With the rising prevalence of diabetes, effective means of successful management of blood glucose levels are increasingly important. To improve on the ease of measurements, new technology is being developed to enable less invasive measurements. Some recent efforts have focused on the development of optical microscale glucose sensing systems based on the encapsulation of glucose oxidase within microspheres coated with polyelectrolyte multilayer nanofilms. In such sensors, a phosphorescent oxygen indicator is also co-encapsulated with the enzyme inside so that when glucose is present, glucose oxidase within the sensor reduces the local oxygen levels, causing a corresponding change in the luminescence intensity of the sensors. To test the aforementioned factors, a two-substrate, 2D FEM model of microscale optical glucose sensors in the dermis was developed. The model was used to predict the response time and sensitivity of glucose sensors with varying number and spacing of particles distributed in the dermis and varying physiological characteristics of the surrounding tissue; specifically, capillary density, blood vessel location relative to sensor, and glucose and oxygen consumption in tissue. Simulations were conducted to determine the magnitude of the change in the response time of sensors. Because the steady-state oxygen concentration within the sensors for a given blood glucose level determines the signal output, steady-state concentration of oxygen within sensors and the surrounding tissue for the entire physiological glucose range was evaluated. The utility of the model to predict the performance and efficacy of the sensors in the event of a host response to the foreign body implant was also evaluated. Simulations were performed to evaluate changes in sensor response and sensitivity in the occurrence of inflammation and progression of fibrous encapsulation of various thickness and density. The results from these simulations have provided knowledge on the impact of physiological factors that can potentially degrade sensor function in vivo. Our results indicate that upon the occurrence of a host response, sensitivity is reduced while range is extended. Furthermore, using the model we have been able to determine which conditions in vivo improve response time, sensitivity, and the linear response range for these sensors.

Cell adhesion to a substrate or another cell plays an important role in the activities of the cell, such as cell growth, cell migration and cell signaling and communication with extracellular environment or other cells. The adhesion of the cell to the extracellular matrix also plays a vital role in life, as it involves in healing process of a wound and formation of the blood clot inside a vessel. The spread of cancer metastasis tumors inside the body is mostly dependent on the mechanisms of the cell adhesion. The current work is devoted to studying deformation and adhesion of the cell membrane mediated by receptors and ligands in order to enhance the existing models. In fact phospholipid molecules as the constructive units of the cell membrane grant sufficient in-plane continuity and fluidity to the cell membrane that it can be acceptably modeled as a continuum fluid medium. Therefore a two dimensional isotropic continuum fluid model is proposed in here for cell under implementation of membrane theory. In accordance to lack of sufficient study on direct effect of presence of receptors on membrane dilation, the developed model engages the intensity of presence of receptors with membrane deformation and adhesion. This influence is considered through introduction of spontaneous areal dilation. Another innovation is introduced regarding conception of receptor-ligand bonds formation such that a nonlinear constitutive relation is developed for binding force based on charge-induced dipole interaction, which is physically admissible. This relation becomes also enriched by considering one-to-one shielding phenomenon. Diffusion of the receptors is formulated along the membrane under the influence of receptor-receptor and receptor-ligand interactions. Then the presented models in this work are implemented to an axisymmetric configuration of a cell to study the deformation and adhesion of its membrane. Another target of this work is to clarify the impacts of variety of material, binding and diffusion constitutive factors on membrane deformation and adhesion and to declare a rational comparison among them. / Graduate / 0548 / 0346 / golestan@uvic.ca

abstract: Science is a formalized method for acquiring information about the world. In recent years, the ability of science to do so has been scrutinized. Attempts to reproduce findings in diverse fields demonstrate that many results are unreliable and do not generalize across contexts. In response to these concerns, many proposals for reform have emerged. Although promising, such reforms have not addressed all aspects of scientific practice. In the social sciences, two such aspects are the diversity of study participants and incentive structures. Most efforts to improve scientific practice focus on replicability, but sidestep issues of generalizability. And while researchers have speculated about the effects of incentive structures, there is little systematic study of these hypotheses. This dissertation takes one step towards filling these gaps. Chapter 1 presents a cross-cultural study of social discounting – the purportedly fundamental human tendency to sacrifice more for socially-close individuals – conducted among three diverse populations (U.S., rural Indonesia, rural Bangladesh). This study finds no independent effect of social distance on generosity among Indonesian and Bangladeshi participants, providing evidence against the hypothesis that social discounting is universal. It also illustrates the importance of studying diverse human populations for developing generalizable theories of human nature. Chapter 2 presents a laboratory experiment with undergraduates to test the effect of incentive structures on research accuracy, in an instantiation of the scientific process where the key decision is how much data to collect before submitting one’s findings. The results demonstrate that rewarding novel findings causes respondents to make guesses with less information, thereby reducing their accuracy. Chapter 3 presents an evolutionary agent-based model that tests the effect of competition for novel findings on the sample size of studies that researchers conduct. This model demonstrates that competition for novelty causes the cultural evolution of research with smaller sample sizes and lower statistical power. However, increasing the startup costs to conducting single studies can reduce the negative effects of competition, as can rewarding publication of secondary findings. These combined chapters provide evidence that aspects of current scientific practice may be detrimental to the reliability and generalizability of research and point to potential solutions. / Dissertation/Thesis / Doctoral Dissertation Anthropology 2018

