Distribution Of Endpoints Research Articles

Effect of site-specific bronchial radon progeny deposition on the spatial and temporal distributions of cellular responses

Inhaled short-lived radon progenies may deposit in bronchial airways and interact with the epithelium by the emission of alpha particles. Simulation of the related radiobiological effects requires the knowledge of space and time distributions of alpha particle hits and biological endpoints. Present modelling efforts include simulation of radioaerosol deposition patterns in a central bronchial airway bifurcation, modelling of human bronchial epithelium, generation of alpha particle tracks, and computation of spatio-temporal distributions of cell nucleus hits, cell killing and cell transformation events. Simulation results indicate that the preferential radionuclide deposition at carinal ridges plays an important role in the space and time evolution of the biological events. While multiple hits are generally rare for low cumulative exposures, their probability may be quite high at the carinal ridges of the airway bifurcations. Likewise, cell killing and transformation events also occur with higher probability in this area. In the case of uniform surface activities, successive hits as well as cell killing and transformation events within a restricted area (say 0.5mm(2)) are well separated in time. However, in the case of realistic inhomogeneous deposition, they occur more frequently within the mean cycle time of cells located at the carinal ridge even at low cumulative doses. The site-specificity of radionuclide deposition impacts not only on direct, but also on non-targeted radiobiological effects due to intercellular communication. Incorporation of present results into mechanistic models of carcinogenesis may provide useful information concerning the dose-effect relationship in the low-dose range.

Dendritic versus Linear Polymer Brushes: Self-Consistent Field Modeling, Scaling Theory, and Experiments

Equilibrium structural properties of polymer brushes formed by dendritic polymer chains (dendrons) are studied by means of Scheutjens−Fleer self-consistent field (SF-SCF) modeling and scaling analysis. Limiting cases of minimal and maximal possible losses of conformational entropy corresponding to different assumptions concerning distribution of elastic tension in the end-grafted dendrons are analyzed on the basis of the Flory-type scaling approach. The numerical SCF modeling indicates that the effective exponent of the power-law dependence for the height of dendritic brush on the grafting density differs from that derived within the Flory-type approximation. This is explained by changing of the intramolecular elastic tension distribution upon an increase in grafting density. The distributions of end and branching points are wide and exhibit multiple maxima, pointing to a broad distribution in the chain stretching. This distribution leads to monotonically decreasing overall density profiles. The theoretical results are in line with experimental findings on linear and dendritic poly(ethylene glycol) layers end-grafted onto TiO2 surfaces.

The Pearson walk with shrinking steps in two dimensions

We study the shrinking Pearson random walk in two dimensions and greater, in which the direction of theNth step is random andits length equals λN−1, with λ<1. Asλ increases past acritical value λc, the endpoint distribution in two dimensions,P(r), changes from having a global maximum away from the origin to beingpeaked at the origin. The probability distribution for a single coordinate,P(x), undergoes a similar transition, but exhibits multiple maxima on a fine length scale forλ close toλc. We numericallydetermine P(r) and P(x) by applying a known algorithm that accurately inverts the exact Bessel function productform of the Fourier transform for the probability distributions.

A model of top-down attentional control during visual search in complex scenes

Recently, there has been great interest among vision researchers in developing computational models that predict the distribution of saccadic endpoints in naturalistic scenes. In many of these studies, subjects are instructed to view scenes without any particular task in mind so that stimulus-driven (bottom-up) processes guide visual attention. However, whenever there is a search task, goal-driven (top-down) processes tend to dominate guidance, as indicated by attention being systematically biased toward image features that resemble those of the search target. In the present study, we devise a top-down model of visual attention during search in complex scenes based on similarity between the target and regions of the search scene. Similarity is defined for several feature dimensions such as orientation or spatial frequency using a histogram-matching technique. The amount of attentional guidance across visual feature dimensions is predicted by a previously introduced informativeness measure. We use eye-movement data gathered from participants' search of a set of naturalistic scenes to evaluate the model. The model is found to predict the distribution of saccadic endpoints in search displays nearly as accurately as do other observers' eye-movement data in the same displays.

