Master of Science / Department of Physics / Jeremy Schmit / In this work, we present a model for the kinetics of amyloid fibril aggregation. In the model we mapped the process of Hydrogen bond (H-bond) formation and breakage to a random-walk. we captured the effect of side chains using position dependent H-bonds free energies which allows us to calculated the residence time for different binding alignments with the fibril. The residence time can be compared to the diffusion-limited attachment rate to give net aggregation stability. This stability increases exponentially with increasing number of bonds or binding energy in homopolymer chains, however for chains with patterned sequences, the residence time shows strong effects of the binding alignment. Using the residence time for uniform structures combined with estimate of the diffusion rate, we modeled and simulated the kinetics of amyloid aggregation. Results of the simulations gives the bond energies and concentrations required for the onset of growth of aggregates.

As we navigate in the world around us, previous experience generally prepares us well to deal with most situations. Cognitive control is required in situations that do not afford a rapidly retrieved solution to a current problem. In the laboratory, cognitive control is usually studied in the context of distractor interference tasks with reaction time as the dependent measure. These studies investigate the ability to selective attend to relevant information presented amidst distraction in space. However, we must also attend to relevant information presented amidst distraction in time. A procedure used to study the temporal constraints of selective attention is the attentional blink (AB) task. Here, a modified AB task is utilized to investigate the memorial consequences of engaging in selective attention at one point in time, on the ability to encode new information presented shortly thereafter, with identification accuracy as the dependent measure. This new procedure enables the empirical investigation of the relationship between selective attention and memory processes that are generally studied in isolation. The current research systematically investigated the relative contribution of intentional and automatic influences over selective attention in an AB task, by manipulating the context in which difficult T1 selection trials were presented. The results suggest that contextual influences of control over selective attention occur via a blend of intentional and automatic processes. Whereas intentional processes may be required to establish control settings in novel contexts, once established, control settings can be recruited automatically. These results extend current research on contextual control of selective attention to a novel domain, and consequently, provide insight into the underlying processes that produce the AB effect. Moreover, these results highlight the important role of context-specific learning in the study of cognitive control. Abstract As we navigate in the world around us, previous experience generally prepares us well to deal with most situations. Cognitive control is required in situations that do not afford a rapidly retrieved solution to a current problem. In the laboratory cognitive control is usually studied in the context of distractor interference tasks with reaction time as the dependent measure. These studies investigate the ability to selective attend to relevant information presented amidst distraction in space. However, we must also attend to relevant information presented amidst distraction in time. A procedure used to study the temporal constraints of selective attention is the attentional blink (AB) task. Here, a modified AB task is utilized to investigate the memorial consequences of engaging in selective attention at one point in time, on the ability to encode new information presented shortly thereafter, with identification accuracy as the dependent measure. This new procedure enables the empirical investigation of the relationship between selective attention and memory processes that are generally studied in isolation. The current research systematically investigated the relative contribution of intentional and automatic influences over selective attention in an AB task, by manipulating the context in which difficult T1 selection trials were presented. The results suggest that contextual influences of control over selective attention occur via a blend of intentional and automatic processes. Whereas intentional processes may be required to establish control settings in novel contexts, once established, control settings can be recruited automatically. These results extend current research on contextual control of selective attention to a novel domain, and consequently, provide insight into the underlying processes that produce the AB effect. Moreover, these results highlight the important role of context-specific learning in the study of cognitive control. Abstract As we navigate in the world around us, previous experience generally prepares us well to deal with most situations. Cognitive control is required in situations that do not afford a rapidly retrieved solution to a current problem. In the laboratory cognitive control is usually studied in the context of distractor interference tasks with reaction time as the dependent measure. These studies investigate the ability to selective attend to relevant information presented amidst distraction in space. However, we must also attend to relevant information presented amidst distraction in time. A procedure used to study the temporal constraints of selective attention is the attentional blink (AB) task. Here, a modified AB task is utilized to investigate the memorial consequences of engaging in selective attention at one point in time, on the ability to encode new information presented shortly thereafter, with identification accuracy as the dependent measure. This new procedure enables the empirical investigation of the relationship between selective attention and memory processes that are generally studied in isolation. The current research systematically investigated the relative contribution of intentional and automatic influences over selective attention in an AB task, by manipulating the context in which difficult T1 selection trials were presented. The results suggest that contextual influences of control over selective attention occur via a blend of intentional and automatic processes. Whereas intentional processes may be required to establish control settings in novel contexts, once established, control settings can be recruited automatically. These results extend current research on contextual control of selective attention to a novel domain, and consequently, provide insight into the underlying processes that produce the AB effect. Moreover, these results highlight the important role of context-specific learning in the study of cognitive control. As we navigate in the world around us, previous experience generally prepares us well to deal with most situations. Cognitive control is required in situations that do not afford a rapidly retrieved solution to a current problem. In the laboratory cognitive control is usually studied in the context of distractor interference tasks with reaction time as the dependent measure. These studies investigate the ability to selective attend to relevant information presented amidst distraction in space. However, we must also attend to relevant information presented amidst distraction in time. A procedure used to study the temporal constraints of selective attention is the attentional blink (AB) task. Here, a modified AB task is utilized to investigate the memorial consequences of engaging in selective attention at one point in time, on the ability to encode new information presented shortly thereafter, with identification accuracy as the dependent measure. This new procedure enables the empirical investigation of the relationship between selective attention and memory processes that are generally studied in isolation. The current research systematically investigated the relative contribution of intentional and automatic influences over selective attention in an AB task, by manipulating the context in which difficult T1 selection trials were presented. The results suggest that contextual influences of control over selective attention occur via a blend of intentional and automatic processes. Whereas intentional processes may be required to establish control settings in novel contexts, once established, control settings can be recruited automatically. These results extend current research on contextual control of selective attention to a novel domain, and consequently, provide insight into the underlying processes that produce the AB effect. Moreover, these results highlight the important role of context-specific learning in the study of cognitive control. / Thesis / Doctor of Philosophy (PhD) / Cognitive control refers to our ability to direct our actions in accordance with our goals. Traditionally, the construct of cognitive control was assumed to be synonymous with the construct of free will. In recent years, cognitive psychologists have questioned the volitional nature of cognitive control. Generally speaking, this thesis investigates the following question; to what extent is control over the allocation of our attentional resources governed by our conscious intentions, or, to what extent are such processes recruited automatically? The results suggest that controlled and automatic processes are not dichotomous in nature, but rather, contribute to performance interactively. While conscious intentions may play a role in the establishment of control procedures in novel contexts, once established these control procedures can be brought online automatically. Decisions regarding the need for effortful processing, given the current context, likely shape the construction of these automatized routines.

