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A common metaphor for visual attention is the spotlight (Posner, 1980). It follows from the spotlight metaphor and other similar models (e.g., zoom-lens model; Eriksen and Yeh, 1985) that attention can, according to task-demands, be constricted into a focused beam (i.e., analogous to selective attention) or dilated to encompass a larger breadth (i.e., analogous to divided attention). It is currently unclear how variations in perceptual load of a display affect the FFOV. Lavie (1995; Lavie et al., 2004) proposed that the critical determinant of selective attention (i.e., a constriction of the FFOV) was the perceptual load imposed by the taskselective attention is a necessary outcome of limited perceptual processing capacity. Age-related differences in perceptual processing capacity (e.g., Maylor and Lavie, 1998) may then explain observed age-related differences in FFOV size (e.g., Ball, Beard, Roenker, Miller, and Griggs, 1988). The current study examined how perceptual load and aging affected the FFOV. Younger and older participants viewed brief displays in which they engaged in two tasks: the first task was a perceptual load manipulation, while the second task was a measure of the FFOV. Multiple measures of peripheral task performance suggest that the size of the FFOV for older adults was significantly reduced by increasing perceptual load and this effect of load was greater with increasing distance from fixation. As predicted from the perceptual load model, when perceptual load of the task increased, perceptual sensitivity for the distant peripheral task decreased for older adults. This decrease was greater when the task was farther from fixationindicative of a shrinking spotlight. However, for younger adults, increasing load did not affect peripheral task performance. This age-related difference may be attributable to older adults reduced perceptual processing capacity. The current results support the notion that older adults reduced perceptual processing capacity may be one cause of their reduced FFOV. Limitations of the current study as well as future research are discussed.

Cognitive control allows us to function in a world filled with constant stimulation. For example, the act of reading a book requires the ability to inhibit irrelevant information while focusing attention towards the letters on the page. Our cognitive control system regulates what information receives attention and what is denied resources. The goal of the current paper is to investigate the mechanisms underlying the activation and maintenance of the control system and how this process changes in healthy aging. First, the ability of younger and older adults to activate and maintain control in response to trial type manipulations is investigated. Second, improvements are made to recent experimental evidence suggesting younger adults are able to modulate performance based on specific stimulus history. Third, this work is extended to an older population suggesting the ability to modulate performance based on specific stimulus history is maintained in healthy aging. Finally, it is demonstrated that current theories of control fail to account for age-related differences in performance based on the comparison of trial type and specific stimulus manipulations.

Human immunodeficiency virus reverse transcriptase (HIV RT) is a virally encoded polymerase responsible for replicating the HIV genome. Most HIV treatments include nucleotide RT inhibitors (NRTIs) which inhibit HIV RT replication by serving as a substrate for the polymerase reaction but then blocks subsequent polymerization after incorporation. However, resistance to these NRTIs may occur through specific mutations in HIV RT that increase the discrimination of HIV RT for natural nucleotides over NRTIs. The role of enzyme conformational dynamics in specificity and substrate selection was studied using transient kinetic methods on HIV RT enzymes that have been site-specifically labeled with a conformationally sensitive fluorophore, to measure the rates of binding and catalysis. First, HIV RT with the mutation of lysine to arginine at the residue position 65 (K65R) was examined for its resistance against the NRTI tenofovir diphosphate (TFV), an acyclic deoxyadenosine triphosphate (dATP) analog. It was found that HIV RT K65R resistance to TFV was achieved through decreased rates of catalysis and increased rates of dissociation for TFV over dATP when compared with the kinetics of wild-type HIV RT. Moreover, global fitting analysis confirmed a mechanism where a large conformational change, after initial ground state binding of the substrate, contributed significantly to enzyme specificity. This led to our investigation of the molecular basis for enzyme specificity using HIV RT as a model system. Again, transient kinetic methods were applied with the addition of molecular dynamics simulations. The simulated results were substantiated by the corroborating experimental results. It was found that a substrate-induced conformational change in the transition of HIV RT from an open nucleotide-bound state to a closed nucleotide-bound state was the major determinant in enzyme specificity. The molecular basis for substrate selection resulted from the molecular alignments of the substrate in the active-site, which induced the conformational change. When the correct nucleotide was bound, optimal molecular interactions in the active-site yielded a stably closed complex, which promoted nucleotide incorporation. In contrast, when an incorrect nucleotide was bound, the molecular interactions at the active-site were not ideal, which yielded an unstable closed complex, which promoted substrate dissociation rather than incorporation. / text

