VictorJuiz/thesis huggingface dataset:
MEMS-based Mechanical Characterization of Micrometer-sized Biomaterials

The mechanical properties of biomaterials play important roles in performing their specialized functions: synthesizing, storing, and transporting biomolecules; maintaining internal structures; and responding to external environments. Besides biological cells, there are also many other biomaterials that are highly deformable and have a diameter between 1μm and 100μm, comparable to that of most biological cells. For example, many polymeric microcapsules for drug delivery use are spherical particles of micrometers size. In order to mechanically characterize individual micrometer-sized biomaterials, the capability of capturing high-resolution and low-magnitude force feedback is required. This research focuses on the development of micro devices and experimental techniques for quantifying the mechanical properties of alginate-chitosan microcapsules. The micro devices include microelectromechanical systems (MEMS) capacitive force sensors and force-feedback microgrippers, capable of measuring sub-μN forces. Employing the MEMS devices, systems were constructed to perform the micro-scale compression testing of microcapsules. The force sensors are capable of resolving forces up to 110μN with a resolution of 33.2nN along two independent axes. The force sensors were applied to characterizing the mechanical properties of hydrogel microparticles without assembling additional end-effectors. The microcapsules were immobilized by a PDMS holding device and compressed between the sensor probe and holding device. Young's modulus values of individual microcapsules with 1%, 2%, and 3% chitosan coating were determined through the micro-scale compression testing in both distilled deionized (DDI) water and pH 7.4 phosphate buffered saline (PBS). The Young's modulus values were also correlated to protein release rates. Instead of compressing the microcapsule against the wall of the holding device, a force-feedback MEMS microgripper with the capability of directly compressing the microcapsule between two gripping arms has been used for characterizing both the elastic and viscoelastic properties of the microcapsules during micromanipulation. The single-chip microgripper integrates an electrothermal microactuator and two capacitive force sensors, one for contact detection (force resolution: 38.5nN) and the other for gripping force measurements (force resolution: 19.9nN). Through nanoNewton force measurements, closed-loop force control, and visual tracking, the system quantified the Young's modulus values and viscoelastic parameters of alginate microcapsules, demonstrating an easy-to-operate, accurate compression testing technique for characterizing soft, micrometer-sized biomaterials.

Keywords: MEMS force sensor
Microgripper
Micro-scale compression test
Drug delivery microcapsule
Young's modulus
Viscoelastic parameters
Advisor: Sun, Yu
Enhancing the Intracellular Delivery of Engineered Nanoparticles for Cancer Imaging and Therapeutics

Recent advances in the field of bionanotechnology have enabled researchers to design a variety of tools to detect, image and monitor biological process in cells. Despite this progress, the limited understanding of nanomaterial-cellular interactions has hindered the widespread use of these nanomaterials in biological systems. In this thesis, we examined the potential effects of metallic nanoparticle geometry on important cellular processes such as membrane trafficking, intracellular transport and subcellular signalling. We found that the size of nanoparticles plays an important role on their ability to interact with the cell surface receptors thus dictating their subsequent ability to activate intracellular signalling cascades. Interestingly, trafficking of these nanoparticles was dependent on their size due to biochemical and thermodynamical constraints. These findings suggest that nanomaterials actively interact with biological systems, thus, directly modulating vital cellular processes. In addition, by utilizing various physical and chemical properties of nanomaterials, we developed a novel class of hybrid nanoscaled carrier systems capable of delivering semiconductor quantum dots (QDs) into live cells without inducing membrane damage. Using biodegradable polymeric nanoparticles, bioconjugated QDs were encapsulated and delivered into trafficking vesicles of live cells. The environmentally sensitive surface charge of the polymeric nanoparticles exhibited positive zeta potential inside acidic endo-lysosomes, thus enabling their escape from the vesicular sequestration into the cytosol. Hydrolytic-induced degradation then releases the bioconjugate QDs for active labelling of subcellular structures for real-time studies. Unlike previously described intracellular QD delivery methods, the proposed system offers an efficient way to non-invasively deliver bioconjugated QDs without inducing cell damage, enabling researchers to accurately monitor cellular processes in real-time. The understanding of both physical and chemical properties of nanomaterials is crucial to the design of biocompatible nanosystems to study fundamental processes in biological systems. Here, we demonstrated that both the size and surface chemistry of nanoparticles can be modified to obtain desired biological responses. Future experimental efforts to study other physical and chemical properties could allow the development of more sophisticated and effective platforms for biological applications.