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Die vorliegende Dissertation beinhaltet drei Studien, welche die kognitiven und neuronalen Grundlagen der Kontrollregulation – ausgelöst durch vorherige Konflikte, konfliktankündigende Hinweise sowie Arousal – untersuchen. Jede Studie basierte auf Interferenzaufgaben mit Durchgängen, die Reaktionskonflikt auslösten (inkompatibel) oder nicht (kompatibel). Studie 1 untersuchte, ob Abfolge abhängigen Verhaltensanpassungen äquivalent sind mit erwartungsbasierten Kontrollprozessen, die durch Hinweise auf die Kompatibilität der nächsten Aufgabe ausgelöst werden. Behaviorale und elektroenzephalographische (EEG) Maße belegten, dass diese Prozesse dissoziieren. Die kontingente negative Variation (CNV), eine EEG Komponente, die Aufgabenantizipation indiziert, zeigte, dass von der Abfolge anhängige Kontrollanpassungen bereits zwischen den Durchgängen agieren. Studie 2 fokussierte auf Prozesse und neuronale Substrate der Kontrollantizipation durch Hinweise. Kompatibilitätshinweise begünstigten effektiv die Leistung, vergrößerten die CNV vor dem nächsten Durchgang und reduzierten konfliktbezogene Konfliktverarbeitung, wie sie durch die N2 Komponente indiziert wird. Im Gegensatz zur Kontrollbedingung gab es keine Anzeichen von Reaktionskonflikt, was auf präemptive Strategien hinweist (d.h. a priori Konfliktverhinderung durch Umschreibung von Bedingungs-Handlungs-Regeln). Funktionelle Bildgebung bestätigte dies, da sie Beteiligung neuronaler Netzwerke zeigte, die eher mit Regelelaboration und –aufrechterhaltung einhergehen als mit Konfliktüberwachung und –lösung. Studie 3 untersuchte das Verhältnis von Handlungskontrolle und Arousalniveau. Toninduziertes Arousal verbesserte Leistung in inkompatiblen und kompatiblen Durchgängen, wobei letztere stärker begünstigt wurden. N1 und N2 im EEG wiesen darauf hin, dass die Effekte auf bessere frühe perzeptuelle Diskriminierung und Aufmerksamkeitszuteilung zurückgehen. / The present dissertation contains three studies that investigated the cognitive and neuronal basis underlying action control regulation prompted by prior conflicts, cues predicting conflict, as well as the state of arousal. These studies were based on inference paradigms involving trials that either induced response conflict (incompatible trials) or did not (compatible trials). Study 1 examined whether behavioral adjustments due to the trial sequence are equivalent to expectancy-based adjustments triggered by cues predicting compatibility. Behavioral and electroencephalographic (EEG) measures showed dissociation of these processes. The contingent negative variation (CNV), a pre-target EEG component indexing task anticipation, further indicated that sequence-related control adjustments already act in the intertrial interval. Study 2 focused on processes and neural substrates underlying cue-based anticipatory control. Cues predicting compatibility effectively benefitted behavioral performance, enhanced the pre-target CNV, and reduced post-target conflict-related processing, as indicated by the N2 component. In contrast to the control condition, indicators of response conflict were absent, a result pointing to conflict preemption strategies (a priori avoidance of conflict via transformation of condition-action rules). Functional neuroimaging fostered this conclusion by showing the involvement of neuronal networks associated with rule elaboration and maintenance rather than with conflict monitoring or resolution. Study 3 investigated the interrelation of action control and the state of arousal. Tone-induced arousal improved performance in both incompatible and compatible trials, whereas the latter ones were relatively more accelerated. N1 and N2 in EEG indicated that these effects are due to enhanced early perceptual discrimination and attentional allocation.

The previous view of DNA as a linear sequence of bases is evolving to consider structure, topology and dynamics. Sequences surrounding damage lesions have been shown to effect enzyme recognition and processing. Here we present an in depth investigation of subtle structural and dynamical features imparted to nucleic acid duplexes by a designed modification or damage lesions. Highly restrained solution structures were generated and validated utilizing a range of NMR techniques. This allowed for the characterization of multiple features of the nucleic acid duplex; such as base pairing, backbone torsion angles, deoxyribose sugar pucker, and intra and inter nucleotide proton distances. Additional experiments provided insight into dynamic movements of the nucleic bases. These features are then correlated to enzyme data in order to explain the observed modulation of activity.