Large-Scale Population Analysis Challenges the Current Criteria for the Molecular Diagnosis of Fascioscapulohumeral Muscular Dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is a common hereditary myopathy causally linked to reduced numbers (<= 8) of 3.3 kilobase D4Z4 tandem repeats at 4q35. However, because individuals carrying D4Z4-reduced alleles and no FSHD and patients with FSHD and no short allele have been observed, additional markers have been proposed to support an FSHD molecular diagnosis. In particular a reduction in the number of D4Z4 elements combined with the 4A(159/161/168)PAS haplotype (which provides the possibility of expressing DUX4) is currently used as the genetic signature uniquely associated with FSHD. Here, we analyzed these DNA elements in more than 800 Italian and Brazilian samples of normal individuals unrelated to any FSHD patients. We find that 3% of healthy subjects carry alleles with a reduced number (4-8) of D4Z4 repeats on chromosome 4q and that one-third of these alleles, 1.3%, occur in combination with the 4A161PAS haplotype. We also systematically characterized the 4q35 haplotype in 253 unrelated FSHD patients. We find that only 127 of them (50.1%) carry alleles with 1-8 D4Z4 repeats associated with 4A161PAS, whereas the remaining FSHD probands carry different haplotypes or alleles with a greater number of D4Z4 repeats. The present study shows that the current genetic signature of FSHD is a common polymorphism and that only half of FSHD probands carry this molecular signature. Our results suggest that the genetic basis of FSHD, which is remarkably heterogeneous, should be revisited, because this has important implications for genetic counseling and prenatal diagnosis of at-risk families.

Divertor map with freedom of geometry and safety factor profile

An explicit, area-preserving and integrable magnetic field line map for a single-null divertor tokamak is obtained using a trajectory integration method to represent equilibrium magnetic surfaces. The magnetic surfaces obtained from the map are capable of fitting different geometries with freely specified position of the X-point, by varying free model parameters. The safety factor profile of the map is independent of the geometric parameters and can also be chosen arbitrarily. The divertor integrable map is composed of a nonintegrable map that simulates the effect of external symmetry-breaking resonances, so as to generate a chaotic region near the separatrix passing through the X-point. The composed field line map is used to analyze escape patterns (the connection length distribution and magnetic footprints on the divertor plate) for two equilibrium configurations with different magnetic shear profiles at the plasma edge.

Harmonic deformation of Delaunay triangulations

We construct harmonic functions on random graphs given by Delaunay triangulations of ergodic point processes as the limit of the zero-temperature harness process. (C) 2012 Elsevier B.V All rights reserved.

Nontwist symplectic maps in tokamaks

We review symplectic nontwist maps that we have introduced to describe Lagrangian transport properties in magnetically confined plasmas in tokamaks. These nontwist maps are suitable to describe the formation and destruction of transport barriers in the shearless region (i.e., near the curve where the twist condition does not hold). The maps can be used to investigate two kinds of problems in plasmas with non-monotonic field profiles: the first is the chaotic magnetic field line transport in plasmas with external resonant perturbations. The second problem is the chaotic particle drift motion caused by electrostatic drift waves. The presented analytical maps, derived from plasma models with equilibrium field profiles and control parameters that are commonly measured in plasma discharges, can be used to investigate long-term transport properties. (C) 2011 Elsevier B.V. All rights reserved.

Signal Transceiver Transit Times and Propagation Delay Corrections for Ranging and Georeferencing Applications

The accuracy of ranging measurements depends critically on the knowledge of time delays undergone by signals when retransmitted by a remote transponder and due to propagation effects. A new method determines these delays for every single pulsed signal transmission. It utilizes four ground-based reference stations, synchronized in time and installed at well-known geodesic coordinates and a repeater in space, carried by a satellite, balloon, aircraft, and so forth. Signal transmitted by one of the reference bases is retransmitted by the transponder, received back by the four bases, producing four ranging measurements which are processed to determine uniquely the time delays undergone in every retransmission process. A minimization function is derived comparing repeater's positions referred to at least two groups of three reference bases, providing the signal transit time at the repeater and propagation delays, providing the correct repeater position. The method is applicable to the transponder platform positioning and navigation, time synchronization of remote clocks, and location of targets. The algorithm has been demonstrated by simulations adopting a practical example with the transponder carried by an aircraft moving over bases on the ground.

In adults: 47.2% have periodontitis! How about in orthodontic patients?

The occurrence of chronic inflammatory periodontal disease due to dental plaque in adults over 30 years of age was noticed in 47.2% of the 3,742 subjects studied, representing a 64.7 million people population in the 50 states of the U.S. and the District of Columbia. The methods used by the authors were uniquely precise and the results brought us to great insight on the correlation between orthodontic treatment and periodontal health, which is described below.

