Machine Learning Based Classification of Textual Stimuli to Promote Ideation in Bioinspired Design

Bioinspired design uses biological systems to inspire engineering designs. One of bioinspired design’s challenges is identifying relevant information sources in biology for an engineering design task. Currently information can be retrieved by searching biology texts or journals using biology-focused keywords that map to engineering functions. However, this search technique can overwhelm designers with unusable results. This work explores the use of text classification tools to identify relevant biology passages for design. Further, this research examines the effects of using biology passages as stimuli during idea generation. Four human-subjects studies are examined in this work. Two surveys are performed in which participants evaluate sentences from a biology corpus and indicate whether each sentence prompts an idea for solving a specific design problem. The surveys are used to develop and evaluate text classification tools. Two idea generation studies are performed in which participants generate and record solutions for designing a corn shucker using either different sets of biology passages as design stimuli, or no stimuli. Based 286 sentences from the surveys, a k Nearest Neighbor classifier is developed that is able to identify helpful sentences relating to the function “separate” with a precision of 0.62 and recall of 0.48. This classifier could potentially double the number of helpful results found using a keyword search. The developed classifier is specific to the function “separate” and performs poorly when used for another function. Classifiers developed using all sentences and participant responses from the surveys are not able to reliably identify helpful sentences. From the idea generation studies, we determine that using any biology passages as design stimuli increases the quantity and variety of participant solutions. Solution quantity and variety are also significantly increased when biology passages are presented one at a time instead of all at once. Quality and variety are not significantly affected by the presence of design stimuli. Biological stimuli are also found to lead designers to types of solution that are not typically produced otherwise. This work develops a means for designers to find more useful information when searching biology and demonstrates several ways that biology passages can improve ideation

Biomedical Sensing and Imaging

This book mainly deals with recent advances in biomedical sensing and imaging. More recently, wearable/smart biosensors and devices, which facilitate diagnostics in a non-clinical setting, have become a hot topic. Combined with machine learning and artificial intelligence, they could revolutionize the biomedical diagnostic field. The aim of this book is to provide a research forum in biomedical sensing and imaging and extend the scientific frontier of this very important and significant biomedical endeavor

Pre-complexation of talin and vinculin without tension is required for efficient nascent adhesion maturation

Talin and vinculin are mechanosensitive proteins that are recruited early to integrin- based nascent adhesions (NAs). In two epithelial cell systems with well-delineated NA formation, we find these molecules concurrently recruited to the subclass of NAs maturing to focal adhesions. After the initial recruitment under minimal load, vinculin accumulates in maturing NAs at a ~ fivefold higher rate than in non-maturing NAs, and is accompanied by a faster traction force increase. We identify the R8 domain in talin, which exposes a vinculin-binding-site (VBS) in the absence of load, as required for NA maturation. Disruption of R8 domain function reduces load- free vinculin binding to talin, and reduces the rate of additional vinculin recruitment. Taken together, these data show that the concurrent recruitment of talin and vinculin prior to mechanical engagement with integrins is essential for the traction-mediated unfolding of talin, exposure of additional VBSs, further recruitment of vinculin, and ultimately, NA maturation

Formation of talin-vinculin pre-complexes dictates maturation of nascent adhesions by accelerated force transmission and vinculin recruitment

Talin, vinculin, and paxillin are mechanosensitive proteins that are recruited early to nascent integrin-based adhesions (NAs). Using machine learning, high-resolution traction force microscopy, single-particle-tracking and fluorescence fluctuation time-series analysis, we find that, only in the NAs that eventually mature to focal adhesions, all three molecules are recruited concurrently and in synchrony with force onset. Thereafter, vinculin assembles at ~5 fold higher rates than in non-maturing NAs. We identify a domain in talin, R8, which exposes a vinculin- binding-site (VBS) without requiring tension. Stabilizing this domain via mutation lowers tension- free vinculin binding in conjunction with talin, impairs maturation of NAs, and reduces the rate of additional vinculin recruitment after force onset. Taken together, our data show that talin forms a complex with vinculin, before association with integrins, which is essential for NA maturation by talin’s effective unfolding and exposure of additional VBSs that induce fast force growth and further vinculin binding

Cell Migration within 3D Microenvironments: an Integrative Perspective from the Membrane to the Nucleus

