Analysis of feedback mechanisms with unknown delay using sparse multivariate autoregressive method

This paper discusses the study of two interacting processes in which a feedback mechanism exists between the processes. The study was motivated by problems such as the circadian oscillation of gene expression where two interacting protein transcriptions form both negative and positive feedback loops with long delays to equilibrium. Traditionally, data of this type could be examined using autoregressive analysis. However, in circadian oscillation the order of an autoregressive model cannot be determined a priori. We propose a sparse multivariate autoregressive method that incorporates mixed linear effects into regression analysis, and uses a forward-backward greedy search algorithm to select nonzero entries in the regression coefficients, the number of which is constrained not to exceed a pre-specified number. A small simulation study provides preliminary evidence of the validity of the method. Besides the circadian oscillation example, an additional example of blood pressure variations using data from an intervention study is used to illustrate the method and the interpretation of the results obtained from the sparse matrix method. These applications demonstrate how sparse representation can be used for handling high dimensional variables that feature dynamic, reciprocal relationships

Chronically shortened rod outer segments accompany photoreceptor cell death in Choroideremia

X-linked choroideremia (CHM) is a disease characterized by gradual retinal degeneration caused by loss of the Rab Escort Protein, REP1. Despite partial compensation by REP2 the disease is characterized by prenylation defects in multiple members of the Rab protein family that are master regulators of membrane traffic. Remarkably, the eye is the only organ affected in CHM patients, possibly because of the huge membrane traffic burden of the post mitotic photoreceptors, which synthesise outer segments, and the adjacent retinal pigment epithelium that degrades the spent portions each day. In this study, we aimed to identify defects in membrane traffic that might lead to photoreceptor cell death in CHM. In a heterozygous null female mouse model of CHM (Chmnull/WT), degeneration of the photoreceptor layer was clearly evident from increased numbers of TUNEL positive cells compared to age matched controls, small numbers of cells exhibiting signs of mitochondrial stress and greatly increased microglial infiltration. However, most rod photoreceptors exhibited remarkably normal morphology with well-formed outer segments and no discernible accumulation of transport vesicles in the inner segment. The major evidence of membrane trafficking defects was a shortening of rod outer segments that was evident at 2 months of age but remained constant over the period during which the cells die. A decrease in rhodopsin density found in the outer segment may underlie the outer segment shortening but does not lead to rhodopsin accumulation in the inner segment. Our data argue against defects in rhodopsin transport or outer segment renewal as triggers of cell death in CHM

Manufacture of multilayered artificial cell membranes through sequential bilayer deposition on emulsion templates.

Efforts to manufacture artificial cells that replicate the architectures, processes and behaviours of biological cells are rapidly increasing. Perhaps the most commonly reconstructed cellular structure is the membrane, through the use of unilamellar vesicles as models. However, many cellular membranes, including bacterial double membranes, nuclear envelopes, and organelle membranes, are multilamellar. Due to a lack of technologies available for their controlled construction, multilayered membranes are not part of the repertoire of cell-mimetic motifs used in bottom-up synthetic biology. To address this, we developed emulsion-based technologies that allow cell-sized multilayered vesicles to be produced layer-by-layer, with compositional control over each layer, thus enabling studies that would otherwise remain inaccessible. We discovered that bending rigidities scale with the number of layers and demonstrate inter-bilayer registration between coexisting liquid-liquid domains. These technologies will contribute to the exploitation of multilayered membrane structures, paving the way for incorporating protein complexes that span multiple bilayers

Adult native knee extensor mechanism ruptures.

Extensor mechanism rupture is a serious event requiring prompt diagnosis and treatment. Patella fractures are reportedly six times more frequent than soft tissue injuries such as quadriceps or patella tendon ruptures. Classically quadriceps and patella tendon ruptures are seen more in males, with those over 40 predominantly suffering from quadriceps tendon ruptures, often associated with an underlying condition, whereas patella tendon ruptures are mostly associated with sport injuries and are commonly seen in the under 40s. Almost all types of extensor mechanism ruptures benefit from early management which typically involves surgery. Diagnosis can be deemed easy to make by demonstrating inability to actively extend the knee, this however can be easily overlooked and missed in a busy emergency department leading to a late diagnosis and necessitating more complex surgery. Earlier surgical intervention and rehabilitation tend to produce improved outcomes.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.injury.2016.06.03

Non-thermal Origin of the EUV and Soft X-rays from the Coma Cluster - Cosmic Rays in Equipartition with the Thermal Medium

The role of cosmic rays (CR) in the formation and evolution of clusters of galaxies has been much debated. It may well be related to other fundamental questions, such as the mechanism which heats and virializes the intracluster medium (ICM), and the frequency at which the ICM is shocked. There is now compelling evidence both from the cluster soft excess (CSE) and the `hard-tail' emissions at energies above 10 keV, that many clusters are luminous sources of inverse-Compton (IC) emission. This is the first direct measurement of cluster CR: the technique is free from our uncertainties in the ICM magnetic field, and is not limited to the small subset of clusters which exhibit radio halos. The CSE emitting electrons fall within a crucial decade of energy where they have the least spectral evolution, and where most of the CR pressure resides. However their survival times do not date them back to the relic CR population. By using the CSE data of the Coma cluster, we demonstrate that the CR are energetically as important as the thermal ICM: the two components are in pressure equiparition. Thus, contrary to previous expectations, CR are a dominant component of the ICM, and their origin and effects should be explored. The best-fit CR spectral index is in agreement with the Galactic value.Comment: ApJ accepted; 10 pages LaTeX; 2 figures and 1 table in PostScrip

Azimuthal anisotropy of jet quenching at LHC

We analyze the azimuthal anisotropy of jet spectra due to energy loss of hard partons in quark-gluon plasma, created initially in nuclear overlap zone in collisions with non-zero impact parameter. The calculations are performed for semi-central Pb-Pb collisions at LHC energy.Comment: Talk given at Fourth International Conference "Physics and Astrophysics of Quark-Gluon Plasma", November 26-30, 2001; 4 pages including 4 eps-figure

Porous carbons from inverse vulcanised polymers

Elemental sulfur is an underutilised industrial by-product. It has been recently shown that it can be simply and scalably co-polymerised, by “inverse vulcanisation” with organic crosslinkers. The properties of porous carbons, which have extensive uses in science and industry, are influenced by the materials from which they are generated. Reported here are the first examples of porous carbons produced from high-sulfur inverse vulcanised polymers. The materials produced show micro-porosity, gas selectivity, and are doped with sulfur. The simplicity of the technique, and wide range of other potential inverse vulcanised feedstocks, gives scope for transferability and control of properties