Possible correlation between work-hardening and fatigue-failure

Conceptual theory proposes that cyclic hardening due to non-uniform strain and stress amplitudes during testing, especially during the initial application of stress to a specimen, may correlate positively with the ultimate strength of the specimen under test

Does landscape-scale conservation management enhance the provision of ecosystem services?

Biodiversity conservation approaches are increasingly being implemented at the landscape-scale to support the maintenance of metapopulations and metacommunities. However, the impact of such interventions on the provision of ecosystem services is less well defined. Here we examine the potential impacts of landscape-scale conservation initiatives on ecosystem services, through analysis of five case study areas in England and Wales. The provision of multiple ecosystem services was projected according to current management plans and compared with a baseline scenario. Multicriteria analysis indicated that in most cases landscape-scale approaches lead to an overall increase in service provision. Consistent increases were projected in carbon storage, recreation and aesthetic value, as well as biodiversity value. However, most study areas provided evidence of trade-offs, particularly between provisioning services and other types of service. Results differed markedly between study areas, highlighting the importance of local context. These results suggest that landscape-scale conservation approaches are likely to be effective in increasing ecosystem service provision, but also indicate that associated costs can be significant, particularly in lowland areas

Anaerobic removal of 1-methoxy-2-propanol under ambient temperature in an EGSB reactor

Two laboratory-scale expanded granular sludge bed (EGSB) reactors were operated at 18 and 25 C, respectively, for the treatment of synthetic wastewater composed of ethanol and 1-methoxy-2-propanol (M2P) in a mass ratio of 4:1. Reactors were operated first with continuous wastewater supply and after with discontinuous substrate supply (5 days a week, 16 h a day) to simulate shift working conditions. Under continuous wastewater supply chemical oxygen demand (COD), removal efficiency higher than 95 % was achieved at the end of the trial applying organic loading rates (OLR) of 29 and 43 kg COD m-3 day-1 at 18 and 25 C; thus, corresponding to M2P OLR of 6.4 and 9.3 kg COD m-3 day-1, respectively. During intermittent supply of substrate, good performance was recorded at both temperatures with an OLR of 30 kg COD m-3 day-1 (M2P OLR of 6.6 kg COD m-3 day-1). After 56 h without substrate supply, a decline in methane yield of 15¿30 % was observed due to the deactivation of the biomass. Specific methanogenic activity (SMA) assays were carried out at the end of the experiments. SMA values using 1-methoxy-2-propanol as substrate were 24.3 and 7.8 ml CH4 gVSS-1 day-1 at 25 C and at 18 C, respectively. This is the first attempt to investigate the removal of 1-methoxy-2-propanol by EGSB reactors

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Ex vivo modelling of drug efficacy in a rare metastatic urachal carcinoma

Background Ex vivo drug screening refers to the out-of-body assessment of drug efficacy in patient derived vital tumor cells. The purpose of these methods is to enable functional testing of patient specific efficacy of anti-cancer therapeutics and personalized treatment strategies. Such approaches could prove powerful especially in context of rare cancers for which demonstration of novel therapies is difficult due to the low numbers of patients. Here, we report comparison of different ex vivo drug screening methods in a metastatic urachal adenocarcinoma, a rare and aggressive non-urothelial bladder malignancy that arises from the remnant embryologic urachus in adults. Methods To compare the feasibility and results obtained with alternative ex vivo drug screening techniques, we used three different approaches; enzymatic cell viability assay of 2D cell cultures and image-based cytometry of 2D and 3D cell cultures in parallel. Vital tumor cells isolated from a biopsy obtained in context of a surgical debulking procedure were used for screening of 1160 drugs with the aim to evaluate patterns of efficacy in the urachal cancer cells. Results Dose response data from the enzymatic cell viability assay and the image-based assay of 2D cell cultures showed the best consistency. With 3D cell culture conditions, the proliferation rate of the tumor cells was slower and potency of several drugs was reduced even following growth rate normalization of the responses. MEK, mTOR, and MET inhibitors were identified as the most cytotoxic targeted drugs. Secondary validation analyses confirmed the efficacy of these drugs also with the new human urachal adenocarcinoma cell line (MISB18) established from the patient’s tumor. Conclusions All the tested ex vivo drug screening methods captured the patient’s tumor cells’ sensitivity to drugs that could be associated with the oncogenic KRASG12V mutation found in the patient’s tumor cells. Specific drug classes however resulted in differential dose response profiles dependent on the used cell culture method indicating that the choice of assay could bias results from ex vivo drug screening assays for selected drug classes