The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability

The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

Evaluation of the BEASY program using linear and piecewise linear approaches for the boundary conditions

The boundary element method (BEM) was used to study galvanic corrosion using linear and logarithmic boundary conditions. The linear boundary condition was implemented by using the linear approach and the piecewise linear approach. The logarithmic boundary condition was implemented by the piecewise linear approach. The calculated potential and current density distribution were compared with the prior analytical results. For the linear boundary condition, the BEASY program using the linear approach and the piecewise linear approach gave accurate predictions of the potential and the galvanic current density distributions for varied electrolyte conditions, various film thicknesses, various electrolyte conductivities and various area ratio of anode/cathode. The 50-point piecewise linear method could be used with both linear and logarithmic polarization curves.

Improved slope adjustment functions for soil erosion prediction

Numerous studies in the last 60 years have investigated the relationship between land slope and soil erosion rates. However, relatively few of these have investigated slope gradient responses: ( a) for steep slopes, (b) for specific erosion processes, and ( c) as a function of soil properties. Simulated rainfall was applied in the laboratory on 16 soils and 16 overburdens at 100 mm/h to 3 replicates of unconsolidated flume plots 3 m long by 0.8 m wide and 0.15 m deep at slopes of 20, 5, 10, 15, and 30% slope in that order. Sediment delivery at each slope was measured to determine the relationship between slope steepness and erosion rate. Data from this study were evaluated alongside data and existing slope adjustment functions from more than 55 other studies from the literature. Data and the literature strongly support a logistic slope adjustment function of the form S = A + B/[1 + exp (C - D sin theta)] where S is the slope adjustment factor and A, B, C, and D are coefficients that depend on the dominant detachment and transport processes. Average coefficient values when interill-only processes are active are A - 1.50, B 6.51, C 0.94, and D 5.30 (r(2) = 0.99). When rill erosion is also potentially active, the average slope response is greater and coefficient values are A - 1.12, B 16.05, C 2.61, and D 8.32 (r(2) = 0.93). The interill-only function predicts increases in sediment delivery rates from 5 to 30% slope that are approximately double the predictions based on existing published interill functions. The rill + interill function is similar to a previously reported value. The above relationships represent a mean slope response for all soils, yet the response of individual soils varied substantially from a 2.5-fold to a 50-fold increase over the range of slopes studied. The magnitude of the slope response was found to be inversely related ( log - log linear) to the dispersed silt and clay content of the soil, and 3 slope adjustment equations are proposed that provide a better estimate of slope response when this soil property is known. Evaluation of the slope adjustment equations proposed in this paper using independent datasets showed that the new equations can improve soil erosion predictions.

Biotelemetry: a mechanistic approach to ecology

Remote measurement of the physiology, behaviour and energetic status of free-living animals is made possible by a variety of techniques that we refer to collectively as 'biotelemetry'. This set of tools ranges from transmitters that send their signals to receivers up to a few kilometers away to those that send data to orbiting satellites and, more frequently, to devices that log data. They enable researchers to document, for long uninterrupted periods, how undisturbed organisms interact with each other and their environment in real time. In spite of advances enabling the monitoring of many physiological and behavioural variables across a range of taxa of various sizes, these devices have yet to be embraced widely by the ecological community. Our review suggests that this technology has immense potential for research in basic and applied animal ecology. Efforts to incorporate biotelemetry into broader ecological research programs should yield novel information that has been challenging to collect historically from free-ranging animals in their natural environments. Examples of research that would benefit from biotelemetry include the assessment of animal responses to different anthropogenic perturbations and the development of life-time energy budgets.

A composite DOP approach to excluding bottom reflectance in mapping water parameters of shallow coastal zones from TM imagery

In this paper we proposed a composite depth of penetration (DOP) approach to excluding bottom reflectance in mapping water quality parameters from Landsat thematic mapper (TM) data in the shallow coastal zone of Moreton Bay, Queensland, Australia. Three DOPs were calculated from TM1, TM2 and TM3, in conjunction with bathymetric data, at an accuracy ranging from +/-5% to +/-23%. These depths were used to segment the image into four DOP zones. Sixteen in situ water samples were collected concurrently with the recording of the satellite image. These samples were used to establish regression models for total suspended sediment (TSS) concentration and Secchi depth with respect to a particular DOP zone. Containing identical bands and their transformations for both parameters, the models are linear for TSS concentration, logarithmic for Secchi depth. Based on these models, TSS concentration and Secchi depth were mapped from the satellite image in respective DOP zones. Their mapped patterns are consistent with the in situ observed ones. Spatially, overestimation and underestimation of the parameters are restricted to localised areas but related to the absolute value of the parameters. The mapping was accomplished more accurately using multiple DOP zones than using a single zone in shallower areas. The composite DOP approach enables the mapping to be extended to areas as shallow as <3 m. (C) 2004 Elsevier Inc. All rights reserved.

