Linkage disequilibrium assessment via log-linear modeling of SNP haplotype frequencies

Analyses of high-density single-nucleotide polymorphism (SNP) data, such as genetic mapping and linkage disequilibrium (LD) studies, require phase-known haplotypes to allow for the correlation between tightly linked loci. However, current SNP genotyping technology cannot determine phase, which must be inferred statistically. In this paper, we present a new Bayesian Markov chain Monte Carlo (MCMC) algorithm for population haplotype frequency estimation, particulary in the context of LD assessment. The novel feature of the method is the incorporation of a log-linear prior model for population haplotype frequencies. We present simulations to suggest that 1) the log-linear prior model is more appropriate than the standard coalescent process in the presence of recombination (>0.02cM between adjacent loci), and 2) there is substantial inflation in measures of LD obtained by a "two-stage" approach to the analysis by treating the "best" haplotype configuration as correct, without regard to uncertainty in the recombination process. Genet Epidemiol 25:106-114, 2003. (C) 2003 Wiley-Liss, Inc.

Mineralised organic remains from cesspits at the Roman town of Silchester: processes and preservation

Mineralised organic remains (including apple pips and cereal grains) collected during the ongoing excavations of Insula IX at the Roman town of Silchester, Hampshire have been analysed by a combination of SEM-EDX, powder XRD and IR spectroscopy. The experiments included mapping experiments using spatially resolved versions of each technique. IR and powder XRD mapping have been carried out utilising the synchrotron source at The Daresbury Laboratory oil stations 11.1 and 9.6. It is concluded that these samples are preserved by rapid mineralisation in the carbonate-substituted calcium phosphate mineral, dahllite. The rapid mineralisation leads to excellent preservation of the samples and a small crystal size. The value of IR spectroscopy in studying materials like this where the crystal size is small is demonstrated. A comparison is made between the excellent preservation seen in this context and the much poorer preservation of mineralised remains seen in Context 5276 or Cesspit 5251. Comments on the possible mechanism of mineralisation of these samples are made. (C) 2008 Elsevier B.V.. All rights reserved.

Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents

Covariation in the structural composition of the gut microbiome and the spectroscopically derived metabolic phenotype (metabotype) of a rodent model for obesity were investigated using a range of multivariate statistical tools. Urine and plasma samples from three strains of 10-week-old male Zucker rats (obese (fa/fa, n = 8), lean (fal-, n = 8) and lean (-/-, n = 8)) were characterized via high-resolution H-1 NMR spectroscopy, and in parallel, the fecal microbial composition was investigated using fluorescence in situ hydridization (FISH) and denaturing gradient gel electrophoresis (DGGE) methods. All three Zucker strains had different relative abundances of the dominant members of their intestinal microbiota (FISH), with the novel observation of a Halomonas and a Sphingomonas species being present in the (fa/fa) obese strain on the basis of DGGE data. The two functionally and phenotypically normal Zucker strains (fal- and -/-) were readily distinguished from the (fa/fa) obese rats on the basis of their metabotypes with relatively lower urinary hippurate and creatinine, relatively higher levels of urinary isoleucine, leucine and acetate and higher plasma LDL and VLDL levels typifying the (fa/fa) obese strain. Collectively, these data suggest a conditional host genetic involvement in selection of the microbial species in each host strain, and that both lean and obese animals could have specific metabolic phenotypes that are linked to their individual microbiomes.

Kinetic modeling of the generation of 2-and 3-methylbutanal in a heated extract of beef liver

Quantitative control of aroma generation during the Maillard reaction presents great scientific and industrial interest. Although there have been many studies conducted in simplified model systems, the results are difficult to apply to complex food systems, where the presence of other components can have a significant impact. In this work, an aqueous extract of defatted beef liver was chosen as a simplified food matrix for studying the kinetics of the Mallard reaction. Aliquots of the extract were heated under different time and temperature conditions and analyzed for sugars, amino acids, and methylbutanals, which are important Maillard-derived aroma compounds formed in cooked meat. Multiresponse kinetic modeling, based on a simplified mechanistic pathway, gave a good fit with the experimental data, but only when additional steps were introduced to take into account the interactions of glucose and glucose-derived intermediates with protein and other amino compounds. This emphasizes the significant role of the food matrix in controlling the Maillard reaction.

