Altered Hemodynamic Control in the Skeletal Muscle Microcirculation in the Metabolic Syndrome: The Emergence of a new Attractor

Peripheral vascular disease is a pathological disease state whereby the peripheral vascular system becomes progressively limited in its ability to adequately perfuse extremities despite increases in metabolic demand. One of the primary risk factors for development of peripheral disease is the Metabolic Syndrome. It is the presentation of three simultaneous comorbidities, with obesity being the most common denominator in most metabolic syndrome patients, but also including a pro-inflammatory state, pro-oxidant state, pro-thrombotic state, increased blood pressure, atherogenic dyslipidemia, or insulin resistance. Currently, the population of the United States is approximately 75% overweight, obese, or extremely obese and the prevalence of obesity related consequences is rising, including but not limited to diabetes, cardiovascular disease, and peripheral vascular disease.;Our laboratory has demonstrated that a defining characteristic of metabolic syndrome is microvascular dysfunction. Increasing evidence has indicated that the mechanisms responsible for microvascular dysfunction in metabolic syndrome are oxidant stress-based alterations to arachidonic acid metabolism and increased sensitivity to adrenergic stimulation. However, it remains unclear if the altered microvascular reactivity that presents with metabolic syndrome plays a role in the perfusion: demand mismatch that accompanies and defines peripheral vascular disease. This dissertation seeks to understand the altered hemodynamic control found in metabolic syndrome. It set out to examine: 1. The effect of altered microvascular reactivity in metabolic syndrome on vascular tone and performance outcomes. 2. Identify the spatial and temporal alterations to perfusion distribution in metabolic syndrome. 3. Determine the effect of metabolic syndrome on erythrocyte distribution in the microvasculature and capillaries.;The results of these studies determined that a key contributor to the development, maintenance, and progression of peripheral vascular disease is microvascular dysfunction. This dysfunction increases the microvascular perfusion distribution by spatially distinct mechanisms, with adrenergic dysfunction dominating in larger microvessels and oxidant stress-based increases in thromboxane A2 dominating in smaller microvessels. Additionally, metabolic syndrome blunts the temporal compensation that would serve to attenuate the increased perfusion distribution. Combined, the spatial and temporal impairments to microvasculature serve to alter erythrocyte distribution on a network level in skeletal muscle. These data shed light on how metabolic syndrome insidiously alters microvascular control of blood flow, leading to a perfusion: demand mismatch, and ultimately contributing to pathological disease states like peripheral vascular disease

Family Reflections on the District of Columbia Opportunity Scholarship Program: Final Summary Report

During the spring of 2004, the first federally funded voucher program – the District of Columbia Opportunity Scholarship Program (OSP) - was established. The School Choice Demonstration Project (SCDP) recognized that publicly-funded school vouchers represent a relatively new and unstudied approach to school choice and education reform. To address this need, the SCDP requested and received funding from the Annie E. Casey Foundation to capture the “Parent and Student Voices on the OSP.” A total of 110 families, representing 180 students, that applied during the first two years of the Program volunteered to participate in this study. As the last installment in a four-part annual series that began in 2005, this report summarizes key findings from the previous reports and provides a general overview of the respondents’ “reflections” upon their three or four years in the Program. Using a phenomenological approach, which includes focus groups, personal interviews and keypad polling information gathering techniques, participants were given multiple opportunities to share or describe their experiences. A consumer framework was often used to contextualize the families’ experiences. Their insights continue to shape the scope and direction of the OSP, and they will help inform other efforts to provide low income families with access to quality school options

Optimization of metal-cyclization of alpha-MSH peptide analogs used in the treatment and detection of melanoma

