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      • Axonal guidance: Molecular mechanisms, biology of neurodevelopment, and a discussion of potential roles in nerve repair

        Rowe Urquhart, Erica G The Johns Hopkins University 2000 해외박사(DDOD)

        RANK : 2591

        The semaphorins are a diverse family of secreted and transmembrane proteins; most are expressed during development throughout the nervous system and in non-neuronal tissues. Many secreted semaphorins, including the well-characterized semaphorin, Sema3A, can function as repulsive axonal guidance cues. <italic> In vitro</italic> co-culture experiments have shown that Sema3A functions as a selective repulsive guidance cue, and <italic>in vivo</italic> genetic studies show that Sema3A plays an essential role in the projection and fasciculation of several populations of axons during development. We have demonstrated that the axonal glycoprotein neuropilin-1 is a receptor, or a component of a receptor, for Sema3A. Neuropilin-1 is expressed in all known Sema3A-responsive neurons. Neuropilin-1 is the founding member of a gene family, and is 44% identical to neuropilin-2, which has similar domain structure as neuropilin-1. Neuropilin-2 is also expressed in specific populations of neurons during development. Like neuropilin-1, neuropilin-2 is a high affinity binding protein for secreted semaphorins. However, it differs from neuropilin-1 in that it binds Sema3C and Sema3F, but not Sema3A, with high affinity. To better understand the function of neuropilin-2, we have undertaken an analysis of its expression and role during neurodevelopment. We generated antibodies directed against neuropilin-2 to describe its axonal distribution. In addition, we used these antibodies as function-blocking reagents to determine whether, like neuropilin-1, neuropilin-2 is a receptor for repulsive semaphorin guidance cues. Sema3F, which binds to neuropilin-2 <italic>in vitro</italic> with high affinity, also binds endogenous receptors located on superior cervical ganglia (SCG) neurons. Neuropilin-2, in addition to neuropilin-1, is expressed on SCG axons. We performed co-culture experiments and found that Sema3F, like Sema3A, repels this population of neurons. In contrast, E15 NGF-responsive dorsal root ganglion neurons, which express neuropilin-1 but not neuropilin-2, were not repelled by Sema3F. Antibody blocking studies have shown that neuropilin-2 is required to mediate Sema3F repulsive guidance in SCG neurons. Neuropilin-2 is, therefore, a functional semaphorin, receptor for secreted semaphorins. The characterization of neuropilins and their selective interactions with semaphorins will contribute to our understanding of the roles played by repulsive guidance cues in central and peripheral neuronal guidance events during development.

      • INVESTIGATIONS OF THE GROUND-STATE HYPERFINE ATOMIC STRUCTURE AND BETA DECAY MEASUREMENT PROSPECTS OF SODIUM-21 WITH IMPROVED LASER TRAPPING TECHNIQUES (SODIUM-21)

        ROWE, MARY ANDERSON UNIVERSITY OF CALIFORNIA, BERKELEY 1999 해외박사(DDOD)

        RANK : 2591

        This thesis describes an experiment in which a neutral atom laser trap loaded with radioactive <super>21</super>Na was improved and then used for measurements. The sodium isotope (half-life = 22 sec.) is produced on-line at the 88&inches; cyclotron at Lawrence Berkeley National Laboratory. We developed an effective magnesium oxide target system which is crucial to deliver a substantive beam of <super>21</super>Na to the experiment. Efficient manipulation of the <super> 21</super>Na beam with lasers allowed 30,000 atoms to be contained in a magneto-optical trap. Using the cold trapped atoms, we measured to high precision the hyperfine splitting of the atomic ground state of <super>21</super>Na. We measured the 3<italic>S</italic><sub>1/2</sub>(<italic>F</italic> = 1, <italic>m</italic> = 0) − 3<italic>S</italic><sub>1/2</sub>(<italic>F</italic> = 2, <italic> m</italic> = 0) atomic level splitting of <super>21</super>Na to be 1,906,471,870 ± 200 Hz. Additionally, we achieved initial detection of beta decay from the trap and evaluated the prospects of precision beta decay correlation studies with trapped atoms.

