High-resolution computer simulation of the dynamics of isoelectric focusing using carrier ampholytes: focusing with concurrent electrophoretic mobilization is an isotachophoretic process

Focusing of four hemoglobins with concurrent electrophoretic mobilization was studied by computer simulation. A dynamic electrophoresis simulator was first used to provide a detailed description of focusing in a 100-carrier component, pH 6-8 gradient using phosphoric acid as anolyte and NaOH as catholyte. These results are compared to an identical simulation except that the catholyte contained both NaOH and NaCl. A stationary, steady-state distribution of carrier components and hemoglobins is produced in the first configuration. In the second, the chloride ion migrates into and through the separation space. It is shown that even under these conditions of chloride ion flux a pH gradient forms. All amphoteric species acquire a slight positive charge upon focusing and the whole pattern is mobilized towards the cathode. The cathodic gradient end is stable whereas the anodic end is gradually degrading due to the continuous accumulation of chloride. The data illustrate that the mobilization is a cationic isotachophoretic process with the sodium ion being the leading cation. The peak height of the hemoglobin zones decreases somewhat upon mobilization, but the zones retain a relatively sharp profile, thus facilitating detection. The electropherograms that would be produced by whole column imaging and by a single detector placed at different locations along the focusing column are presented and show that focusing can be commenced with NaCl present in the catholyte at the beginning of the experiment. However, this may require detector placement on the cathodic side of the catholyte/sample mixture interface.

Resolving the tragedy of the commons: the feedback between intraspecific conflict and population density

Competition and conflict among individuals can favour exploitative strategies that undermine the common good. Theory suggests that this can lead to a tragedy of the commons and ultimately population extinction, a phenomenon known as evolutionary suicide. Here, I present a model of the evolutionary tragedy of the commons that explicitly considers the population dynamics where individuals invest in individually costly competitive traits. In the simplest form, this supports the notion that selection for high levels of conflict can cause evolutionary suicide. However, as competition comes with survival and fecundity costs, a feedback between the investment in competition and population density can act to reduce the level of conflict and prevent the population from going extinct. This suggests that the interaction between population ecology and the evolution of competition and conflict among individuals may be an important mechanism in resolving the level of competition and conflict among individuals.

Concurrent monitoring of cerebral electrophysiology and metabolism after traumatic brain injury: an experimental and clinical study

Multiparameter cerebral monitoring has been widely applied in traumatic brain injury to study posttraumatic pathophysiology and to manage head-injured patients (e.g., combining O(2) and pH sensors with cerebral microdialysis). Because a comprehensive approach towards understanding injury processes will also require functional measures, we have added electrophysiology to these monitoring modalities by attaching a recording electrode to the microdialysis probe. These dual-function (microdialysis/electrophysiology) probes were placed in rats following experimental fluid percussion brain injuries, and in a series of severely head-injured human patients. Electrical activity (cell firing, EEG) was monitored concurrently with microdialysis sampling of extracellular glutamate, glucose and lactate. Electrophysiological parameters (firing rate, serial correlation, field potential occurrences) were analyzed offline and compared to dialysate concentrations. In rats, these probes demonstrated an injury-induced suppression of neuronal firing (from a control level of 2.87 to 0.41 spikes/sec postinjury), which was associated with increases in extracellular glutamate and lactate, and decreases in glucose levels. When placed in human patients, the probes detected sparse and slowly firing cells (mean = 0.21 spike/sec), with most units (70%) exhibiting a lack of serial correlation in the spike train. In some patients, spontaneous field potentials were observed, suggesting synchronously firing neuronal populations. In both the experimental and clinical application, the addition of the recording electrode did not appreciably affect the performance of the microdialysis probe. The results suggest that this technique provides a functional monitoring capability which cannot be obtained when electrophysiology is measured with surface or epidural EEG alone.

