265 research outputs found
Kawasaki Dynamics with Two Types of Particles: Stable/Metastable Configurations and Communication Heights
No full textThis is the second in a series of three papers in which we study a two-dimensional lattice gas consisting of two types of particles subject to Kawasaki dynamics at low temperature in a large finite box with an open boundary. Each pair of particles occupying neighboring sites has a negative binding energy provided their types are different, while each particle has a positive activation energy that depends on its type. There is no binding energy between particles of the same type. At the boundary of the box particles are created and annihilated in a way that represents the presence of an infinite gas reservoir. We start the dynamics from the empty box and are interested in the transition time to the full box. This transition is triggered by a critical droplet appearing somewhere in the box. In the first paper we identified the parameter range for which the system is metastable, showed that the first entrance distribution on the set of critical droplets is uniform, computed the expected transition time up to and including a multiplicative factor of order one, and proved that the nucleation time divided by its expectation is exponentially distributed, all in the limit of low temperature. These results were proved under three hypotheses, and involve three model-dependent quantities: the energy, the shape and the number of critical droplets. In the second paper we prove the first and the second hypothesis and identify the energy of critical droplets. In the third paper we settle the rest. Both the second and the third paper deal with understanding the geometric properties of subcritical, critical and supercritical droplets, which are crucial in determining the metastable behavior of the system, as explained in the first paper. The geometry turns out to be considerably more complex than for Kawasaki dynamics with one type of particle, for which an extensive literature exists. The main motivation behind our work is to understand metastability of multi-type particle systems. © 2011 The Author(s)
Mutations in MFSD8, Encoding a Lysosomal Membrane Protein, Are Associated with Nonsyndromic Autosomal Recessive Macular Dystrophy
No full textPURPOSE:
This study aimed to identify the genetic defects in 2 families with autosomal recessive macular dystrophy with central cone involvement.
DESIGN:
Case series.
PARTICIPANTS:
Two families and a cohort of 244 individuals with various inherited maculopathies and cone disorders.
METHODS:
Genome-wide linkage analysis and exome sequencing were performed in 1 large family with 5 affected individuals. In addition, exome sequencing was performed in the proband of a second family. Subsequent analysis of the identified mutations in 244 patients was performed by Sanger sequencing or restriction enzyme digestion. The medical history of individuals carrying the MFSD8 variants was reviewed and additional ophthalmic examinations were performed, including electroretinography (ERG), multifocal ERG (mfERG), perimetry, optical coherence tomography (OCT), fundus autofluorescence, and fundus photography.
MAIN OUTCOME MEASURES:
MFSD8 variants, age at diagnosis, visual acuity, fundus appearance, color vision defects, visual field, ERG, mfERG, fundus autofluorescence, and OCT findings.
RESULTS:
Compound heterozygous variants in MFSD8, a gene encoding a lysosomal transmembrane protein, were identified in 2 families with macular dystrophy with a normal or subnormal ERG, but reduced mfERG. In both families, a heterozygous missense variant p.Glu336Gln was identified, which was predicted to have a mild effect on the protein. In the first family, a protein-truncating variant (p.Glu381*) was identified on the other allele, and in the second family, a variant (c.1102G>C) was identified that results in a splicing defect leading to skipping of exon 11 (p.Lys333Lysfs*3). The p.Glu336Gln allele was found to be significantly enriched in patients with maculopathies and cone disorders (6/488) compared with ethnically matched controls (35/18 682; P < 0.0001), suggesting that it may act as a genetic modifier.
CONCLUSIONS:
In this study, we identified variants in MFSD8 as a novel cause of nonsyndromic autosomal recessive macular dystrophy with central cone involvement. Affected individuals showed no neurologic features typical for variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), a severe and devastating multisystem lysosomal storage disease previously associated with mutations in MFSD8. We propose a genotype-phenotype model in which a combination of a severe and a mild variant cause nonsyndromic macular dystrophy with central cone involvement, and 2 severe mutations cause vLINCL
Mutation screening of retinal dystrophy patients by targeted capture from tagged pooled DNAs and next generation sequencing.