Glutathione transferases (GSTs, EC 2.5.1.18) possess multiple functions and have potential applications in biotechnology. This thesis contributes to knowledge about glutathione transferases from Sus scrofa (pig). The study is needed for better understanding of biochemical processes in this species and is desirable for drug development, for food industry research and in medicine. A primary role of GSTs is detoxication of electrophilic compounds. Our study presents porcine GST A1-1 as a detoxication enzyme expressed in many tissues, in particular adipose tissue, liver and pituitary gland. Based on comparison of activity and expression profiles, this enzyme can be expected to function in vivo similarly to human GST A2-2 (Paper II). In addition to its protective function, human GST A3-3 is an efficient steroid isomerase and contributes to the biosynthesis of steroid hormones in vivo. We characterized a porcine enzyme, pGST A2-2, displaying high steroid-isomerase activity and resembling hGST A3-3 in other properties as well. High levels of pGST A2-2 expression were found in ovary, testis and liver. The properties of porcine enzyme strengthen the notion that particular GSTs play an important role in steroidogenesis (Paper I). Combination of time-dependent and enzyme concentration-dependent losses of activity as well as the choice of the organic solvent for substrates were found to cause irreproducibility of activity measurements of GSTs. Enzyme adsorption to surfaces was found to be the main explanation of high variability of activity values of porcine GST A2-2 and human Alpha-class GSTs reported in the literature. Several approaches to improved functional comparison of highly active GSTs were proposed (Paper III). / Felaktigt tryckt som Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 733

The function of the metalloenzymes is mainly determined by four structural features: the metal core, the metal binding motif, the second sphere residues in the active site and the electronic statistics. Cysteamine dioxygenase (ADO) and cysteine dioxygenase (CDO) are the only known enzymes that oxidize free thiol containing molecules in mammals by inserting of a dioxygen molecue. Both ADO and CDO are known as non-heme iron dependent enzymes with 3-His metal binding motif. However, the mechanistic understanding of both enzymes is obscure. The understanding of the mechanistic features of the two thiol dioxygenases is approached through spectroscopic and metal substitution in this dissertation. Another focus of the dissertation is the understanding of the function of a second sphere residue His228 in a 3-His-1-carboxyl zinc binding decarboxylase α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD). ACMSD catalyzes the decarboxylation through a hydrolase-like mechanism that is initialized by the deprotonation of metal bounded water molecule. Our study reveled that the second sphere residue His228 is responsible for the water deprotonation through hydrogen bonding. The spectroscopic and crystallographic data showed the H228Y mutation binds ferric iron instead of native zinc metal and the active site water is replaced by the Tyr228 residue ligation. Thus, we concluded that, H228Y not only plays a role of stabilizing and deprotonating the active site water but also is an essential residue on metal selectivity.

Darbe atliktas relinės apsaugos nuo įžemėjimo atrankamo tyrimas, išnagrinėti neutralės įžeminimo režimai ir jų įtaka įžemėjimo atrankumui. Išanalizuotas apsaugų skirstymas pagal kontroliuojamą elementą. Atlikta Akcinės bendrovės „VST“ Šiaulių regione naudojamų relinės apsaugos įrenginių analizė ir funkcijų palyginimas. Ištirtos keturių tipų neteisingos relinės apsaugos nuo įžemėjimo suveiktys. Nustačius, kad įžemėjimo pažaidos metu nulinės sekos srovėje atsiranda aukštesnės eilės harmonikų atliktas bandymas, kurio metu išanalizuotas aukštesnių dažnių įtaka nulinės sekos transformatorių paklaidoms. Nustatyti dėsningumai susiję tarp dažnio ir paklaidos. Tyrimo metu išaiškintos priežastys lemiančios atrankumą įžemėjimo pažaidos metu. / The selectivity research of link protection of grounding has been done and the grounding modes of neutrality and their influence to grounding selectivity have been analyzed. Moreover, the distribution of protection under a controlling element has been studied. The research of the equipment of link protection used in the Stock Company “VST” Šiauliai region has been implemented and compared its functions. There have also been analyzed four types of effect due to wrong link protection of grounding. It was estimated that during the period of disturbance of grounding a higher line of harmonic appears in the current of null string. The experiment was implemented which estimated bias of transformers of null string by the influence of higher rates. Regularity related between rates and bias has been estimated. In addition the research explained the reasons which determines selectivity during the period of the grounding disturbance.