Modeling of carrier transport in nanowires

We consider a physical model of ultrafast evolution of an initial electron distribution in a quantum wire. The electron evolution is described by a quantum-kinetic equation accounting for the interaction with phonons. A Monte Carlo approach has been developed for solving the equation. The corresponding Monte Carlo algorithm is NP-hard problem concerning the evolution time. To obtain solutions for long evolution times with small stochastic error we combine both variance reduction techniques and distributed computations. Grid technologies are implemented due to the large computational efforts imposed by the quantum character of the model.

Applying semiotic analysis to the design and modeling of distributed multimedia systems

Semiotics is the study of signs. Application of semiotics in information systems design is based on the notion that information systems are organizations within which agents deploy signs in the form of actions according to a set of norms. An analysis of the relationships among the agents, their actions and the norms would give a better specification of the system. Distributed multimedia systems (DMMS) could be viewed as a system consisted of many dynamic, self-controlled normative agents engaging in complex interaction and processing of multimedia information. This paper reports the work of applying the semiotic approach to the design and modeling of DMMS, with emphasis on using semantic analysis under the semiotic framework. A semantic model of DMMS describing various components and their ontological dependencies is presented, which then serves as a design model and implemented in a semantic database. Benefits of using the semantic database are discussed with reference to various design scenarios.

Mixed initial-boundary value problem in particle modeling of microelectronic devices

The Boltzmann equation in presence of boundary and initial conditions, which describes the general case of carrier transport in microelectronic devices is analysed in terms of Monte Carlo theory. The classical Ensemble Monte Carlo algorithm which has been devised by merely phenomenological considerations of the initial and boundary carrier contributions is now derived in a formal way. The approach allows to suggest a set of event-biasing algorithms for statistical enhancement as an alternative of the population control technique, which is virtually the only algorithm currently used in particle simulators. The scheme of the self-consistent coupling of Boltzmann and Poisson equation is considered for the case of weighted particles. It is shown that particles survive the successive iteration steps.

Classification-based probabilistic modeling of texture transition for fast line search tracking and delineation

We introduce a classification-based approach to finding occluding texture boundaries. The classifier is composed of a set of weak learners, which operate on image intensity discriminative features that are defined on small patches and are fast to compute. A database that is designed to simulate digitized occluding contours of textured objects in natural images is used to train the weak learners. The trained classifier score is then used to obtain a probabilistic model for the presence of texture transitions, which can readily be used for line search texture boundary detection in the direction normal to an initial boundary estimate. This method is fast and therefore suitable for real-time and interactive applications. It works as a robust estimator, which requires a ribbon-like search region and can handle complex texture structures without requiring a large number of observations. We demonstrate results both in the context of interactive 2D delineation and of fast 3D tracking and compare its performance with other existing methods for line search boundary detection.

Numerical modeling of the propagation environment in the atmospheric boundary layer over the Persian Gulf

Strong vertical gradients at the top of the atmospheric boundary layer affect the propagation of electromagnetic waves and can produce radar ducts. A three-dimensional, time-dependent, nonhydrostatic numerical model was used to simulate the propagation environment in the atmosphere over the Persian Gulf when aircraft observations of ducting had been made. A division of the observations into high- and low-wind cases was used as a framework for the simulations. Three sets of simulations were conducted with initial conditions of varying degrees of idealization and were compared with the observations taken in the Ship Antisubmarine Warfare Readiness/Effectiveness Measuring (SHAREM-115) program. The best results occurred with the initialization based on a sounding taken over the coast modified by the inclusion of data on low-level atmospheric conditions over the Gulf waters. The development of moist, cool, stable marine internal boundary layers (MIBL) in air flowing from land over the waters of the Gulf was simulated. The MIBLs were capped by temperature inversions and associated lapses of humidity and refractivity. The low-wind MIBL was shallower and the gradients at its top were sharper than in the high-wind case, in agreement with the observations. Because it is also forced by land–sea contrasts, a sea-breeze circulation frequently occurs in association with the MIBL. The size, location, and internal structure of the sea-breeze circulation were realistically simulated. The gradients of temperature and humidity that bound the MIBL cause perturbations in the refractivity distribution that, in turn, lead to trapping layers and ducts. The existence, location, and surface character of the ducts were well captured. Horizontal variations in duct characteristics due to the sea-breeze circulation were also evident. The simulations successfully distinguished between high- and low-wind occasions, a notable feature of the SHAREM-115 observations. The modeled magnitudes of duct depth and strength, although leaving scope for improvement, were most encouraging.