Virologic Response and Safety of the Abacavir/Lamivudine Fixed-Dose Formulation as Part of Highly Active Antiretroviral Therapy: Analyses of Six Clinical Studies

Objective: We analyzed virologic response and safety data from six recent clinical studies conducted in antiretroviral-naïve subjects treated with ABC/3TC or its components to assess the impact of baseline viral load on efficacy and safety endpoints used in the ACTG5202 protocol. Methods: Primary endpoints were time to virologic failure (confirmed HIV-1 RNA ⩾1,000 copies/mL at 16–24 weeks or ⩾200 copies/mL at ⩾24 weeks) and time to first grade 3 or 4 adverse event or laboratory abnormality that was at least one grade higher than at baseline. The survival distributions of both endpoints were estimated using the Kaplan-Meier method overall and by baseline viral load (<100,000 vs. ⩾100,000 copies/mL). A weighted mean of the virologic response and 95% confidence intervals (CI) were calculated by inverse-variance weighting for baseline viral load ⩾100,000 copies/mL across studies. Results: For subjects with baseline HIV-1 RNA ⩾100,000 copies/mL, the rate of virologic survival ranged from 87% to 95% by 48 weeks. Few subjects treated with ABC/3TC developed grade 3 or 4 adverse events, laboratory toxicities, or changes in lipid levels. The weighted mean (CI) for the pooled virologic response was 91% (87%–96%). Conclusion: Based on the A5202 endpoints, ABC/3TC-containing regimens in this analysis had a high rate of virologic survival and were generally well tolerated in antiretroviral-naïve subjects regardless of baseline viral load. The pooled virologic response for ABC/3TC in our analysis is higher than the A5202 estimate.

The control parameters used by the CNS to guide the hand depend on the visuo-motor task: Evidence from visually guided pointing

To perform visually guided hand movements the visuo-motor system transforms visual information into movement parameters, invoking both central and peripheral processes. Central visuo-motor processes are active in the CNS, whereas peripheral processes are active at the neuromuscular junction. A major share of research attention regarding central visuo-motor processes concerns the question which parameters the CNS controls to guide the hand from one point to another. Findings in the literature are inconsistent. Whereas some researchers suggest that the CNS controls the hand displacement vector, others suggest that it controls final hand position. The current paper introduces a paradigm and analysis method designed to identify the parameters that the CNS controls to guide the hand. We use simulations to validate our analysis in the presence of peripheral visuo-motor noise and to estimate the level of peripheral noise in our data. Using our new tools, we show that hand movements are controlled either in terms of the hand displacement vector or in terms of final hand position, depending on the way visual information relevant for movement production is specified. Interestingly, our new analysis method reveals a difference in central visuo-motor processes, even though a traditional analysis of movement endpoint distributions does not. We estimate the level of peripheral noise in our data to be less than or equal to 40%. Based on our results we conclude that the CNS is flexible with regard to the parameters it controls to guide the hand; that spatial distributions of movement endpoints are not necessarily indicative of central visuo-motor processes; and that both peripheral and central noise has to be carefully considered in the interpretation of movement data.

SLE on Doubly-Connected Domains and the Winding of Loop-Erased Random Walks

Two-dimensional loop-erased random walks (LERWs) are random planar curves whose scaling limit is known to be a Schramm-Loewner evolution SLEκ with parameter κ=2. In this note, some properties of an SLEκ trace on doubly-connected domains are studied and a connection to passive scalar diffusion in a Burgers flow is emphasised. In particular, the endpoint probability distribution and winding probabilities for SLE2 on a cylinder, starting from one boundary component and stopped when hitting the other, are found. A relation of the result to conditioned one-dimensional Brownian motion is pointed out. Moreover, this result permits to study the statistics of the winding number for SLE2 with fixed endpoints. A solution for the endpoint distribution of SLE4 on the cylinder is obtained and a relation to reflected Brownian motion pointed out.

