Evaluating medication response in ADHD: cognitive, behavioral, and single-subject methodology

We introduce a novel application for linkage analysis: using bone marrow donor-recipient sib pairs to search for genes influential in graft-versus-host disease (GVHD), a major cause of morbidity and mortality following allogeneic bone marrow transplantation. In particular, we show that transplant sib pairs in which the recipient developed severe GVHD can be used to map genes in the same way as traditional discordant (affected/unaffected) sib pairs (DSPs). For a plausible GVHD model, we demonstrate that the transplant/discordant sib pair analog of the "possible triangle test" [Holmans (1993) Am J Hum Genet 52:362-374] has similar power to that of the simpler "restricted test" proposed by Risch [(1990b) Am J Hum Genet 46:229-241; (1992) Am J Hum Genet 51:673-675]. Moreover, we show that the restricted test has superior power in much of the DSP possible triangle and significantly inferior power in only a small region. Thus, we conclude that the restricted test is preferable for localizing genes with transplant/discordant sib pairs. Finally, we examine the effects of heterogeneity on the power to detect GVHD loci and demonstrate the gain in efficiency by dividing the sample into genetically more homogeneous subgroups.     

Role of intimin and bundle-forming pili in enteropathogenic Escherichia coli adhesion to pediatric intestinal tissue in vitro

Attaching and effacing (A/E) lesion formation is central to enteropathogenic Escherichia coli (EPEC) pathogenesis. In vitro experiments with human epithelial cell lines have implicated virulence plasmid-encoded bundle-forming pili (BFP) in initial binding and intimin in intimate attachment and A/E lesion formation. This study investigated the role of BFP and intimin in EPEC interactions with pediatric small intestinal biopsy tissue in in vitro organ culture. Organ culture infections (2 to 8 h) were performed with E2348/69 (a wild-type EPEC O127:H6 clinical isolate) and E2348/69 derivatives including CVD206 (eae deficient), CVD206(pCVD438) (eae-complemented CVD206), CVD206(pCVD438/01) (expressing intimin, which is nonfunctional due to a single amino acid substitution), JPN15 (spontaneous EPEC adherence factor virulence plasmid-cured E2348/69), and 31-6-1(1) (E2348/69 with a TnphoA insertion inactivation mutation in the virulence plasmid-encoded bfpA gene). Scanning and transmission electron microscopy revealed that after 8 h E2348/69 and CVD206 (pCVD438) (both Int+ BFP+) adhered to all specimens, causing A/E lesions with surrounding microvillous elongation. JPN15 and 31-6-1(1) (both Int+ BFP-) adhered and caused A/E lesions although bacteria adhered in "flat," two-dimensional groups. CVD206 and CVD206(pCVD438/01) (both Int- BFP+) did not adhere to any sample, and no pathological tissue changes were seen. Thus, in human intestinal organ culture, BFP do not appear to be involved in the initial stages of EPEC nonintimate adhesion but are implicated in the formation of complex, three-dimensional colonies via bacterium-bacterium interactions. Intimin appears to play an essential role in establishing colonization of EPEC on pediatric small intestinal tissue.     

Interactive visualization and analysis of transitional flow

A stand-alone visualization application has been developed by a multi-disciplinary, collaborative team with the sole purpose of creating an interactive exploration environment allowing turbulent flow researchers to experiment and validate hypotheses using visualization. This system has specific optimizations made in data management, caching computations, and visualization allowing for the interactive exploration of datasets on the order of 1TB in size. Using this application, the user (co-author Calo) is able to interactively visualize and analyze all regions of a transitional flow volume, including the laminar, transitional and fully turbulent regions. The underlying goal of the visualizations produced from these transitional flow simulations is to localize turbulent spots in the laminar region of the boundary layer, determine under which conditions they form, and follow their evolution. The initiation of turbulent spots, which ultimately lead to full turbulence, was located via a proposed feature detection condition and verified by experimental results. The conditions under which these turbulent spots form and coalesce are validated and presented.     

The turnover and distribution of labelled corticosterone during post-natal development of the duckling (Anas platyrhynchos)

During 6 months of post-natal development in the laboratory, the weight of the adrenal gland relative to body weight decreases exponentially. In the 3 day-old duckling a single intravenous dose of labelled corticosterone becomes distributed in a very large apparent volume and an "extracellular" pool that is greater than the extracellular fluid volume and the pattern of disappearance of labelled hormone from plasma is biphasic. Later during development the volumes of distribution decrease and the biphasic pattern of disappearance becomes less distinct until at 6 months only one phase of disappearance can be detected with confidence. No significant change in plasma corticosterone concentration occurs during this period of development in the laboratory. Estimations of the corticosterone secretory rates, however, indicate that whereas the adrenal weight-specific rate os secretion increases during the first 3 weeks and declines therafter, the bodyf weight-specific secretory rate continues to decline throughtout the period of increasing body weight.     

