No evidence of a significant role for CTLA-4 in multiple sclerosis

Variation in the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene plays a significant role in determining susceptibility to autoimmune thyroid disease and type 1 diabetes. Its role in multiple sclerosis is more controversial. In order to explore this logical candidate more thoroughly, we genotyped 771 multiple sclerosis trio families from the United Kingdom for the 3? untranslated region variable number tandem repeat, the CT60 single nucleotide polymorphism (SNP) and five haplotype-tagging SNPs. No individual marker or common haplotype showed evidence of association with disease. These data suggest that any effect of CTLA-4 on multiple sclerosis susceptibility is likely to be very small

UV solar irradiance in observations and the NRLSSI and SATIRE-S models

Total solar irradiance and UV spectral solar irradiance have been monitored since 1978 through a succession of space missions. This is accompanied by the development of models aimed at replicating solar irradiance by relating the variability to solar magnetic activity. The NRLSSI and SATIRE-S models provide the most comprehensive reconstructions of total and spectral solar irradiance over the period of satellite observation currently available. There is persistent controversy between the various measurements and models in terms of the wavelength dependence of the variation over the solar cycle, with repercussions on our understanding of the influence of UV solar irradiance variability on the stratosphere. We review the measurement and modelling of UV solar irradiance variability over the period of satellite observation. The SATIRE-S reconstruction is consistent with spectral solar irradiance observations where they are reliable. It is also supported by an independent, empirical reconstruction of UV spectral solar irradiance based on UARS/SUSIM measurements from an earlier study. The weaker solar cycle variability produced by NRLSSI between 300 and 400 nm is not evident in any available record. We show that although the method employed to construct NRLSSI is principally sound, reconstructed solar cycle variability is detrimentally affected by the uncertainty in the SSI observations it draws upon in the derivation. Based on our findings, we recommend, when choosing between the two models, the use of SATIRE-S for climate studies

Through the looking-glass:Mirror feedback modulates temporal and spatial aspects of bimanual coordination

Mirror therapy has become an effective and recommended intervention for a range of conditions affecting the upper limb (e.g. hemiparesis following stroke). However, little is known about how mirror feedback affects the control of bimanual movements (as performed during mirror therapy). In this study, in preparation for future clinical investigations, we examined the kinematics of bimanual circle drawing in unimpaired participants both with (Experiment 1) and without (Experiment 2) a visual template to guide movement. In both experiments, 15 unimpaired right-handed participants performed self-paced continuous bimanual circle-drawing movements with a mirror/symmetrical coordination pattern. For the mirror condition, vision was directed towards the mirror in order to monitor the reflected limb. In the no mirror condition, the direction of vision was unchanged, but the mirror was replaced with an opaque screen. Movements of both hands were recorded using motion capture apparatus. In both experiments, the most striking feature of movements was that the hand behind the mirror drifted spatially during the course of individual trials. Participants appeared to be largely unaware of this marked positional change of their unseen hand, which was most pronounced when a template to guide movement was visible (Experiment 1). Temporal asynchrony between the limbs was also affected by mirror feedback in both experiments; in the mirror condition, illusory vision of the unseen hand led to a relative phase lead for that limb. Our data highlight the remarkable impact that the introduction of a simple mirror can have on bimanual coordination. Modulation of spatial and temporal features is consistent with the mirror inducing a rapid and powerful visual illusion, the latter appearing to override proprioceptive signals.</p

Non-commutative field theory approach to two-dimensional vortex liquid system

We investigate the non-commutative (NC) field theory approach to the vortex liquid system restricted to the lowest Landau level (LLL) approximation. NC field theory effectively takes care of the phase space reduction of the LLL physics in a $\star$-product form and introduces a new gauge invariant form of a quartic potential of the order parameter in the Ginzburg-Landau (GL) free energy. This new quartic interaction coupling term has a non-trivial equivalence relation with that obtained by Br\'ezin, Nelson and Thiaville in the usual GL framework. The consequence of the equivalence is discussed.Comment: Add vortex lattice formation, more references, and one autho

CRISPR/Cas9-based editing of a sensitive transcriptional regulatory element to achieve cell type-specific knockdown of the NEMO scaffold protein