No full textPurpose: Retinal dystrophies are genetically heterogeneous, resulting from mutations in over 200 genes. Prior to the development of massively parallel sequencing, comprehensive genetic screening was unobtainable for most patients. Identifying the causative genetic mutation facilitates genetic counselling, carrier testing and prenatal/pre-implantation diagnosis, and often leads to a clearer prognosis. In addition, in a proportion of cases, when the mutation is known treatment can be optimised and patients are eligible for enrolment into clinical trials for gene-specific therapies. Methods: Patient genomic DNA was sheared, tagged and pooled in batches of four samples, prior to targeted capture and next generation sequencing. The enrichment reagent was designed against genes listed on the RetNet database (July 2010). Sequence data were aligned to the human genome and variants were filtered to identify potential pathogenic mutations. These were confirmed by Sanger sequencing. Results: Molecular analysis of 20 DNAs from retinal dystrophy patients identified likely pathogenic mutations in 12 cases, many of them known and/or confirmed by segregation. These included previously described mutations in ABCA4 (c.6088C>T,p.R2030*; c.5882G>A,p.G1961E), BBS2 (c.1895G>C,p.R632P), GUCY2D (c.2512C>T,p.R838C), PROM1 (c.1117C>T,p.R373C), RDH12 (c.601T>C,p.C201R; c.506G>A,p.R169Q), RPGRIP1 (c.3565C>T,p.R1189*) and SPATA7 (c.253C>T,p.R85*) and new mutations in ABCA4 (c.3328+1G>C), CRB1 (c.2832_2842+23del), RP2 (c.884-1G>T) and USH2A (c.12874A>G,p.N4292D). Conclusions: Tagging and pooling DNA prior to targeted capture of known retinal dystrophy genes identified mutations in 60% of cases. This relatively high success rate may reflect enrichment for consanguineous cases in the local Yorkshire population, and the use of multiplex families. Nevertheless this is a promising high throughput approach to retinal dystrophy diagnostics
Random sampling methods for two-view geometry estimation
No full textThis thesis treats efficient estimation algorithms for the epipolar geometry, the model underlying two views of the same scene or object. The epipolar geometry is computed from image correspondences that are found by local feature matching. These correspondences are used to calculate the fundamental matrix, which is the mathematical representation of the epipolar geometry. Since there are outliers among the correspondences, the fundamental matrix is usually calculated by the robust RANSAC (RANdom SAmple Consensus) algorithm which is very well suited for this purpose. A disadvantage of the algorithm, however, is that it shows a considerable complexity for higher outlier ratios. This hampers its application in vision algorithms dealing with many views. In this thesis we investigate techniques for faster fundamental matrix estimation using RANSAC. The first approach that is taken is the computation of inlier probabilities for the correspondences, that are used during sampling in the RANSAC algorithm to stimulate the selection of inliers. The second approach is the reduction of the required number of RANSAC samples by the selection of fewer correspondences per sample. The fundamental matrix hypotheses are then completed using the remaining correspondences.Electrical Engineering, Mathematics and Computer Scienc
Comprehensive analysis of copy number variation of genes at chromosome 1 and 10 Loci associated with late age related macular degeneration
No full textCopy Number Variants (CNVs) are now recognized as playing a significant role in complex disease etiology. Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world. While a number of genes and environmental factors have been associated with both risk and protection in AMD, the role of CNVs has remained largely unexplored. We analyzed the two major AMD risk-associated regions on chromosome 1q32 and 10q26 for CNVs using Multiplex Ligation-dependant Probe Amplification. The analysis targeted nine genes in these two key regions, including the Complement Factor H (CFH) gene, the 5 CFH-related (CFHR) genes representing a known copy number "hotspot", the F13B gene as well as the ARMS2 and HTRA1 genes in 387 cases of late AMD and 327 controls. No copy number variation was detected at the ARMS2 and HTRA1 genes in the chromosome 10 region, nor for the CFH and F13B genes at the chromosome 1 region. However, significant association was identified for the CFHR3-1 deletion in AMD cases (p = 2.38 × 10(-12)) OR = 0.31, CI-0.95 (0.23-0.44), for both neovascular disease (nAMD) (p = 8.3 × 10(-9)) OR = 0.36 CI-0.95 (0.25-0.52) and geographic atrophy (GA) (p = 1.5 × 10(-6)) OR = 0.36 CI-0.95 (0.25-0.52) compared to controls. In addition, a significant association with deletion of CFHR1-4 was identified only in patients who presented with bilateral GA (p = 0.02) (OR = 7.6 CI-0.95 1.38-41.8). This is the first report of a phenotype specific association of a CNV for a major subtype of AMD and potentially allows for pre-diagnostic identification of individuals most likely to proceed to this end stage of disease
Stability of open granular filters under wave loading
No full textA filter can be applied to protect a bed against scour. Normally, these filters are geometrically closed, to prevent winnowing of the base material through the filter. However, geometrically closed filters are expensive and difficult to realize in the field. Geometrically open filters can serve as an alternative. Within an open filter, the pores of the filter material are large enough for the base material to move trough. The philosophy behind this concept is to reduce the hydraulic loading within the filter, in order to avoid initiation of the base material. This research focusses on open filters. A design formula for open filters was established by Hoffmans (2012). This formula is recently validated for uniform flow (Van de Sande, 2012) and for flow with additional turbulence by a sill and a pier (Joustra, 2013). The applicability for wave loading - although suggested by Hoffmans- is not yet confirmed. No validations study was carried out in which Hoffmans formula was validated for wave loading. In this research, the use of Hoffmans formula for horizontal filters under wave loading was evaluated. Laboratory experiments are carried out in a wave flume. For several configurations, the critical wave