Abstract only availableOver the past few years Dr. Quinn and his lab have made significant progress in the development of a melanoma treatment drug. Based upon peptide analogs of the alpha-melanocyte stimulating hormone, Α-MSH, Dr. Quinn has developed a metal cyclized drug that shows very promising results in therapy as well as early detection/imaging of melanoma tumors. The cyclization of the peptide around a metal core was shown to greatly increase the affinity of the peptide for its target. There are slight problems with the cyclization process that needed to be resolved or limited in order to make the synthesis of the drug as efficient as possible. The primary problem with the cyclization of the peptide is the fact that two main products are produced. One of these products is caused by the histidine residue swinging down and binding with the metal core. Histidine is one of the four amino acids directly involved with receptor recognition and thus this product's tumor uptake is at least 50% lower. Three variables were explored in hopes of reducing this second unwanted product. A new and simpler process developed by Fridkin et. al. ¹ was first considered. HPLC was used to purify the two major products and their identities were confirmed using mass spectrometry. The new procedure proved to be slightly more effective as the old procedure. With the old procedure roughly 32.3% of the two major products were of the undesired compound, however, using this new procedure this was reduced to 23.4%. A variation of the new procedure was then tried. Instead of dissolving the linear peptide in water, as the procedure called to do, the peptide was dissolved using DMF. This modification showed a significant change in the percentage of the two products. Of the two major products only 12.8% of the total was of the unwanted product thus producing 87.2% of the desired cyclized peptide. Finally an addition of an extra amino acid residue near the beginning of the sequence was tried in hopes of moving the histidine residue far enough away from the metal core in order to limit their interaction. Current tests are still being performed to determine whether or not this will be successful. (1) Fridkin, G., Bonsera, T.A., Litman, P., and Gilon, C. Nucl. Med Biol 32, 39-50, 2005.Molecular Imaging Progra

Concept description for the use of fibre-optic measurements for seismic tomography

High resolution mapping of CO2 plumes in the geological storage formations can be obtained using cross well seismic experiments designed to characterise velocity changes in the subsurface, see figure 1. High resolution studies are facilitated by using dense measurement surveys with many wireline operations that adjust seismic source and detector positions. Distributed fibre optic acoustic sensing may enhance traditional wireline cross wire surveys by providing an aliasing-free method for characterising seismic waveforms, and potentially enable a reduction in the number of individual measurements (and therefore cost) required for performing cost sensitive CO2 plume surveys. In addition, seismic tomography involving fibre optic receivers and ambient noise techniques, could enable permanent monitoring of subsea CO2 storage with seismic tomography. This document gives a basic concept description of cross-well seismic technology, both with active seismics and ambient noise, and their application with distributed fiber optics sensing. The document also describes the infrastructure for carrying out cross well/fibre optic measurements at Svelvik, and a proposal for a measurement campaign to be carried out as part of the DigiMon project.Concept description for the use of fibre-optic measurements for seismic tomographypublishedVersio

Cross hole seismic experiment with DAS/DTS data. Svelvik CO2 field lab

Primary purposes of the fieldwork at Svelvik include the provision of datasets which supports task 1.2 ‘determining the DAS transfer function’ and task 1.3 ‘develop DAS data processing techniques and workflow’. The fieldwork also serves as a test of the novel SV wave seismic source developed as part of Task 1.4. ‘Active source technology development and optimising monitoring design.Cross hole seismic experiment with DAS/DTS data. Svelvik CO2 field labpublishedVersio