Keywords: 0794
0541
0379
0307
Advisor: Chan, Warren C. W.
Rutka, James T.
Judgments and Perceptions Of Blame: The Impact Of Benevolent Sexism And Rape Type On Attributions Of Responsibility In Sexual Assault

Observers’ attributions of culpability in sexual assault cases have been studied in the context of psycholegal variables to explain how they come to their conclusions. Most research has revealed that there are differences between stranger and acquaintance rape, where victims of the latter are more likely to be blamed (Allgeier & Allgeier, 1995; Bridges & McGrail, 1989; Littleton, 2001; Mynatt & Allgeier, 1990; Scronce & Corcoran, 1995; Schuller & Klippenstine, 2004; Tetreault & Barnett, 1987). However, the work has been largely limited to examining rape myth acceptance and gender differences of observers. The present study addressed these limitations. The goals of this study were: (1) to examine judgments of perpetrator responsibility, (2) to examine the relationship between benevolent sexism and victim blame in an acquaintance rape, (3) to examine as to how benevolent sexism influences assailant blame, and (4) to examine differences between males and females on a sexism measure in relation to attribution of blame. This research utilized a community sample. Several groups of measures were utilized, including sexual assault vignettes with a questionnaire that assessed perceptions of sexual assault. Also administered were measures that assessed for social desirability, benevolent sexism, the preference for unequal relationships, and demographics. Two studies were conducted. The first one was a pilot study, which gathered qualitative and descriptive data for a measure designed specifically for this research. Participants (n= 20) reported that the measure was simple to read, understand and complete. The second study (200 participants) focused on the goals outlined and obtained reliability and principal components analysis information. Findings from study 2 revealed no significant differences between men and women in attribution of responsibility. However, assailant-victim relationship, and the presence of alcohol were statistically significant for blame. Although men scored higher on benevolent sexism in general, women obtained high scores when assailant-victim relationship and the presence of alcohol in the scenarios were taken into account. Similar to previous research (Abrams, Viki, Masser, & Bohner, 2003; Viki & Abrams, 2002; Viki, Masser, & Abrams, 2004), benevolent sexism was found to act as a moderator. Implications from results from this study were also discussed.

Keywords: sexual assault
jury decision-making
Advisor: Stermac, Lana
Social Construction of Health Inequities: A Critical Ethnography on Day Labourers in Japan

Although evidence of health inequities abound, why people in lower socio-economic classes have poorer health has not been sufficiently explored. The purpose of this study is to examine day labourers’ pathways to health inequities in a segregated, urban district in Japan. Critical ethnography was employed to investigate day labourers’ social environments and cultural behaviours in order to reveal the ways that social inequalities embedded in mainstream society and the day labourers’ sub-culture produce and sustain day labourers’ disadvantages, leading them into poorer health than the average population. Data were collected through observations of day labourer’s daily activities, events within the district and their interactions with social workers at a hospital. In addition, interviews were conducted with 16 day labourers and 11 professionals and advocates. The study found several components in the pathways to health inequities of day labourers. First, certain people in Japan are ostracized from the social, economic and political mainstream due to an inability to enact traditional Japanese labour practices. Commonly such exclusions make men become day labourers to survive. In a day labourer district, they are exposed to further social inequalities embedded in the work system and their living circumstance. Living and working as a member of the day labour community, they develop collective strategies in order to survive and preserve their social identities as day labourers. However, such strategies do not provide people with opportunities to lead healthy lives. The study also identified several social determinants of health for day labourers, including: 1) employment, 2) working conditions, 3) temporary living, 4) housing quality, 5) social networks and support, 6) marginalized neighbourhood, 7) access to health care, and 8) gender. The findings contribute to a better understanding of social construction of health inequities, which provides insight on the impact of precarious work in the Japanese society at large. Implications of these findings for public health policy and practice are also discussed.

Keywords: health inequities
social determinants of health
critical ethnography
precarious employment
Japan
social inequalities
Advisor: Gastaldo, Denise
Development Of High Throughput Epigenomic Profiling Technologies And Their Application To Twin Based DNA Methylation Studies

Epigenetic studies hold the promise of addressing some of the fundamental questions of human biology including development, cell differentiation, and the aetiological mechanisms of complex disease. Over the last years, several new large scale high throughput technologies have been developed to allow genome wide profiling of epigenetic signals such as DNA methylation and histone modifications. Two of such technologies were developed in our laboratory enabling a genome wide microarray based profiling of DNA methylation signatures and a high throughput method for the site specific interrogation of the density of methylated cytosine. Using these techniques, we identified a DNA methylation difference in the 3’UTR of the DLX1 gene with potentially functional implications to discordance in risk taking behavior in a single pair of MZ twins. We modeled a power analysis on the effect size of the detected difference and determined that approximately 6~25 discordant twin pairs will be adequate to yield 80% power across the entire 12 K CpG island microarray platform using our epigenomic microarray profiling technique. We performed a DNA methylome analysis of MZ twins in white blood cells (WBC), buccal epithelial cells, and gut (rectum) biopsies (N=57 pairs in total) using 12K CpG island microarrays providing the basis for the first annotation of epigenetic metastability of ~6,000 unique genomic regions in MZ twins. We performed a classical twin study on DNA methylation differences in WBC and buccal epithelial cells from 39 pairs of MZ twins to 40 pairs of DZ twins. DZ co-twins exhibited significantly higher epigenetic difference compared to the MZ co-twins in buccal cells (p=1.2x10-294). While such higher epigenetic discordance in DZ twins can result from DNA sequence differences, our in silico SNP analyses and comparison of methylomes in inbred vs. outbred mice favour the hypothesis that this is due to epigenomic differences in the zygotes. This study suggests that molecular mechanisms of heritability may not be limited to DNA sequence differences.

Keywords: epigenetic
heritability
twin
technique
Advisor: Petronis, Arturas
Effect of De-icer and Anti-icer Chemicals on the Durability, Microstructure, and Properties of Cement-based Materials

A comprehensive study was conducted on the effects of de-icer and anti-icer chemicals on cement-based materials. Portland cement mortars and concretes were exposed to over 16 chloride-based and non-chloride-based generic and commercial products and changes in cement-based material properties were measured. Deleterious chemical actions of several types of these products on cement-based materials were observed, departing from the well-known position that attributes the concrete damage from such salts mainly to physical actions under freezing and thawing exposure. Independent of freezing and thawing exposure, mortars and concretes exposed to concentrated calcium chloride and magnesium chloride solutions were found to undergo severe deterioration whereas those exposed to sodium chloride did not. The mechanisms of deterioration are complex with factors such as concentration, temperature, and availability of calcium hydroxide playing important roles. It was found that the formation of calcium oxychloride of the form 3Ca(OH)2.CaCl2.12H2O, and the 3- and 5-form magnesium oxychloride, 3Mg(OH)2.MgCl2.8H2O and 5Mg(OH)2.MgCl2.8H2O, were the main causes for the severe deterioration, and to a lesser extent brucite, gypsum, and magnesium silicate hydrate (M-S-H). The instability of these oxychloride compounds when subjected to conditions normally encountered in sample preparation is suggested as the reason why field investigations have failed to relate distressed concrete to chemical attack by such de-icer and anti-icer chemicals. Concentrated solutions of calcium magnesium acetate were also found to be harmful to cement-based materials by dissolution of calcium hydroxide and formation of calcium acetate hydrate, whereas low concentrated solutions tended to cause slow deterioration by magnesium attack forming brucite, gypsum, and M-S-H. Potassium acetate chemicals did not cause significant deterioration in mortars when these products were diluted (25% by mass), but undiluted products (50% by mass) caused considerable distress in concrete specimens. The combined effect of chemical attack impairing concrete mechanical properties and subsequent salt scaling damage was proposed as the most likely mechanisms of field deterioration.

Keywords: cement
concrete
durability
chemical attack
oxychlorides
de-icers
anti-icers
calcium chloride
magnesium chloride
sodium chloride
potassium acetate
calcium magnesium acetate
salt scaling
freezing and thawing
Advisor: Hooton, Robert Douglas
Causes and Consequences of Genomic Instability in Prostatic Carcinogenesis

The evolution of prostate cancer from normal epithelium via the preneoplastic lesion of high-grade prostatic intraepithelial neoplasia to invasive carcinoma is characterised by a number of particular genomic abnormalities that are predominantly generated in the preneoplastic phase. Whilst there are numerous candidates for the cause of these alterations, telomere dysfunction is thought to be a major contributor. Telomeres are the terminal ends of human chromosomes, and when dysfunctional can lead to break-fusion-bridge cycles and multi-polar mitoses that generate numerical and structural chromosomal instability. The results presented reinforce the association of telomere dysfunction with the generation of certain markers of genomic instability such as abnormalities of the arms of chromosome 8. Furthermore, this work clarifies that the TMPRSSS2-ERG aberrations are not telomere related phenomena and are associated with a genomic deletion in a proportion of cases. Similarly, the PTEN microdeletions did not appear to have an association with telomere attrition. A previously unrecognised association between the telomere length in various types of prostatic epithelia and adjacent stroma is defined, suggesting evidence of a micro-environmental field effect in the generation of prostatic neoplasia. Finally, when examined retrospectively, it appears that telomere attrition, both in the HPIN epithelium and the stroma has independent prognostic value in the diagnosis of prostate cancer after a previous diagnosis of HPIN. Taken together, the research presented suggests important avenues for further research to determine the nature of barriers to the evolution of prostatic carcinogenesis such as oncogene- and telomere-induced senescence that may be exploited for therapeutic gain. These understandings may also help tailor management for prostate cancer such as risk stratification for men with HPIN and the use of targeted agents such as AKT inhibitors and telomerase inhibitors. In more advanced disease, translational application of this work has enabled a clinical trial of cytarabine in the treatment of metastatic hormone refractory prostate cancer.

