Event-related Potential Measurements of Long-term Orientation-specific Contrast Adaptation

University of Minnesota Ph.D. dissertation. October 2019. Major: Psychology. Advisor: Stephen Engel. 1 computer file (PDF); vii, 69 pages.The visual system continuously adjusts how it responds to current stimulus based on the history of the incoming stimuli, a process referred to as visual adaptation. Most of the previous studies focused on short-term adaptation effects ranging from milliseconds to minutes. Recent work has showed behavioral effects of long-term adaptation (hours and days), but their neural mechanisms remain unexplored. We aimed to uncover the neural bases of long-term orientation-specific contrast adaptation in an electroencephalography (EEG) experiment. Subjects were deprived of vertical contrast for 4 hours using altered reality goggles, which filtered out vertical energy from the scene in real-time. Event-related potentials (ERPs) in response to vertical and horizontal gratings were recorded before and after the long-term deprivation. We hypothesized that ERP response to vertical stimulation would increase in strength, and might decrease in latency, after the long-term deprivation. Results were analyzed by computing simple amplitudes of response, by comparing model fits to the ERP time courses, and by using the spatial pattern of ERP responses to classify trials by stimulation type. Early ERP components in response to vertical increased in amplitude and decreased in latency following adaptation, relative to responses to horizontal, but these differences were not significant. However, model fitting and classification results both revealed significantly greater differences in ERP responses between vertical and horizontal stimulation following adaptation. Collectively, these results suggest that long-term adaptation changes the amplitude of response in early visual cortex

Modulating the Granularity of Category Formation by Global Cortical States

The unsupervised categorization of sensory stimuli is typically attributed to feedforward processing in a hierarchy of cortical areas. This purely sensory-driven view of cortical processing, however, ignores any internal modulation, e.g., by top-down attentional signals or neuromodulator release. To isolate the role of internal signaling on category formation, we consider an unbroken continuum of stimuli without intrinsic category boundaries. We show that a competitive network, shaped by recurrent inhibition and endowed with Hebbian and homeostatic synaptic plasticity, can enforce stimulus categorization. The degree of competition is internally controlled by the neuronal gain and the strength of inhibition. Strong competition leads to the formation of many attracting network states, each being evoked by a distinct subset of stimuli and representing a category. Weak competition allows more neurons to be co-active, resulting in fewer but larger categories. We conclude that the granularity of cortical category formation, i.e., the number and size of emerging categories, is not simply determined by the richness of the stimulus environment, but rather by some global internal signal modulating the network dynamics. The model also explains the salient non-additivity of visual object representation observed in the monkey inferotemporal (IT) cortex. Furthermore, it offers an explanation of a previously observed, demand-dependent modulation of IT activity on a stimulus categorization task and of categorization-related cognitive deficits in schizophrenic patients

Block Copolymer Self-Assembled and Cross-linked Nanoassemblies for Combination Delivery of Iron Oxide and Doxorubicin

We describe the development of nanoscale polymer drug carriers for the combinational delivery of an anticancer drug (doxorubicin: DOX) along with super paramagnetic iron oxide nanoparticles (IONPs). The drug molecules were electrostatically loaded into both block copolymer self-assembled nanoassemblies (SNAs) and cross-linked nanoassemblies (CNAs). Both nanoassemblies entrapped DOX and IONPs either individually or in tandem, maintaining sub-100 nm diameter. The IONP-loaded nanoassemblies generated heat in the presence of an alternating magnetic field (AMF). Incorporation of the drug payload, DOX, showed no adverse effects on the heating profile. Drug release from the SNAs and CNAs was accelerated as temperature increased from the normal body temperature (37°C) to a mild hyperthermic condition (40 ~ 42°C). CNAs released DOX faster than SNAs regardless of an incubation temperature. CNAs co-entrapped IONPs and DOX were more stable than SNAs in aqueous solutions for five days. These results suggest that block copolymer cross-linked nanoassemblies provide viable delivery platforms for combination delivery of inorganic molecules, anticancer drugs, and potentially other various biologically active substances

Reconstruction and simulation of neocortical microcircuitry

We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm3 containing ∼31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ∼8 million connections with ∼37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies

Chemical and photochemical reactivity in aggregates of tensoactives in water/acetonitrile

