4 resultados para control over life
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Resumo:
The semiconductor nanowire has been widely studied over the past decade and identified as a promising nanotechnology building block with application in photonics and electronics. The flexible bottom-up approach to nanowire growth allows for straightforward fabrication of complex 1D nanostructures with interesting optical, electrical, and mechanical properties. III-V nanowires in particular are useful because of their direct bandgap, high carrier mobility, and ability to form heterojunctions and have been used to make devices such as light-emitting diodes, lasers, and field-effect transistors. However, crystal defects are widely reported for III-V nanowires when grown in the common out-of-plane <111>B direction. Furthermore, commercialization of nanowires has been limited by the difficulty of assembling nanowires with predetermined position and alignment on a wafer-scale. In this thesis, planar III-V nanowires are introduced as a low-defect and integratable nanotechnology building block grown with metalorganic chemical vapor deposition. Planar GaAs nanowires grown with gold seed particles self-align along the <110> direction on the (001) GaAs substrate. Transmission electron microscopy reveals that planar GaAs nanowires are nearly free of crystal defects and grow laterally and epitaxially on the substrate surface. The nanowire morphology is shown to be primarily controlled through growth temperature and an ideal growth window of 470 +\- 10 °C is identified for planar GaAs nanowires. Extension of the planar growth mode to other materials is demonstrated through growth of planar InAs nanowires. Using a sacrificial layer, the transfer of planar GaAs nanowires onto silicon substrates with control over the alignment and position is presented. A metal-semiconductor field-effect transistor fabricated with a planar GaAs nanowire shows bulk-like low-field electron transport characteristics with high mobility. The aligned planar geometry and excellent material quality of planar III-V nanowires may lead to highly integrated III-V nanophotonics and nanoelectronics.
Resumo:
During the early Stuart period, England’s return to male monarchal rule resulted in the emergence of a political analogy that understood the authority of the monarch to be rooted in the “natural” authority of the father; consequently, the mother’s authoritative role within the family was repressed. As the literature of the period recognized, however, there would be no family unit for the father to lead without the words and bodies of women to make narratives of dynasty and legitimacy possible. Early modern discourse reveals that the reproductive roles of men and women, and the social hierarchies that grow out of them, are as much a matter of human design as of divine or natural law. Moreover, despite the attempts of James I and Charles I to strengthen royal patriarchal authority, the role of the monarch was repeatedly challenged on stage and in print even prior to the British Civil Wars and the 1649 beheading of Charles I. Texts produced at moments of political crisis reveal how women could uphold the legitimacy of familial and political hierarchies, but they also disclose patriarchy’s limits by representing “natural” male authority as depending in part on women’s discursive control over their bodies. Due to the epistemological instability of the female reproductive body, women play a privileged interpretive role in constructing patriarchal identities. The dearth of definitive knowledge about the female body during this period, and the consequent inability to fix or stabilize somatic meaning, led to the proliferation of differing, and frequently contradictory, depictions of women’s bodies. The female body became a site of contested meaning in early modern discourse, with men and women struggling for dominance, and competitors so diverse as to include kings, midwives, scholars of anatomy, and female religious sectarians. Essentially, this competition came down to a question of where to locate somatic meaning: In the opaque, uncertain bodies of women? In women’s equally uncertain and unreliable words? In the often contradictory claims of various male-authored medical treatises? In the whispered conversations that took place between women behind the closed doors of birthing rooms? My dissertation traces this representational instability through plays by William Shakespeare, John Ford, Thomas Middleton, and William Rowley, as well as in monstrous birth pamphlets, medical treatises, legal documents, histories, satires, and ballads. In these texts, the stories women tell about and through their bodies challenge and often supersede male epistemological control. These stories, which I term female bodily narratives, allow women to participate in defining patriarchal authority at the