An analysis of Taguchi's on-line quality monitoring procedure for variables based on the results of a sequence of inspections

In this paper, a procedure for the on-line process control of variables is proposed. This procedure consists of inspecting the m-th item from every m produced items and deciding, at each inspection, whether the process is out-of-control. Two sets of limits, warning (µ0 ± W) and control (µ0 ± C), are used. If the value of the monitored statistic falls beyond the control limits or if a sequence of h observations falls between the warning limits and the control limits, the production is stopped for adjustment; otherwise, production goes on. The properties of an ergodic Markov chain are used to obtain an expression for the average cost per item. The parameters (the sampling interval m, the widths of the warning, the control limits W and C(W < C), and the sequence length (h) are optimized by minimizing the cost function. A numerical example illustrates the proposed procedure.

Records of migration in the exoplanet configurations

When compared to our Solar System, many exoplanet systems exhibit quite unusual planet configurations; some of these are hot Jupiters, which orbit their central stars with periods of a few days, others are resonant systems composed of two or more planets with commensurable orbital periods. It has been suggested that these configurations can be the result of a migration processes originated by tidal interactions of the planets with disks and central stars. The process known as planet migration occurs due to dissipative forces which affect the planetary semi-major axes and cause the planets to move towards to, or away from, the central star. In this talk, we present possible signatures of planet migration in the distribution of the hot Jupiters and resonant exoplanet pairs. For this task, we develop a semi-analytical model to describe the evolution of the migrating planetary pair, based on the fundamental concepts of conservative and dissipative dynamics of the three-body problem. Our approach is based on an analysis of the energy and the orbital angular momentum exchange between the two-planet system and an external medium; thus no specific kind of dissipative forces needs to be invoked. We show that, under assumption that dissipation is weak and slow, the evolutionary routes of the migrating planets are traced by the stationary solutions of the conservative problem (Birkhoff, Dynamical systems, 1966). The ultimate convergence and the evolution of the system along one of these modes of motion are determined uniquely by the condition that the dissipation rate is sufficiently smaller than the roper frequencies of the system. We show that it is possible to reassemble the starting configurations and migration history of the systems on the basis of their final states, and consequently to constrain the parameters of the physical processes involved.

A uniqueness theorem for the determination of sources in the Germain–Lagrange plate equation

We prove a uniqueness result related to the Germain–Lagrange dynamic plate differential equation. We consider the equation {∂2u∂t2+△2u=g⊗f,in ]0,+∞)×R2,u(0)=0,∂u∂t(0)=0, where uu stands for the transverse displacement, ff is a distribution compactly supported in space, and g∈Lloc1([0,+∞)) is a function of time such that g(0)≠0g(0)≠0 and there is a T0>0T0>0 such that g∈C1[0,T0[g∈C1[0,T0[. We prove that the knowledge of uu over an arbitrary open set of the plate for any interval of time ]0,T[]0,T[, 0uniquely f∈E′(R2)f∈E′(R2).

The Social City : Middle-way approaches to housing and sub-urban golvernmentality in southern Stockholm, 1900-1945

This dissertation deals with the period bridging the era of extreme housing shortages in Stockholm on the eve of industrialisation and the much admired programmes of housing provision that followed after the second world war, when Stockholm district Vällingby became an example for underground railway-serviced ”new towns”. It is argued that important changes were made in the housing and town planning policy in Stockholm in this period that paved the way for the successful ensuing period. Foremost among these changes was the uniquely developed practice of municipal leaseholding with the help of site leasehold rights (Erbbaurecht). The study is informed by recent developments in Foucauldian social research, which go under the heading ’governmentality’. Developments within urban planning are understood as different solutions to the problem of urban order. To a large extent, urban and housing policies changed during the period from direct interventions into the lives of inhabitants connected to a liberal understanding of housing provision, to the building of a disciplinary city, and the conduct of ’governmental’ power, building on increased activity on behalf of the local state to provide housing and the integration and co-operation of large collectives. Municipal leaseholding was a fundamental means for the implementation of this policy. When the new policies were introduced, they were limited to the outer parts of the city and administered by special administrative bodies. This administrative and spatial separation was largely upheld throughout the period, and represented as the parallel building of a ’social’ outer city, while things in the inner ’mercantile’ city proceeded more or less as before. This separation was founded in a radical difference in land holding policy: while sites in the inner city were privatised and sold at market values, land in the outer city was mostly leasehold land, distributed according to administrative – and thus politically decided – priorities. These differences were also understood and acknowledged by the inhabitants. Thorough studies of the local press and the organisational life of the southern parts of the outer city reveals that the local identity was tightly connected with the representations connected to the different land holding systems. Inhabitants in the south-western parts of the city, which in this period was still largely built on private sites, displayed a spatial understanding built on the contradictions between centre and periphery. The inhabitants living on leaseholding sites, however, showed a clear understanding of their position as members of model communities, tightly connected to the policy of the municipal administration. The organisations on leaseholding sites also displayed a deep co-operation with the administration. As the analyses of election results show, the inhabitants also seemed to have felt a greater degree of integration with the society at large, than people living in other parts of the city. The leaseholding system in Stockholm has persisted until today and has been one of the strongest in the world, although the local neo-liberal politicians are currently disposing it off.