      • The gating of the bacterial mechanosensitive channel MscS reflects its function as a sensor of both crowding and lateral pressure as well as its role in osmoregulation

        Rowe, Ian Donald University of Maryland, College Park 2014 해외박사(DDOD)

        RANK : 2591

        The mechanosensitive channel MscS is a ubiquitous bacterial membrane valve that opens by increased tension in the event of osmotic down-shock, releasing small internal osmolytes and thus preventing the cell from excessive hydration and possible lysis. This osmolyte release is accompanied by a reduction of osmotic pressure and volume of the cell, which simultaneously increases crowding. The large catalogue of MscS homologs in both prokaryotes and eukaryotes makes the study of this channel enticing to the field of physical biochemistry. Here are the results of three different studies, two of which focus on the gating of MscS in the presence of large osmolytes and amphipathic compounds and a third which describes the first electrophysiological examination of the inner membrane of the facultative pathogen Vibrio cholerae. The first study in Chapter 2 describes the sensitivity of gating transitions in MscS to large intracellular macromolecules. This sensitivity originates at the cytoplasmic cage domain and the perceived crowding alters the rate of opening, closing and inactivation. Chapter 3 details the utilization of MscS as a sensor for changes in the lateral pressure profile of native bilayers and how this technique can be used to resolve the potential of antibacterial agents to partition into the membrane. The third and final study describes our development of a procedure to generate giant spheroplasts of Vibrio cholerae and the subsequent characterization of its two major mechanosensitive channels in terms of gating, inactivation, conductivity, and compatible osmolyte sensitivity as well as the durability of the pathogen in response to osmotic shock. These contributions to the field of mechanobiology and channel biophysics suggest that environmental feedback during osmoregulation is recognized by the cell, provide a potential method to monitor the partitioning of antibiotics into a cell membrane, and lastly detail the mechano-electrical response of a relevant, disease-causing bacteria.

      • Consuming animals as an educational act

        Rowe, Bradley D The Ohio State University 2012 해외박사(DDOD)

        RANK : 2591

        The main purpose of this dissertation is to demonstrate that consuming animals is an educational act that warrants sustained attention. The main question I address is: What does the consumption of animals have to do with the life of the educated person? I argue that we should learn more about the lives---which is to say, the deprivation, torment, and death---of the animals we eat. This sort of learning requires a fresh way to think about not only education, but also food, eating, and animals. I aim to illuminate the extent to which we are implicated in systems of immense suffering, and at the same time, provoke us to grow by questioning deeply-entrenched habit of consuming animals. This dissertation is a theoretical exploration that may or may not lead to dietary change, but that does, I believe, hold potential to change the way we think and act in the world. In Chapter 1, I lay out the reasons why consuming animals is a rich subject for educational philosophy. Chapter 2 is a brief overview of the animal ethics literature to analyze the moral arguments for bringing nonhuman beings into the realm of human moral consideration. Clearly, eating animals is an ethical act and it is important to review who has said what about it. In Chapter 3, I explore John Dewey's conception of growth and argue that, for human moral growth, we should consider the habit of consuming animals. In Chapter 4, I shift the focus to (mis)education at the cultural level. I argue that it is important to understand the consumption of animals---as a problem of cultural miseducation---so that we are better situated to rethink and resist the cultural forces that shape the consenting attitudes underlying this fundamental act of consumption. Chapter 5 examines the educational significance of understanding animals-becoming-meat---that is, the agricultural and slaughtering practices that turn living, full-bodied animals into fragmented, edible pieces of meat. This chapter has a broader function, too, as I make a case for extending scholarly inquiry addressing consumerism and commercialism to (re)encompass production and labor. Animals-becoming-meat is a particular form of production and labor that illustrates and exposes the larger problems of distance, ignorance, and alienation in contemporary life; it also demonstrates how the foundational role of production is largely concealed and thus taken for granted in consumer society. I end with Chapter 6 where I argue that the most effective and transformative pedagogical means to understand animals-becoming-meat is to watch the process unfold, with our own eyes. Given the great extent that corporate agriculture goes to conceal the brutality behind its walls, I believe we must be unsettled with disturbing visuals of animals-becoming-meat. I argue that education should unveil the exploitive practices that remain deliberately hidden from public view---even if it is culturally taboo to do so.