levels of both the family and the state. After laying out these controversies and instabilities surrounding early modern women’s bodies in my first chapter, my remaining chapters analyze the impact of women’s words on four distinct but overlapping reproductive issues: virginity, pregnancy, birthing room rituals, and paternity. In chapters 2 and 3, I reveal how women construct the inner, unseen “truths” of their reproductive bodies through speech and performance, and in doing so challenge the traditional forms of male authority that depend on these very constructions for coherence. Chapter 2 analyzes virginity in Thomas Middleton and William Rowley’s play The Changeling (1622) and in texts documenting the 1613 Essex divorce, during which Frances Howard, like Beatrice-Joanna in the play, was required to undergo a virginity test. These texts demonstrate that a woman’s ability to feign virginity could allow her to undermine patriarchal authority within the family and the state, even as they reveal how men relied on women to represent their reproductive bodies in socially stabilizing ways. During the British Civil Wars and Interregnum (1642-1660), Parliamentary writers used Howard as an example of how the unruly words and bodies of women could disrupt and transform state politics by influencing court faction; in doing so, they also revealed how female bodily narratives could help recast political historiography. In chapter 3, I investigate depictions of pregnancy in John Ford’s tragedy, ‘Tis Pity She’s a Whore (1633) and in early modern medical treatises from 1604 to 1651. Although medical texts claim to convey definitive knowledge about the female reproductive body, in actuality male knowledge frequently hinged on the ways women chose to interpret the unstable physical indicators of pregnancy. In Ford’s play, Annabella and Putana take advantage of male ignorance in order to conceal Annabella’s incestuous, illegitimate pregnancy from her father and husband, thus raising fears about women’s ability to misrepresent their bodies. Since medical treatises often frame the conception of healthy, legitimate offspring as a matter of national importance, women’s ability to conceal or even terminate their pregnancies could weaken both the patriarchal family and the patriarchal state that the family helped found. Chapters 4 and 5 broaden the socio-political ramifications of women’s words and bodies by demonstrating how female bodily narratives are required to establish paternity and legitimacy, and thus help shape patriarchal authority at multiple social levels. In chapter 4, I study representations of birthing room gossip in Thomas Middleton’s play, A Chaste Maid in Cheapside (1613), and in three Mistris Parliament pamphlets (1648) that satirize parliamentary power. Across these texts, women’s birthing room “gossip” comments on and critiques such issues as men’s behavior towards their wives and children, the proper use of household funds, the finer points of religious ritual, and even the limits of the authority of the monarch. The collective speech of the female-dominated birthing room thus proves central not only to attributing paternity to particular men, but also to the consequent definition and establishment of the political, socio-economic, and domestic roles of patriarchy. Chapter 5 examines anxieties about paternity in William Shakespeare’s The Winter’s Tale (1611) and in early modern monstrous birth pamphlets from 1600 to 1647, in which children born with congenital deformities are explained as God’s punishment for the sexual, religious, and/or political transgressions of their parents or communities. Both the play and the pamphlets explore the formative/deformative power of women’s words and bodies over their offspring, a power that could obscure a father’s connection to his children. However, although the pamphlets attempt to contain and discipline women’s unruly words and bodies with the force of male authority, the play reveals the dangers of male tyranny and the crucial role of maternal authority in reproducing and authenticating dynastic continuity and royal legitimacy. My emphasis on the socio-political impact of women’s self-representation distinguishes my work from that of scholars such as Mary Fissell and Julie Crawford, who claim that early modern beliefs about the female reproductive body influenced textual depictions of major religious and political events, but give little sustained attention to the role female speech plays in these representations. In contrast, my dissertation reveals that in such texts, patriarchal society relies precisely on the words women speak about their own and other women’s bodies. Ultimately, I argue that female bodily narratives were crucial in shaping early modern culture, and they are equally crucial to our critical understanding of sexual and state politics in the literature of the period.