Characterization of the cellulolytic and hydrogen-producing activities of six mesophilic Clostridium species

To characterize cellulolytic, hydrogen-producing clostridia on a comparable basis. H(2) production from cellulose by six mesophilic clostridia was characterized in standardized batch experiments using MN301 cellulose, Avicel and cellobiose. Daily H(2) production, substrate degradation, biomass production and the end-point distribution of soluble fermentation products varied with species and substrates. All species produced a significant amount of H(2) from cellobiose, with Clostridium acetobutylicum achieving the highest H(2) yield of 2.3 mol H(2) mol(-1) hexose, but it did not degrade cellulose. Clostridium cellulolyticum and Clostridium populeti catalysed the highest H(2) production from cellulose, with yields of 1.7 and 1.6 mol H(2 )mol(-1) hexose from MN301 and 1.6 and 1.4 mol H(2) mol(-1) hexose from Avicel, respectively. These species also achieved 25-100% higher H(2) production rates from cellulose than the other species. These cellulolytic, hydrogen-producing clostridia varied in H(2) production, with Cl. cellulolyticum and Cl. populeti achieving the highest H(2) yields and cellulose degradation. The fermentation of cellulosic materials presents a means of H(2) production from renewable resources. This standardized comparison provides a quantitative baseline for improving H(2) production from cellulose through medium and process optimization and metabolic engineering.

Frames of Reference for Gaze Saccades Evoked During Stimulation of Lateral Intraparietal Cortex

Previous studies suggest that stimulation of lateral intraparietal cortex (LIP) evokes saccadic eye movements toward eye- or head-fixed goals, whereas most single-unit studies suggest that LIP uses an eye-fixed frame with eye-position modulations. The goal of our study was to determine the reference frame for gaze shifts evoked during LIP stimulation in head-unrestrained monkeys. Two macaques (M1 and M2) were implanted with recording chambers over the right intraparietal sulcus and with search coils for recording three-dimensional eye and head movements. The LIP region was microstimulated using pulse trains of 300 Hz, 100-150 microA, and 200 ms. Eighty-five putative LIP sites in M1 and 194 putative sites in M2 were used in our quantitative analysis throughout this study. Average amplitude of the stimulation-evoked gaze shifts was 8.67 degrees for M1 and 7.97 degrees for M2 with very small head movements. When these gaze-shift trajectories were rotated into three coordinate frames (eye, head, and body), gaze endpoint distribution for all sites was most convergent to a common point when plotted in eye coordinates. Across all sites, the eye-centered model provided a significantly better fit compared with the head, body, or fixed-vector models (where the latter model signifies no modulation of the gaze trajectory as a function of initial gaze position). Moreover, the probability of evoking a gaze shift from any one particular position was modulated by the current gaze direction (independent of saccade direction). These results provide causal evidence that the motor commands from LIP encode gaze command in eye-fixed coordinates but are also subtly modulated by initial gaze position.

Parietal stimulation destabilizes spatial updating across saccadic eye movements

Saccadic eye movements cause sudden and global shifts in the retinal image. Rather than causing confusion, however, eye movements expand our sense of space and detail. In macaques, a stable representation of space is embodied by neural populations in intraparietal cortex that redistribute activity with each saccade to compensate for eye displacement, but little is known about equivalent updating mechanisms in humans. We combined noninvasive cortical stimulation with a double-step saccade task to examine the contribution of two human intraparietal areas to transsaccadic spatial updating. Right hemisphere stimulation over the posterior termination of the intraparietal sulcus (IPSp) broadened and shifted the distribution of second-saccade endpoints, but only when the first-saccade was directed into the contralateral hemifield. By interleaving trials with and without cortical stimulation, we show that the shift in endpoints was caused by an enduring effect of stimulation on neural functioning (e.g., modulation of neuronal gain). By varying the onset time of stimulation, we show that the representation of space in IPSp is updated immediately after the first-saccade. In contrast, stimulation of an adjacent IPS site had no such effects on second-saccades. These experiments suggest that stimulation of IPSp distorts an eye position or displacement signal that updates the representation of space at the completion of a saccade. Such sensory-motor integration in IPSp is crucial for the ongoing control of action, and may contribute to visual stability across saccades.

