Guided Migration and Collective Behavior: Cell Dynamics during Cancer Progression

This dissertation focuses on gaining understanding of cell migration and collective behavior through a combination of experiment, analysis, and modeling techniques. Cell migration is a ubiquitous process that plays an important role during embryonic development and wound healing as well as in diseases like cancer, which is a particular focus of this work. As cancer cells become increasingly malignant, they acquire the ability to migrate away from the primary tumor and spread throughout the body to form metastatic tumors. During this process, changes in gene expression and the surrounding tumor environment can lead to changes in cell migration characteristics. In this thesis, I analyze how cells are guided by the texture of their environment and how cells cooperate with their neighbors to move collectively. The emergent properties of collectively moving groups are a particular focus of this work as collective cell dynamics are known to change in diseases such as cancer. The internal machinery for cell migration involves polymerization of the actin cytoskeleton to create protrusions that---in coordination with retraction of the rear of the cell---lead to cell motion. This actin machinery has been previously shown to respond to the topography of the surrounding surface, leading to guided migration of amoeboid cells. Here we show that epithelial cells on nanoscale ridge structures also show changes in the morphology of their cytoskeletons; actin is found to align with the ridge structures. The migration of the cells is also guided preferentially along the ridge length. These ridge structures are on length scales similar to those found in tumor microenvironments and as such provide a system for studying the response of the cells' internal migration machinery to physiologically relevant topographical cues. In addition to sensing surface topography, individual cells can also be influenced by the pushing and pulling of neighboring cells. The emergent properties of collectively migrating cells show interesting dynamics and are relevant for cancer progression, but have been less studied than the motion of individual cells. We use Particle Image Velocimetry (PIV) to extract the motion of a collectively migrating cell sheet from time lapse images. The resulting flow fields allow us to analyze collective behavior over multiple length and time scales. To analyze the connection between individual cell properties and collective migration behavior, we compare experimental flow fields with the migration of simulated cell groups. Our collective migration metrics allow for a quantitative comparison between experimental and simulated results. This comparison shows that tissue-scale decreases in collective behavior can result from changes in individual cell activity without the need to postulate the existence of subpopulations of leader cells or global gradients. In addition to tissue-scale trends in collective behavior, the migration of cell groups includes localized dynamic features such as cell rearrangements. An individual cell may smoothly follow the motion of its neighbors (affine motion) or move in a more individualistic manner (non-affine motion). By decomposing individual motion into both affine and non-affine components, we measure cell rearrangements within a collective sheet. Finally, finite-time Lyapunov exponent (FTLE) values capture the stretching of the flow field and reflect its chaotic character. Applying collective migration analysis techniques to experimental data on both malignant and non-malignant human breast epithelial cells reveals differences in collective behavior that are not found from analyzing migration speeds alone. Non-malignant cells show increased cooperative motion on long time scales whereas malignant cells remain uncooperative as time progresses. Combining multiple analysis techniques also shows that these two cell types differ in their response to a perturbation of cell-cell adhesion through the molecule E-cadherin. Non-malignant MCF10A cells use E-cadherin for short time coordination of collective motion, yet even with decreased E-cadherin expression, the cells remain coordinated over long time scales. In contrast, the migration behavior of malignant and invasive MCF10CA1a cells, which already shows decreased collective dynamics on both time scales, is insensitive to the change in E-cadherin expression.

Investigation into the Influence of Build Parameters on Failure of 3D Printed Parts

Additive manufacturing, including fused deposition modeling (FDM), is transforming the built world and engineering education. Deep understanding of parts created through FDM technology has lagged behind its adoption in home, work, and academic environments. Properties of parts created from bulk materials through traditional manufacturing are understood well enough to accurately predict their behavior through analytical models. Unfortunately, Additive Manufacturing (AM) process parameters create anisotropy on a scale that fundamentally affects the part properties. Understanding AM process parameters (implemented by program algorithms called slicers) is necessary to predict part behavior. Investigating algorithms controlling print parameters (slicers) revealed stark differences between the generation of part layers. In this work, tensile testing experiments, including a full factorial design, determined that three key factors, width, thickness, infill density, and their interactions, significantly affect the tensile properties of 3D printed test samples.