La migración celular es fundamental para la vida y el desarrollo. Desafortunadamente, la movilidad celular también está asociada con algunas de las principales causas de morbilidad y mortalidad, incluidos los trastornos inmunitarios, esqueléticos y cardiovasculares, así como la metástasis del cáncer. Las células dependen en su capacidad para percibir y responder a estímulos externos en muchos procesos fisiológicos y patológicos (p. ej., desarrollo embrionario, angiogénesis, reparación de tejidos y progresión tumoral). El objetivo global de esta tesis doctoral fue investigar la respuesta migratoria de células individuales a señales bioquímicas y biofísicas. En particular, el enfoque de esta investigación se centró en los mecanismos que permiten a las células percibir e internalizar señales bioquímicas y biofísicas y la influencia de estos estímulos en la respuesta migratoria de las células individuales.El primer estudio tuvo como objetivo establecer una metodología para facilitar la integración de estudios teóricos con datos experimentales. Al minimizar la intervención del usuario, el sistema propuesto basado en técnicas de optimización Bayesiana gestionó de manera eficiente la calibración de los modelos in silico, que de otro modo sería tediosa y propensa a errores. Posteriormente, se construyó un modelo in silico para investigar cómo los estímulos bioquímicos y biofísicos influyen en el movimiento celular en tres dimensiones. Este modelo computacional integró algunos de los principales actores que permiten a las células percibir y responder a señales externas, que pueden actuar a diferentes escalas e interactuar entre sí. Los resultados mostraron, por un lado, que las células cambian su comportamiento migratorio en función de la pendiente de los gradientes químicos y la concentración absoluta de factores químicos (por ejemplo, factores de crecimiento) a su alrededor. Por otro lado, estos resultados revelaron que la respuesta migratoria de las células a la rigidez y densidad de la matriz depende de su fenotipo. En general, la tesis destaca la dependencia de la migración celular tridimensional al fenotipo de las células (es decir, el tamaño de su núcleo, la deformabilidad del mismo) y las propiedades del microambiente circundante (por ejemplo, el perfil químico, la rigidez de la matriz, el confinamiento).Cell migration is fundamental for life and development. Unfortunately, cell motility is also associated with some of the leading causes of morbidity and mortality, including immune, skeletal, and cardiovascular disorders as well as cancer metastasis. Cells rely on their ability to perceive and respond to external stimuli in many physiological and pathological processes (e.g., embryonic development, angiogenesis, tissue repair, and tumor progression). The global objective of this doctoral thesis was to investigate the migratory response of individual cells to biochemical and biophysical cues. In particular, the focus of this research was on the mechanisms enabling cells to perceive and internalize biochemical and biophysical cues and the influence of these stimuli on the migratory response of individual cells. The first study aimed at establishing a methodology to facilitate the integration of theoretical studies with experimental data. By minimizing user intervention, the proposed framework based on Bayesian optimization techniques efficiently handled the otherwise tedious and error-prone calibration of in silico models. Afterward, an in silico model was built to investigate how biochemical and biophysical stimuli influence three-dimensional cell motion. This computational model integrated some of the main actors enabling cells to probe and respond to external cues, which may act at different scales and interact with each other. The results showed, on the one hand, that cells change their migratory behavior based on the slope of chemical gradients and the absolute concentration of chemical factors (e.g., growth factors) around them. On the other hand, these results revealed that cells’ migratory response to matrix stiffness and density depends on their phenotype. Overall, this thesis highlights the dependence of three-dimensional cell migration on both cells’ phenotype (i.e., nucleus size, deformability) and the properties of the surrounding microenvironment (e.g., chemical profile, matrix rigidity, confinement).<br /

Machine Learning Based Classification of Textual Stimuli to Promote Ideation in Bioinspired Design

Bioinspired design uses biological systems to inspire engineering designs. One of bioinspired design’s challenges is identifying relevant information sources in biology for an engineering design task. Currently information can be retrieved by searching biology texts or journals using biology-focused keywords that map to engineering functions. However, this search technique can overwhelm designers with unusable results. This work explores the use of text classification tools to identify relevant biology passages for design. Further, this research examines the effects of using biology passages as stimuli during idea generation. Four human-subjects studies are examined in this work. Two surveys are performed in which participants evaluate sentences from a biology corpus and indicate whether each sentence prompts an idea for solving a specific design problem. The surveys are used to develop and evaluate text classification tools. Two idea generation studies are performed in which participants generate and record solutions for designing a corn shucker using either different sets of biology passages as design stimuli, or no stimuli. Based 286 sentences from the surveys, a k Nearest Neighbor classifier is developed that is able to identify helpful sentences relating to the function “separate” with a precision of 0.62 and recall of 0.48. This classifier could potentially double the number of helpful results found using a keyword search. The developed classifier is specific to the function “separate” and performs poorly when used for another function. Classifiers developed using all sentences and participant responses from the surveys are not able to reliably identify helpful sentences. From the idea generation studies, we determine that using any biology passages as design stimuli increases the quantity and variety of participant solutions. Solution quantity and variety are also significantly increased when biology passages are presented one at a time instead of all at once. Quality and variety are not significantly affected by the presence of design stimuli. Biological stimuli are also found to lead designers to types of solution that are not typically produced otherwise. This work develops a means for designers to find more useful information when searching biology and demonstrates several ways that biology passages can improve ideation

Genetics of Golgi apparatus regulation in mammalian cells

Ph.DDOCTOR OF PHILOSOPH

Computer vision for sequential non-invasive microscopy imaging cytometry with applications in embryology

Many in vitro cytometric methods requires the sample to be destroyed in the process. Using image analysis of non-invasive microscopy techniques it is possible to monitor samples undisturbed in their natural environment, providing new insights into cell development, morphology and health. As the effect on the sample is minimized, imaging can be sustained for long un-interrupted periods of time, making it possible to study temporal events as well as individual cells over time. These methods are applicable in a number of fields, and are of particular importance in embryological studies, where no sample interference is acceptable. Using long term image capture and digital image cytometry of growing embryos it is possible to perform morphokinetic screening, automated analysis and annotation using proper software tools. By literature reference, one such framework is suggested and the required methods are developed and evaluated. Results are shown in tracking embryos, embryo cell segmentation, analysis of internal cell structures and profiling of cell growth and activity. Two related extensions of the framework into three dimensional embryo analysis and adherent cell monitoring are described