Proprioceptive Guidance of Saccades in Eye–Hand Coordination

The saccade generator updates memorized target representations for saccades during eye and head movements. Here, we tested if proprioceptive feedback from the arm can also update handheld object locations for saccades, and what intrinsic coordinate system(s) is used in this transformation. We measured radial saccades beginning from a central light-emitting diode to 16 target locations arranged peripherally in eight directions and two eccentricities on a horizontal plane in front of subjects. Target locations were either indicated 1) by a visual flash, 2) by the subject actively moving the handheld central target to a peripheral location, 3) by the experimenter passively moving the subject's hand, or 4) through a combination of the above proprioceptive and visual stimuli. Saccade direction was relatively accurate, but subjects showed task-dependent systematic overshoots and variable errors in radial amplitude. Visually guided saccades showed the smallest overshoot, followed by saccades guided by both vision and proprioception, whereas proprioceptively guided saccades showed the largest overshoot. In most tasks, the overall distribution of saccade endpoints was shifted and expanded in a gaze- or head-centered cardinal coordinate system. However, the active proprioception task produced a tilted pattern of errors, apparently weighted toward a limb-centered coordinate system. This suggests the saccade generator receives an efference copy of the arm movement command but fails to compensate for the arm's inertia-related directional anisotropy. Thus the saccade system is able to transform hand-centered somatosensory signals into oculomotor coordinates and combine somatosensory signals with visual inputs, but it seems to have a poorly calibrated internal model of limb properties.

A lower visual field advantage for endpoint stability but no advantage for online movement precision

It has been proposed that visually guided reaching movements performed in the lower visual field (LVF) of peripersonal space are more effective and efficient than their upper visual field (UVF) counterparts (Danckert and Goodale 2001). In the present investigation we sought to determine whether this purported visual field asymmetry reflects advantaged processing of online visual feedback. To accomplish that objective, participants performed discrete reaching movements to each of three target locations in the LVF and UVF. In addition, reaches were completed under conditions wherein target location remained constant throughout a reaching response (i.e., control trials) and a separate condition wherein target location unexpectedly perturbed at movement onset (i.e., experimental trials). We reasoned that the target perturbation paradigm would provide a novel means to assess a possible superior-inferior visual field asymmetry for online reaching control. In terms of the impact of a target perturbation, both visual fields demonstrated equal proficiency integrating visual feedback for online limb adjustments. Interestingly, however, the spatial distribution of movement endpoints in the LVF was less than UVF counterparts (cf. Binsted and Heath 2005). Taken together, the present findings suggest that although LVF and UVF reaches readily use visual feedback to accommodate an unexpected target perturbation, reaches in the LVF elicit advantaged spatial benefits influencing the effectiveness of online limb corrections.

Correction-to-Scaling Exponents for Two-Dimensional Self-Avoiding Walks

We study the correction-to-scaling exponents for the two-dimensional self-avoiding walk, using a combination of series-extrapolation and Monte Carlo methods. We enumerate all self-avoiding walks up to 59 steps on the square lattice, and up to 40 steps on the triangular lattice, measuring the mean-square end-to-end distance, the mean-square radius of gyration and the mean-square distance of a monomer from the endpoints. The complete endpoint distribution is also calculated for self-avoiding walks up to 32 steps (square) and up to 22 steps (triangular). We also generate self-avoiding walks on the square lattice by Monte Carlo, using the pivot algorithm, obtaining the mean-square radii to ≈ 0.01% accuracy up to N=4000. We give compelling evidence that the first non-analytic correction term for two-dimensional self-avoiding walks is Δ1=3/2. We compute several moments of the endpoint distribution function, finding good agreement with the field-theoretic predictions. Finally, we study a particular invariant ratio that can be shown, by conformal-field-theory arguments, to vanish asymptotically, and we find the cancellation of the leading analytic correction.

