Fractional diffusion models of cardiac electrical propagation: role of structural heterogeneity in dispersion of repolarization

Structural heterogeneity constitutes one of the main substrates influencing impulse propagation in living tissues. In cardiac muscle, improved understanding on its role is key to advancing our interpretation of cell-to-cell coupling, and how tissue structure modulates electrical propagation and arrhythmogenesis in the intact and diseased heart. We propose fractional diffusion models as a novel mathematical description of structurally heterogeneous excitable media, as a mean of representing the modulation of the total electric field by the secondary electrical sources associated with tissue inhomogeneities. Our results, validated against in-vivo human recordings and experimental data of different animal species, indicate that structural heterogeneity underlies many relevant characteristics of cardiac propagation, including the shortening of action potential duration along the activation pathway, and the progressive modulation by premature beats of spatial patterns of dispersion of repolarization. The proposed approach may also have important implications in other research fields involving excitable complex media

Regionalisation of climate impacts on flood flows to support the development of climate change guidance for Flood Management

Current Defra / Environment Agency guidance (FCDPAG3 supplementary note: http://www.defra.gov.uk/environ/fcd/pubs/pagn/climatechangeupdate.pdf) requires all flood management plans to allow for climate change by incorporating, within a sensitivity analysis, an increase in river flows of up 20% over the next 50 years, and beyond. This guidance is the same for all of England and Wales, making no allowance for regional variation in climate change or catchment type. This reflects the lack of scientific evidence to resolve the spatial distribution of potential impacts on flood flows with enough confidence to set such policy regionally. The 20% allowance was first raised in 1999 for MAFF and subsequently reviewed following the release of the UKCIP02 scenarios. Although the 20% figure is a memorable precautionary target, there is the risk that it leads to a significant under- or over-estimation of future flood risk in individual catchments. Defra and the Environment Agency procured project FD2020 (Regionalisation of climate change impacts on flood flows) to provide a more rigorous science base for refreshing the FCDPAG3: supplementary note guidance. The FD2020 approach is exploring the relationships between catchment characteristics and climate change impacts on peak flows in a “scenario neutral” way. This is done by defining a regular set of changes in climate that encompass all the current knowledge from the new scenarios available from the IPCC Fourth Assessment Report. For each of the 155 catchments included in the research, this broad approach will provide multiple scenarios to produce a “vulnerability surface” for change in the metrics of peak flows (e.g. the 20-year flood flow). Some of the UKCP09 products have also been used to understand what these projections may mean for changes to peak flow. The catchment-based analysis will be used to generalise to other gauged sites across Britain, using relationships with catchment characteristics, providing the scientific evidence for the development of regional guidance on climate change allowances. Specifically the project is: Investigating the impact of climate change on peak river flows in over 150 catchments across Britain to assess the suitability of the FCDPAG3 20% climate change allowance. Investigating catchment response to climate change to identify potential similarities such that the FCDPAG3 nationwide allowance could be regionalised. Investigating the uncertainty in changes to future peak river flows from climate change. Developing an approach that has longevity beyond the project timeframe and the lifetime of the latest generation of climate model results

Born in difficult times: the founding of the Volksmission and the work of Karl Fix

While in 1933 Adolf Hitler emerged from the brown quagmire of National Socialism to become Chancellor of the Reich and to establish his totalitarian state, a New-Testament apostolic church developed in the same city. Its leader, Karl Fix, bravely offered Hitler resistance. Neither the ban on public gatherings issued in 1934, nor the permanent control by the GESTAPO could quench the burning zeal of the new converts. In 1934, many more than 1,000 participants were counted in the services; many of them experienced miraculous healings. Through his literature mission, Fix was able to distribute around two million tracts in more than 12 countries. Thus the movement rapidly spread beyond the German borders. Encouraged by his prophetic view, Fix frankly warned the people of the self-proclaimed “Fuehrer”. The Swiss historian Walter Hollenweger, whose standard work Enthusiastisches Christentum - Die Pfingstbewegung in Geschichte und Gegenwart published in 1969, which, in its translation of 1997, was entitled Pentecostalism Origins and Developments Worldwide, merely mentions the Volksmission in a marginal note without dealing with its historical significance. This article, after giving a short survey of how the German Pentecostal Movement came into being, points out the contribution of the Volksmission, focusing on its establishment over the years between 1933 and 1945. The theology of the Volksmission, which is classically Pentecostal, awaits a further article

Random field spin models beyond one loop: a mechanism for decreasing the lower critical dimension

The functional RG for the random field and random anisotropy O(N) sigma-models is studied to two loop. The ferromagnetic/disordered (F/D) transition fixed point is found to next order in d=4+epsilon for N > N_c (N_c=2.8347408 for random field, N_c=9.44121 for random anisotropy). For N < N_c the lower critical dimension plunges below d=4: we find two fixed points, one describing the quasi-ordered phase, the other is novel and describes the F/D transition. The lower critical dimension can be obtained in an (N_c-N)-expansion. The theory is also analyzed at large N and a glassy regime is found.Comment: 4 pages, 5 figure