Unbinding traditions: rhetoric, hermeneutics, and the Akedah

This thesis explores and explicates the relationship between rhetoric and hermeneutics in two separate contexts: Jewish and Christian hermeneutic traditions, and secular philosophical hermeneutics. The impetus for this division is an analysis of Kierkegaard’s work, Fear and Trembling, which contains interpretations of the story of Genesis 22, the binding of Isaac; this event is referred to in the Jewish tradition as the Akedah. Kierkegaard’s own position as a Christian, philosopher and poet situate him on the dividing line between Christian and Jewish hermeneutics, as well as secular philosophical hermeneutic positions. To show these connections, the thesis undertakes two necessary literature reviews: a review of the current theoretical positions on the status of meaning, interpretation, and how rhetoric and hermeneutics intersect; and a review of the history of interpretations of the Akedah in Christian and Jewish traditions. Out of the first review come three separate and general categories of secular hermeneutics: intentionalist, phenomenological, and deconstructive. Within each of these positions is a different understanding and application of rhetoric. Similarly, the second review reveals differences between Jewish and Christian hermeneutics which contain separate understandings and applications of rhetoric. Kierkegaard’s own interpretation is situated within these contexts. Finally, modern Jewish responses to Kierkegaard are examined to further explicate the differences between Jewish and Christian hermeneutics as well as the separate philosophical positions. This is done through an analysis of Levinas’ and Derrida’s separate critiques and appropriations of Kierkegaard’s interpretation of the Akedah in Fear and Trembling. The conclusion drawn from these reviews and analyses is that intentionalist hermeneutics has the most comprehensive understanding and application of classical rhetoric, which in turn makes intentionalist hermeneutics the most capable of preserving the possibility of rhetorical agency

Developing Identity: Exploring The History Of Indonesian Nationalism

This thesis examines the history of Indonesian nationalism over the course of the twentieth century. In this thesis, I argue that the country’s two main political leaders of the twentieth century, Presidents Sukarno (1945-1967) and Suharto (1967-1998) manipulated nationalist ideology to enhance and extend their executive powers. The thesis begins by looking at the ways that the nationalist movement originated during the final years of the Dutch East Indies colonial period. The first section highlights how the nationalist movement was disunified in its attempts to gain political autonomy from Dutch colonial control. It moves on to talk about the impact of the Japanese occupation period (1942-1945) on the nationalist movement, detailing how Sukarno was able to unify the various nationalist groups by presenting his form of Indonesian ideology, Pancasila. The paper briefly touches on the Indonesian Revolutionary War (1945-1949) before discussing the impact of Sukarno’s gradual move towards communist and anti-Western sentiments. The paper examines several speeches given by Sukarno during this period to emphasize the ways by which he directed national ideology in his favor. The narrative continues to explain the Indonesian public’s backlash against communism, briefly detailing the Communist Massacre of 1965-1966 and explaining how Suharto grabbed power in the ensuing chaos. An analysis of Suharto’s early speeches reveals the ways that Suharto was able to appropriate Sukarno’s Pancasila to fit his own political goals. The thesis moves on to discuss the Pancasila indoctrination programs which Suharto enacts during the late 1970s and into the 1980s and how the Suharto regime became associated with repression and state violence. The thesis concludes by examining the similarities and differences between Sukarno’s and Suharto’s manipulation of ideology to enhance their political agendas

Seeing a drummer’s performance modulates the subjective experience of groove when listening to popular music drum patterns

Spontaneous rhythmical movements, like foot-tapping and head-bobbing, often emerge when people listen to music, promoting the sensation of being in the ‘groove’: a psychological construct that additionally incorporates positive affect. Here we report the first study to investigate if seeing the music maker modulates this subjective experience of groove. Across trials participants (n = 36) listened to high and low groove drum beats, while concurrently observing a task-irrelevant point-light display (PLD) of the drummer. The PLD was either fully-corresponding with the audio or was incompatible across three other visual display conditions: a static PLD, a corresponding but asynchronous PLD (0.5s time shifted); or a non-corresponding PLD (e.g. low groove audio paired with high groove PLD). Participants rated: (a) their desire to move; and (b) the perceived groove in response to the auditory beats only, using 8-point Likert scales. In both measurements there were significant main effects of groove level and of visual display. Ratings were higher for high compared to low groove audio, and for the fully-corresponding condition compared to the other three visual conditions. The participants’ desire to move was also rated higher in the static condition compared to the non-corresponding condition, while the two-way interaction was also significant: ratings were higher for the high compared to low groove audio in the fully-corresponding, static and asynchronous conditions, but not in the non-corresponding condition. These findings identify the importance of seeing as well as hearing the musician for an enhanced listening experience, which necessitates a multimodal account of music perception