Migration of green turtles Chelonia mydas from Tortuguero, Costa Rica

During 1955–2003, flipper tags were attached to 46,983 green turtles and ten turtles were fitted with satellite transmitters at Tortuguero, Costa Rica. Eight satellite-tracked turtles stayed within 135 km of the beach and probably returned to nest after release. The internesting area is more extensive than previously documented. Post-nesting migration routes of satellite-tracked turtles varied. Seven turtles swam close to the coast and three turtles swam through oceanic waters before moving toward nearshore areas. Sea surface height anomaly maps indicate that oceanic movements were consistent with the southwestern Caribbean gyre. Circling and semi-circling turtles could have been disoriented but submergence and surface times suggest they may have been feeding in Sargassum sp. concentrations. Rapid post-nesting migrations (mean 2.2 km hr−1) ended on benthic feeding grounds in shallow waters (<20 m) off Belize (n=1), Honduras (n=1) and Nicaragua (n=8). The spatial distribution of migration end points (n=10) and tag returns (n=4,669) are similar. Fishermen in Nicaragua target green turtles along migratory corridors and on foraging grounds. Management efforts are urgently needed in Nicaragua, particularly in the high-density feeding areas south and east of the Witties (N14°09 W82°45). The proximity of foraging grounds to the nesting beach (mean 512 km) may permit female turtles to invest more energy in reproduction and hence the Tortuguero population may have greater potential for recovery than other green turtle nesting populations. Recovery of the Tortuguero green turtle population will benefit countries and marine ecosystems throughout the Caribbean, especially Nicaragua.

The problem of response in epidemiological studies in Germany (part I)

To achieve high response rates in German epidemiological studies is growing more difficult. Low response in epidemiological studies may decrease the acceptance of the results. Response, however, is not identical with the quality of a study. In the first part of this paper various definitions of response (contact, cooperation, response, recruitment proportions) are introduced and discussed in the context of different study designs with reference to practical examples. A population-based survey such as the Study of Health in Pomerania (SHIP) investigates the distribution of risk factors and health-related endpoints. Surveys should yield representative results which can be generalised to apply to the entire population (external validity). This study design usually requires large participitation proportions. In a prospective cohort study such as the European Investigation into Cancer and Nutrition (EPIC) the emphasis is on internal validity. A stable study population willing to participate in regular follow-ups is a primary recruitment goal. If the response in a case-control study such as the Northern Germany Leukaemia and Lymphoma Study (NLL) is low, the priority is to achieve approximately equal response proportions for cases and controls. Simultaneous public relation and media activities can improve participitation in a study. Multidimensional strategies combining public communications, cooperation with local and regional officials and frequent press and media coverage are emphasised. The second part of this paper will discuss methods to quantify the effects of the response proportions on the validity of the study results.

Excursions and Lévy System of Boundary Process

In this paper, the authors investigate the joint distribution of end points of excursion away from a closed set straddling on a fixed time and use this result to compute the Levy system and the Dirichlet form of the boundary process.