Resumo:
Membrane proteins, which reside in the membranes of cells, play a critical role in many important biological processes including cellular signaling, immune response, and material and energy transduction. Because of their key role in maintaining the environment within cells and facilitating intercellular interactions, understanding the function of these proteins is of tremendous medical and biochemical significance. Indeed, the malfunction of membrane proteins has been linked to numerous diseases including diabetes, cirrhosis of the liver, cystic fibrosis, cancer, Alzheimer's disease, hypertension, epilepsy, cataracts, tubulopathy, leukodystrophy, Leigh syndrome, anemia, sensorineural deafness, and hypertrophic cardiomyopathy.1-3 However, the structure of many of these proteins and the changes in their structure that lead to disease-related malfunctions are not well understood. Additionally, at least 60% of the pharmaceuticals currently available are thought to target membrane proteins, despite the fact that their exact mode of operation is not known.4-6 Developing a detailed understanding of the function of a protein is achieved by coupling biochemical experiments with knowledge of the structure of the protein. Currently the most common method for obtaining three-dimensional structure information is X-ray crystallography. However, no a priori methods are currently available to predict crystallization conditions for a given protein.7-14 This limitation is currently overcome by screening a large number of possible combinations of precipitants, buffer, salt, and pH conditions to identify conditions that are conducive to crystal nucleation and growth.7,9,11,15-24 Unfortunately, these screening efforts are often limited by difficulties associated with quantity and purity of available protein samples. While the two most significant bottlenecks for protein structure determination in general are the (i) obtaining sufficient quantities of high quality protein samples and (ii) growing high quality protein crystals that are suitable for X-ray structure determination,7,20,21,23,25-47 membrane proteins present additional challenges. For crystallization it is necessary to extract the membrane proteins from the cellular membrane. However, this process often leads to denaturation. In fact, membrane proteins have proven to be so difficult to crystallize that of the more than 66,000 structures deposited in the Protein Data Bank,48 less than 1% are for membrane proteins, with even fewer present at high resolution (< 2Å)4,6,49 and only a handful are human membrane proteins.49 A variety of strategies including detergent solubilization50-53 and the use of artificial membrane-like environments have been developed to circumvent this challenge.43,53-55 In recent years, the use of a lipidic mesophase as a medium for crystallizing membrane proteins has been demonstrated to increase success for a wide range of membrane proteins, including human receptor proteins.54,56-62 This in meso method for membrane protein crystallization, however, is still by no means routine due to challenges related to sample preparation at sub-microliter volumes and to crystal harvesting and X-ray data collection. This dissertation presents various aspects of the development of a microfluidic platform to enable high throughput in meso membrane protein crystallization at a level beyond the capabilities of current technologies. Microfluidic platforms for protein crystallization and other lab-on-a-chip applications have been well demonstrated.9,63-66 These integrated chips provide fine control over transport phenomena and the ability to perform high throughput analyses via highly integrated fluid networks. However, the development of microfluidic platforms for in meso protein crystallization required the development of strategies to cope with extremely viscous and non-Newtonian fluids. A theoretical treatment of highly viscous fluids in microfluidic devices is presented in Chapter 3, followed by the application of these strategies for the development of a microfluidic mixer capable of preparing a mesophase sample for in meso crystallization at a scale of less than 20 nL in Chapter 4. This approach was validated with the successful on chip in meso crystallization of the membrane protein bacteriorhodopsin. In summary, this is the first report of a microfluidic platform capable of performing in meso crystallization on-chip, representing a 1000x reduction in the scale at which mesophase trials can be prepared. Once protein crystals have formed, they are typically harvested from the droplet they were grown in and mounted for crystallographic analysis. Despite the high throughput automation present in nearly all other aspects of protein structure determination, the harvesting and mounting of crystals is still largely a manual process. Furthermore, during mounting the fragile protein crystals can potentially be damaged, both from physical and environmental shock. To circumvent these challenges an X-ray transparent microfluidic device architecture was developed to couple the benefits of scale, integration, and precise fluid control with the ability to perform in situ X-ray analysis (Chapter 5). This approach was validated successfully by crystallization and subsequent on-chip analysis of the soluble proteins lysozyme, thaumatin, and ribonuclease A and will be extended to microfluidic platforms for in meso membrane protein crystallization. The ability to perform in situ X-ray analysis was shown to provide extremely high quality diffraction data, in part as a result of not being affected by damage due to physical handling of the crystals. As part of the work described in this thesis, a variety of data collection strategies for in situ data analysis were also tested, including merging of small slices of data from a large number of crystals grown on a single chip, to allow for diffraction analysis at biologically relevant temperatures. While such strategies have been applied previously,57,59,61,67 they are potentially challenging