High Resolution Ion Mobility Spectrometry with Increased Ion Transmission: Exploring the Analytical Utility of Periodic-Focusing DC Ion Guide Drift Cells

Drift tube ion mobility spectrometry (IMS) is a powerful, post-ionization separation that yields structural information of ions through an ion-neutral collision cross section. The ion-neutral collision cross section is governed by the collision frequency of the ion with the neutral drift gas. Consequently, ions of different size will have different collision frequencies with the gas and be separated in the drift cell. A significant challenge for IMS, however, is to separate ions with very similar collision cross sections, requiring higher resolution ion mobility spectrometers. Resolution in IMS is of utmost importance for the separation of complex mixtures, e.g. crude oil samples, proteolytic digests, positional isomers, and ion conformers. However, most methods employed to increase mobility resolution significantly decrease ion transmission through the mobility device. Herein, a periodic-focusing DC ion guide drift cell (PDC IG) is presented to display its potential capabilities for higher mobility resolution with increased ion transmission. The PDC IG utilizes unique electrode geometry compared to the conventional uniform field electrode design. Electrode geometry can be defined by the electrode inner diameter (d), thickness (t), and spacing (s). Specifically, the ratio of d : t : s is equal to, or very near, 1:1:1. The PDC IG electrode design creates a non-uniform (fringing) electric field-especially near the electrode walls. The design also causes variations in the radial electric field which provides an effective RF as ions move through the device and a radially confining effective potential that improves ion transmission through the device. In this dissertation the analytical utility of the PDC IG drift cell for ion mobility separations will be explored. The radial focusing properties of the device will be presented along with studies of electrode geometry and its effect on ion mobility resolution and ion transmission through the drift cell. PDC IG drift cell length is also examined to determine its effect on mobility resolution and ion transmission. Finally, the PDC IG drift cell device is coupled to an orthogonal-acceleration time-of-flight mass spectrometer as well as a modular, PDC IG drift cell being adapted to a commercial qTOF mass spectrometer for IM-MS experiments

Using averaged models from 4D ultrasound strain imaging allows to signifcantly diferentiate local wall strains in calcifed regions of abdominal aortic aneurysms

Abdominal aortic aneurysms are a degenerative disease of the aorta associated with high mortality. To date, in vivo information to characterize the individual elastic properties of the aneurysm wall in terms of rupture risk is lacking. We have used time-resolved 3D ultrasound strain imaging to calculate spatially resolved in-plane strain distributions characterized by mean and local maximum strains, as well as indices of local variations in strains. Likewise, we here present a method to generate averaged models from multiple segmentations. Strains were then calculated for single segmentations and averaged models. After registration with aneurysm geometries based on CT-A imaging, local strains were divided into two groups with and without calcifications and compared. Geometry comparison from both imaging modalities showed good agreement with a root mean squared error of 1.22 ± 0.15 mm and Hausdorff Distance of 5.45 ± 1.56 mm (mean ± sd, respectively). Using averaged models, circumferential strains in areas with calcifications were 23.2 ± 11.7% (mean ± sd) smaller and significantly distinguishable at the 5% level from areas without calcifications. For single segmentations, this was possible only in 50% of cases. The areas without calcifications showed greater heterogeneity, larger maximum strains, and smaller strain ratios when computed by use of the averaged models. Using these averaged models, reliable conclusions can be made about the local elastic properties of individual aneurysm (and long-term observations of their change), rather than just group comparisons. This is an important prerequisite for clinical application and provides qualitatively new information about the change of an abdominal aortic aneurysm in the course of disease progression compared to the diameter criterion

Charting the future of cancer health disparities research: A position statement from the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138314/1/caac21404_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138314/2/caac21404.pd

Carbon Nanotube Based Magnetic Tunnel Junctions

Spin-coherent quantum transport in carbon nanotube magnetic tunnel junctions was investigated theoretically. A spin-valve effect is found for metallic, armchair tubes, with a magneto-conductance ratio ranging up to 20%. Because of the finite length of the nanotube junctions, transport is dominated by resonant transmission. The magnetic tunnel junctions are found to have distinctly different transport behavior depending on whether or not the length of the tubes is commensurate with a 3N+1 rule, with N the number of basic carbon repeat units along the nanotube length.Comment: 4 pages with 3 figures. to appear in PR

Th17 cells are more protective than Th1 cells against the intracellular parasite Trypanosoma cruzi

Th17 cells are a subset of CD4+ T cells known to play a central role in the pathogenesis of many autoimmune diseases, as well as in the defense against some extracellular bacteria and fungi. However, Th17 cells are not believed to have a significant function against intracellular infections. In contrast to this paradigm, we have discovered that Th17 cells provide robust protection against Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas disease. Th17 cells confer significantly stronger protection against T. cruzi-related mortality than even Th1 cells, traditionally thought to be the CD4+ T cell subset most important for immunity to T. cruzi and other intracellular microorganisms. Mechanistically, Th17 cells can directly protect infected cells through the IL-17A-dependent induction of NADPH oxidase, involved in the phagocyte respiratory burst response, and provide indirect help through IL-21-dependent activation of CD8+ T cells. The discovery of these novel Th17 cell-mediated direct protective and indirect helper effects important for intracellular immunity highlights the diversity of Th17 cell roles, and increases understanding of protective T. cruzi immunity, aiding the development of therapeutics and vaccines for Chagas disease