INDO-PACIFIC BIODIVERSITY OF CORAL REEFS: DEVIATIONS FROM A MID-DOMAIN MODEL

Understanding the nature and causes of global gradients in species richness is a perennial ecological problem, and recent work has highlighted the need to assess these gradients relative to an appropriate statistical expectation. This paper examines latitudinal and longitudinal gradients in species richnesses of corals and reef fishes in the Indo-Pacific domain and compares them with gradients predicted by a mid-domain model in which geographic domains are located at random between the latitudinal and longitudinal boundaries of this region. We test for significant differences between observed and predicted species-richness patterns, and we identify regions that are enriched or depauperate in species, relative to expectation. In addition, we move beyond previous mid-domain analyses by directly comparing observed spatial distributions of geographic ranges with those predicted by a mid-domain model. This comparison indicates precisely how species-richness anomalies are produced by nonrandomness in the distribution of species ranges. For both corals and fishes, large and statistically significant differences exist between observed latitudinal and longitudinal species-richness gradients and those predicted by mid-domain models. Longitudinally, species richness is markedly higher than predicted along the African coast and, to a lesser extent, within the Indo-Australian Archipelago (IAA), and it is markedly lower than expected in the eastern Pacific. Latitudinally, species richness becomes increasingly higher than predicted as one moves from the equator to the tropical margins; then it becomes sharply lower than predicted beyond the tropics. Unexpectedly, differences between observed and predicted spatial distributions of range endpoints and midpoints reveal a pattern of nonrandomness that is highly congruent with the hypothesis that gyres in the Indian and Pacific Oceans, with the IAA forming a porous boundary between them, have a major influence on Indo-Pacific species-richness patterns. Our analyses indicate that the perspective offered by a focus on explaining nonrandomness in the location of geographic ranges (rather than explaining why species numbers vary in space) is likely to dramatically alter our assessments of alternative explanations for global species-richness gradients.

Development of a Stochastic Pig Compositional Growth Model

A stochastic pig compositional growth model was developed using mixed model nonlinear functions. Serial BW measurements were fitted to mixed model nonlinear equations with three parameters and two random effects. Empty body protein mass (EBPRO) data were predicted from serial real-time ultrasound and BW measurements. Predicted EBPRO data were fitted to a nonlinear function of predicted BW (PBW) with one random effect: EBPRO = C (¦(PBW)) + cpi (¦(PBW))D, where ¦(PBW) = (1 - exp (b0 + b1 PBW + b2 (PBW)2), C and D are fixed parameters, and cpi is a random effect. The model also accounts for the relationship among the random effects for BW growth and cpi. Daily lipid accretion was predicted from genetic population-sex specific relationships between BW, EBPRO, and empty body lipid mass: empty BW = 0.93 BW and empty BW = a1 EBPROb1 + a2 (empty body lipid mass)b2. The model predicts a BW growth curve and daily compositional growth rate for carcass fat-free lean, carcass fat tissue, EBPRO, and empty body lipid. To reproduce the total variance, the residual variance of each variable was produced by multiplying the residual standard deviation of each prediction equation by a value sampled from a standard normal distribution. The stochastic model can be used to develop strategies to target a specified mean and distribution of carcass composition end points.

Area activation: a computational model of saccadic selectivity in visual search

AbstractThe Area Activation Model (Pomplun, Reingold, Shen, &amp; Williams, 2000) is a computational model predicting the statistical distribution of saccadic endpoints in visual search tasks. Its basic assumption is that saccades in visual search tend to foveate display areas that provide a maximum amount of task‐relevant information for processing during the subsequent fixation. In the present study, a counterintuitive prediction by the model is empirically tested, namely that saccadic selectivity towards stimulus features depends on the spatial arrangement of search items. We find good correspondence between simulated and empirically observed selectivity patterns, providing strong support for the Area Activation Model.

Area activation: a computational model of saccadic selectivity in visual search

The Area Activation Model (Pomplun, Reingold, Shen, & Williams, 2000) is a computational model predicting the statistical distribution of saccadic endpoints in visual search tasks. Its basic assumption is that saccades in visual search tend to foveate display areas that provide a maximum amount of task-relevant information for processing during the subsequent fixation. In the present study, a counterintuitive prediction by the model is empirically tested, namely that saccadic selectivity towards stimulus features depends on the spatial arrangement of search items. We find good correspondence between simulated and empirically observed selectivity patterns, providing strong support for the Area Activation Model.