Adaptive phase measurements in linear optical quantum computation

Photon counting induces an effective non-linear optical phase shift in certain states derived by linear optics from single photons. Although this non-linearity is non-deterministic, it is sufficient in principle to allow scalable linear optics quantum computation (LOQC). The most obvious way to encode a qubit optically is as a superposition of the vacuum and a single photon in one mode-so-called 'single-rail' logic. Until now this approach was thought to be prohibitively expensive (in resources) compared to 'dual-rail' logic where a qubit is stored by a photon across two modes. Here we attack this problem with real-time feedback control, which can realize a quantum-limited phase measurement on a single mode, as has been recently demonstrated experimentally. We show that with this added measurement resource, the resource requirements for single-rail LOQC are not substantially different from those of dual-rail LOQC. In particular, with adaptive phase measurements an arbitrary qubit state a alpha/0 > + beta/1 > can be prepared deterministically.

Construction of the cyclovibsanin core via a biogenetically modeled approach

Construction of the 15-O-methylcyclovibsanin B core was achieved expediently in eight linear steps utilizing a biogenetically modeled approach.

The population pharmacokinetics of citalopram after deliberate self-poisoning: A Bayesian approach

Defining the pharmacokinetics of drugs in overdose is complicated. Deliberate self-poisoning is generally impulsive and associated with poor accuracy in dose history. In addition, early blood samples are rarely collected to characterize the whole plasma-concentration time profile and the effect of decontamination on the pharmacokinetics is uncertain. The aim of this study was to explore a fully Bayesian methodology for population pharmacokinetic analysis of data that arose from deliberate self-poisoning with citalopram. Prior information on the pharmacokinetic parameters was elicited from 14 published studies on citalopram when taken in therapeutic doses. The data set included concentration-time data from 53 patients studied after 63 citalopram overdose events (dose range: 20-1700 mg). Activated charcoal was administered between 0.5 and 4 h after 17 overdose events. The clinical investigator graded the veracity of the patients' dosing history on a 5-point ordinal scale. Inclusion of informative priors stabilised the pharmacokinetic model and the population mean values could be estimated well. There were no indications of non-linear clearance after excessive doses. The final model included an estimated uncertainty of the dose amount which in a simulation study was shown to not affect the model's ability to characterise the effects of activated charcoal. The effect of activated charcoal on clearance and bioavailability was pronounced and resulted in a 72% increase and 22% decrease, respectively. These findings suggest charcoal administration is potentially beneficial after citalopram overdose. The methodology explored seems promising for exploring the dose-exposure relationship in the toxicological settings.

Dietary analysis of the herbivorous hemiramphid Hyporhamphus regularis ardelio: an isotopic approach

The stable isotope values for a range of size classes of Hyporhamphus regularis ardelio from Moreton Bay, south-east Australia were determined. There was a positive linear relationship between 613 C and standard length (L-s) (delta(13)C = 0.034 Ls - 16-23; r(2) = 0.78). delta(13)C ranged from -8.48 to - 17.29 parts per thousand with the smallest size class (50 mm Ls) being on average 1.04 parts per thousand enriched with respect to that of zooplankton (Temora turbinata) and 7.97 parts per thousand depleted compared to Zostera capricorni. delta(13)C was positively correlated with Ls (P 0.0 1) with delta(15) N, ranging from 9.18 to 11.00 parts per thousand. Fish of all size classes were on average 2.32 and 7.63 parts per thousand more enriched than zooplankton and seagrass, respectively. Carbon isotope data indicate that H. r. ardelio commence life as carnivores and change to a diet in which seagrass is the primary carbon source. The dependence on animal matter, however, is always present. Due to the low percentage of nitrogen in Z. capricorni (2.5%) compared to zooplankton (9.1%) it appears that nitrogen from zooplankton is necessary throughout their life history with the carbon requirements for these fish coming chiefly from Z. capricorni. (c) 2005 The Fisheries Society of the British Isles.

Linear temporal logic and z refinement

Since Z, being a state-based language, describes a system in terms of its state and potential state changes, it is natural to want to describe properties of a specified system also in terms of its state. One means of doing this is to use Linear Temporal Logic (LTL) in which properties about the state of a system over time can be captured. This, however, raises the question of whether these properties are preserved under refinement. Refinement is observation preserving and the state of a specified system is regarded as internal and, hence, non-observable. In this paper, we investigate this issue by addressing the following questions. Given that a Z specification A is refined by a Z specification C, and that P is a temporal logic property which holds for A, what temporal logic property Q can we deduce holds for C? Furthermore, under what circumstances does the property Q preserve the intended meaning of the property P? The paper answers these questions for LTL, but the approach could also be applied to other temporal logics over states such as CTL and the mgr-calculus.