Optimal Extraction of Fibre Optic Spectroscopy

We report an optimal extraction methodology, for the reduction of multi-object fibre spectroscopy data, operating in the regime of tightly packed (and hence significantly overlapping) fibre profiles. The routine minimises crosstalk between adjacent fibres and statistically weights the extraction to reduce noise. As an example of the process we use simulations of the numerous modes of operation of the AAOmega fibre spectrograph and observational data from the SPIRAL Integral Field Unit at the Anglo-Australian Telescope.Comment: Accepted for publication in PAS

Gene therapy for pyoderma gangrenosum: optimal transfection conditions and effect of drugs on gene delivery in the HaCaT cell line using cationic liposomes

Background/Aims: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, currently treated empirically with immunosuppression. PG is a good target for gene therapy since the skin is easily accessible. This study used the FDA-approved vector Lipofectamine® 2000 to investigate in vitro transfection of skin keratinocytes. The aim was to determine an optimum transfection protocol, including the effect of drugs currently used to treat PG on the efficiency of gene transfer, since gene therapy is unlikely to be used as monotherapy. Methods: Cells of the HaCaT line were transfected with the lacZ reporter gene, and transgene expression was measured after a given time period. Conditions tested were: relative concentrations of DNA and Lipofectamine®, time from transfection to measurement of expression, pH, and exposure to clinically relevant drugs (hydrocortisone, methotrexate, infliximab). Results: The greatest levels of β-galactosidase expression were observed using a DNA:Lipofectamine® ratio of 1:5 (μg/μl) on day 3 after transfection, using culture medium at pH 7, and in the presence of hydrocortisone. Transfection efficiency was reduced by the presence of methotrexate and not significantly affected by infliximab. Conclusion: Gene therapy is a potential future strategy for the management of PG; this study is a step towards the development of a topical gene-based agent

Assessing cellular response to functionalized α-helical peptide hydrogels

α-Helical peptide hydrogels are decorated with a cell-binding peptide motif (RGDS), which is shown to promote adhesion, proliferation, and differentiation of PC12 cells. Gel structure and integrity are maintained after functionalization. This opens possibilities for the bottom-up design and engineering of complex functional scaffolds for 2D and 3D cell cultures.</p

Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g(-1)). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM(-1) s(-1) and 185.58 mM(-1) s(-1) respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed

Parity Violation in Proton-Proton Scattering

Measurements of parity-violating longitudinal analyzing powers (normalized asymmetries) in polarized proton-proton scattering provide a unique window on the interplay between the weak and strong interactions between and within hadrons. Several new proton-proton parity violation experiments are presently either being performed or are being prepared for execution in the near future: at TRIUMF at 221 MeV and 450 MeV and at COSY (Kernforschungsanlage Juelich) at 230 MeV and near 1.3 GeV. These experiments are intended to provide stringent constraints on the set of six effective weak meson-nucleon coupling constants, which characterize the weak interaction between hadrons in the energy domain where meson exchange models provide an appropriate description. The 221 MeV is unique in that it selects a single transition amplitude (3P2-1D2) and consequently constrains the weak meson-nucleon coupling constant h_rho{pp}. The TRIUMF 221 MeV proton-proton parity violation experiment is described in some detail. A preliminary result for the longitudinal analyzing power is Az = (1.1 +/-0.4 +/-0.4) x 10^-7. Further proton-proton parity violation experiments are commented on. The anomaly at 6 GeV/c requires that a new multi-GeV proton-proton parity violation experiment be performed.Comment: 13 Pages LaTeX, 5 PostScript figures, uses espcrc1.sty. Invited talk at QULEN97, International Conference on Quark Lepton Nuclear Physics -- Nonperturbative QCD Hadron Physics & Electroweak Nuclear Processes --, Osaka, Japan May 20--23, 199

Novel HSPB1 mutation causes both motor neuronopathy and distal myopathy.

OBJECTIVE: To identify the cause of isolated distal weakness in a family with both neuropathic and myopathic features on EMG and muscle histology. METHODS: Case study with exome sequencing in 2 affected individuals, bioinformatic prioritization of genetic variants, and segregation analysis of the likely causal mutation. Functional studies included Western blot analysis of the candidate protein before and after heat shock treatment of primary skin fibroblasts. RESULTS: A novel HSPB1 variant (c.387C>G, p.Asp129Glu) segregated with the phenotype and was predicted to alter the conserved α-crystallin domain common to small heat shock proteins. At baseline, there was no difference in HSPB1 protein levels nor its binding partner αB-crystallin. Heat shock treatment increased HSPB1 protein levels in both patient-derived and control fibroblasts, but the associated increase in αB-crystallin expression was greater in patient-derived than control fibroblasts. CONCLUSIONS: The HSPB1 variant (c.387C>G, p.Asp129Glu) is the likely cause of distal neuromyopathy in this pedigree with pathogenic effects mediated through binding to its partner heat shock protein αB-crystallin. Mutations in HSBP1 classically cause a motor axonopathy, but this family shows that the distal weakness can be both myopathic and neuropathic. The traditional clinical classification of distal weakness into "myopathic" or "neuropathic" forms may be misleading in some instances, and future treatments need to address the pathology in both tissues.This study was funded by Wellcome Trust (101876/Z/13/Z and 096919Z/11/Z), Medical Research Council (UK) (G0601943), and Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2). Funding bodies had no influence on study design or data interpretation.This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1212/NXG.000000000000011