Made available in DSpace on 2014-06-11T19:24:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T20:31:20Z : No. of bitstreams: 1 buchi_at_me_botfm.pdf: 494324 bytes, checksum: 8a45f84c2c6a750412659b4b78ff10f4 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / As serpentes do gênero Crotalus durissus terrificus possuem em seu veneno diversas substâncias, entre elas uma serinoprotease com atividade trombina símile denominada giroxina, a qual é capaz de coagular o fibrinogênio plasmástico, promovendo a formação de fibrina. O objetivo do estudo foi a purificação e caracterização estrutural da enzima giroxina de Crotalus durissus terrificus. Para tanto, foram utilizadas métodos cromatográficos de gel filtração em Sephadex G75 e afinidade em Benzamidina-Sepharose 6B para isolamento e purificação; eletroforéticos de SDSPAGE 12% reduzido e de seqüenciamento do N-terminal da enzima purificada para identificação e avaliação do grau de pureza; clonagem e expressão do cDNA da glândula venenífera por RT-PCR e testes de cristalização. A modelagem teórica molecular foi realizada a partir de ferramentas de bioinformática baseadas em análises comparativas de outras serinoproteases depositadas no NCBI (National Center for Biotechnology Information). O seqüenciamento N-terminal da giroxina purificada, produziu uma proteína de cadeia única com massa molecular aproximada de 30 KDa e sua seqüência completa de cDNA apresentou 714 pb os quais codificaram uma proteína completa contendo 238 aminoácidos. Foram obtidos cristais a partir das soluções nos 2 e 5 do Kit Crystal Screen® 2 e 1 respectivamente, verificando-se sua constituição protéica. Para os alinhamentos múltiplos da sequência molde giroxina símile B2.1 com outras seis serinoproteases derivadas de veneno de serpentes (SVSPs) indicou-se a preservação de resíduos de cisteína e de seus principais elementos de estruturais (α-hélices, β-barris e loops).Evidenciou-se a localização da tríade catalítica nos aminoácidos His57, Asp102, Ser198 e os sítios de atividade especifica S1 e S2 nos aminoácidos Thr193 e Gli215 respectivamente... / The venom of snakes Crotalus durissus terrificus genus have in their various substances, including a serinoproteases with thrombin-like activity called gyroxin, which clot the plasmatic fibrinogen and promote the fibrin formation. The objective of this study was purificate and characterize structurally the gyroxin enzyme from Crotalus durissus terrificus. For this, we used chromatographic gel filtration with Sephadex G75 and affinity benzamidine-Sepharose 6B for isolation and purification, SDS-PAGE 12% in reduce conditions for assessment purity, N-terminal sequencing of purified enzyme for identification and assessment purity; the cloning and expression of cDNA from venom gland by RT-PCR and crystallization tests. The theoretical molecular modeling was performed with bioinformatics tools based on comparative analysis of other serinoproteases deposited in the NCBI (National Center for Biotechnology Information). The N-terminal sequencing purified gyroxin protein produced a single chain with a molecular mass of approximately 30 kDa and its full-length cDNA had 714 bp which encoded a complete protein containing 238 amino acids. Crystals were obtained from the solutions 2 and 5 of the Crystal Screen Kit ® 2 and 1 respectively and was verificated a protein constitution. For multiple sequence alignments such gyroxin-like B2.1 with six other serinoproteases derived from snake venom (SVSPs) indicated the preservation of cysteine residues and its main structural elements (α helices, β-barrel and loops). Identificated the amino acids positions in the catalytic triad His57, Asp102, Ser198 and sites of specific activity in S1 and S2 amino acids Thr193 and Gli215 respectively. The recognition area of fibrinogen cleavage in SVSPs to template sequence gyroxin B2.1 was located in residues Arg60, Arg72, Gln75, Arg81, Arg82, Lis85, Glu86, Lis87... (Complete abstract click electronic access below)