Early experimental work suggested that the retina’s main role was to detect changes in brightness and contrast, namely working as a light detector, and that most of the complex computations in the visual system happened upstream in the brain. In reality, there is a growing wealth of literature indicating that the retina itself processes multiple channels of visual information (contrast, motion, orientation, etc.), making it much more complex than it originally appeared. For instance, there now appear to be over 20 types of retinal ganglion cells. To this end, the work in this thesis will focus on the identification and characterization of a single type of retinal ganglion cell in the mouse retina. In the first section of my results, I will show that this cell type, identified as the only GFP+ ganglion cell in the transgenic Hb9::eGFP retina, is a directionally selective ganglion cell (DSGC), that preferentially responds to objects moving upward through the visual field. This cell has a pronounced morphological asymmetry that helps it to synergistically (along with asymmetric inhibition) generate directionally selective responses. In the second results section, I will describe a novel phenomenon exhibited by Hb9+ DSGCs: Thanks to gap junction mediated signals, Hb9+ cells are able to anticipate moving stimuli and correct for lags that are inherent in visual signals generated by photoreceptors. In the third results section I will elucidate the mechanisms for the gap junction mediated anticipatory signals outlined in the second results section. Together, these results provide a significant advancement in our understanding of how the retina processes moving stimuli and provide a compelling example of how chemical and electrical synapses interact to allow for exquisite signal multiplexing.

Soybean aphid, Aphis glycines Matsumura, is an important pest of North American soybean. This dissertation identifies and addresses knowledge gaps, and integrates existing knowledge regarding distribution and abundance of this species. Early summer soybean colonization patterns by A. glycines were examined relative to landscape parameters, including density of overwintering hosts (buckthorn). An information-theoretic model selection approach was used to determine which landscape parameters were most influential in the distribution of colonizing aphids. Though buckthorn abundance best explained aphid colonization and population density, a density-dependent effect was observed. When aphid populations were low, more aphids were found in the vicinity of buckthorn, when aphid populations were higher, more aphids were found farther from buckthorn. Suction trap captures of migrating populations of A. glycines from 2005-2009 from a suction trap network covering much of central North America were examined. A model selection approach was used to determine the environmental triggers of summer and fall aphid flights, and spatial analysis and modeled wind trajectories were used to examine patterns in the abundance of alates. Two alate activity peaks were observed in fall. In summer, formation of alates was a function of field infestation. A tritrophic population model was built using DYMEX, a mechanistic lifecycle based modeling software package. The model incorporated soybean, A. glycines, and three natural enemy species, interacting based on phenological, physiological and functional response data available in the literature. The model was validated using Ontario field data, and several simulations were performed and are discussed. An evaluation of proposed control strategies for efficacy and impact on natural enemies and the environment was conducted. Two novel concepts are presented: the natural enemy unit, a standardization of the impact of predator guild on prey populations by the number of prey an individual predator can eat, and the selectivity index, where the selectivity of a pesticide is a function of the change in ratio of natural enemy units to prey before and after treatment. The selectivity index was inversely correlated with the Environmental Impact Quotient (EIQ), a theoretical measure of impact, validating EIQ's field applicability. / Natural Sciences and Engineering Research Council of Canada; The Keefer family trust; the Mary Edmunds Williams trust, the family of Fred W. Presant, and the University of Guelph provided scholarship and fellowship funds. Research was funded by a grant to Rebecca Hallett and Art Schaafsma from the Agriculture and Agri-Food Canada Pest Management Centre’s Pesticide Risk Reduction Program.