Guided Migration and Collective Behavior: Cell Dynamics during Cancer Progression

This dissertation focuses on gaining understanding of cell migration and collective behavior through a combination of experiment, analysis, and modeling techniques. Cell migration is a ubiquitous process that plays an important role during embryonic development and wound healing as well as in diseases like cancer, which is a particular focus of this work. As cancer cells become increasingly malignant, they acquire the ability to migrate away from the primary tumor and spread throughout the body to form metastatic tumors. During this process, changes in gene expression and the surrounding tumor environment can lead to changes in cell migration characteristics. In this thesis, I analyze how cells are guided by the texture of their environment and how cells cooperate with their neighbors to move collectively. The emergent properties of collectively moving groups are a particular focus of this work as collective cell dynamics are known to change in diseases such as cancer. The internal machinery for cell migration involves polymerization of the actin cytoskeleton to create protrusions that---in coordination with retraction of the rear of the cell---lead to cell motion. This actin machinery has been previously shown to respond to the topography of the surrounding surface, leading to guided migration of amoeboid cells. Here we show that epithelial cells on nanoscale ridge structures also show changes in the morphology of their cytoskeletons; actin is found to align with the ridge structures. The migration of the cells is also guided preferentially along the ridge length. These ridge structures are on length scales similar to those found in tumor microenvironments and as such provide a system for studying the response of the cells' internal migration machinery to physiologically relevant topographical cues. In addition to sensing surface topography, individual cells can also be influenced by the pushing and pulling of neighboring cells. The emergent properties of collectively migrating cells show interesting dynamics and are relevant for cancer progression, but have been less studied than the motion of individual cells. We use Particle Image Velocimetry (PIV) to extract the motion of a collectively migrating cell sheet from time lapse images. The resulting flow fields allow us to analyze collective behavior over multiple length and time scales. To analyze the connection between individual cell properties and collective migration behavior, we compare experimental flow fields with the migration of simulated cell groups. Our collective migration metrics allow for a quantitative comparison between experimental and simulated results. This comparison shows that tissue-scale decreases in collective behavior can result from changes in individual cell activity without the need to postulate the existence of subpopulations of leader cells or global gradients. In addition to tissue-scale trends in collective behavior, the migration of cell groups includes localized dynamic features such as cell rearrangements. An individual cell may smoothly follow the motion of its neighbors (affine motion) or move in a more individualistic manner (non-affine motion). By decomposing individual motion into both affine and non-affine components, we measure cell rearrangements within a collective sheet. Finally, finite-time Lyapunov exponent (FTLE) values capture the stretching of the flow field and reflect its chaotic character. Applying collective migration analysis techniques to experimental data on both malignant and non-malignant human breast epithelial cells reveals differences in collective behavior that are not found from analyzing migration speeds alone. Non-malignant cells show increased cooperative motion on long time scales whereas malignant cells remain uncooperative as time progresses. Combining multiple analysis techniques also shows that these two cell types differ in their response to a perturbation of cell-cell adhesion through the molecule E-cadherin. Non-malignant MCF10A cells use E-cadherin for short time coordination of collective motion, yet even with decreased E-cadherin expression, the cells remain coordinated over long time scales. In contrast, the migration behavior of malignant and invasive MCF10CA1a cells, which already shows decreased collective dynamics on both time scales, is insensitive to the change in E-cadherin expression.

Saúde e bem-estar na empresa Boa Vista Golf & Spa Resort. Implementação de um plano de bem-estar

Dissertação de Mestrado, Gestão de Recursos Humanos, Escola Superior de Gestão, Hotelaria e Turismo, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2016

MINING AND VERIFICATION OF TEMPORAL EVENTS WITH APPLICATIONS IN COMPUTER MICRO-ARCHITECTURE RESEARCH

Computer simulation programs are essential tools for scientists and engineers to understand a particular system of interest. As expected, the complexity of the software increases with the depth of the model used. In addition to the exigent demands of software engineering, verification of simulation programs is especially challenging because the models represented are complex and ridden with unknowns that will be discovered by developers in an iterative process. To manage such complexity, advanced verification techniques for continually matching the intended model to the implemented model are necessary. Therefore, the main goal of this research work is to design a useful verification and validation framework that is able to identify model representation errors and is applicable to generic simulators. The framework that was developed and implemented consists of two parts. The first part is First-Order Logic Constraint Specification Language (FOLCSL) that enables users to specify the invariants of a model under consideration. From the first-order logic specification, the FOLCSL translator automatically synthesizes a verification program that reads the event trace generated by a simulator and signals whether all invariants are respected. The second part consists of mining the temporal flow of events using a newly developed representation called State Flow Temporal Analysis Graph (SFTAG). While the first part seeks an assurance of implementation correctness by checking that the model invariants hold, the second part derives an extended model of the implementation and hence enables a deeper understanding of what was implemented. The main application studied in this work is the validation of the timing behavior of micro-architecture simulators. The study includes SFTAGs generated for a wide set of benchmark programs and their analysis using several artificial intelligence algorithms. This work improves the computer architecture research and verification processes as shown by the case studies and experiments that have been conducted.