Anti-parasitic and anti-viral immune responses in insects

Insects encounter many microorganisms in nature and to survive they have developed counter measures against the invading pathogens. In Drosophila melanogaster research on insect immunity has mainly been focused on infections by bacteria and fungi. We have explored the immune response against natural infections of the parasite Octosporea muscaedomesticae and the Drosophila C virus as compared to natural infections of bacteria and fungi. By using Affymetrix Drosophila GeneChips, we were able to obtain 48 genes uniquely induced after parasitic infection. It was also clearly shown that natural infections led to different results than when injecting the pathogens. In order to search for the ultimate role of the lepidopteran protein hemolin, we used RNA interference (RNAi). We could show that injection of double stranded RNA (dsRNA) of Hemolin in pupae of Hyalophora cecropia led to embryonic malformation and lethality and that there was a sex specific difference. We continued the RNAi investigation of hemolin in another lepidopteran species, Antheraea pernyi, and discovered that hemolin was induced by dsRNA per se. A similar induction of hemolin was seen after infection with baculovirus and we therefore performed in vivo experiments on baculovirus infected pupae. We could show that a low dose of dsHemolin prolonged the period before the A. pernyi pupae showed any symptoms of infection, while a high dose led to a more rapid onset of symptoms. By performing in silico analysis of the hemolin sequence from A. pernyi in comparison with other Hemolin sequences, it was possible to select a number of sites that either by being strongly conserved or variable could be important targets for future studies of hemolin function.

Direct estimation of the backward flow

[EN] The aim of this work is to propose a new method for estimating the backward flow directly from the optical flow. We assume that the optical flow has already been computed and we need to estimate the inverse mapping. This mapping is not bijective due to the presence of occlusions and disocclusions, therefore it is not possible to estimate the inverse function in the whole domain. Values in these regions has to be guessed from the available information. We propose an accurate algorithm to calculate the backward flow uniquely from the optical flow, using a simple relation. Occlusions are filled by selecting the maximum motion and disocclusions are filled with two different strategies: a min-fill strategy, which fills each disoccluded region with the minimum value around the region; and a restricted min-fill approach that selects the minimum value in a close neighborhood. In the experimental results, we show the accuracy of the method and compare the results using these two strategies.

Sviluppo, implementazione e valutazione funzionale di un nuovo modello protesico di caviglia

Total ankle arthroplasty (TAA) is still not as satisfactory as total hip and total knee arthroplasty. For the TAA to be considered a valuable alternative to ankle arthrodesis, an effective range of ankle mobility must be recovered. The disappointing clinical results of the current generation of TAA are mostly related to poor understanding of the structures guiding ankle joint mobility. A new design (BOX Ankle) has been developed, uniquely able to restore physiologic ankle mobility and a natural relationship between the implanted components and the retained ligaments. For the first time the shapes of the tibial and talar components in the sagittal plane were designed to be compatible with the demonstrated ligament isometric rotation. This resulted in an unique motion at the replaced ankle where natural sliding as well as rolling motion occurs while at the same time full conformity is maintained between the three components throughout the flexion arc. According to prior research, the design features a spherical convex tibial component, a talar component with radius of curvature in the sagittal plane longer than that of the natural talus, and a fully conforming meniscal component. After computer-based modelling and preliminary observations in several trial implantation in specimens, 126 patients were implanted in the period July 2003 – December 2008. 75 patients with at least 6 months follow-up are here reported. Mean age was 62,6 years (range 22 – 80), mean follow-up 20,2 months. The AOFAS clinical score systems were used to assess patient outcome. Radiographs at maximal dorsiflexion and maximal plantar flexion confirmed the meniscalbearing component moves anteriorly during dorsiflexion and posteriorly during plantarflexion. Frontal and lateral radiographs in the patients, show good alignment of the components, and no signs of radiolucency or loosening. The mean AOFAS score was observed to go from 41 pre-op to 74,6 at 6 month follow-up, with further improvement at the following follow-up. These early results reveal satisfactory clinical scores, with good recovery of range of motion and reduction of pain. Radiographic assessment reveals good osteointegration. All these preliminary results confirm biomechanical studies and the validity of this novel ligamentcompatible prosthesis design. Surely it will be important to re-evaluate these patients later.