How European Human Rights Law Will Reshape U.S. Business

In recent years several European states have enacted human rights due diligence laws, culminating in the imminent EU-wide Corporate Sustainability Due Diligence Directive. This article provides a comprehensive analysis of these laws and explores their potential impact on U.S. businesses. Human rights due diligence emerges from the United Nations Guiding Principles on Business and Human Rights (2011) and was originally conceived as a voluntary means by which corporations could demonstrate that they proactively monitor and manage potential human rights abuses within their corporate group and supply chains. Since 2017, European states have begun enacting binding human rights due diligence laws. These laws are innately extraterritorial in nature, designed to ensure that corporations that operate in the European market comply with human rights standards throughout their value chain, including through their suppliers and business partners. The emergence of European due diligence laws will thus impact U.S. businesses and industries: an estimated 10,000 U.S. businesses will be directly affected, and far more will have to comply as a result of supplying or partnering with EU-based firms. The effect on U.S. business could be dramatic, particularly with major divergences between the EU and United States in relation to labor law and other legal regimes. The article analyzes how U.S. businesses will be affected, what businesses may need to do, and how divergent legal regimes may be addressed. It further discusses options for the U.S. Government to take a proactive approach to the European incursion on U.S. law and business in the interest of protecting rights while providing business certainty

The design of systems for learning and working in librarianship.

The paper presents a philosophy and theory for the design of a system that would mediate between the librarian as a knowledge worker and the library as a learning organization. It does this by combining Activity Theory and Ecological Interface Design. The task to be supported is that of classification. The hypothesis is that the task of library classification can be supported by using the surrounding organization as an interactive learning environment, as the process of organizational learning depends on an appreciation of the cognitive process of classification

Older adults experiences of rehabilitation in acute health care

Rehabilitation is a key component of nursing and allied healthcare professionals’ roles in most health and social care settings. This paper reports on stage 2 of an action research project to ascertain older adult's experience of rehabilitation. Twenty postdischarge interviews were conducted and the interview transcripts were analysed using thematic content analysis. All older adults discharged from an acute older acute rehabilitation ward to their own homes in the community were eligible to participate. The only exclusion criterion was older adults who were thought to be unable to give consent to participate by the nurse in charge and the researcher. Whilst 92 older adults were eligible to participate in this research study, only 20 were interviewed. The findings from this study suggest that older adults valued communication with health professionals but were aware of their time constraints that hindered communication. This study suggests that both nurses and allied health professionals are not actively providing rehabilitative services to promote health and well-being, which contradicts the focus of active ageing. Furthermore, there was evidence of unmet needs on discharge, and older adults unable to recall the professions that were involved in their interventions and the rationale for therapy input. It is suggested that further research is needed to explore the effectiveness of allied health rehabilitation in the acute setting. This study highlights the need for further research into older adults’ perceptions of the rehabilitation process in the acute setting

FlgN is required for flagellum based motility by <em>Bacillus subtilis</em>

The assembly of the bacterial flagellum is exquisitely controlled. Flagellar biosynthesis is underpinned by a specialized type III secretion system that allows export of proteins from the cytoplasm to the nascent structure. Bacillus subtilis regulates flagellar assembly using both conserved and species-specific mechanisms. Here, we show that YvyG is essential for flagellar filament assembly. We define YvyG as an orthologue of the Salmonella enterica serovar Typhimurium type III secretion system chaperone, FlgN, which is required for the export of the hook-filament junction proteins, FlgK and FlgL. Deletion of flgN (yvyG) results in a nonmotile phenotype that is attributable to a decrease in hag translation and a complete lack of filament polymerization. Analyses indicate that a flgK-flgL double mutant strain phenocopies deletion of flgN and that overexpression of flgK-flgL cannot complement the motility defect of a ΔflgN strain. Furthermore, in contrast to previous work suggesting that phosphorylation of FlgN alters its subcellular localization, we show that mutation of the identified tyrosine and arginine FlgN phosphorylation sites has no effect on motility. These data emphasize that flagellar biosynthesis is differentially regulated in B. subtilis from classically studied Gram-negative flagellar systems and questions the biological relevance of some posttranslational modifications identified by global proteomic approaches