Fit for work? Health, employability and challenges for the UK welfare reform agenda

This article introduces a special issue of Policy Studies entitled “Fit for work? Health, employability and challenges for the UK welfare reform agenda”. Growing from a shared concern over the need to expand the evidence base around the processes that led to large numbers of people claiming disability benefits in the UK, it brings together contributions from leading labour market and social policy researchers providing evidence and commentary on major reforms to Incapacity Benefit (IB) in the UK. This special issue address three key questions: what are the main causes of the long-term rise in the number of people claiming IBs; what will reduce the number of claimants; and what is likely to deliver policy effectively and efficiently? This introduction first explains and examines the challenges to reforms to IB in the UK, and then, in conclusion, highlights the answers to the previous three questions – first, labour market restructuring and marginalisation have driven the rise in numbers claiming IBs. Second, economic regeneration in the Britain’s less prosperous areas coupled with intensive and sustained supply-side support measures will bring numbers down. Third, delivery need to be flexible and tailored to individual needs and needs to be able to access local and expert knowledge in a range of organisations, including Job Centre Plus, the NHS as well as the private and voluntary sectors

Matching people to jobs and hours : drivers and productivity impacts of under-employment

This report details the findings of research conducted by the University of Strathclyde and the University of Portsmouth. The research was funded by the Productivity Insights Network under the award: “Drivers and productivity impacts of under-employment – insights on labour market effects and employers’ decision-making in contrasting local labour markets” (ESRC Grant Award ES/R007810/1). The research was supported by the Universities of Strathclyde and Portsmouth and the Scottish Trades Union Congress. The aims of the research were to: a) explore spatial patterns in short-hours working and under-employment and identify associated local labour market conditions using relevant national survey data; b) conduct qualitative research with employer representatives to understand better the drivers of under-employment, employers’ understanding of the problem, and views of its impact on productivity and performance; and c) draw on these mixed methods analyses, along with engagement with policy and workplace stakeholders, to arrive at policy implications and insights on reducing under-employment and enhancing productivity and skills formation

MBASED: allele-specific expression detection in cancer tissues and cell lines

Allele-specific gene expression, ASE, is an important aspect of gene regulation. We developed a novel method MBASED, meta-analysis based allele-specific expression detection for ASE detection using RNA-seq data that aggregates information across multiple single nucleotide variation loci to obtain a gene-level measure of ASE, even when prior phasing information is unavailable. MBASED is capable of one-sample and two-sample analyses and performs well in simulations. We applied MBASED to a panel of cancer cell lines and paired tumor-normal tissue samples, and observed extensive ASE in cancer, but not normal, samples, mainly driven by genomic copy number alterations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0405-3) contains supplementary material, which is available to authorized users

It takes three to tango: The length of the oligothiophene chain determines the nature of the long‐lived excited state and the resulting photocytotoxicity of a ruthenium(II) Photodrug

Abstract TLD1433 is the first Ru(II) complex to be tested as a photodynamic therapy agent in a clinical trial. In this contribution we study TLD1433 in the context of structurally‐related Ru(II)‐imidozo[4,5‐f][1,10]phenanthroline (ip) complexes appended with thiophene rings to decipher the unique photophysical properties which are associated with increasing oligothiophene chain length. Substitution of the ip ligand with ter‐ or quaterthiophene changes the nature of the long‐lived triplet state from metal‐to‐ligand charge‐transfer to 3 ππ* character. The addition of the third thiophene thus presents a critical juncture which not only determines the photophysics of the complex but most importantly its capacity for 1 O 2 generation and hence the potential of the complex to be used as a photocytotoxic agent

Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification

The fundamental process of endochondral ossification is under tight regulation in the healthy individual so as to prevent disturbed development and/or longitudinal bone growth. As such, it is imperative that we further our understanding of the underpinning molecular mechanisms involved in such disorders so as to provide advances towards human and animal patient benefit. The mouse metatarsal organ explant culture is a highly physiological ex vivo model for studying endochondral ossification and bone growth as the growth rate of the bones in culture mimic that observed in vivo. Uniquely, the metatarsal organ culture allows the examination of chondrocytes in different phases of chondrogenesis and maintains cell-cell and cell-matrix interactions, therefore providing conditions closer to the in vivo situation than cells in monolayer or 3D culture. This protocol describes in detail the intricate dissection of embryonic metatarsals from the hind limb of E15 murine embryos and the subsequent analyses that can be performed in order to examine endochondral ossification and longitudinal bone growth

Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization

UNLABELLED: PHOSPHO1 is a phosphatase highly expressed in bone. We studied its functional involvement in mineralization through the use of novel small molecule inhibitors. PHOSPHO1 expression was present within matrix vesicles, and inhibition of enzyme action caused a decrease in the ability of matrix vesicles to calcify. INTRODUCTION: The novel phosphatase, PHOSPHO1, belongs to the haloacid dehalogenase superfamily of hydrolases and is capable of cleaving phosphoethanolamine (PEA) and phosphocholine to generate inorganic phosphate. Our aims in this study were to examine the expression of PHOSPHO1 in murine mineralizing cells and matrix vesicles (MV) and to screen a series of small-molecule PHOSPHO1-specific inhibitors for their ability to pharmacologically inhibit the first step of MV-mediated mineralization. MATERIALS AND METHODS: q-PCR and immunohistochemistry were used to study the expression and localization profiles of PHOSPHO1. Inhibitors of PHOSPHO1's PEA hydrolase activity were discovered using high-throughput screening of commercially available chemical libraries. To asses the efficacy of these inhibitors to inhibit MV mineralization, MVs were isolated from TNAP-deficient (Akp2(-/-)) osteoblasts and induced to calcify in their presence. RESULTS: q-PCR revealed a 120-fold higher level of PHOSPHO1 expression in bone compared with a range of soft tissues. The enzyme was immunolocalized to the early hypertrophic chondrocytes of the growth plate and to osteoblasts of trabecular surfaces and infilling primary osteons of cortical bone. Isolated MVs also contained PHOSPHO1. PEA hydrolase activity was observed in sonicated MVs from Akp2(-/-) osteoblasts but not intact MVs. Inhibitors to PHOSPHO1 were identified and characterized. Lansoprazole and SCH202676 inhibited the mineralization of MVs from Akp2(-/-) osteoblasts by 56.8% and 70.7%, respectively. CONCLUSIONS: The results show that PHOSPHO1 localization is restricted to mineralizing regions of bone and growth plate and that the enzyme present within MVs is in an active state, inhibition of which decreases the capacity of MVs to mineralize. These data further support our hypothesis that PHOSPHO1 plays a role in the initiation of matrix mineralization

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)2(IP-4T)](PF6)2 with bpy=2,2′-bipyridine and IP-4T=2-{5′-[3′,4′-diethyl-(2,2′-bithien-5-yl)]-3,4-diethyl-2,2′-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived 3ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug. © 2020 The Authors. Published by Wiley-VCH Gmb

Nanoscale structural and chemical analysis of F-implanted enhancement-mode InAlN/GaN heterostructure field effect transistors

We investigate the impact of a fluorine plasma treatment used to obtain enhancement-mode operation on the structure and chemistry at the nanometer and atomic scales of an InAlN/GaN field effect transistor. The fluorine plasma treatment is successful in that enhancement mode operation is achieved with a +2.8 V threshold voltage. However, the InAlN barrier layers are observed to have been damaged by the fluorine treatment with their thickness being reduced by up to 50%. The treatment also led to oxygen incorporation within the InAlN barrier layers. Furthermore, even in the as-grown structure, Ga was unintentionally incorporated during the growth of the InAlN barrier. The impact of both the reduced barrier thickness and the incorporated Ga within the barrier on the transistor properties has been evaluated theoretically and compared to the experimentally determined two-dimensional electron gas density and threshold voltage of the transistor. For devices without fluorine treatment, the two-dimensional electron gas density is better predicted if the quaternary nature of the barrier is taken into account. For the fluorine treated device, not only the changes to the barrier layer thickness and composition, but also the fluorine doping needs to be considered to predict device performance. These studies reveal the factors influencing the performance of these specific transistor structures and highlight the strengths of the applied nanoscale characterisation techniques in revealing information relevant to device performance.</jats:p

Receding ice drove parallel expansions in Southern Ocean penguins

International audienceClimate shifts are key drivers of ecosystem change. Despite the critical importance of Antarctica and the Southern Ocean for global climate, the extent of climate-driven ecological change in this region remains controversial. In particular, the biological effects of changing sea ice conditions are poorly understood. We hypothesize that rapid postglacial reductions in sea ice drove biological shifts across multiple widespread Southern Ocean species. We test for demographic shifts driven by climate events over recent millennia by analyzing population genomic datasets spanning 3 penguin genera ( Eudyptes , Pygoscelis , and Aptenodytes ). Demographic analyses for multiple species (macaroni/royal, eastern rockhopper, Adélie, gentoo, king, and emperor) currently inhabiting southern coastlines affected by heavy sea ice conditions during the Last Glacial Maximum (LGM) yielded genetic signatures of near-simultaneous population expansions associated with postglacial warming. Populations of the ice-adapted emperor penguin are inferred to have expanded slightly earlier than those of species requiring ice-free terrain. These concerted high-latitude expansion events contrast with relatively stable or declining demographic histories inferred for 4 penguin species (northern rockhopper, western rockhopper, Fiordland crested, and Snares crested) that apparently persisted throughout the LGM in ice-free habitats. Limited genetic structure detected in all ice-affected species across the vast Southern Ocean may reflect both rapid postglacial colonization of subantarctic and Antarctic shores, in addition to recent genetic exchange among populations. Together, these analyses highlight dramatic, ecosystem-wide responses to past Southern Ocean climate change and suggest potential for further shifts as warming continues