Resumo: As serpentes do gênero Crotalus durissus terrificus possuem em seu veneno diversas substâncias, entre elas uma serinoprotease com atividade trombina símile denominada giroxina, a qual é capaz de coagular o fibrinogênio plasmástico, promovendo a formação de fibrina. O objetivo do estudo foi a purificação e caracterização estrutural da enzima giroxina de Crotalus durissus terrificus. Para tanto, foram utilizadas métodos cromatográficos de gel filtração em Sephadex G75 e afinidade em Benzamidina-Sepharose 6B para isolamento e purificação; eletroforéticos de SDSPAGE 12% reduzido e de seqüenciamento do N-terminal da enzima purificada para identificação e avaliação do grau de pureza; clonagem e expressão do cDNA da glândula venenífera por RT-PCR e testes de cristalização. A modelagem teórica molecular foi realizada a partir de ferramentas de bioinformática baseadas em análises comparativas de outras serinoproteases depositadas no NCBI (National Center for Biotechnology Information). O seqüenciamento N-terminal da giroxina purificada, produziu uma proteína de cadeia única com massa molecular aproximada de 30 KDa e sua seqüência completa de cDNA apresentou 714 pb os quais codificaram uma proteína completa contendo 238 aminoácidos. Foram obtidos cristais a partir das soluções nos 2 e 5 do Kit Crystal Screen® 2 e 1 respectivamente, verificando-se sua constituição protéica. Para os alinhamentos múltiplos da sequência molde giroxina símile B2.1 com outras seis serinoproteases derivadas de veneno de serpentes (SVSPs) indicou-se a preservação de resíduos de cisteína e de seus principais elementos de estruturais (α-hélices, β-barris e loops).Evidenciou-se a localização da tríade catalítica nos aminoácidos His57, Asp102, Ser198 e os sítios de atividade especifica S1 e S2 nos aminoácidos Thr193 e Gli215 respectivamente... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The venom of snakes Crotalus durissus terrificus genus have in their various substances, including a serinoproteases with thrombin-like activity called gyroxin, which clot the plasmatic fibrinogen and promote the fibrin formation. The objective of this study was purificate and characterize structurally the gyroxin enzyme from Crotalus durissus terrificus. For this, we used chromatographic gel filtration with Sephadex G75 and affinity benzamidine-Sepharose 6B for isolation and purification, SDS-PAGE 12% in reduce conditions for assessment purity, N-terminal sequencing of purified enzyme for identification and assessment purity; the cloning and expression of cDNA from venom gland by RT-PCR and crystallization tests. The theoretical molecular modeling was performed with bioinformatics tools based on comparative analysis of other serinoproteases deposited in the NCBI (National Center for Biotechnology Information). The N-terminal sequencing purified gyroxin protein produced a single chain with a molecular mass of approximately 30 kDa and its full-length cDNA had 714 bp which encoded a complete protein containing 238 amino acids. Crystals were obtained from the solutions 2 and 5 of the Crystal Screen Kit ® 2 and 1 respectively and was verificated a protein constitution. For multiple sequence alignments such gyroxin-like B2.1 with six other serinoproteases derived from snake venom (SVSPs) indicated the preservation of cysteine residues and its main structural elements (α helices, β-barrel and loops). Identificated the amino acids positions in the catalytic triad His57, Asp102, Ser198 and sites of specific activity in S1 and S2 amino acids Thr193 and Gli215 respectively. The recognition area of fibrinogen cleavage in SVSPs to template sequence gyroxin B2.1 was located in residues Arg60, Arg72, Gln75, Arg81, Arg82, Lis85, Glu86, Lis87... (Complete abstract click electronic access below) / Orientador: Benedito Barravieira / Coorientador: Marcos R. M. Fontes / Banca: Patrick Jack Spencer / Banca: Andreimar Martins Soares / Mestre

This dissertation presents theoretical and experimental investigations into the dynamical behavior of Micro electromechanical systems (MEMS) resonators and their exploitation for filtering, sensing, and logic applications. The dissertation is divided into two parts: MEMS coupled structures and MEMS dynamic logic devices. First, a theoretical and experimental investigation is presented on both electrostatically and mechanically coupled resonator. Static and dynamic analysis is presented for weakly electrostatically coupled silicon microbeams and also for strongly mechanically coupled polyimide microbeams. The static analysis focuses on revealing pull-in characteristics, while the dynamic analysis focuses on the frequency response of the system and its exploitation for potential applications in filtering and amplification. Next, the phenomenon of mode localization is explored theoretically and experimentally on both electrostatically and mechanically weakly coupled resonators. Eigenvalue analysis is conducted and the dynamic response of the coupled system under different external perturbations is investigated. It is observed, that the exploitation of mode localization depends on the choice of the resonator to be under direct excitation, its stiffness to be perturbed, and which resonator is used to record the output results. These understandings will potentially help improve the performance of MEMS mode-localized sensors. Finally, three techniques to realize cascadable MEMS logic devices are presented. MEMS logic device vibrates at two steady states; a high on-resonance state (1) and a low off-resonance state (0). First, a MEMS logic device is presented capable of performing the AND/NAND logic gate and a tri-state logic gate using mixed-frequency excitation. This work is based on the concept of activation (1) and deactivation (0) of combination resonances due to the mixing of two or more input signals. Second, exploitation of subharmonic resonance under an AC only excitation to perform AND logic operation is presented. Finally, another MEMS logic device is presented working on the principal of activation (1) and deactivation (0) of second resonant mode of a clamped-clamped microbeam. This device is capable of performing OR, XOR and NOT gate. Experimental demonstration of the cascadability is shown for this case cascading OR and NOT gate to perform a logically complete NOR logic gate.