      • Determinants of community health workers' adherence to clinical guidelines for the management of ill children in Siaya, Kenya

        Rowe, Samantha Y Emory University 2005 해외박사(DDOD)

        RANK : 2591

        This dissertation describes 4 studies of determinants of community health workers' (CHW) adherence to clinical guidelines for the management of ill children in Siaya, Kenya. Study I. To assess the effect of several quality improvement interventions and other factors on CHW practices, we analyzed a sample of ill-child consultations performed in a hospital from February--March 2001. Refresher training, supervision, community women's involvement in CHW selection, adequacy of medicine supplies, and use of a guideline flipchart during consultations were not significantly associated with adherence to overall or treatment-specific guidelines for the integrated management of all illnesses in a child. Several patient characteristics were significantly associated with adherence. Study II. To identify which interventions were related specifically to malaria treatment quality, we analyzed a sample of children with malaria treated during Study I. An adequate medicine supply in the past year and use of a flipchart during the consultation were significantly associated with correct malaria treatment. Refresher training, supervision, and community women's involvement in CHW selection were not related to correct malaria treatment. Several patient characteristics were significantly associated with correct malaria treatment. Study III. To assess the effect of refresher training on adherence, we analyzed a sample of ill-child consultations performed in communities from March 1997--May 2002. The first refresher training's effect on adherence differed by several patient characteristics, including severity of illness and symptoms. The second refresher training was associated with a decline in adherence. Study IV. To assess whether results from an evaluation where CHWs were observed reflected normal everyday CHW practices, we compared the proportion of ill-child consultations with treatment errors when CHWs were observed and not observed. CHWs made fewer treatment errors when they were observed. Conclusions. This dissertation found that several quality improvement interventions were generally ineffective for a CHW program in a real life setting, and several "non-intervention" factors influenced adherence. We recommend that the CHW program revise its strategies to improve and maintain CHWs' adherence to guidelines, particularly its refresher training strategy.

      • Practicing policy and making myth: Applied anthropology and homeless service delivery in Glendale, California

        Rowe, Stacy University of Southern California 2003 해외박사(DDOD)

        RANK : 2591

        This dissertation analyzes how and why myths are generated around the development and implementation of homeless policy and how the myths and patterns of implementation are affected by Federal policy, local politics and the organizational culture of the participating stakeholders. I also discuss the conflicting roles of the practitioner-anthropologist, how this role has impacted this dissertation, and my ideas for future research and policy implications. Federal policy and regulations regarding homeless programs set the parameters for the design and implementation of local service delivery systems. They also create the conditions under which some of the myths regarding the delivery of these services are created and promoted. This dissertation gives a history of Federal funding for homeless programs and the evolution of Federal policies and regulations governing the issue. It then provides a case study which compares idealized (albeit technically accurate) accounts of program implementation, i.e., excerpts from documents created for submission to the U.S. Department of Housing and Urban Development, with an observed account of program implementation which highlights the challenges created, in part, by the Federal regulations. Local politics---concerns about a "magnet effect", difficulties with siting programs, the need to exert local control---also affect homeless program design and delivery. In addition, the organizational cultures of the various stakeholders---public agencies, non-profit service providers, health and mental healthcare providers, churches and community groups---also impact program design and present special challenges with implementation. Again, idealized versions presented in local media and City-generated reports are compared with an observed account of program implementation. This comparison provides insights to how conflicts are negotiated in the public/political arena and within the context of day to day service delivery. This dissertation also discusses how my roles as an applied anthropologist, and as the City's Homeless Coordinator---a key actor in the development of the homeless continuum of care---presented unique challenges to the construction of an ethnography. Finally, the dissertation presents specific suggestions for the direction of future policy and research initiatives in the area of homeless service delivery, and for the potential role of practitioner-anthropologists in such endeavors.

      • Synthesis and characterization of monolayer-protected gold nanoparticles and their organoplatinum composites as vapor-sensitive microsensor interface materials

        Rowe, Michael Paul University of Michigan 2006 해외박사(DDOD)

        RANK : 2591

        Organothiolate-monolayer-protected gold nanoparticles (MPNs) offer numerous advantages as vapor-sensitive interface materials in microfabricated chemiresistor (CR) arrays. Small quantities of gas-phase species partitioning into thin MPN films cause large changes in resistance. In these studies, the synthesis, characterization, and testing of MPNs, alone and as composites with organoplatinum charge-transfer complexes, are explored. A new single-phase MPN synthesis is described, which avoids persistent ionic contamination from the phase-transfer catalyst (PTC) necessary in the conventional dualphase synthesis. Residual PTC leads to a frequency-dependent current through the MPN film, over two hour stabilization times, and anomalous vapor responses. The new method retains the high yield, particle-size control, and thiolate-monolayer functional-group diversity associated with the conventional MPN synthesis, while producing materials of higher purity in less than three minutes. MPNs with several different thiolate-ligand functionalities (e.g., aromatic and ester) were prepared by this single-phase method and fully characterized. Composite films of n-octanethiolate MPNs with charge-transfer complexes of the general formula PtCl2(olefin)(pyridine) were then tested and found to selectively interact with gas-phase olefins. A spontaneously reversible Pt-olefin interaction occurs that is accompanied by a decrease in film resistance. Structurally analogous non-olefins invariably cause an increase in film resistance associated with MPN swelling. The mechanism for the conduction enhancement was elucidated from the 33 nm red-shift in the UV-vis absorbance spectrum of PtCl2(styrene)(pyridine) when titrated with styrene. Detection limit reductions, for examined olefins, by as much as 104-fold are achieved by use of these composite CR interface films. Tethering Pt-complexes to unsaturated MPN ligands was successful but did not provide the selectivity and sensitivity observed with the composite films. In a follow-on study, composite films of n-octanethiolate MPNs with PtCl2(pyridine)2 were shown to reversibly and selectively interact with pyridine vapor and its derivatives, including the environmental tobacco smoke markers 4-vinylpyridine and nicotine. UV-vis absorbance spectrum red-shifts confirm a charge-transfer interaction similar to that observed with the Pt-olefin MPN composites. Although the degree of selectivity is less than that observed with the olefins, the results support the use of organometallic additives in MPN films as a general means of enhancing sensitivity and selectivity.

