Mechanosensitivity of the 2nd Kind: TGF-β Mechanism of Cell Sensing the Substrate Stiffness.

Cells can sense forces applied to them, but also the stiffness of their environment. These are two different phenomena, and here we investigate the mechanosensitivity of the 2nd kind: how the cell can measure an elastic modulus at a single point of adhesion-and how the cell can receive and interpret the chemical signal released from the sensor. Our model uses the example of large latent complex of TGF-β as a sensor. Stochastic theory gives the rate of breaking of latent complex, which initiates the signaling feedback loop after the active TGF-β release and leads to a change of cell phenotype driven by the α-smooth muscle actin. We investigate the dynamic and steady-state behaviors of the model, comparing them with experiments. In particular, we analyse the timescale of approach to the steady state, the stability of the non-linear dynamical system, and how the steady-state concentrations of the key markers vary depending on the elasticity of the substrate. We discover a crossover region for values of substrate elasticity closely corresponding to that of the fibroblast to myofibroblast transition. We suggest that the cell could actively vary the parameters of its dynamic feedback loop to 'choose' the position of the transition region and the range of substrate elasticity that it can detect. In this way, the theory offers the unifying mechanism for a variety of phenomena, such as the myofibroblast conversion in fibrosis of wounds and lungs and smooth muscle cell dysfunction in cardiac disease.This work was supported by the EPSRC Critical Mass grant for Theoretical Condensed Matter, the Sims Scholarship, and the Cambridge Trusts, and the University of Sydney.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.013995

Vacuum phototriodes for the CMS electromagnetic calorimeter endcap

The measurement of scintillation light from the lead tungstate crystals of the Compact Muon Solenoid (CMS) electromagnetic calorimeter (ECAL) poses a substantial technical challenge, particularly in the endcap regions, where the radiation levels are highest. The photodetectors must be fast, sensitive, radiationhard, and operate with significant internal gain in a magnetic field of 4 Tesla. The measured performance characteristics of the first batches of series production vacuum phototriodes (VPT), developed to satisfy the needs of CMS, will be described

The response to high magnetic fields of the vacuum phototriodes for the compact muon solenoid endcap electromagnetic calorimeter

The endcap electromagnetic calorimeter of the Compact Muon Solenoid (CMS) detects particles with the dense fast scintillator lead tungstate (PbWO4). Due to the low light yield of this scintillator photodetectors with internal gain are required. Silicon avalanche photodiodes cannot be used in the endcap region due to the intense neutron flux. Following an extensive R&D programme 26 mm diameter single-stage photomultipliers (vacuum phototriodes) have been chosen as the photodetector in the endcap region. The first 1400 production devices are currently being evaluated following recent tests of a pre-production batch of 500 tubes. Tubes passing our acceptance tests have responses, averaged over the angular acceptance of the endcap calorimeter, corresponding to the range 20 to 55 electrons per MeV deposited in PbWO4. These phototriodes operate, with a typical gain of 10, in magnetic fields up to 4T.PPARC, EC(INTAS-CERN scheme 99-424

Technical benefits of energy storage and electricity interconnections in future British power systems

There are concerns that the GB (Great Britain) electricity system may not be able to fully absorb increasing levels of variable renewables with consequent implications for emission reduction targets. This study considers the technical benefits of additional energy storage and interconnections in future GB electricity systems. Initially a reference model of the GB electricity system was developed using the EnergyPLAN tool. The model was validated against actual data and was confirmed to accurately represent the GB electricity system. Subsequently, an analysis of four possible scenarios, for the years 2020 and 2030, has been performed and the maximum technically feasible wind penetration calculated. Finally, the level of interconnection and energy storage has been varied to assess the technical benefits to the operation of a 2030 GB electricity system. We conclude that increasing levels of interconnection and energy storage allow a further reduction in the primary energy supply and an increase in maximum technically feasible wind penetration, permitting the system emissions intensity to be reduced from 483 gCO/kWh in 2012 to 113 gCO/kWh in 2030. Increasing the levels of interconnection and energy storage has significant technical benefits in the potential future GB systems considered

On the government scheme: a sociological study of work experience on employers' premises

This research examines the Work Experience on Employers' Premises element, (WEEP) of the Youth Opportunities Programme, a government sponsored scheme, which arose as a response to increasing levels of youth unemployment in the late nineteen seventies. It looks at WEEP schemes as they were experienced by eighty, sixteen to nineteen year old, unemployed young people, living in Washington New. Town, Tyne and Wear. The young people are studied against their family backgrounds, their experience of schooling, entry into unemployment, involvement with government schemes and from their present view of the world outside of work. It looks at the interlocking nature of the agencies and significant others who are involved with the young people in this transitional phase of their lives - the family, careers service, school. Manpower Services Commission and sponsors. It provides an understanding of WEEP schemes as they are variously experienced, by all the parties involved with their operation. The sudden emergence of the MSG and its massive growth is seen within the context of the schemes; together with the changes and the need for change which this brought to the careers service. The relevance of schooling, notably the final year of schooling is questioned, in terms of preparing young people for the world outside of school. The research took place during the early years of the operation of the Youth Opportunities Programme, and gives the background to the extended government measures, the Youth Training Scheme, for coping with youth unemployment, due to be operational in September 1983