Intergranular Corrosion and Stress Corrosion Cracking of Extruded AA6005A

A research program focused on understanding the intergranular corrosion (IGC) and stress corrosion cracking (SCC) behavior of AA6005A aluminum extrusions is presented in this dissertation. The relationship between IGC and SCC susceptibility and the mechanisms of SCC in AA6005A extrusions were studied by examining two primary hypotheses. IGC susceptibility of the elongated grain structure in AA6005A exposed to low pH saltwater was found to depend primarily on the morphology of Cu-containing precipitates adjacent to the grain boundaries in the elongated grain structure. IGC susceptibility was observed when a continuous (or semi-continuous) film of Cu-containing phase was present along the grain boundaries. When this film coarsened to form discrete Cu-rich precipitates, no IGC was observed. The morphology of the Cu-rich phase depended on post-extrusion heat treatment. The rate of IGC penetration in the elongated grain structure of AA6005A-T4 and AA6005A-T6 extrusions was found to be anisotropic with IGC propagating most rapidly along the extrusion direction, and least rapidly along the through thickness direction. A simple 3-dimensional geometric model of the elongated grain structure was accurately described the observed IGC anisotropy, therefore it was concluded that the anisotropic IGC susceptibility in the elongated grain structure was primarily due to geometric elongation of the grains. The velocity of IGC penetration along all directions in AA6005A-T6 decreased with exposure time. Characterization of the local environment within simulated corrosion paths revealed that a pH gradient existed between the tip of the IGC path and the external environment. Knowledge of the local environment within an IGC path allowed development of a simple model based on Fick's first law that considered diffusion of Al3+ away from the tip of the IGC path. The predicted IGC velocity agreed well with the observed IGC velocity, therefore it was determined that diffusion of Al3+ was the primary factor in determining the velocity of IGC penetration. The velocity of crack growth in compact tensile (CT) specimens of AA6005A-T6 extrusion exposed to 3.5% NaCl at pH = 1.5 was nearly constant over a range of applied stress intensities, exposure times, and crack lengths. The crack growth behavior of CT specimens of AA6005A-T6 extrusion exposed to a solution of 3.5% NaCl at pH = 2.0 exhibited similar behavior, but the crack velocity was ~10.5X smaller than that those exposed to a solution at pH =1.5. Analysis of the local stress state and polarization behavior at the crack tip predicted that increasing the pH of the bulk solution from 1.5 to 2.0 would decrease the corrosion current density at the crack tip by approximately 11.8X. This predicted decrease in corrosion current density was in reasonable agreement with the observed decrease in SCC velocity associated with increasing the solution pH from 1.5 to 2.0. The agreement between the predicted and observed SCC velocities suggested that the electrochemical reactions controlling SCC in AA6005A-T6 extrusions are ultimately controlled by the pH gradient that exists between the crack tip and external environment.

MICHIGAN TEACHER EXCELLENCE PROGRAM: PERSONAL EXPERIENCES AND IMPACT

This report is a summary of the effects of the Michigan Teacher Excellence Program (MITEP) on me as a science educator. The first chapter is a report of an action research project jointly authored with two other science teachers participating in the MITEP program titled “Station Activities and Misconceptions in the Chemistry Classroom.” The second chapter is a reflective essay evaluating the impacts of the MITEP experience on my teaching skills and practice, knowledge of science education and science education research, and leadership skills. The most significant impacts were a dramatic increase in my earth science content knowledge, a deeper understanding of inquiry-based teaching methods, and an expanded professional network of science educators.