Preferential attachment in the protein network evolution

The Saccharomyces cerevisiae protein-protein interaction map, as well as many natural and man-made networks, shares the scale-free topology. The preferential attachment model was suggested as a generic network evolution model that yields this universal topology. However, it is not clear that the model assumptions hold for the protein interaction network. Using a cross genome comparison we show that (a) the older a protein, the better connected it is, and (b) The number of interactions a protein gains during its evolution is proportional to its connectivity. Therefore, preferential attachment governs the protein network evolution. The evolutionary mechanism leading to such preference and some implications are discussed.Comment: Minor changes per referees requests; to appear in PR

The direct synthesis of sulfobetaine-containing amphiphilic block copolymers and their self-assembly behavior

Diblock copolymers containing the thermo-responsive sulfobetaine, [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (DMAPS), were synthesized by the aqueous RAFT polymerization of DMAPS, followed by direct chain extension in hexafluoroisopropanol (HFIP) with methyl methacrylate (MMA). This was shown to give lower dispersity polymers than RAFT emulsion polymerization. The diblock copolymers self-assembled in water to form micelles, as analyzed by light scattering (LS) and transmission electron microscopy (TEM). Micelles formed from diblocks bearing a long PDMAPS block were shown to swell with temperature, rather than display a traditional UCST cloud point. This was due to the polymers retaining hydrophilicity, even at temperatures well below the UCST for the corresponding PDMAPS homopolymer, as shown by variable temperature NMR. This swelling behavior was utilized in the release of a hydrophobic dye in response to temperature. This approach has great potential for applications in controlled release whilst maintaining the structure of the carrier nanoparticles

Nonstationary dynamics of the Alessandro-Beatrice-Bertotti-Montorsi model

We obtain an exact solution for the motion of a particle driven by a spring in a Brownian random-force landscape, the Alessandro-Beatrice-Bertotti-Montorsi (ABBM) model. Many experiments on quasi-static driving of elastic interfaces (Barkhausen noise in magnets, earthquake statistics, shear dynamics of granular matter) exhibit the same universal behavior as this model. It also appears as a limit in the field theory of elastic manifolds. Here we discuss predictions of the ABBM model for monotonous, but otherwise arbitrary, time-dependent driving. Our main result is an explicit formula for the generating functional of particle velocities and positions. We apply this to derive the particle-velocity distribution following a quench in the driving velocity. We also obtain the joint avalanche size and duration distribution and the mean avalanche shape following a jump in the position of the confining spring. Such non-stationary driving is easy to realize in experiments, and provides a way to test the ABBM model beyond the stationary, quasi-static regime. We study extensions to two elastically coupled layers, and to an elastic interface of internal dimension d, in the Brownian force landscape. The effective action of the field theory is equal to the action, up to 1-loop corrections obtained exactly from a functional determinant. This provides a connection to renormalization-group methods.Comment: 18 pages, 3 figure

Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential

Caspases are a group of proteolytic enzymes involved in the co-ordination of cellular processes, including cellular homeostasis, inflammation and apoptosis. Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation. Furthermore, we found a clear correlation between stromal caspase-4 and -5 expression levels, inflammation and disease activity in ulcerative colitis patients. Deregulated intestinal inflammation in IBD patients is associated with an increased risk of developing CRC. We found robust expression of caspases-4 and -5 within intestinal epithelial cells, exclusively within neoplastic tissue, of colorectal tumours. An examination of adjacent normal, inflamed and tumour tissue from patients with colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is increased in inflamed and dysplastic tissue, while epithelial expression is restricted to neoplastic tissue. In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC

Cusps and shocks in the renormalized potential of glassy random manifolds: How Functional Renormalization Group and Replica Symmetry Breaking fit together

We compute the Functional Renormalization Group (FRG) disorder- correlator function R(v) for d-dimensional elastic manifolds pinned by a random potential in the limit of infinite embedding space dimension N. It measures the equilibrium response of the manifold in a quadratic potential well as the center of the well is varied from 0 to v. We find two distinct scaling regimes: (i) a "single shock" regime, v^2 ~ 1/L^d where L^d is the system volume and (ii) a "thermodynamic" regime, v^2 ~ N. In regime (i) all the equivalent replica symmetry breaking (RSB) saddle points within the Gaussian variational approximation contribute, while in regime (ii) the effect of RSB enters only through a single anomaly. When the RSB is continuous (e.g., for short-range disorder, in dimension 2 <= d <= 4), we prove that regime (ii) yields the large-N FRG function obtained previously. In that case, the disorder correlator exhibits a cusp in both regimes, though with different amplitudes and of different physical origin. When the RSB solution is 1-step and non- marginal (e.g., d < 2 for SR disorder), the correlator R(v) in regime (ii) is considerably reduced, and exhibits no cusp. Solutions of the FRG flow corresponding to non-equilibrium states are discussed as well. In all cases the regime (i) exhibits a cusp non-analyticity at T=0, whose form and thermal rounding at finite T is obtained exactly and interpreted in terms of shocks. The results are compared with previous work, and consequences for manifolds at finite N, as well as extensions to spin glasses and related models are discussed.Comment: v2: Note added in proo