The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor.

Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids; however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood. Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein is detectable in the compartment where ligand is recognized. Notably, although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non-functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids

Overview report on definition and concept of the circular economy in a European perspective : CICERONE D1.1

On the basis of a literature research, this subtask develops a conceptional framework for a common understanding of CE within the project team and for the following work packages and tasks. After a brief introduction into the objectives and the context of a circular economy, a more elaborated look into the necessity of an explicit understanding of CE, the objectives, the spatial perspective of CE and the specific challenges within the CICERONE context will be done, in order to develop a basis for a common understanding within the project context. Circular economy can and has to be understood as an (eco-)innovation agenda. Therefore, the paper investigates the role policy has to play to support innovation for a CE transition, for creating the framework conditions and why CE has also to be build from the ground up. Finally, the paper looks from two perspectives at emerging trends and business models in a CE to sketch next steps towards the transition in a selection of central sectors. Conclusions are drawn on the basis of the insights gained by the preceding chapters

TEACHERS' MOTIVATION TO INTEGRATE TECHNOLOGY: A STUDY OF EXPECTANCY-VALUE, PERCEIVED INSTRUMENTALITY, AND PROSOCIAL GOALS

Research suggests that technology integration can improve student achievement and attitudes towards school and learning (Englert, Zhao, Collings, & Romig, 2005; Kulik, 2003; Martindale, Pearson, Curda, & Pilcher, 2005). However, much of the research that has examined technology use in schools has revealed that there is a disappointing lack of integration, and frequent and meaningful technology use is not the norm (Barron, Kemker, Harmes, & Kalaydjian, 2003; Becker, 2006; Wozney, Venkatesh, and Abrami, 2006; Zhao & Frank, 2003). This study used a correlational design and an online self-report survey of 197 PreK-12 teachers to investigate the relationships between teachers' technology use and their motivation to use technology. Teachers' expectancy of success, intrinsic valuing, utility valuing, and perceived instrumentality of technology were related to the frequency of their own use at school. Teachers' expectancy of success with technology and their beliefs about their responsibility for teaching students about technology were related to the frequency of teacher-directed student technology use

Prediction of equivalent sand-grain size and identification of drag-relevant scales of roughness -- a data driven approach

The purpose of the present work is to examine two possibilities; firstly, predicting equivalent sand-grain roughness size $k_s$ based on the roughness height probability density function and power spectrum leveraging machine learning as a regression tool, and secondly, extracting information about relevance of different roughness scales to skin-friction drag by interpreting the output of the trained data-driven model. The model is an ensemble neural network consisting of 50 deep neural networks. The data for the training of the model is obtained from direct numerical simulations (DNSs) of turbulent flow in plane channels over 85 irregular multi-scale roughness samples at friction Reynolds number Re$_\tau=800$. The 85 roughness samples are selected from a repository of 4200 samples, covering a wide parameter space, through an active learning (AL) framework. The selection is made in several iterations, based on the informativeness of samples in the repository, quantified by the variance of ENN predictions. This AL framework aims to maximize the generalizability of the predictions with a certain amount of data. This is examined using three different testing data sets with different types of roughness, including 21 surfaces from the literature. The model yields an overall mean error of 5\% to 10\% on different testing data sets. Subsequently, a data interpretation technique, known as layer-wise relevance propagation, is applied to measure the contributions of different roughness wave-lengths to the predicted $k_s$. High-pass filtering is then applied to the roughness PS to exclude the wave-numbers identified as drag-irrelevant. The filtered rough surfaces are investigated using DNS, and it is demonstrated that, despite significant impact of filtering on the roughness topographical appearance and statistics, the skin-friction coefficient of the original roughness is successfully preserved.Comment: 24 pages, 11 figures, submitted to JF

Association of common variation in the PPARAgene with incident myocardial infarction in individuals with type 2 diabetes: A Go-DARTS study

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Background Common variants of the PPARA gene have been found to associate with ischaemic heart disease in non diabetic men. The L162V variant was found to be protective while the C2528G variant increased risk. L162V has also been associated with altered lipid measures. We therefore sought to determine the effect of PPARA gene variation on susceptibility to myocardial infarction in patients with type 2 diabetes. 1810 subjects with type 2 diabetes from the prospective Go-DARTS study were genotyped for the L162V and C2528G variants in the PPARA gene and the association of the variants with incident non-fatal myocardial infarction was examined. Cox's proportional hazards was used to interrogate time to event from recruitment, and linear regression for analysing association of genotype with quantitative clinical traits. Results The V162 allele was associated with decreased risk of non-fatal myocardial infarction (HR = 0.31, 95%CI 0.10–0.93 p = 0.037) whereas the C2528 allele was associated with increased risk (HR = 2.77 95%CI 1.34–5.75 p = 0.006). Similarly V162 was associated with a later mean age of diagnosis with type 2 diabetes and C2582 an earlier age of diagnosis. C2528 was also associated with increased total cholesterol and LDL cholesterol, which did not account for the observed increased risk. Haplotype analysis demonstrated that when both rare variants occurred on the same haplotype the effect of each was abrogated. Conclusion Genetic variation at the PPARA locus is important in determining cardiovascular risk in both male and female patients with diabetes. This genotype associated risk appears to be independent of the effect of these genotypes on lipid profiles and age of diagnosis with diabetes.Published versio