Keywords: Prostate Cancer
Genomic Instability
FISH
Telomere
Advisor: Squire, Jeremy A.
Free-Space Metamaterial Superlenses Using Transmission-line Techniques

Free-space imaging with a resolution beyond that dictated by the classical diffraction limit may be achieved with a `Veselago-Pendry' superlens made from a metamaterial possessing a number of specific properties, including a negative refractive index (NRI). Although a planar NRI transmission-line (NRI-TL) metamaterial based on the periodic lumped loading of a host TL network has successfully verified the phenomenon of superlensing in a 2D microstrip environment, a true Veselago-Pendry superlens capable of interacting with and manipulating fields in free space remained elusive, largely due to the difficulty of meeting its stringent design constraints and also to the problem of realizing a full 3D isotropic, polarization-independent structure. This work presents the first experimental verification of free-space Veselago-Pendry superlensing using a new class of volumetric metamaterials based on 2D NRI-TL layers that, although polarization-specific, may be easily constructed using available lithographic techniques to interact with free-space sources. An equivalent-circuit model is developed to enable accurate design of the metamaterial's dispersion and transmission characteristics, including those associated with Veselago-Pendry superlensing, and is validated using full-wave simulations. First, a volumetric NRI-TL metamaterial employing fully printed loading elements is fabricated to verify the salient properties of a free-space metamaterial-slab lens. This lens demonstrates diffraction-limited focusing at X-band and, thus, affirms theoretical results that suggest that electrically thick and lossy metamaterials are unable to perform superlensing. Thereafter, a volumetric NRI-TL metamaterial based on discrete lumped elements is designed to meet the conditions of the Veselago-Pendry superlens at 2.40GHz, and experimentally demonstrates a resolution ability over three times better than that afforded by the classical diffraction limit. A microwave superlens designed in this fashion can be particularly useful for illumination and discrimination of closely spaced buried objects over practical distances by way of back-scattering, for example, in tumour or landmine detection, or for targeted irradiation over electrically small regions in tomography or hyperthermia applications. Possible optical implementations of the volumetric topology are also suggested, and finally, a fully isotropic, polarization-independent 3D metamaterial structure related to the volumetric NRI-TL structure is proposed.

Keywords: Electromagnetic
Metamaterial
Microwave
Lens
Advisor: Eleftheriades, George V.
Abortable and Query-abortable Types and Their Efficient Implementation

We introduce abortable and query-abortable object types intended for implementation in asynchronous shared-memory systems with low contention. Implementations of such types behave like ordinary objects when accessed sequentially, but may abort operations when accessed concurrently. An aborted operation may or may not take effect, i.e., cause a state transition, and it returns no indication of which possibility occurred. Since this uncertainty can be problematic, a query-abortable type supports a QUERY operation that each process can use to determine its last non-QUERY operation on the object that caused a state transition, and the response associated with this state transition. Our research is closely related to obstruction-free implementations (introduced by Herlihy, Luchangco and Moir) and responsive obstruction-free implementations (introduced by Attiya, Guerraoui and Kouznetsov). Like abortable and query-abortable types, these implementations may exhibit degraded behaviour in the face of contention. We show that abortable registers--registers strictly weaker than safe registers--can be used to obtain obstruction-free and responsive obstruction-free implementations for any type. We present universal constructions for abortable and query-abortable types that are novel and efficient in the number of registers used. Specifically, they are based on a simple timestamping mechanism for detecting concurrent executions, and, in systems with n processes, use only n abortable registers or only O(n^2) single-reader, single-writer abortable registers. The timestamping mechanism we introduce is based on the inc&read counter type and appears to be interesting in its own right. As a generalization, we study the k-inc&read counter types, for k>0. We also identify a potential problem with correctness properties based on step contention: with such properties, the composition of correct object implementations may result in an implementation that is not correct. In other words, implementations defined in terms of step contention are not always composable. To avoid this problem, we introduce a property based on interval contention, namely non-triviality, to define the correct behaviour of abortable and query-abortable object implementations.

Keywords: shared memory
memory contention
universal constructions
abortable types
query-abortable types
obstruction-freedom
inc&read counter
non-triviality
composability
Advisor: Toueg, Sam