A Review of the Impact of Occupational Contact Dermatitis on Quality of Life

Occupational contact dermatitis (OCD) is the most common occupational skin disease in many countries. We reviewed the current evidence on how OCD impacts on quality of life (QoL). The three commonly used QoL questionnaires in OCD were the Short-Form Health Survey (SF-36), the Dermatology Life Quality Index (DLQI), and the Skindex. Despite the availability of a variety of validated QoL instruments, none of them is specific to OCD or entirely adequate in capturing the impact of OCD on QoL. Nonetheless, the results of this paper do suggest a significant impact. Use of QoL measures in clinical settings will provide patients with an opportunity to express their concerns and assist clinicians to evaluate the effectiveness of management beyond the clinical outcomes. This paper also highlights the lack of a disease-specific QOL instrument and the importance of developing a validated measure to assess QOL in OCD, enabling comparison across countries and occupational groups

AIMs: a new strategy to control physical aging and gas transport in mixed-matrix membranes

The effect of controlling interactions between the components in a mixed-matrix membrane at the molecular level has been explored. A systematic series of soluble metal–organic polyhedra (MOPs) of varying external organic chain length were prepared and applied within polymer membranes to produce anti-aging intercalated membranes (AIMs). Use of a soluble porous additive allowed for intimate mixing between the polymer and the porous additive, eliminating the formation of non-selective gas transport voids at the interface, typically found in traditional mixed-matrix membranes. Moreover, the molecular interaction thus created provided a valuable tool for tailoring the physical aging rates of the membranes. Aging was slowed by a factor of three with the optimal tBu-MOP additive, and viscosity measurements revealed they held the strongest MOP–polymer interaction, confirming the utility of the AIMs approach. MOP loading was therefore able to be optimized for the maximum anti-aging effect by monitoring the relative change in viscosity. Absolute gas permeability scaled with the MOP external organic chain length, revealing solubility-driven diffusion.Melanie Kitchin, Jesse Teo, Kristina Konstas, Cher Hon Lau, Christopher J. Sumby, Aaron W. Thornton, Christian J. Doonan, and Matthew R. Hil

自己中心座標に基づく観光用ナビゲーション

電気通信大学201

Arrays of holes fabricated by electron-beam lithography combined with image reversal process using nickel pulse reversal plating

Abstract : A critical issue in fabricating arrays of holes is to achieve high-aspect-ratio structures. Formation of ordered arrays of nanoholes in silicon nitride was investigated by the use of ultrathin hard etch mask formed by nickel pulse reversal plating to invert the tonality of a dry e-beam resist patterned by e-beam lithography. Ni plating was carried out using a commercial plating solution based on nickel sulfamate salt without organic additives. Reactive ion etching using SF6/CH4SF6/CH4 was found to be very effective for pattern transfer to silicon nitride. Holes array of 100 nm diam, 270 nm period, and 400 nm depth was fabricated on a 5×5 mm2 area

Broadly neutralizing antibodies from an individual that naturally cleared multiple hepatitis c virus infections uncover molecular determinants for E2 targeting and vaccine design

Cumulative evidence supports a role for neutralizing antibodies contributing to spontaneous viral clearance during acute hepatitis C virus (HCV) infection. Information on the timing and specificity of the B cell response associated with clearance is crucial to inform vaccine design. From an individual who cleared three sequential HCV infections with genotypes 1b, 1a and 3a strains, respectively, we employed peripheral B cells to isolate and characterize neutralizing human monoclonal antibodies (HMAbs) to HCV after the genotype 1 infections. The majority of isolated antibodies, designated as HMAbs 212, target conformational epitopes on the envelope glycoprotein E2 and bound broadly to genotype 1–6 E1E2 proteins. Further, some of these antibodies showed neutralization potential against cultured genotype 1–6 viruses. Competition studies with defined broadly neutralizing HCV HMAbs to epitopes in distinct clusters, designated antigenic domains B, C, D and E, revealed that the selected HMAbs compete with B, C and D HMAbs, previously isolated from subjects with chronic HCV infections. Epitope mapping studies revealed domain B and C specificity of these HMAbs 212. Sequential serum samples from the studied subject inhibited the binding of HMAbs 212 to autologous E2 and blocked a representative domain D HMAb. The specificity of this antibody response appears similar to that observed during chronic infection, suggesting that the timing and affinity maturation of the antibody response are the critical determinants in successful and repeated viral clearance. While additional studies should be performed for individuals with clearance or persistence of HCV, our results define epitope determinants for antibody E2 targeting with important implications for the development of a B cell vaccine.</div

ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling

The transcription factor Nrf2 and its repressor protein Keap1 play key roles in the regulation of antioxidant stress responses and both Keap1-Nrf2 signalling and oxidative stress have been implicated in the pathogenesis of the ALS-FTLD spectrum of neurodegenerative disorders. The Keap1-binding partner and autophagy receptor SQSTM1/p62 has also recently been linked genetically to ALS-FTLD, with some missense mutations identified in patients mapping within or close to its Keap1-interacting region (KIR, residues 347–352) of SQSTM1/p62. Here we report the effects on protein function of four different disease associated mutations of SQSTM1/p62 which affect the KIR region. Only mutations mapping precisely to the KIR (P348L and G351 A) were associated with a loss of Keap1 binding in co-immunoprecipitations comparable to wild-type SQSTM1/p62. These selective effects on Keap1 recognition were entirely rational based on protein structural models. Consistent with impaired Keap1 binding, the P348L and G351A KIR mutants showed reduced ability to activate Nrf2 signalling compared to wild-type SQSTM1/p62 in antioxidant response element (ARE)-luciferase reporter assays. The results suggest that SQSTM1 mutations within the KIR of SQSTM1/p62 contribute to aetiology of some cases of ALS-FTLD through a mechanism involving aberrant expression or regulation of oxidative response genes

Chapter 4 Design Options, Implementation Issues and Evaluating Success of Ecologically Engineered Shorelines

Human population growth and accelerating coastal development have been the drivers for unprecedented construction of artificial structures along shorelines globally. Construction has been recently amplified by societal responses to reduce flood and erosion risks from rising sea levels and more extreme storms resulting from climate change. Such structures, leading to highly modified shorelines, deliver societal benefits, but they also create significant socioeconomic and environmental challenges. The planning, design and deployment of these coastal structures should aim to provide multiple goals through the application of ecoengineering to shoreline development. Such developments should be designed and built with the overarching objective of reducing negative impacts on nature, using hard, soft and hybrid ecological engineering approaches. The design of ecologically sensitive shorelines should be context-dependent and combine engineering, environmental and socioeconomic considerations. The costs and benefits of ecoengineered shoreline design options should be considered across all three of these disciplinary domains when setting objectives, informing plans for their subsequent maintenance and management and ultimately monitoring and evaluating their success. To date, successful ecoengineered shoreline projects have engaged with multiple stakeholders (e.g. architects, engineers, ecologists, coastal/port managers and the general public) during their conception and construction, but few have evaluated engineering, ecological and socioeconomic outcomes in a comprehensive manner. Increasing global awareness of climate change impacts (increased frequency or magnitude of extreme weather events and sea level rise), coupled with future predictions for coastal development (due to population growth leading to urban development and renewal, land reclamation and establishment of renewable energy infrastructure in the sea) will increase the demand for adaptive techniques to protect coastlines. In this review, we present an overview of current ecoengineered shoreline design options, the drivers and constraints that influence implementation and factors to consider when evaluating the success of such ecologically engineered shorelines

Origin and History of Mitochondrial DNA Lineages in Domestic Horses

Domestic horses represent a genetic paradox: although they have the greatest number of maternal lineages (mtDNA) of all domestic species, their paternal lineages are extremely homogeneous on the Y-chromosome. In order to address their huge mtDNA variation and the origin and history of maternal lineages in domestic horses, we analyzed 1961 partial d-loop sequences from 207 ancient remains and 1754 modern horses. The sample set ranged from Alaska and North East Siberia to the Iberian Peninsula and from the Late Pleistocene to modern times. We found a panmictic Late Pleistocene horse population ranging from Alaska to the Pyrenees. Later, during the Early Holocene and the Copper Age, more or less separated sub-populations are indicated for the Eurasian steppe region and Iberia. Our data suggest multiple domestications and introgressions of females especially during the Iron Age. Although all Eurasian regions contributed to the genetic pedigree of modern breeds, most haplotypes had their roots in Eastern Europe and Siberia. We found 87 ancient haplotypes (Pleistocene to Mediaeval Times); 56 of these haplotypes were also observed in domestic horses, although thus far only 39 haplotypes have been confirmed to survive in modern breeds. Thus, at least seventeen haplotypes of early domestic horses have become extinct during the last 5,500 years. It is concluded that the large diversity of mtDNA lineages is not a product of animal breeding but, in fact, represents ancestral variability

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts