Implementing an apparent-horizon finder in three dimensions

Locating apparent horizons is not only important for a complete understanding of numerically generated spacetimes, but it may also be a crucial component of the technique for evolving black-hole spacetimes accurately. A scheme proposed by Libson et al., based on expanding the location of the apparent horizon in terms of symmetric trace-free tensors, seems very promising for use with three-dimensional numerical data sets. In this paper, we generalize this scheme and perform a number of code tests to fully calibrate its behavior in black-hole spacetimes similar to those we expect to encounter in solving the binary black-hole coalescence problem. An important aspect of the generalization is that we can compute the symmetric trace-free tensor expansion to any order. This enables us to determine how far we must carry the expansion to achieve results of a desired accuracy. To accomplish this generalization, we describe a new and very convenient set of recurrence relations which apply to symmetric trace-free tensors.Comment: 14 pages (RevTeX 3.0 with 3 figures

The spectrum of mutations and molecular pathogenesis of hemophilia A in 181 Portuguese patients

Disease-causing alterations within the F8 gene were identified in 177 hemophilia A families of Portuguese origin. The spectrum of non-inversion F8 mutations in 101 families included 67 different alterations, namely: 36 missense, 8 nonsense and 4 splice site mutations, as well as 19 insertions/deletions. Thirty-four of these mutations are novel. Molecular modeling allowed prediction of the conformational changes introduced by selected amino acid substitutions and their correlation with the patients' phenotypes. The relatively frequent, population-specific, missense mutations together with de novo alterations can lead to significant differences in the spectrum of F8 mutations among different populationsThis study was partially supported by Fundação para a Ciência e a Tecnologia: research grant PBIC/C/SAU/1588/92 and Programa de Financiamento Plurianual do CIGM

Finding Apparent Horizons in Dynamic 3D Numerical Spacetimes

We have developed a general method for finding apparent horizons in 3D numerical relativity. Instead of solving for the partial differential equation describing the location of the apparent horizons, we expand the closed 2D surfaces in terms of symmetric trace--free tensors and solve for the expansion coefficients using a minimization procedure. Our method is applied to a number of different spacetimes, including numerically constructed spacetimes containing highly distorted axisymmetric black holes in spherical coordinates, and 3D rotating, and colliding black holes in Cartesian coordinates.Comment: 19 pages, 13 figures, LaTex, to appear in Phys. Rev. D. Minor changes mad

High-levelexpression of functional recombinant human coagulation factor VII in insect cells

Abstract: Recombinant coagulation factor VII (FVII) is used as a potential therapeutic intervention in hemophilia patients who produce antibodies against the coagulation factors. Mammalian cell lines provide low levels of expression, however, the Spodoptera frugiperda Sf9 cell line and baculovirus expression system are powerful systems for high-level expression of recombinant proteins, but due to the lack of endogenous vitamin K-dependent carboxylase, expression of functional FVII using this system is impossible. In the present study, we report a simple but versatile method to overcome the defect for high-level expression of the functional recombinant coagulation FVII in Sf9 cells. This method involves simultaneous expression of both human γ-carboxylase (hGC) and human FVII genes in the host. It may be possible to express other vitamin K-dependent coagulation factors using this method in the future. Keywords: Baculovirus; γ-carboxylase; Coagulation FVII; Factor VII; Insect cel

Genetic analysis of haemophilia A in Bulgaria

BACKGROUND: Haemophilias are the most common hereditary severe disorders of blood clotting. In families afflicted with heamophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostical strategy for carriership determination and prenatal diagnostics of haemophilia A in Bulgarian haemophilic population. METHODS: A diagnostical strategy consisting of screening for most common mutations in the factor VIII gene and analysis of a panel of eight linked to the factor VIII gene locus polymorphisms was established. RESULTS: Polymorphic analysis for carrier status determination of haemophilia A was successful in 30 families out of 32 (94%). Carrier status was determined in 25 of a total of 28 women at risk (89%). Fourteen prenatal diagnoses in women at high risk of having a haemophilia A – affected child were performed, resulting in 6 healthy boys and 5 girls. CONCLUSION: The compound approach proves to be a highly informative and cost-effective strategy for prevention of recurrence of haemophilia A in Bulgaria. DNA analysis facilitates carriership determination and subsequent prenatal diagnosis in the majority of Bulgarian families affected by haemophilia A

An integrated approach to the interpretation of Single Amino Acid Polymorphisms within the framework of CATH and Gene3D

Background The phenotypic effects of sequence variations in protein-coding regions come about primarily via their effects on the resulting structures, for example by disrupting active sites or affecting structural stability. In order better to understand the mechanisms behind known mutant phenotypes, and predict the effects of novel variations, biologists need tools to gauge the impacts of DNA mutations in terms of their structural manifestation. Although many mutations occur within domains whose structure has been solved, many more occur within genes whose protein products have not been structurally characterized.<p></p> Results Here we present 3DSim (3D Structural Implication of Mutations), a database and web application facilitating the localization and visualization of single amino acid polymorphisms (SAAPs) mapped to protein structures even where the structure of the protein of interest is unknown. The server displays information on 6514 point mutations, 4865 of them known to be associated with disease. These polymorphisms are drawn from SAAPdb, which aggregates data from various sources including dbSNP and several pathogenic mutation databases. While the SAAPdb interface displays mutations on known structures, 3DSim projects mutations onto known sequence domains in Gene3D. This resource contains sequences annotated with domains predicted to belong to structural families in the CATH database. Mappings between domain sequences in Gene3D and known structures in CATH are obtained using a MUSCLE alignment. 1210 three-dimensional structures corresponding to CATH structural domains are currently included in 3DSim; these domains are distributed across 396 CATH superfamilies, and provide a comprehensive overview of the distribution of mutations in structural space.<p></p> Conclusion The server is publicly available at http://3DSim.bioinfo.cnio.es/ webcite. In addition, the database containing the mapping between SAAPdb, Gene3D and CATH is available on request and most of the functionality is available through programmatic web service access.<p></p&gt

Application of MJO Simulation Diagnostics to Climate Models

The ability of eight climate models to simulate the Madden-Julian oscillation (MJO) is examined using diagnostics developed by the U.S. Climate Variability and Predictability (CLIVAR) MJO Working Group. Although the MJO signal has been extracted throughout the annual cycle, this study focuses on the boreal winter (November-April) behavior. Initially, maps of the mean state and variance and equatorial space-time spectra of 850-hPa zonal wind and precipitation are compared with observations. Models best represent the intraseasonal space-time spectral peak in the zonal wind compared to that of precipitation. Using the phase-space representation of the multivariate principal components (PCs), the life cycle properties of the simulated MJOs are extracted, including the ability to represent how the MJO evolves from a given subphase and the associated decay time scales. On average, the MJO decay (e-folding) time scale for all models is shorter (~20- 29 days) than observations (~31 days). All models are able to produce a leading pair of multivariate principal components that represents eastward propagation of intraseasonal wind and precipitation anomalies, although the fraction of the variance is smaller than observed for all models. In some cases, the dominant time scale of these PCs is outside of the 30-80-day band. Several key variables associated with the model's MJO are investigated, including the surface latent heat flux, boundary layer (925 hPa) moisture convergence, and the vertical structure of moisture. Low-level moisture convergence ahead (east) of convection is associated with eastward propagation in most of the models. A few models are also able to simulate the gradual moistening of the lower troposphere that precedes observed MJO convection, as well as the observed geographical difference in the vertical structure of moisture associated with the MJO. The dependence of rainfall on lower tropospheric relative humidity and the fraction of rainfall that is stratiform are also discussed, including implications these diagnostics have for MJO simulation. Based on having the most realistic intraseasonal multivariate empirical orthogonal functions, principal component power spectra, equatorial eastward propagating outgoing longwave radiation (OLR), latent heat flux, low-level moisture convergence signals, and vertical structure of moisture over the Eastern Hemisphere, the superparameterized Community Atmosphere Model (SPCAM) and the ECHAM4/Ocean Isopycnal Model (OPYC) show the best skill at representing the MJO.open1149