Evaluating the placement of PIT tags in tropical river fishes: a case study involving two Mekong River species

Fish communities are becoming increasingly threatened in many tropical river-floodplain systems due to the construction of dams and other physical barriers. Efficient tagging techniques are urgently needed to better understand the movement ecology of tropical river-floodplain species — both at a fundamental level and in response to the effects of barriers. Passive Integrated Transponder (PIT) tagging has been successfully used to quantify fish movements in many temperate riverine species, but its effectiveness on tropical riverine species remains largely untested. We investigated the potential use of PIT tags in two tropical species from the Mekong River — Pangasianodon hypophthalmus (Striped catfish) and Hypsibarbus malcolmi (Goldfin tinfoil barbs). Two separate, but concurrent, 50-day experiments were conducted on the two species to determine whether (1) the PIT tags can be retained within the fish, without affecting their mortality or growth, and (2) the outcomes for tag retention, fish mortality, and/or fish growth are influenced by the location of the tags in the fish. Results indicated that, for both species, PIT tags can be retained in the chest, gut or shoulder without affecting mortality or growth. This suggests that PIT tags could be successfully used in a range of body locations in Striped catfish and Goldfin tinfoil barbs in the Mekong River. However, the Mekong fishery is a highly important food source for the people of its neighbouring countries — thus, the most suitable tag location in large-bodied species would be the gut region, as the gut, and tag, are most likely to be removed prior to human consumption

Effects of Macromolecular Crowding on Human Adipose Stem Cell Culture in Fetal Bovine Serum, Human Serum, and Defined Xeno-Free/Serum-Free Conditions

Microenvironment plays an important role for stem cell proliferation and differentiation. Macromolecular crowding (MMC) was recently shown to assist stem cells in forming their own matrix microenvironment in vitro. The ability of MMC to support adipose stem cell (ASC) proliferation, metabolism, and multilineage differentiation was studied under different conditions: fetal bovine serum- (FBS-) and human serum- (HS-) based media and xeno- and serum-free (XF/SF) media. Furthermore, the immunophenotype of ASCs under MMC was evaluated. The proliferative capacity of ASCs under MMC was attenuated in each condition. However, osteogenic differentiation was enhanced under MMC, shown by increased deposition of mineralized matrix in FBS and HS cultures. Likewise, significantly greater lipid droplet accumulation and increased collagen IV deposition indicated enhanced adipogenesis under MMC in FBS and HS cultures. In contrast, chondrogenic differentiation was attenuated in ASCs expanded under MMC. The ASC immunophenotype was maintained under MMC with significantly higher expression of CD54. However, MMC impaired metabolic activity and differentiation capacity of ASCs in XF/SF conditions. Both the supportive and inhibitory effects of MMC on ASC are culture condition dependent. In the presence of serum, MMC maintains ASC immunophenotype and enhances adipogenic and osteogenic differentiation at the cost of reduced proliferation.Peer reviewe

Stimuli-responsive 2D polyelectrolyte photonic crystals for optically encoded pH sensing.

A versatile photonic crystal sensing motif based on a twodimensional (2D) inverse opal monolayer of stimuli-responsive polyelectrolyte gel with tunable optical properties is reported. The photonic membrane shows prompt response to pH and can be readily read out from either its optical spectra or interference colours

Effects of macromolecular crowding on human adipose stem cell culture in fetal bovine serum, human serum and defined xeno-free/serum-free conditions

Microenvironment plays an important role for stem cell proliferation and differentiation. Macromolecular crowding (MMC) was recently shown to assist stem cells in forming their own matrix microenvironment in vitro. The ability of MMC to support adipose stem cell (ASC) proliferation, metabolism, and multilineage differentiation was studied under different conditions: fetal bovine serum- (FBS-) and human serum- (HS-) based media and xeno- and serum-free (XF/SF) media. Furthermore, the immunophenotype of ASCs under MMC was evaluated. The proliferative capacity of ASCs under MMC was attenuated in each condition. However, osteogenic differentiation was enhanced under MMC, shown by increased deposition of mineralized matrix in FBS and HS cultures. Likewise, significantly greater lipid droplet accumulation and increased collagen IV deposition indicated enhanced adipogenesis under MMC in FBS and HS cultures. In contrast, chondrogenic differentiation was attenuated in ASCs expanded under MMC. The ASC immunophenotype was maintained under MMC with significantly higher expression of CD54. However, MMC impaired metabolic activity and differentiation capacity of ASCs in XF/SF conditions. Both the supportive and inhibitory effects of MMC on ASC are culture condition dependent. In the presence of serum, MMC maintains ASC immunophenotype and enhances adipogenic and osteogenic differentiation at the cost of reduced proliferation