Charakterisierung und Konvergenz mehrdimensionaler kontinuierlicher Verzweigungsprozesse

In dieser Arbeit wird eine Klasse von stochastischen Prozessen untersucht, die eine abstrakte Verzweigungseigenschaft besitzen. Die betrachteten Prozesse sind homogene Markov-Prozesse in stetiger Zeit mit Zuständen im mehrdimensionalen reellen Raum und dessen Ein-Punkt-Kompaktifizierung. Ausgehend von Minimalforderungen an die zugehörige Übergangsfunktion wird eine vollständige Charakterisierung der endlichdimensionalen Verteilungen mehrdimensionaler kontinuierlicher Verzweigungsprozesse vorgenommen. Mit Hilfe eines erweiterten Laplace-Kalküls wird gezeigt, dass jeder solche Prozess durch eine bestimmte spektral positive unendlich teilbare Verteilung eindeutig bestimmt ist. Umgekehrt wird nachgewiesen, dass zu jeder solchen unendlich teilbaren Verteilung ein zugehöriger Verzweigungsprozess konstruiert werden kann. Mit Hilfe der allgemeinen Theorie Markovscher Operatorhalbgruppen wird sichergestellt, dass jeder mehrdimensionale kontinuierliche Verzweigungsprozess eine Version mit Pfaden im Raum der cadlag-Funktionen besitzt. Ferner kann die (funktionale) schwache Konvergenz der Prozesse auf die vage Konvergenz der zugehörigen Charakterisierungen zurückgeführt werden. Hieraus folgen allgemeine Approximations- und Konvergenzsätze für die betrachtete Klasse von Prozessen. Diese allgemeinen Resultate werden auf die Unterklasse der sich verzweigenden Diffusionen angewendet. Es wird gezeigt, dass für diese Prozesse stets eine Version mit stetigen Pfaden existiert. Schließlich wird die allgemeinste Form der Fellerschen Diffusionsapproximation für mehrtypige Galton-Watson-Prozesse bewiesen.

Monte Carlo simulations of Potts glasses

A complete understanding of the glass transition isstill a challenging problem. Some researchers attributeit to the (hypothetical) occurrence of a static phasetransition, others emphasize the dynamical transitionof mode coupling-theory from an ergodic to a non ergodicstate. A class of disordered spin models has been foundwhich unifies both scenarios. One of these models isthe p-state infinite range Potts glass with p>4, whichexhibits in the thermodynamic limit both a dynamicalphase transition at a temperature T_D, and a static oneat T_0 < T_D. In this model every spins interacts withall the others, irrespective of distance. Interactionsare taken from a Gaussian distribution.In order to understand better its behavior forfinite number N of spins and the approach to thethermodynamic limit, we have performed extensive MonteCarlo simulations of the p=10 Potts glass up to N=2560.The time-dependent spin-autocorrelation function C(t)shows strong finite size effects and it does not showa plateau even for temperatures around the dynamicalcritical temperature T_D. We show that the N-andT-dependence of the relaxation time for T > T_D can beunderstood by means of a dynamical finite size scalingAnsatz.The behavior in the spin glass phase down to atemperature T=0.7 (about 60% of the transitiontemperature) is studied. Well equilibratedconfigurations are obtained with the paralleltempering method, which is also useful for properlyestablishing static properties, such as the orderparameter distribution function P(q). Evidence is givenfor the compatibility with a one step replica symmetrybreaking scenario. The study of the cumulants of theorder parameter does not permit a reliable estimation ofthe static transition temperature. The autocorrelationfunction at low T exhibits a two-step decay, and ascaling behavior typical of supercooled liquids, thetime-temperature superposition principle, is observed. Inthis region the dynamics is governed by Arrheniusrelaxations, with barriers growing like N^{1/2}.We analyzed the single spin dynamics down to temperaturesmuch lower than the dynamical transition temperature. We found strong dynamical heterogeneities, which explainthe non-exponential character of the spin autocorrelationfunction. The spins seem to relax according to dynamicalclusters. The model in three dimensions tends to acquireferromagnetic order for equal concentration of ferro-and antiferromagnetic bonds. The ordering has differentcharacteristics from the pure ferromagnet. The spinglass susceptibility behaves like chi_{SG} proportionalto 1/T in the region where a spin glass is predicted toexist in mean-field. Also the analysis of the cumulantsis consistent with the absence of spin glass orderingat finite temperature. The dynamics shows multi-scalerelaxations if a bimodal distribution of bonds isused. We propose to understand it with a model based onthe local spin configuration. This is consistent with theabsence of plateaus if Gaussian interactions are used.