Knowledge of HIV transmission risk behavior, and perceptions of risk among Haitian women living in Miami, Florida

This study was conducted to gain a more comprehensive understanding of HIV risk among Haitian women. The variables measured were: knowledge of HIV transmission, sexual risk behaviors, and perceptions of risk among Haitian women. The sociocultural aspect of the Haitian women's lives with regard to their risky behaviors was also examined. A total of 101 Haitian women (aged 25-53) who attended two comprehensive health clinics were interviewed. A combined questionnaire derived from both the ARM-Q and the RBA was used. In general, the women had good knowledge of the sexual transmission of HIV I AIDS and indicated that they were susceptible to HIV infection. However, knowledge and perceptions of risk were not translated into sexual risk-reduction behaviors with their partners. Multiplicity of partners and low incidence of condom use were the two major sexual risk factors isolated in this study. Results indicate Haitian women were more likely to use condoms if they possessed greater HIV knowledge and their sexual partners held more positive attitudes toward using condoms. Also, Haitian women may have failed to protect themselves because behavior changes could have involved threats to their social and economic survival, relationships and culturally sanctioned roles. This suggests the need to include male partners in HIV prevention interventions with Haitian women. Future research should focus on preventing high-risk behavior by improving knowledge, altering the male partners' attitudes toward condoms, and enhancing communication and negotiation skills. Nursing implications and recommendations for culturally sensitive and relevant AIDS prevention efforts are discussed.

Effect of the Supplemental Nutrition Assistance Program (SNAP) and Nutrition Education on Nutrition and Health Outcomes of HIV+ Individuals

Factors associated with and barriers to participation in Supplemental Nutrition Assistance Program (SNAP) and the effect participation has on food security, nutrition status, disease status and quality of life was investigated in a cross-sectional study including 175 HIV infected individuals. In addition, the effect of a targeted nutrition education on nutrition knowledge, readiness to dietary behavior change, nutrition status, disease status and quality of life was also investigated among a subset of the population (N = 45) in a randomized clinical control trial. SNAP participation rate was 70.3%, similar to the State of Florida and national participation rates. SNAP participation was positively and independently associated with being born in the US (P < 0.001), having monthly income less than $1000 (P = 0.006), and receiving antiretroviral treatment (P < 0.001). Participation barriers include denial of participation by program, recent incarceration, living in a shelter where participation is not allowed and unawareness of eligibility status. In regression analyses, SNAP participation was not significantly associated with improved food security, nutrition status, disease status and health related quality of life (HRQOL). Over half (56%) of the population experienced food insecurity and had inadequate intakes of half of the nutrients assessed. Illicit drug, alcohol and cigarette use were high in this population (31%, 55% and 63% respectively), and affected food security, nutrients intake, disease status and HRQOL. The nutrition education intervention resulted in a trend towards improvements nutrition knowledge, self-efficacy, and readiness to change without impacting nutrition status, disease state and quality of life. Food insecurity and other nutrition related issues, with implications for treatment, management and cost of HIV disease, continue to plague infected individuals living in poverty. More resources, including food and nutrition programs, specifically targeted towards this population are needed to address these issues.

Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior

There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders.

Review of Managing the Fraud Risk in the Disaster Supplemental Nutrition Assistance Program (D-SNAP), Administered by the Department of Social Services

This review was initiated based upon allegations from multiple sources of possible fraud in the Disaster Supplemental Nutrition Assistance Program (D-SNAP) administered by the South Carolina Department of Social Services (SCDSS), which was implemented in response to the 10/3/2015 statewide flooding from Hurricane Joaquin. This review’s scope and objectives were: Assess SCDSS’s D-SNAP implementation for compliance with federal guidelines, with emphasis on fraud preventative controls; Assess the SCDSS’s post-disaster review and audit methodology for compliance with federal guidelines, with emphasis on understanding the fraud risks and resolution strategies; and Identify residual risk/suspected fraud not addressed through the SCDSS review and available opportunities to address.

Performance sismique sous charge axiale nulle des murs en maçonnerie armée entièrement remplis de coulis

Résumé : Cette juxtaposition de matériaux solides -blocs, pierres ou briques,...- liés ou non entre eux que nous appelons maçonnerie ne se comporte pas très bien vis-à-vis des forces latérales, surtout si elle n’a pas été réalisée suivant les normes parasismiques ou de façon adéquate. Cette vulnérabilité (glissement, cisaillement, déchirure en flexion, ou tout autre) vient souvent du fait même de ce processus d’empilement, des problèmes d’interaction avec le reste de la structure et aussi à cause des caractéristiques mécaniques peu fiables de certains éléments utilisés. Malgré cette défaillance structurale, la maçonnerie est encore utilisée aujourd’hui grâce à son côté traditionnel, sa facilité de mise en œuvre et son coût d’utilisation peu élevé. Depuis quelques années, la maçonnerie s’est enrichie de documents qui ont été publiés par divers chercheurs dans le but d’une meilleure compréhension des caractéristiques mécaniques des éléments et aussi, et surtout, des mécanismes de rupture des murs de maçonnerie pour une meilleure réponse face aux sollicitations sismiques. Beaucoup de programmes expérimentaux ont alors été effectués et tant d’autres sont encore nécessaires. Et c’est dans ce contexte que cette recherche a été conduite. Elle présentera, entre autres, le comportement sous charges latérales d’un mur en maçonnerie armée entièrement rempli de coulis. Ce projet de recherche fait partie d’un programme plus large visant à une meilleure connaissance du comportement sismique de la maçonnerie pour une amélioration des techniques de construction et de réparation des ouvrages en maçonnerie.