when applied via traditional methods due to the need to grow and then mount a large number of crystals with minimal crystal-to-crystal variability. The integrated nature of microfluidic platforms easily enables the generation of a large number of reproducible crystallization trials. This, coupled with in situ analysis capabilities has the potential of being able to acquire high resolution structural data of proteins at biologically relevant conditions for which only small crystals, or crystals which are adversely affected by standard cryocooling techniques, could be obtained (Chapters 5 and 6). While the main focus of protein crystallography is to obtain three-dimensional protein structures, the results of typical experiments provide only a static picture of the protein. The use of polychromatic or Laue X-ray diffraction methods enables the collection of time resolved structural information. These experiments are very sensitive to crystal quality, however, and often suffer from severe radiation damage due to the intense polychromatic X-ray beams. Here, as before, the ability to perform in situ X-ray analysis on many small protein crystals within a microfluidic crystallization platform has the potential to overcome these challenges. An automated method for collecting a "single-shot" of data from a large number of crystals was developed in collaboration with the BioCARS team at the Advanced Photon Source at Argonne National Laboratory (Chapter 6). The work described in this thesis shows that, even more so than for traditional structure determination efforts, the ability to grow and analyze a large number of high quality crystals is critical to enable time resolved structural studies of novel proteins. In addition to enabling X-ray crystallography experiments, the development of X-ray transparent microfluidic platforms also has tremendous potential to answer other scientific questions, such as unraveling the mechanism of in meso crystallization. For instance, the lipidic mesophases utilized during in meso membrane protein crystallization can be characterized by small angle X-ray diffraction analysis. Coupling in situ analysis with microfluidic platforms capable of preparing these difficult mesophase samples at very small volumes has tremendous potential to enable the high throughput analysis of these systems on a scale that is not reasonably achievable using conventional sample preparation strategies (Chapter 7). In collaboration with the LS-CAT team at the Advanced Photon Source, an experimental station for small angle X-ray analysis coupled with the high quality visualization capabilities needed to target specific microfluidic samples on a highly integrated chip is under development. Characterizing the phase behavior of these mesophase systems and the effects of various additives present in crystallization trials is key for developing an understanding of how in meso crystallization occurs. A long term goal of these studies is to enable the rational design of in meso crystallization experiments so as to avoid or limit the need for high throughput screening efforts. In summary, this thesis describes the development of microfluidic platforms for protein crystallization with in situ analysis capabilities. Coupling the ability to perform in situ analysis with the small scale, fine control, and the high throughput nature of microfluidic platforms has tremendous potential to enable a new generation of crystallographic studies and facilitate the structure determination of important biological targets. The development of platforms for in meso membrane protein crystallization is particularly significant because they enable the preparation of highly viscous mixtures at a previously unachievable scale. Work in these areas is ongoing and has tremendous potential to improve not only current the methods of protein crystallization and crystallography, but also to enhance our knowledge of the structure and function of proteins which could have a significant scientific and medical impact on society as a whole. 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Resumo:
Ultrasonic tomography is a powerful tool for identifying defects within an object or structure. This method can be applied on structures where x-ray tomography is impractical due to size, low contrast, or safety concerns. By taking many ultrasonic pulse velocity (UPV) readings through the object, an image of the internal velocity variations can be constructed. Air-coupled UPV can allow for more automated and rapid collection of data for tomography of concrete. This research aims to integrate recent developments in air-coupled ultrasonic measurements with advanced tomography technology and apply them to concrete structures. First, non-contact and semi-contact sensor systems are developed for making rapid and accurate UPV measurements through PVC and concrete test samples. A customized tomographic reconstruction program is developed to provide full control over the imaging process including full and reduced spectrum tomographs with percent error and ray density calculations. Finite element models are also used to determine optimal measurement configurations and analysis procedures for efficient data collection and processing. Non-contact UPV is then implemented to image various inclusions within 6 inch (152 mm) PVC and concrete cylinders. Although there is some difficulty in identifying high velocity inclusions, reconstruction error values were in the range of 1.1-1.7% for PVC and 3.6% for concrete. Based upon the success of those tests, further data are collected using non-contact, semi-contact, and full contact measurements to image 12 inch (305 mm) square concrete cross-sections with 1 inch (25 mm) reinforcing bars and 2 inch (51 mm) square embedded damage regions. Due to higher noise levels in collected signals, tomographs of these larger specimens show reconstruction error values in the range of 10-18%. Finally, issues related to the application of these techniques to full-scale concrete structures are discussed.