Neste trabalho, estudou-se o efeito da adição de acetonitrila na reatividade química em soluções micelares do detergente aniônico dodecil sulfato de sódio (SDS) e do detergente catiônico brometo de hexadeciltrimetilamônio (CTAB) e em agregados supramoleculares do sal biliar, colato de sódio (NaCh). Os sistemas utilizados para estudar a reatividade química na presença de acetonitrila foram: (a) fotorreatividade do estado excitado triplete de n-butil-3-nitrofenil éter (em SDS); (b) reação de hidrólise ácida do 2-(p-octoxifenil)-1,3-dioxolano no estado fundamental (em SDS); (c) constante de incorporação do co-íon N-dodecil-4-cianopiridínio (em CTAB); (d) a protonação/desprotonação do ácido fraco 4-metil-7-hidroxiflavílio, tanto no estado excitado como no estado fundamental (em SDS); e (e) a supressão dos estados excitados de 1-etilnaftaleno e 1-(1-naftil)-etanol (em NaCh). As modificações na estruturação do agregado micelar e nas propriedades do meio aquoso, provocadas pela presença de acetonitrila, fazem com que as moléculas orgânicas e os íons saiam mais rapidamente do agregado para a fase aquosa. As mudanças que ocorrem com a micela e com a partição de solutos diminuem o efeito catalítico da micela sobre a reatividade química. Os agregados de sal biliar possuem dois sítios distintos de ligação de solutos e a concentração mínima de sal biliar necessária para formar esses dois sítios depende da concentração de acetonitrila. Em concentrações de acetonitrila acima de 10 %, ocorre somente a formação de agregados com sítio primário, enquanto que acima de 30 % os agregados se desfazem por completo. Em baixas concentrações de acetonitrila (até aproximadamente 10 %), a dinâmica de dissociação de solutos do sítio secundário do agregado de sal biliar não modifica muito, enquanto que a velocidade de saída de solutos do sítio primário aumenta com a presença da acetonitrila. Desse modo, a acetonitrila pode ser empregada para acelerar a saída de uma espécie, tal como um intermediário reativo, do agregado primário, facilitando a aplicação de agregados de sal biliar como micro-reatores com dois sítios distintos de reação.This work reports a study of the effect of the addition of acetonitrile on chemical reactivity in micellar solutions of the anionic detergent sodium dodecyl sulfate (SDS) and the cationic detergent hexadecyltrimethylammonium bromide (CTAB) and in supramolecular aggregates of the bile salt sodium cholate (NaCh). The systems employed in the study of chemical reactivity in the presence of acetonitrile were: (a) photoreactivity of the excited triplet state of N-butyl-3-nitrophenyl ether in SDS; (b) the acid catalyzed of 2-(p-octoxy-nitrophenyl)-1,3-dioxolane in the ground state in SDS; (c) incorporation of the coion N-dodecyl-4-cyanopyridine in CTAB; (d) protonation/deprotonation of the weak acid of the 4-methyl-7-hydroxyflavilium ion in the ground and excited state in SDS; and (e) quenching of the excited state of 1-ethylnaphthalene and 1-(1-naphthyl)-ethanol in NaCh. The modifications of the structure of the micellar aggregate and of the properties of the bulk aqueous phase induced by acetonitrile result in a faster rate of exit of organic molecules and ions from the aggregate into the aqueous phase. The changes that occur in the micelle and in the partitioning of solutes tend to diminish the catalytic effect of micelles on chemical reactivity. Bile salt aggregates possess two distinct sites for solubilization of solutes and the minimum concentration of bile salt necessary for the formation of these two sites depends on the concentration of acetonitrile. At acetonitrile concentrations above 10 %, only aggregates with the primary solubilization site are formed and, above 30 %, the aggregates are completely disrupted. At low acetonitrile concentrations (below 10 %), the dynamics of dissociation of solutes from the secondary site of bile salt aggregates changes very little, while the rate of exit of solutes from the primary site increases in the presence of acetonitrile. Thus, acetonitrile can be employed to accelerate the rate of exit of species such as reactive intermediates, facilitating the application of bile salt aggregates as two-reaction-site microreactors