Methods for kinematic modeling of biological and robotic systems

The main objective is to develop methods that automatically generate kinematic models for the movements of biological and robotic systems. Two methods for the identification of the kinematics are presented. The first method requires the elimination of the displacement variables that cannot be measured while the second method attempts to estimate the changes in these variables. The methods were tested using a planar two-revolute-joint linkage. Results show that the model parameters obtained agree with the actual parameters to within 5%. Moreover, the methods were applied to model head and neck movements in the sagittal plane. The results indicate that these movements are well modeled by a two-revolute-joint system. A spatial three-revolute-joint model was also discussed and tested.

Kinematic modeling of head-neck movements

The main objective is to generate kinematic models for the head and neck movements. The motivation comes from our study of individuals with quadriplegia and the need to design rehabilitation aiding devices such as robots and teletheses that can be controlled by head-neck movements. It is then necessary to develop mathematical models for the head and neck movements. Two identification methods have been applied to study the kinematics of head-neck movements of able-body as well as neck-injured subjects. In particular, sagittal plane movements are well modeled by a planar two-revolute-joint linkage. In fact, the motion in joint space seems to indicate that sagittal plane movements may be classified as a single DOF motion. Finally, a spatial three-revolute-joint system has been employed to model 3D head-neck movements.

Numerical modeling of inhaled charged aerosol deposition in human airways

A new numerical modeling of inhaled charge aerosol has been developed based on a modified Weibel's model. Both the velocity profiles (slug and parabolic flows) and the particle distributions (uniform and parabolic distributions) have been considered. Inhaled particles are modeled as a dilute dispersed phase flow in which the particle motion is controlled by fluid force and external forces acting on particles. This numerical study extends the previous numerical studies by considering both space- and image-charge forces. Because of the complex computation of interacting forces due to space-charge effect, the particle-mesh (PM) method is selected to calculate these forces. In the PM technique, the charges of all particles are assigned to the space-charge field mesh, for calculating charge density. The Poisson's equation of the electrostatic potential is then solved, and the electrostatic force acting on individual particle is interpolated. It is assumed that there is no effect of humidity on charged particles. The results show that many significant factors also affect the deposition, such as the volume of particle cloud, the velocity profile and the particle distribution. This study allows a better understanding of electrostatic mechanism of aerosol transport and deposition in human airways.

Modeling of complex-valued Wiener systems using B-spline neural network

In this brief, a new complex-valued B-spline neural network is introduced in order to model the complex-valued Wiener system using observational input/output data. The complex-valued nonlinear static function in the Wiener system is represented using the tensor product from two univariate B-spline neural networks, using the real and imaginary parts of the system input. Following the use of a simple least squares parameter initialization scheme, the Gauss-Newton algorithm is applied for the parameter estimation, which incorporates the De Boor algorithm, including both the B-spline curve and the first-order derivatives recursion. Numerical examples, including a nonlinear high-power amplifier model in communication systems, are used to demonstrate the efficacy of the proposed approaches.

Necessary and sufficient conditions for realizability of point processes

We give necessary and sufficient conditions for a pair of (generali- zed) functions 1(r1) and 2(r1, r2), ri 2X, to be the density and pair correlations of some point process in a topological space X, for ex- ample, Rd, Zd or a subset of these. This is an infinite-dimensional version of the classical “truncated moment” problem. Standard tech- niques apply in the case in which there can be only a bounded num- ber of points in any compact subset of X. Without this restriction we obtain, for compact X, strengthened conditions which are necessary and sufficient for the existence of a process satisfying a further re- quirement—the existence of a finite third order moment. We general- ize the latter conditions in two distinct ways when X is not compact.