Untersuchungen zur Beteiligung des Aktin-Zytoskeletts an der Volumenregulation von humanen Keratinocyten

Das Volumen von tierischen Zellen ist durch äußere und innere Einflüsse Veränderungen unterworfen. Um die zelluläre Homöostase zu gewährleisten und bedrohliche Volumenänderungen zu verhindern, verfügen die meisten Zellen daher über regulatorische Mechanismen zur Verringerung (regulatory volume decrease, RVD) oder Erhöhung (regulatory volume increase, RVI) des Zellvolumens. Darüber hinaus finden diese Mechanismen auch im Rahmen physiologischer Prozesse, wie z. B. der Zellbewegung oder der Proliferation Verwendung. Der RVD erfordert einen Sensor-Mechanismus, der die Veränderung des Zellvolumens registriert. Die nachfolgende Signaltransduktion führt zur Aktivierung von Transportmechanismen, die v. a. dem Export von K+- und Cl--Ionen, aber auch organischen Osmolyten, dienen und zum Ausstrom von Wasser aus der Zelle führen, bis das Sollvolumen erreicht ist. Bisher ist noch nicht sicher, welcher Mechanismus den RVD einleitet; in verschiedenen Geweben wurden Hinweise auf mehrere mögliche Kandidaten gefunden. In dieser Arbeit wurde der RVD von HaCaT-Zellen, einer humanen Keratinozyten-Zelllinie hinsichtlich der Beteiligung des Aktin-Zytoskeletts mit mikroskopischen, pharmakologischen und molekularbiologischen Methoden untersucht. HaCaT-Zellen schwellen in hypotonem Medium schnell an (30 s) und führen einen RVD durch, der nach ca. 5 min das Ausgangsvolumen wieder herstellt. Der RVD von HaCaT-Zellen ist vom Einstrom extrazellulärer Ca2+-Ionen abhängig. Dieser Einstrom erfolgt durch einen Kanal, der durch die Inhibitoren von stretch activated channels (SAC) Gd3+ und GsMTx-4, sowie den spezifischen Inhibitor des transient receptor potential vaniloid 4 (TRPV4), Rutheniumrot, gehemmt werden kann. TRPV4 wird in HaCaT-Zellen exprimiert. Der RVD und der damit verbundene Einstrom von Ca2+-Ionen, nicht aber das Anschwellen der Zellen werden durch den Abbau des Aktin-Zytoskeletts durch 2 μM Cytochalasin D (CD) gehemmt. Die Hemmung durch CD ist reversibel; nach dem Entfernen von CD bildet sich innerhalb von 30 min erneut ein Netzwerk von Aktinfilamenten aus. Ein zwei-stufiges Absenken der Osmolarität (jeweils ca. 20%), zunächst in Anwesenheit von CD führt zu einer Volumenzunahme, löst aber keinen RVD aus. Auch nach dem Entzug von CD bleibt das Volumen konstant erhöht. Erst das zweite Absenken löst eine Volumenregulation aus, allerdings nur bis zu dem Volumen, das nach dem Entfernen von CD etabliert war. Die mikroskopische Struktur des Aktin-Zytoskeletts von HaCaT-Zellen ändert sich während des RVD kaum. Durch die Messung der Fluoreszenz von gebundenem Rhodamin-Phalloidin konnte ein vorübergehender Anstieg der Menge von Aktinfilamenten (F-Aktin) während des RVD gezeigt werden. Ein quantitativer biochemischer Ansatz zeigt, dass die relative Menge des Triton- X-100-löslichen Anteils des Aktin-Zytoskeletts im gleichen Zeitraum zunimmt. Der RVD von HaCaT-Zellen hängt ebenfalls von der Geschwindigkeit der Osmolaritätsänderung ab; die langsame Verringerung der Osmolarität (≤ 5 mosM/min) führte zum Anschwellen, nicht aber zum RVD. Auf Basis der erzielten Ergebnisse wird ein Modell für den RVD von HaCaTZellen vorgeschlagen, bei dem der Anstieg des Zellvolumens zu einer Zunahme der mechanischen Spannung im kortikalen Zytoskelett führt. Dadurch wird – indirekt, etwa durch Phospholipase A2, oder direkt - TRPV4 aktiviert. Dies führt zu einem Einstrom von extrazellulären Ca2+-Ionen und über Ca2+-abhängige Aktin-bindende Proteine (z. B. Gelsolin) zu einer Reorganisation des Aktin-Zytoskeletts (Gel-Sol-Übergang) und verbunden damit zu einer Abnahme der mechanischen Spannung. Ca2+-Ionen und kurze Aktinfilamente aktivieren Transportmechanismen, die zum Ausstrom von K+- und Cl-- Ionen und einer Abnahme des Zellvolumens führen

Three Papers Toward a Better Understanding of State Medicaid Programs and Program Efficiency