The use of alternative promoters for the cell type-specific expression of a given mRNA/protein is a common cell strategy. NEMO is a scaffold protein required for canonical NF-κB signaling. Transcription of the NEMO gene is primarily controlled by two promoters: one (promoter B) drives NEMO transcription in most cell types and the second (promoter D) is largely responsible for NEMO transcription in liver cells. Herein, we have used a CRISPR/Cas9-based approach to disrupt a core sequence element of promoter B, and this genetic editing essentially eliminates expression of NEMO mRNA and protein in 293T human kidney cells. By cell subcloning, we have isolated targeted 293T cell lines that express no detectable NEMO protein, have defined genomic alterations at promoter B, and do not support activation of canonical NF-κB signaling in response to treatment with tumor necrosis factor. Nevertheless, noncanonical NF-κB signaling is intact in these NEMO-deficient cells. Expression of ectopic wildtype NEMO, but not certain human NEMO disease mutants, in the edited cells restores downstream NF-κB signaling in response to tumor necrosis factor. Targeting of the promoter B element does not substantially reduce NEMO expression (from promoter D) in the human SNU423 liver cancer cell line. Thus, we have created a strategy for selectively eliminating cell typespecific expression from an alternative promoter and have generated 293T cell lines with a functional knockout of NEMO. The implications of these findings for further studies and for therapeutic approaches to target canonical NF-κB signaling are discussed.Published versio

Liquid-to-liquid phase transition in pancake vortex systems

We study the thermodynamics of a model of pancake vortices in layered superconductors. The model is based on the effective pair potential for the pancake vortices derived from the London approximation of a version of the Lawrence-Doniach model which is valid for extreme type-II superconductors. Using the hypernetted-chain (HNC) approximation, we find that there is a temperature below which multiple solutions to the HNC equations exist. By explicitly evaluating the free energy for each solution we find that the system undergoes a first-order transition between two vortex liquid phases. The low-temperature phase has larger correlations along the field direction than the high-temperature phase. We discuss the possible relation of this phase transition to the liquid-to-liquid phase transition recently observed in Y-Ba-Cu-O superconductors in high magnetic fields in the presence of disorder.Comment: 7 pages, 6 figure

Application of FBG-based sensors in build environment

Fibre Bragg grating (FBG)-based optical fibre sensors have found numerous applications in various industries over nearly 20 years. This is due to their many advantageous features, which include those that are typical of fibre-optic sensors (FOSs), for example being light weight, compact, having immunity to electromagnetic fields and an ability to operate in harsh environment. In addition to that, FBG-based sensors offer intrinsic multiplexing capability and they operate using wavelength-encoded signals which are insensitive to the intensity variations that normally affect the performance of intensity-based FOSs. One particular sector that is developing an interest in the use of FBG sensing technology is the civil engineering industry, where FBG-based sensors have begun to be used as physical sensors in a variety of civil structures, many of which are built using reinforced concrete. These sensors are used as part of structural health monitoring (SHM) systems which are effective in detecting possible damage in civil structures as a result of physical loading and corrosion which can lead to deformation, crack formation, fatigue and overloading. However, such sensors are incapable of providing information pertaining to chemical attacks that cause the degradation of the concrete stmcture before physical damages have been detected or observed. Arising from this, the aim of this thesis is to address the technology gap identified through the exploration and development of a series of FBG-based sensors for structural health monitoring and required by industry. The primary objective of the work is to explore the use of polymer- coated FBGs as sensors in the cementious matrix to monitor moisture which is considered as a main agent involved in most of the chemical attacks, by transporting corrosive ions in concrete structures. The sensing concept used in this work exploits the inherent characteristics of the FBG and is based on the strain effect induced in the FBG through the swelling of the polymer coating. A direct indication of the moisture level is given by the shift of the Bragg wavelength caused by the expansion of the sensing material. The context of the work, both technical and applications- focused and the development and characterisation of the sensors are discussed extensively in this thesis. The effectiveness of the sensors developed was evaluated through a series of tests performed under various harsh conditions using a range of concrete specimens with different porosity and mix composition, designed in collaboration with civil engineers. Results of the work are reported and relevant conclusions drawn for the use of this technology in the civil engineering sector, as well as incorporating a discussion of future trends and potential wider applications