Enrolment, student retention and attrition in the tourism management program.

This paper examines the factors motivating students to enrol in the Tourism Management program at Champlain College, St-Lambert and why a large number of students abandon the program before obtaining their DEC. There is a great deal of literature on student attrition, however there is little consensus on why students withdraw from college programs and the results cannot be easily generalized to this particular set of students at this time. Understanding the factors that influenced the students to choose Tourism Management at Champlain, St-Lambert and why they then leave before completing the six semesters will help with student success and with the marketing of the program.||Résumé : Ce travail s'intéresse aux facteurs qui motivent les étudiants à s'inscrire au programme de tourisme offert au Collège Champlain de St-Lambert. Il cherche à établir les raisons qui font en sorte qu'un si grand nombre d'étudiants abandonnent le programme avant d'obtenir leur DEC. Plusieurs recherches ont été effectuées sur l'abandon scolaire, mais il n'y a pas de consensus quant aux raisons pour lesquelles les étudiants se retirent du programme collégial. Actuellement, il est difficile d'établir des liens entre les résultats de ces recherches et ce groupe d'étudiants. La compréhension des facteurs qui influencent les étudiants à choisir le tourisme au Collège Champlain et les raisons qui font en sorte qu'ils quittent avant d'avoir complété leur formation, nous permettront d'améliorer le taux de rétention des étudiants dans ce programme. De plus, cela favorisera le marketing du programme.

Memoria en publicidad y mercadeo

La psicología y la publicidad son dos disciplinas que desde hace algunos años se han venido complementando, la publicidad es la disciplina que se ha visto beneficiada con esta alianza, ya que el principal aporte que le hace la psicología a la publicidad es poder determinar aquellos factores o estrategias que generan en el consumidor; atención, asociación entre marca y producto, para luego almacenarse en la memoria y así generar una posible conducta de compra en el individuo. Los medios de comunicación cumplen un papel muy importante, ya que son los instrumentos utilizados para la transmisión de la información publicitaria, dependiendo del medio utilizado ya sea prensa, televisión o radio, las estrategias implementadas para dar a conocer la información deben ir dirigidas al campo perceptivo, que se utiliza para recibir la información y lograr una adecuada asociación y posterior almacenamiento en la memoria. La publicidad y el mercadeo hacen uso de una prueba de evaluación; top of mind, que muestra la jerarquía de recuerdo en la memoria de los individuos ante la mención de una categoría de servicio de un producto.

Actividad física, imagen corporal y condiciones de vida. Un abordaje teórico desde los determinantes y la determinación social de la salud

El objetivo de este trabajo fue analizar la construcción social del conocimiento en Actividad física desde dos planteamientos teóricos de la salud centrando el análisis en la relación con la imagen corporal y las condiciones de vida. Se trata de un estudio teórico desde el análisis de contenido de corte narrativo de 98 artículos desarrollado en cinco etapas a través de: rastreo de documentos en bases de datos en el periodo 2000-2014, revisión de artículos, y análisis y hallazgos de significados, sentidos o contenidos. Como hallazgo importante se puede mencionar que en la literatura científica relacionada con la triada Actividad física-imagen corporal-condiciones de vida predomina la construcción del conocimiento a partir de modelos hegemónicos y dominantes que priorizan la intensidad, la frecuencia y el tiempo dedicado a la AF, la estandarización en la comparación de la apariencia física y la medición de elementos materiales en el modo de vivir de las personas, principalmente desde el abordaje de los determinantes sociales de la salud. Se concluye que es necesario revisar las poblaciones que incluyendo en los estudios al estar concentrados el conocimiento en solo unos grupos; así como se hace explícita la necesidad de revisar cuales son los aportes de la Educación Física y otras disciplinas (ciencias sociales) para una mayor comprensión teórica y práctica de la AF.