The use of a group decision support system environment for knowledge acquisition

Knowledge acquisition is not only the most important but also most difficult task knowledge engineers face when they begin to develop expert systems. One of the first problems they encounter is the need to identify at least one individual with appropriate expertise who is able and willing to participate in the development project. They must also be able to use a variety of techniques to elicit the knowledge that they require. These include such traditional knowledge acquisition methods as interviewing, thinking-aloud protocol analysis, on-site observation, and repertory grid analysis. As expert system applications have become more complex, knowledge engineers have found that they must work with and tap the domain knowledge of not one but several individuals. They have also discovered that the traditional methods do not work well in eliciting the knowledge residing in a group of individuals. The complexity of the systems, the difficulties inherent in working with multiple experts, and the lack of appropriate tools have combined to make the knowledge acquisition task even more arduous and time consuming. Group Decision Support Systems (GDSS) have been proven to be useful tools for improving the efficiency and effectiveness of a multiplicity of group activities. It would appear that by bringing experts together in a GDSS environment and using computer-based tools to facilitate group interaction and information exchange, a knowledge engineer could eliminate many of these problems. This research was designed to explore the possibility of using a GDSS environment to facilitate knowledge acquisition from multiple experts. The primary research question was "Does A GDSS environment facilitate the acquisition of knowledge from multiple experts?" The principle contributions of this research are (1) demonstration of the first use of a GDSS environment to elicit knowledge from multiple experts; (2) establishment of a methodology for knowledge acquisition in a GDSS environment; (3) development of process models for acquiring knowledge; (4) development of guidelines for designing and evaluating group support tools; and (5) recognition of some implications of using a computer-supported cooperative approach to extract knowledge from a group of experts. (Abstract shortened with permission of author.

Studies micellar systems in mixtures of water/acetonitrile

Neste trabalho, estudou-se o efeito da adição de acetonitrila nas propriedades de micelas do detergente aniônico, dodecil sulfato de sódio (SDS), e do detergente catiônico, cloreto de hexadeciltrimetilamônio (CTACl). Medidas de condutividade foram utilizadas para determinar a concentração micelar crítica, cmc, e o grau de dissociação, α, das micelas em função da fração molar de acetonitrila, XAc. Medidas de supressão de fluorescência, resolvida no tempo, com pireno como sonda, foram utilizadas para determinar a influência de acetonitrila no número de agregação das micelas, N, e na dinâmica de migração de solutos entre as fases aquosa e micelar. Em baixas frações molares XAc < 0,2), a acetonitrila insere-se nas cavidades da água, quebrando parcialmente as pontes de hidrogênio da água com a formação de novas pontes de hidrogênio entre as moléculas de acetonitrila e as moléculas de água. Nesta faixa de concentração, ocorre um aumento da cmc e do α, acompanhada de uma diminuição de N. Observa-se também alterações na dinâmica da interação de contra-íons e co-íons supressores na micela. Assim, as micelas de SDS e CTACl formadas em misturas acetonitrila-água são menores, mais dissociadas e apresentam maior fluidez interna. Ao redor de XAc = 0,2, as misturas de água-acetonitrila tornam-se microheterogêneos com o aparecimento de microdomínios ricos em acetonitrila e microdomínios ricos em água. A proporção das regiões ricas em acetonitrila aumenta com o aumento da fração molar de acetonitrila, com apenas pequenas modificações das propriedades dos dois tipos de microdomínios. Em XAc > 0,2 a variação de cmc e de α com a XAc passa a ser menos acentuada, sugerindo que o detergente forma agregados preferencialmente nas regiões mais aquosas; a sonda fluorescente pireno começa sair das micelas durante o tempo de vida do estado excitado; e há claras mudanças na dinâmica de incorporação de íons nos agregados.This work presents a study of the effect of added acetonitrile on the properties of the micelles of the anionic detergent sodium dodecylsulfate (SDS) and the cationic detergent hexadecyltrimethylammonium chloride (CTACl). Conductimetric measurements were employed to determine the critical micelle concentration, cmc, and the degree of counterion dissociation, α, of the micelles as a function of the mole fraction of added acetonitrile, XAc. Time resolved fluorescence quenching measurements with pyrene as probe were employed to determine the effect of acetonitrile on the micellar aggregation number, N, and the dynamics of solute migration between the micellar and aqueous phases. At low mole fractions (XAc < 0.2), acetonitrile inserts into the cavities present in liquid water, partially disrupting the hydrogen bonding of water, with formation of new hydrogen bonds between water and acetonitrile. In this range, both the cmc and α increase, while N decreases. The dynamics of incorporation of counterionic and coionic quenchers into the micelles is also altered. Thus, the SDS and CTACl micelles formed in these acetonitrile-water mixtures are smaller, more highly dissociated and internally more fluid than those in aqueous solution. Above XAc of ca. 0,2, acetonitrile-water mixtures become microheterogeneous, the solution containing microdomains rich in acetonitrile and microdomains rich in water. The proportion of acetonitrile-rich microdomians increases with increasing XAc, with only small changes in the properties of the two types of microdomains. Correspondingly, at XAc > > ca. 0.2: the variation of the cmc and α with XAc is much less pronounced, suggesting that the detergent forms aggregates preferentially in the aqueous-rich domains; the fluorescence probe pyrene begins to exit the micelles during its excited state lifetime; and there are distinct changes in the rate constants for the incorporation of ions into the micelles