      • Characteristics of activation domains that control potency and permissiveness of activation domain binding sites

        Rowe, Steven P University of Michigan 2009 해외박사(DDOD)

        RANK : 2591

        The regulation of transcription levels of specific genes is one of the fundamental processes that underlie human physiology. Nearly every human disease is caused by transcriptional mis-regulation or manifests such mis-regulation as an effect. This realization has brought about an interest in more fully understanding transcriptional regulation and developing molecules capable of artificially modulating transcription. Transcriptional regulation in a eukaryotic cell depends on more than 100 different proteins acting in concert. Within this machinery, transcriptional activators and coactivators play two of the most important roles. Transcriptional activators bind to specific DNA sequences and then contact, via their activation domains, surfaces on coactivators to recruit the transcriptional machinery, including RNA polymerase II, and initiate transcription. Transcriptional coactivators transduce information from activators to RNA polymerase II allowing for precise control of transcription. Until recently, the prevailing model was that the abilities of different transcriptional activation domains to up-regulate transcription to particular levels was exclusively a function of their respective binding affinities for coactivators. Upon examination of activation domains that uniquely target the coactivator Med15, we were able to demonstrate that other characteristics of activation domains such as coactivator binding site location and avoidance of proteolytic degradation and non-productive interactions play parts in controlling activation domain potency. In particular, we uncovered a second binding site for the XLY activation domain that limits its interactions with proteases and other proteins and allows it to function as a much more potent activation domain than other short peptides. Activation domain-binding sites on coactivators consist of shallow hydrophobic grooves that can interact with several different activation domains. This suggests that such protein surfaces possess permissive binding profiles and that a variety of non-biopolymer scaffolds appended with appropriate functionality might act as artificial activation domains. Series of peptidomimetic analogs of known activation domains were used to examine the permissiveness of an activation domain-binding site from the CBP KIX domain through cell-free binding assays and inhibition of activation in a cellular context. Activation domain-binding site permissiveness was also demonstrated by our discovery that small molecule isoxazolidines could target the transcriptional machinery and up-regulate transcription to a significant degree inside living cells.

      • Literacy practices of the laboring poor in France, 1800--1860

        Rowe, Steven Edward Duke University 2002 해외박사(DDOD)

        RANK : 2591

        This dissertation focuses on France in the nineteenth century and the uses of literacy by poor, working adults, criticizing previous studies that analyzed literacy as one-half of a literate/non-literate dichotomy. Instead, this dissertation argues that generalizations made about literacy, its meanings in different societies, and its effects on poverty can only be accurately evaluated by studies of literacy practices, or specific uses of writing and reading. This dissertation undertakes a comparative analysis of industrial workers' letter-writing, song-writing, and autobiographical-writing practices in order to examine the relationships between these literacy practices and social life in France between 1800 and 1860. Through these three literacy practices, workers reinforced their multiple social connections and collective identities that, in turn, helped them develop a sociocentric sense of self, rather than isolate them from social life as autonomous individuals. These literacy practices did not always lead them down the path to political liberation, though, as workers also reinforced social hierarchies and created forms of control through such practices. This complex picture of French workers' literacy and its relationship with social and political life in the early nineteenth century can be seen only by approaching literacy as a set of practices. As this dissertation shows, this approach to literacy, with its rejection of the literate/non-literate dichotomy, allows us to develop more nuanced evaluations of literacy, its meanings, and its connections with social life.

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