Fecal Coliform Removal within a Marshland Upwelling System Consisting of Scatlake Soils

The marshland upwelling system (MUS) was installed on private camps in the Grand Bay National Estuarine Research Reserve, Moss Point, Mississippi. The system was evaluated for its effectiveness in removing fecal coliforms from settled, raw wastewater. A suite of studies was performed at flow rates of 1.9, 2.8, and 5.5 L/min and an injection frequency of 30 min every 3 h to investigate fecal coliform removal. An additional study was performed at a flow rate of 2.8 L/min and an injection frequency of 15 min every hour. Overall, the MUS consistently maintained fecal concentrations below effluent regulatory standards for shellfish harvesting waters (14 most probable number of colonies per 100 mL). Mean influent concentrations of 55,269±2,218,016 colony forming units (CFU)/100 mL were reduced to effluent counts of 2.7±14.07 CFU/100 mL (observed in the 1.5 m wells). Three- to four-log reductions in influent counts were observed over the initial 1.4 vector?m from the injection well. The overall removal followed a first-order decay relationship with respect to vector distance, resulting in removal rate constants ranging from 5.6 to 6.6/m and predicted surface concentrations approaching 0 CFU/100 mL. The 2.8 L/min for 30 min every 3 h treatment provided the best effluent quality.     

Rough Terrain Autonomous Mobility—Part 1: A Theoretical Analysis of Requirements

A basic requirement of autonomous vehicles is that of guaranteeing the safety of the vehicle by avoiding hazardous situations. This paper analyses this requirement in general terms of real-time response, throughput, and the resolution and accuracy of sensors and computations. Several nondimensional expressions emerge which characterize requirements in canonical form.The automatic generation of dense geometric models for autonomously navigating vehicles is a computationally expensive process. Using first principles, it is possible to quantify the relationship between the raw throughput required of the perception system and the maximum safely achievable speed of the vehicle. We derive several useful expressions for the complexity of terrain mapping perception under various assumptions. All of them can be reduced to polynomials in the response distance.The significant time consumed by geometric perception degrades real-time response characteristics. Using our results, several strategies of active geometric perception arise which are practical for autonomous vehicles and increasingly important at higher speeds.     

Calorimetric and thermodynamic analysis of palladium-deuterium electrochemical cells

An analysis is made of the chemical heats liberated from a palladium-deuterium electrochemical cell operating inside a calorimeter. It is important, in such an analysis, to carefully identify the chemical and electrochemical sources of heat, before any “excess heats” can be ascribed to non-chemical reactions.⁽¹⁾ The calorimeter measures the enthalpy (ΔH _r ) of the reaction; whereas, the electrochemical voltage of the cell reflects the free energy (ΔG _r ) of the reaction within the Pd-D electrolysis cell. The heat energy from the calorimeter cell therefore doesnot equal the electrical energy supplied to the cell, as might initially be expected. The magnitudes of the differing calorimetric and electrochemical energies were found to be related through the “thermoneutral potential” (ξ_H) of the electrochemical reaction. The chemical heat theoretically expected from the calorimeter is given by (1) I(ξ_L-ξ_H), the cell current (I), multiplied by the difference between the operating cell voltage (ξ_L) and the thermoneutral potential (ξ_H), rather than (2) Iξ_L, the electrical input power. This was verified empirically using a freon vaporization calorimeter, which operates on the principle of accurate measurement of the vaporization rate of liquid freon which completely surrounds the electrochemical cell. The calorimetrically-measured heats observed from a Pt/D₂O, 0.1M LiOD/Pd electrochemical cell were within 2% of the thermoneutral potential predicted value, I(ξ_L-ξ_H); but were found to be 15–30% less than the electrical work supplied to the cell, Iξ_L. Measurements of D₂O consumed by the cell reactions also verified that essentially no significant recombination of D₂ and O₂ gases occurred within the cell. No “excess heats” were observed from this Pd cell during the 36 days of its electrolytic operation. Likewise, no increase in the neutron flux around the cell was found, using three³He radiation detectors.