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No description available.

An integral concern across care settings is the prompt intervention for patients suffering with pain. Long-term care (LTC) settings present with unique challenges to assess and manage pain in resident populations. Pain assessment is especially challenging, because residents have varying degrees of cognition to communicate their pain, and clinician/staff knowledge of pain symptoms may be lacking. The purpose of this research was to improve the measurement of pain and outcomes of care for the elderly residing in skilled nursing care, especially those with cognitive-impairment. The specific aims of this study were to: 1) Determine the magnitude of the relationship between pain behaviors and a measurement model hypothesized for pain; 2) Test the construct validity of a pain measurement model; 3) Examine the concomitance of pain and cognition in a three-year longitudinal analysis. The research questions answered: 1) Is there a difference in the prevalence of pain in cognitively intact versus cognitively-impaired residents; 2) Can a theoretically derived model of pain aid in detecting pain across all cognitive levels; and 3) Do pain and cognitive status concomitantly correlate? The goal was to examine the covariance model of concomitance of pain and cognition to more accurately construct theoretical models of pain to then include additional resident care factors in future research. Traditional self-reports of pain are often under-assessed and under-treated in the cognitively-impaired (CI) elderly resident. Having additional measures to detect pain beyond self-reports of pain intensity and frequency increases the likelihood of detecting pain in populations with complex symptom presentation. Data collected from skilled nursing facilities offer exceptional opportunities to study resident demographics, characteristics, symptoms, medication use, quality indicators, and care outcomes. The Minimum Data Set-Resident Assessment Instrument (MDS-RAI) 2.0, a nationally required resident assessment tool, must be completed on every resident in a Medicare LTC facility within 14 days of admission, quarterly, annually and with significant changes in resident status. Because the MDS is widely used and recognized in LTC settings, core items from MDS [i.e., pain frequency (J2a) and pain intensity (J2b)] along with additional MDS items hypothesized to signify pain were analyzed in the pilot measurement model. Ten core items from MDS were used: 1) Inappropriate behavior frequency (E4da); 2) Repetitive physical movements; 3) Repetitive verbalizations (E1c); 4) Sad facial expressions (E1l); 5) Crying (E1m); 6) Change in mood (E3); 7) Negative statements (E1a); 8) Pain frequency (J2a); 9) Pain intensity (J2b); and 10) Cumulative pain sites scores. All indicators of pain were significant at the <.01 level. A longitudinal cohort design was used to answer if a concomitance exists between pain and cognition. Data were collected from MDS annual assessments from 2001, 2002 and 2003 for residents across the United States. The sample consisted of 56,494 residents age 65 years and older with an average age of 83 [plus or minus] 8.2 years. Descriptive statistics, ANOVA and a covariance model were used to evaluate cognition and pain at the three time intervals. ANOVA indicated a significant effect (<.01) for pain and cognition with protected t-tests indicating scores decreased significantly over time with resident measures of pain and cognition. Results from this study suggest that: 1) Using only pain intensity and frequency, pain prevalence was found in 30% of the pilot population, while 47.7% of cognitively intact residents had documented pain and only 18.2% of the severely CI had documented pain, supporting previous research that pain is potentially under-reported in the CI; 2) Parsimonious measurements models of pain should include dimensions beyond self-reports of pain (i.e., cognitive, affective, behavioral and inferred pain indicators); 3) Model fit was improved by using specific MDS items in the pain construct; 4) Longitudinal analysis revealed relative stability for pain and cognition measures over time (e.g., larger stability or consistency was found in cognitive measures than the measures of pain over the three-year period); 5) Crossed-legged effects between pain and cognition were not consistent; 6) A concomitant relationship was not found between pain and cognition. The relationship was significant (<.01), but associations were weak (r=0.03 to 0. 08). Pain or cognition should not be used as a predictor of the other in theoretical models for similar populations. The MDS is a reliable instrument to follow resident attributes, quality of care, and patient outcomes over time. The development of more accurate assessments of pain may improve resident care outcomes. Ineffectively intervening on the pain cycle is posited to cause secondary unmet needs that affect the resident's quality of life. Findings support the importance of improving clinical outcomes in the management of pain in the elderly residing in long-term care. Deficits in the treatment of pain highlight the impetus to support health policy change that includes pain treatment as a top health priority and a quality indicator for federally funded programs supporting eldercare.

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