height was determined for a wave period of 2.0s, 2.5s and 3.0s. The critical wave height is defined as the height for which incipient motion of the base material occurs. The filter material was stable during all tests. The depth above the filter was held constant for the tests. Together with an older dataset from Halter (1999), the results were analyzed. With the introduction of several assumptions, insight was gained in the damping of the hydraulic load inside the filter. The analysis showed that the Hoffmans formula cannot be applied in the same way as for uniform flow, since no constant value for the load damp coefficient alpha is found under wave loading. Two hypotheses which were stated for the applicability of Hoffmans formula under wave loading by Hoffmans & Verheij (2013). For the experimentally obtained results, these hypothesis did not give accurate results. It is speculated that the hydraulic gradient should be included in Hoffmans formula. In the original formula as proposed by Hoffmans (2012), this term was neglected.Hydraulic EngineeringCivil Engineering and Geoscience
A Variational Approach to Branching Random Walk in Random Environment
No full textThis paper considers an infinite system of particles on the integers that: (1) step to the right with a random delay, and (2) split or die along the way according to a random law depending on their position. The exponential growth rate of the particle density is computed in the long time limit in the form of a variational formula that can be solved explicitly. The result reveals two phase transitions associated with localization vs. delocalization and survival vs. extinction. In addition, the system exhibits an intermittency effect. Greven and den Hollander considered the more difficult situation where the particles may step both to the left and right, but the analysis of the phase diagram was less complete.Electrical Engineering, Mathematics and Computer Scienc
Met een kanon op een mug schieten? De toepassing van de staatssteunregels op natuurbeheer
No full textDe Europese Commissie heeft in twee beschikkingen geoordeekl dat Nederlandse subsidies voor natuurbeheer steunmaatregelen in de zin van art. 107 lid 1 VWEU zijn. Het oordeel van de Commissie leidt er toe dat subsidies voor organisaties die zich Inzetten voor een goed doel, in beginsel als voorgenomen steunmaatregelen moeten worden genotificeerd, indien deze organisaties ook bijvoorbeeld kaarten, tassen, t-shirts of stickers voor het goede doel verkopen. Niet alleen leidt dit ertoe dat veel meer (voorheen onverdachte) subsidies binnen het toepassingsbereik van de staatssteunregels vallen, ook dient de vraag zich aan of de staatssteunregels wel de juiste mechanismen bieden om dit type subsidies te toetsen.Multi Actor SystemsTechnology, Policy and Managemen
Het veelkoppige monster, genaamd 'onderneming'
No full textEen van de centrale begrippen in het staatssteunrecht is 'onderneming'. Het Hof van Justitie heeft daarin een functionele benadering waarin het kijkt naar de aard van de activiteiten die een entiteit verricht. Zijn de activiteiten economisch van aard, dan is sprake van een onderneming, anders niet. Maar wat nu als een entiteit zowel economische als niet-economische activiteiten verricht? Is zij dan een onderneming waarvoor de staatssteunregels gelden of niet? Op deze situatie gaat het Hof van Justitie in het arrest Compass-Datenbank in.Multi Actor SystemsTechnology, Policy and Managemen
Coupling, Concentration and Random Walks in Dynamic Random Environments
No full textIn this thesis we discuss concentration inequalities, relaxation to equilibrium of stochastic dynamics, and random walks in dynamic random environments. In stochastic systems one is interested in macroscopic and/or asymptotic properties as well as in fluctuations around typical behaviour. But the dependence structure induced by the interaction between the components of the system makes the analysis challenging. In order to overcome this in different settings a variety of methods are employed. Additive functionals of Markov processes play important roles in applications. In order to get exponential and moment estimates for their fluctuations a non-standard martingale approximation is used. The resulting general theorems do not require special properties like reversibility or a spectral gap. What is needed is some control on the expected evolution. That is, the difference of the evolution starting from two "adjacent'' configurations has to be controlled. Coupling methods are well suited to do perform this comparison. In concrete examples couplings are used to prove the conditions of the theorems. In statistical mechanics Gibbs measures and Markov random fields play important roles. The Poincaré inequality is an important property describing the regularity of the measure. We prove the Poincaré inequality via a martingale telescoping argument. To control the individual increments of the martingale we use a coupling method called disagreement percolation. If the clusters of this percolation are sufficiently small we obtain the Poincaré inequality. When interacting spin systems and their dynamics have a delicate connection to their ergodic measure(s) one has to take more care. We carefully study the graphical construction of the dynamics to understand how the influence of the measure can be preserved. An assumption is made that one can control how fast the system in equilibrium can compensate for a single spin flip. Under this assumption we obtain relaxation speed estimates for general functions. In attractive spin systems the condition can be reduced to the decay of auto-correlation of the spin at the origin. An application where this is of use is the low-temperature Ising model. Finally we look at random walks in dynamic random environments. Here a time-changing random environment drives the motion of a particle. The goal is to understand under which conditions the macroscopic behaviour of this random walk is like that of a Brownian motion. We use coupling to prove a law of large numbers as well as a functional central limit theorem for the position of the random walk. Only polynomial decay of correlations in time are needed for the environment, and the influence of the environment on the walk can be very general.Applied mathematicsElectrical Engineering, Mathematics and Computer Scienc
- …
