Novel deletion of the E3A ubiquitin protein ligase gene detected by multiplex ligation-dependent probe amplification in a patient with Angelman syndrome

Angelman syndrome (AS) is a severe neurobehavioural disorder caused by failure of expression of the maternal copy of the imprinted domain located on 15q11-q13. There are different mechanisms leading to AS: maternal microdeletion, uniparental disomy, defects in a putative imprinting centre, mutations of the E3 ubiquitin protein ligase (UBE3A) gene. However, some of suspected cases of AS are still scored negative to all the latter mutations. Recently, it has been shown that a proportion of negative cases bear large deletions overlapping one or more exons of the UBE3A gene. These deletions are difficult to detect by conventional gene-scanning methods due to the masking effect by the non-deleted allele. In this study, we have used for the first time multiplex ligation-dependent probe amplification (MLPA) and comparative multiplex dosage analysis (CMDA) to search for large deletions affecting the UBE3A gene. Using this approach, we identified a novel causative deletion involving exon 8 in an affected sibling. Based on our results, we propose the use of MLPA as a fast, accurate and inexpensive test to detect large deletions in the UBE3A gene in a small but significant percentage of AS patients.     

Apportionment methods

Most democratic countries use apportionment methods to transform election results into whole numbers, which usually give the number of seats in a legislative body that the parties obtained. Which apportionment method does this best can be specified by measuring the error between the allocated result and the ideal proportion. We show how to find an apportionment method which is best suited to a given error function. We also discuss several properties of apportionment methods that have been labelled paradoxa. In particular we explain the highly publicised “Alabama” Paradox for the Hare/Hamilton method and show that other popular apportionment methods come with their very own paradoxa.     

Extreme value statistics distributions in spin glasses

We study the probability distribution of the pseudocritical temperature in a mean-field and in a short-range spin-glass model: the Sherrington-Kirkpatrick and the Edwards-Anderson (EA) model. In both cases, we put in evidence the underlying connection between the fluctuations of the pseudocritical point and the extreme value statistics of random variables. For the Sherrington-Kirkpatrick model, both with Gaussian and binary couplings, the distribution of the pseudocritical temperature is found to be the Tracy-Widom distribution. For the EA model, the distribution is found to be the Gumbel distribution. Being the EA model representative of uniaxial magnetic materials with quenched disorder like Fe(0.5)Mn)0.5)TiO(3) or Eu(0.5)Ba(0.5)MnO(3), its pseudocritical point distribution should be a priori experimentally accessible.     

Local 2-Geodesic Transitivity of Graphs

An s-geodesic in a graph Γ is a path connecting two vertices at distance s. Being locally transitive on s-geodesics is not a monotone property: if an automorphism group G of a graph Γ is locally transitive on s-geodesics, it does not follow that G is locally transitive on shorter geodesics. In this paper, we characterise all graphs that are locally transitive on 2-geodesics, but not locally transitive on 1-geodesics.     

Characterization of Commercial Amylases for the Removal of Filter Cake on Petroleum Wells

Drilling fluid has many functions, such as carry cuttings from the hole permitting their separation at the surface, cool and clean the bit, reduce friction between the drill pipe and wellbore, maintain the stability of the wellbore, and prevent the inflow of fluids from the wellbore and form a thin, low-permeable filter cake. Filter cake removal is an important step concerning both production and injection in wells, mainly concerning horizontal completion. The drilling fluids are typically comprised of starch, the most important component of the filter cake. A common approach to remove this filter cake is the use of acid solutions. However, these are non-specific reactants. A possible alternative is the use of enzymatic preparations, like amylases, that are able to hydrolyze starch. Wells usually operate in drastic conditions for enzymatic preparations, such as high temperature, high salt concentration, and high pressure. Thus, the main objective of this work was to characterize four enzymatic preparations for filter cake removal under open hole conditions. The results showed that high salt concentrations (204,000 ppm NaCl) in completion fluid decreased amylolytic activity. All enzymatic preparations were able to catalyze starch hydrolysis at all temperatures tested (30, 65, 80, and 95 °C). An increase of amylolytic activity was observed with the increase of pressure (100, 500 and 1,000 psi) for one commercial amylase.     

Molecular dynamics simulations and free energy calculations on the enzyme 4‐hydroxyphenylpyruvate dioxygenase

4‐Hydroxyphenylpyruvate dioxygenase is a relevant target in both pharmaceutical and agricultural research. We report on molecular dynamics simulations and free energy calculations on this enzyme, in complex with 12 inhibitors for which experimental affinities were determined. We applied the thermodynamic integration approach and the more efficient one‐step perturbation. Even though simulations seem well converged and both methods show excellent agreement between them, the correlation with the experimental values remains poor. We investigate the effect of slight modifications on the charge distribution of these highly conjugated systems and find that accurate models can be obtained when using improved force field parameters. This study gives insight into the applicability of free energy methods and current limitations in force field parameterization. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011     

Immobilized ruthenium complexes and aspects of their reactivity

Methodologies for the immobilization and characterization of ruthenium complexes into/onto functionalized silica gel, zeolites, polymers, dendrimers, sol–gel, nano and microparticles are described. The corresponding spectroscopic, electrochemical, and photochemical properties as well as chemical reactivities are used for their characterization and study. Comparison between the reactivities of immobilized and in solution species is presented. Some biological applications are also described.     

Solution of Set-Covering and Set-Partitioning Problems Using Assignment Relaxations

Graph theoretic relaxations are used to design tree search algorithms for set-covering and set-partitioning problems. In this paper two assignment relaxations for the set-covering and set-partitioning problems are presented and a tree search method is developed which makes use of these relaxations. Computational experience of processing a collection of test problems is reported.