Studies micellar systems in mixtures of water/acetonitrile

Neste trabalho, estudou-se o efeito da adição de acetonitrila nas propriedades de micelas do detergente aniônico, dodecil sulfato de sódio (SDS), e do detergente catiônico, cloreto de hexadeciltrimetilamônio (CTACl). Medidas de condutividade foram utilizadas para determinar a concentração micelar crítica, cmc, e o grau de dissociação, α, das micelas em função da fração molar de acetonitrila, XAc. Medidas de supressão de fluorescência, resolvida no tempo, com pireno como sonda, foram utilizadas para determinar a influência de acetonitrila no número de agregação das micelas, N, e na dinâmica de migração de solutos entre as fases aquosa e micelar. Em baixas frações molares XAc < 0,2), a acetonitrila insere-se nas cavidades da água, quebrando parcialmente as pontes de hidrogênio da água com a formação de novas pontes de hidrogênio entre as moléculas de acetonitrila e as moléculas de água. Nesta faixa de concentração, ocorre um aumento da cmc e do α, acompanhada de uma diminuição de N. Observa-se também alterações na dinâmica da interação de contra-íons e co-íons supressores na micela. Assim, as micelas de SDS e CTACl formadas em misturas acetonitrila-água são menores, mais dissociadas e apresentam maior fluidez interna. Ao redor de XAc = 0,2, as misturas de água-acetonitrila tornam-se microheterogêneos com o aparecimento de microdomínios ricos em acetonitrila e microdomínios ricos em água. A proporção das regiões ricas em acetonitrila aumenta com o aumento da fração molar de acetonitrila, com apenas pequenas modificações das propriedades dos dois tipos de microdomínios. Em XAc > 0,2 a variação de cmc e de α com a XAc passa a ser menos acentuada, sugerindo que o detergente forma agregados preferencialmente nas regiões mais aquosas; a sonda fluorescente pireno começa sair das micelas durante o tempo de vida do estado excitado; e há claras mudanças na dinâmica de incorporação de íons nos agregados.This work presents a study of the effect of added acetonitrile on the properties of the micelles of the anionic detergent sodium dodecylsulfate (SDS) and the cationic detergent hexadecyltrimethylammonium chloride (CTACl). Conductimetric measurements were employed to determine the critical micelle concentration, cmc, and the degree of counterion dissociation, α, of the micelles as a function of the mole fraction of added acetonitrile, XAc. Time resolved fluorescence quenching measurements with pyrene as probe were employed to determine the effect of acetonitrile on the micellar aggregation number, N, and the dynamics of solute migration between the micellar and aqueous phases. At low mole fractions (XAc < 0.2), acetonitrile inserts into the cavities present in liquid water, partially disrupting the hydrogen bonding of water, with formation of new hydrogen bonds between water and acetonitrile. In this range, both the cmc and α increase, while N decreases. The dynamics of incorporation of counterionic and coionic quenchers into the micelles is also altered. Thus, the SDS and CTACl micelles formed in these acetonitrile-water mixtures are smaller, more highly dissociated and internally more fluid than those in aqueous solution. Above XAc of ca. 0,2, acetonitrile-water mixtures become microheterogeneous, the solution containing microdomains rich in acetonitrile and microdomains rich in water. The proportion of acetonitrile-rich microdomians increases with increasing XAc, with only small changes in the properties of the two types of microdomains. Correspondingly, at XAc > > ca. 0.2: the variation of the cmc and α with XAc is much less pronounced, suggesting that the detergent forms aggregates preferentially in the aqueous-rich domains; the fluorescence probe pyrene begins to exit the micelles during its excited state lifetime; and there are distinct changes in the rate constants for the incorporation of ions into the micelles