Teachers observing classroom communication: An application of the Communicating Supporting Classroom Observation Tool for children aged 4-7 years

The nature of ‘Teacher talk’ is likely to have a considerable bearing on the child’s learning but measuring the communication environment in the classroom can present challenges. One tool which does this is the Communication Supporting Classroom Observation Tool (CSCOT). Initial use suggested that it was valid and reliably used by specialists (psychologists and speech and language therapists) and special educational needs coordinators (SENCOs). A key question is whether it can be used routinely by classroom teachers and whether results coincide with those in earlier studies. CSCOT observations were carried out by teachers in 33 schools (32 Reception classrooms, 25 in Year 1 and 25 in Year 2) in two local authorities in the North East of England and teachers were asked afterwards to reflect on their experiences using the tool. Scores were in line with those in earlier studies and were consistently higher on all dimensions for reception compared to Year 2, but there was no difference between other year groups. Results were mostly consistent with the original studies. Language learning environment was higher relative to both language learning opportunities and interactions across all years (which again did not differ). There was a moderate interaction between language learning environment where scores were significantly higher in the Reception group and lower in the Year 2 group. Teachers supported the use of the CSCOT in their feedback, suggesting that CSCOT was easy to use and useful in informing practice. The CSCOT clearly has utility as a starting point in auditing classroom communication. It allows teachers to compare between classrooms and year groups and potentially fosters collaboration between teachers and specialist practitioners who focus on communication such as speech and language therapists. Further work could link the observation tool into an intervention program co-constructed with teachers

The Science Behind The Policy: An Integrated Water Resources Course

Anyone who has reviewed water management practices recognizes that there is often a gap between scientific consensus on water realities and the policies put in place to manage water. The same is true in the academic community. Courses typically segregate the hydrological lessons from the policy lessons. To address this, we have created a course that fully integrates hydrology and policy into a single course

Soup to tree: the phylogeny of beetles inferred by mitochondrial metagenomics of a Bornean rainforest sample

In spite of the growth of molecular ecology, systematics and next-generation sequencing, the discovery and analysis of diversity is not currently integrated with building the tree-of-life. Tropical arthropod ecologists are well placed to accelerate this process if all specimens obtained via masstrapping, many of which will be new species, could be incorporated routinely in phylogeny reconstruction. Here we test a shotgun sequencing approach, whereby mitochondrial genomes are assembled from complex ecological mixtures via mitochondrial metagenomics, and demonstrate how the approach overcomes many of the taxonomic impediments to the study of biodiversity. DNA from ~500 beetle specimens, originating from a single rainforest canopy fogging sample from Borneo, was pooled and shotgun sequenced, followed by de novo assembly of complete and partial mitogenomes for 175 species. The phylogenetic tree obtained from this local sample was highly similar to that from existing mitogenomes selected for global coverage of major lineages of Coleoptera. When all sequences were combined, only minor topological changes are induced against this reference set, indicating an increasingly stable estimate of coleopteran phylogeny, whilst the ecological sample expands the tip-level representation of several lineages. Robust trees generated from ecological samples now enable an evolutionary framework for ecology. Meanwhile, the inclusion of uncharacterized samples in the tree-of-life rapidly expands taxon and biogeographic representation of lineages without morphological identification. Mitogenomes from shotgun sequencing of unsorted environmental samples and their associated metadata, placed robustly into the phylogenetic tree, constitute novel DNA ‘superbarcodes’ for testing hypotheses regarding global patterns of diversity

Community Water Education in Northwestern North Carolina

The southeastern drought has prompted regular media coverage, policy proclamations, and mandatory changes in water use for many communities. While the public is encountering the news and in some cases feeling the effects of water restrictions, there is little evidence that they well understand the connections between hydrological realities and policies regarding water resources. An example of this is the increasing number of requests for well-drilling permits as a way to tap “new” water in some communities. To begin to address this gap in public understanding, MountainKeepers, a non-profit organization based in Boone, NC, has partnered with students and faculty at Appalachian State University to develop community-based water education materials

Hydrogen via reforming aqueous ammonia and biomethane co-products of wastewater treatment: environmental and economic sustainability

Green H2 is increasingly viewed as a key energy carrier for the fight against climate change. Wastewater treatment plants (WWTPs) have the unique potential to be centres of renewable H2 generation with the growing availability of two attractive feedstocks: biomethane and ammonia. An innovative and novel method of ammonia recovery from digestate liquor followed by a state-of-the-art H2 production process named NWaste2H2 is demonstrated for a case-study WWTP. The recovered ammonia is used alongside biomethane for H2 production and its diversion from conventional biological treatment has two other crucial benefits, with reductions in both associated electricity demand and emissions of nitrous oxide, an extremely potent greenhouse gas. Process modelling, supported by extensive experiments in a packed-bed reactor at bench-scale, demonstrate the prized capability of simultaneously performing steam methane reforming and ammonia decomposition to generate a H2-rich syngas with yields close to equilibrium values. Greenhouse gas emission abatement from the replacement of diesel buses and reduced N2O emissions from biological treatment could save up to 17.2 kg CO2 equivalent (CO2e) per year for each person served by the WWTP. An in-depth economic study illustrates the ability to achieve a positive net present value with a 10% discount factor as early as 5.8 years when the H2 is prepared and sold to power fuel cell electric buses