The influence of concurrent disturbances on plant community dynamics in northern hemlock-hardwood forests

Throughout the Upper Great Lakes region, alterations to historic disturbance regimes have influenced plant community dynamics in hemlock-hardwood forests. Several important mesic forest species, eastern hemlock (Tsuga canadensis), yellow birch (Betula alleghaniensis), eastern white pine (Pinus strobus), and Canada yew (Taxus canadensis), are in decline due to exploitive logging practices used at the turn of the 20th century and the wave of intense fires that followed. Continued regeneration and recruitment failure is attributed to contemporary forest management practices and overbrowsing by white-tailed deer (Odocoileus virginianus). Therefore, I examined the influence of two concurrent disturbances, overstory removal and herbivory, on plant community dynamics in two hemlock-hardwood forests. I measured the post-disturbance regeneration response (herbaceous and woody species) inside and outside of deer exclosures in 20 artificial canopy gaps (50 – 450 m2) and monitored survival and growth for hundreds of planted seedlings. The results of this research show that interacting disturbances can play a large role in shaping plant community composition and structure in hemlock-hardwood forests. White-tailed deer herbivory homogenized the post-disturbance plant communities across the experimental gradient of gap areas, essentially making species compositions in small gaps “look like” those in large gaps. Deer browsing also influenced probability of survival for planted Canada yew cuttings; all else being equal an individual was nearly seven times more likely to survive if protected from herbivory (P < 0.001). In contrast, the ability of sugar maple (Acer saccharum) to persist under high levels of herbivory and respond rapidly to overstory release appears to be related to the presence of stem layering(i.e., portions of below-ground prostrate stem). Layering occurred in 52% of excavated saplings (n = 100) and was significantly associated with increased post-disturbance height growth. Understory light was also important to planted seedling establishment and height growth. Higher levels of direct under-canopy light negatively impacted survival for shade-tolerant hemlock and Canada yew, while an increase in diffuse light was linked to a higher probability of survival for yellow birch and height growth for hemlock and Canada yew. Increases in white pine height growth were also significantly associated with a decrease in canopy cover.

GENERATING PLANS IN CONCURRENT, PROBABILISTIC, OVER-SUBSCRIBED DOMAINS

Planning in realistic domains typically involves reasoning under uncertainty, operating under time and resource constraints, and finding the optimal subset of goals to work on. Creating optimal plans that consider all of these features is a computationally complex, challenging problem. This dissertation develops an AO* search based planner named CPOAO* (Concurrent, Probabilistic, Over-subscription AO*) which incorporates durative actions, time and resource constraints, concurrent execution, over-subscribed goals, and probabilistic actions. To handle concurrent actions, action combinations rather than individual actions are taken as plan steps. Plan optimization is explored by adding two novel aspects to plans. First, parallel steps that serve the same goal are used to increase the plan’s probability of success. Traditionally, only parallel steps that serve different goals are used to reduce plan execution time. Second, actions that are executing but are no longer useful can be terminated to save resources and time. Conventional planners assume that all actions that were started will be carried out to completion. To reduce the size of the search space, several domain independent heuristic functions and pruning techniques were developed. The key ideas are to exploit dominance relations for candidate action sets and to develop relaxed planning graphs to estimate the expected rewards of states. This thesis contributes (1) an AO* based planner to generate parallel plans, (2) domain independent heuristics to increase planner efficiency, and (3) the ability to execute redundant actions and to terminate useless actions to increase plan efficiency.

Concurrent activation of dopamine D1 and D2 receptors is required to evoke neural and behavioral phenotypes of cocaine sensitization

Repeated exposure to psychomotor stimulants produces a striking behavioral syndrome involving repetitive, stereotypic behaviors that occur if an additional exposure to the stimulant is experienced. The same stimulant exposure produces specific alterations in gene expression patterns in the striatum. To identify the dopamine receptor subtypes required for the parallel expression of these acquired neural and behavioral responses, we treated rats with different D1-class and D2-class dopamine receptor agonists and compared the responses of drug-naive rats with those of rats given previous intermittent treatment with cocaine. In rats exposed to repeated cocaine treatment, the effects of a subsequent challenge treatment with either a D1-class agonist (SKF 81297) or a D2-class agonist (quinpirole) were not significantly different from those observed in drug-naive animals: the drugs administered singly did not induce robust stereotyped motor behaviors nor produce significantly striosome-predominant expression of early genes in the striatum. In contrast, challenge treatment with the D1-class and D2-class agonists in combination led to marked and correlated increases in stereotypy and striosome-predominant gene expression in the striatum. Thus, immediately after repeated psychomotor stimulant exposure, only the concurrent activation of D1 and D2 receptor subclasses evoked expression of the neural and behavioral phenotypes acquired through repeated cocaine exposure. These findings suggest that D1-D2 dopamine receptor synergisms underlie the coordinate expression of both network-level changes in basal ganglia activation patterns and the repetitive and stereotypic motor response patterns characteristic of psychomotor stimulant sensitization.