Chemical and photochemical reactivity in aggregates of tensoactives in water/acetonitrile

Neste trabalho, estudou-se o efeito da adição de acetonitrila na reatividade química em soluções micelares do detergente aniônico dodecil sulfato de sódio (SDS) e do detergente catiônico brometo de hexadeciltrimetilamônio (CTAB) e em agregados supramoleculares do sal biliar, colato de sódio (NaCh). Os sistemas utilizados para estudar a reatividade química na presença de acetonitrila foram: (a) fotorreatividade do estado excitado triplete de n-butil-3-nitrofenil éter (em SDS); (b) reação de hidrólise ácida do 2-(p-octoxifenil)-1,3-dioxolano no estado fundamental (em SDS); (c) constante de incorporação do co-íon N-dodecil-4-cianopiridínio (em CTAB); (d) a protonação/desprotonação do ácido fraco 4-metil-7-hidroxiflavílio, tanto no estado excitado como no estado fundamental (em SDS); e (e) a supressão dos estados excitados de 1-etilnaftaleno e 1-(1-naftil)-etanol (em NaCh). As modificações na estruturação do agregado micelar e nas propriedades do meio aquoso, provocadas pela presença de acetonitrila, fazem com que as moléculas orgânicas e os íons saiam mais rapidamente do agregado para a fase aquosa. As mudanças que ocorrem com a micela e com a partição de solutos diminuem o efeito catalítico da micela sobre a reatividade química. Os agregados de sal biliar possuem dois sítios distintos de ligação de solutos e a concentração mínima de sal biliar necessária para formar esses dois sítios depende da concentração de acetonitrila. Em concentrações de acetonitrila acima de 10 %, ocorre somente a formação de agregados com sítio primário, enquanto que acima de 30 % os agregados se desfazem por completo. Em baixas concentrações de acetonitrila (até aproximadamente 10 %), a dinâmica de dissociação de solutos do sítio secundário do agregado de sal biliar não modifica muito, enquanto que a velocidade de saída de solutos do sítio primário aumenta com a presença da acetonitrila. Desse modo, a acetonitrila pode ser empregada para acelerar a saída de uma espécie, tal como um intermediário reativo, do agregado primário, facilitando a aplicação de agregados de sal biliar como micro-reatores com dois sítios distintos de reação.This work reports a study of the effect of the addition of acetonitrile on chemical reactivity in micellar solutions of the anionic detergent sodium dodecyl sulfate (SDS) and the cationic detergent hexadecyltrimethylammonium bromide (CTAB) and in supramolecular aggregates of the bile salt sodium cholate (NaCh). The systems employed in the study of chemical reactivity in the presence of acetonitrile were: (a) photoreactivity of the excited triplet state of N-butyl-3-nitrophenyl ether in SDS; (b) the acid catalyzed of 2-(p-octoxy-nitrophenyl)-1,3-dioxolane in the ground state in SDS; (c) incorporation of the coion N-dodecyl-4-cyanopyridine in CTAB; (d) protonation/deprotonation of the weak acid of the 4-methyl-7-hydroxyflavilium ion in the ground and excited state in SDS; and (e) quenching of the excited state of 1-ethylnaphthalene and 1-(1-naphthyl)-ethanol in NaCh. The modifications of the structure of the micellar aggregate and of the properties of the bulk aqueous phase induced by acetonitrile result in a faster rate of exit of organic molecules and ions from the aggregate into the aqueous phase. The changes that occur in the micelle and in the partitioning of solutes tend to diminish the catalytic effect of micelles on chemical reactivity. Bile salt aggregates possess two distinct sites for solubilization of solutes and the minimum concentration of bile salt necessary for the formation of these two sites depends on the concentration of acetonitrile. At acetonitrile concentrations above 10 %, only aggregates with the primary solubilization site are formed and, above 30 %, the aggregates are completely disrupted. At low acetonitrile concentrations (below 10 %), the dynamics of dissociation of solutes from the secondary site of bile salt aggregates changes very little, while the rate of exit of solutes from the primary site increases in the presence of acetonitrile. Thus, acetonitrile can be employed to accelerate the rate of exit of species such as reactive intermediates, facilitating the application of bile salt aggregates as two-reaction-site microreactors