the protein partners is very important for the modeling of cell signaling networks. However, the experimentally-derived data are sufficiently not complete for the reconstruction of signaling pathways. This problem can be solved by the network enrichment with predicted protein interactions. The previously published <it>in silico </it>method PAAS was applied for prediction of interactions between protein kinases and their substrates.</p> <p>Results</p> <p>We used the method for recognition of the protein classes defined by the interaction with the same protein partners. 1021 protein kinase substrates classified by 45 kinases were extracted from the Phospho.ELM database and used as a training set. The reasonable accuracy of prediction calculated by leave-one-out cross validation procedure was observed in the majority of kinase-specificity classes. The random multiple splitting of the studied set onto the test and training set had also led to satisfactory results. The kinase substrate specificity for 186 proteins extracted from TRANSPATH^®database was predicted by PAAS method. Several kinase-substrate interactions described in this database were correctly predicted. Using the previously developed ExPlain™ system for the reconstruction of signal transduction pathways, we showed that addition of the newly predicted interactions enabled us to find the possible path between signal trigger, TNF-alpha, and its target genes in the cell.</p> <p>Conclusions</p> <p>It was shown that the predictions of protein kinase substrates by PAAS were suitable for the enrichment of signaling pathway networks and identification of the novel signaling pathways. The on-line version of PAAS for prediction of protein kinase substrates is freely available at <url>http://www.ibmc.msk.ru/PAAS/</url>.</p

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Biallelic variants in SLC38A3 encoding a glutamine transporter cause epileptic encephalopathy

The solute carrier (SLC) superfamily encompasses >400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https://www.omim.org) are associated with rare Mendelian disorders including developmental and epileptic encephalopathy (DEE) and severe neurodevelopmental disorders (NDDs). Exome sequencing and family-based rare variant analyses on a cohort with NDD identified two siblings with DEE and a shared deleterious homozygous splicing variant in SLC38A3. The gene encodes SNAT3, a sodium-coupled neutral amino acid transporter and a principal transporter of the amino acids asparagine, histidine, and glutamine, the latter being the precursor for the neurotransmitters GABA and glutamate. Additional subjects with a similar DEE phenotype and biallelic predicted-damaging SLC38A3 variants were ascertained through GeneMatcher and collaborations with research and clinical molecular diagnostic laboratories. Untargeted metabolomic analysis was performed to identify novel metabolic biomarkers. Ten individuals from seven unrelated families from six different countries with deleterious biallelic variants in SLC38A3 were identified. Global developmental delay, intellectual disability, hypotonia, and absent speech were common features while microcephaly, epilepsy, and visual impairment were present in the majority. Epilepsy was drug-resistant in half. Metabolomic analysis revealed perturbations of glutamate, histidine, and nitrogen metabolism in plasma, urine, and cerebrospinal fluid of selected subjects, potentially representing biomarkers of disease. Our data support the contention that SLC38A3 is a novel disease gene for DEE and illuminate the likely pathophysiology of the disease as perturbations in glutamine homeostasis

Ethnicity and incidence of Hodgkin lymphoma in Canadian population

<p>Abstract</p> <p>Background</p> <p>Research has shown that ethnicity is a significant predictor of Hodgkin lymphoma (HL). Variations in cancer incidence among ethnic groups in the same country can lead to important information in the search for etiological factors. Other risk factors important in the etiology of HL are medical history and exposure to pesticides. In this report we investigated the association between ethnicity and HL in the presence of medical history, and exposure to pesticides.</p> <p>Methods</p> <p>The data resulting from a matched population-based case-control study conducted in six provinces of Canada (Ontario, Quebec, Manitoba, Saskatchewan, Alberta, and British Columbia) was analyzed to determine whether or not there was any association between ethnicity and incidence of HL when adjusted for personal medical history and pesticide exposure. Information on ethnicity, personal medical history, and pesticide exposure was collected by questionnaires via mail on 316 men diagnosed with HL; and on 1506 controls. A conditional logistic regression was utilized and results were presented as odds ratios and 95% confidence intervals.</p> <p>Results</p> <p>In our study population, the distribution of ethnic groups was: 38.5% North American, 15% British, 8.4% Western European, 8.2% Eastern European, 1.7% Asian, 1.4% Scandinavian and 27% of other ethnic origin. Compared to North Americans (i) the risk of HL was greater among the Eastern European descendents (Odds Ratio (OR_adj): 1.82; 95% confidence interval (CI): 1.02, 3.25) and Western European (OR_adj: 1.62; 95% CI: 0.95–2.76) descent population (borderline significance at 5% level); and (ii) the risk of HL was lower in Asian descents. Diagnosis with measles (OR_adj: 0.72, 95% C.I.: 0.53–0.98) and/or positive history of allergy desensitization shots (OR_adj: 0.55, 95% C.I.: 0.30–0.99) were negatively associated with the incidence of HL, while diagnosis with acne (OR_adj: 2.12, 95% C.I.: 1.19–3.78), shingles (OR_adj: 2.41, 95% C.I.: 1.38–4.22) and positive family history of cancer (OR_adj: 1.93, 95% C.I.: 1.40–2.65) increased the risk of HL. Exposure to individual herbicide dichlorprop showed an increased risk of HL (OR_adj: 6.35, 95% C.I.: 1.56–25.92).</p> <p>Conclusion</p> <p>In Canada, compared to North Americans descendents, the risk of HL was significantly greater among the Eastern European and Western European descent population. Our results related to association between ethnicity and HL support the findings reported by other researchers. Our data showed that subjects who were diagnosed with measles or had allergy desensitization shots negatively associated with the incidence of HL; and other medical conditions, ever diagnosed with acne, and positive family history of cancer were positively associated with the incidence of HL.</p

Stencil Nano Lithography Based on a Nanoscale Polymer Shadow Mask: Towards Organic Nanoelectronics

A stencil lithography technique has been developed to fabricate organic-material-based electronic devices with sub-micron resolution. Suspended polymethylmethacrylate ( PMMA) membranes were used as shadow masks for defining organic channels and top electrodes. Arrays of pentacene field effect transistors (FETs) with various channel lengths from 50 mu m down to 500 nm were successfully produced from the same batch using this technique. Electrical transport measurements showed that the electrical contacts of all devices were stable and the normalized contact resistances were much lower than previously studied organic FETs. Scaling effects, originating from the bulk space charge current, were investigated by analyzing the channel-length-dependent mobility and hysteresis behaviors. This novel lithography method provides a reliable means for studying the fundamental transport properties of organic materials at the nanoscale as well as enabling potential applications requiring the fabrication of integrated organic nanoelectronic devices.open1155sciescopu