The federal government provides an uncapped reimbursement of state Medicaid spending. In theory, states can use the federal Medicaid funds as a replacement for state funds or the federal funds, which take the form of a matching grant that reduces the relative price of Medicaid, can increase (or stimulate) spending on Medicaid with state-raised tax revenue. In the first dissertation paper, Subsidizing Medicaid Growth: The Impact of the Federal Reimbursement on State Medicaid Programs, I use a state panel data set from 1992 to 2006 to assess the impact of the federal reimbursement on the size of state Medicaid programs. I find that a one point increase in a state's Medicaid reimbursement percentage increases state per capita Medicaid spending between $5 and$16 and increases the percentage of the state's population receiving Medicaid benefits by 0.04 percent to 0.29 percent. The first paper also utilizes a case study that shows significant growth in Alaska's Medicaid program after its effective federal Medicaid reimbursement increased 50 percent between 1998 and 1999. The large growth in Alaska's Medicaid program after this increase provides evidence that states respond to large increases in the federal Medicaid subsidy in a stimulative manner by increasing spending with state-raised revenue. Overall, the results in the first paper are consistent with the hypothesis that decentralization in the form of intergovernmental matching grants increases the size of government. I also find that states with wealthier and more liberal populations tend to have larger Medicaid programs and that states with Democratic legislatures tend to have more Medicaid beneficiaries than states with Republican legislatures all else equal. Since 2008, states have experienced significant budgetary pressure; in large part, because of rising Medicaid enrollment due to the recession and weak recovery. Between 2009 and 2011, many states enacted health care provider taxes as a way to bring in additional revenue through the federal Medicaid reimbursement. Provider taxes are generally supported by health care providers since states often give providers an implicit or explicit guarantee of a return of at least as much funding through higher payment rates or supplemental payments. In the second dissertation paper, Impact of Hospital and Nursing Home Taxes on State Medicaid Spending, I assess the impact of the two largest provider taxes, the hospital tax and the nursing home tax, on state Medicaid expenditures using a panel dataset of 42 states from between 2007 and 2011. I find significantly larger Medicaid spending growth for hospitals in states that added hospital taxes and significantly larger Medicaid spending growth for nursing homes in states that added nursing home taxes within the first two years of the enactment of the tax. I also find some evidence that states with hospital taxes were able to increase their total Medicaid spending more than states without hospital taxes during the economic downturn and initial recovery period. This paper also contains evidence that nursing home taxes diverted Medicaid spending from home and community based services to nursing homes. In the third dissertation paper, Statewide Health Impact of Tennessee's Medicaid Expansion, I utilize a quasi-experimental approach to assess the impact of a large statewide public health insurance expansion on access to health care services, health care utilization, and health outcomes. In 1994, Tennessee expanded its state Medicaid program, called TennCare, by about ten percent of the state's population. Along with a major Medicaid expansion, Tennessee increased government subsidies for individuals to purchase health insurance coverage and emphasized managed care. Using a difference-in-difference methodology with Tennessee's neighboring states as controls, I found that TennCare's impact on utilization was mixed as blood pressure and cholesterol checks increased but regular physician check-ups decreased relative to the surrounding region. Surprisingly, both self-reported health and mortality rates were less favorable in Tennessee relative to the control states after TennCare. Ultimately, the evidence in this paper suggests that health reform built around a significant public insurance expansion is likely to result in minimal, if any, overall health gains measured in the entire population, at least in the short run. The final dissertation section summarizes the findings from the three dissertation papers, discusses the economic efficiency of the uncapped federal Medicaid reimbursement and state provider taxes, and makes several predictions related to the Medicaid expansion in the Patient Protection and Affordable Care Act

Ultraschneller 3D-Druck: Additive High-Speed-Fertigung von Kunststoffbauteilen aus Standardgranulat

3D printing is a fast-growing market, opening up completely new product and manufacturing options for customers and industry. The newly developed SEAM process significantly extends the options for the efficient manufacture of printed components. An impression of this is conveyed by the example of a fiber-reinforced clamping fixture

Neuartige Hybridbauweisen durch Kombination von Textilhalbzeugen und additiv gefertigten Strukturen

Durch die Entwicklung eines extrusionsbasierten 3D-Druckverfahren (SEAM) konnten Steigerungen der Prozessgeschwindigkeit dadurch erreicht werden, dass Plastifizierleistungen und Verfahrgeschwindigkeiten der Bauplattform weit über die üblichen Grenzen hinaus betrieben werden. Dabei ist es ebenso möglich variable Strangbreiten zu fahren, als auch Standardgranulate zu verwenden. Die so hergestellten Bauteile haben dabei einen hohen Kostenvorteil, stark reduzierte Bauzeiten und erreichen bis zu 80% der mechanischen Eigenschaften spritzge-gossener Bauteile. In dieser Studie wurden mittels des SEAM-Verfahren hybride 3D-Druckbauteile mit unidirektionaler Kohlenstofffaserverstärkung hergestellt. Die Haftung und deren Haupteinflussparameter wurden in Schälprüfungen und durch Schliffbildaufnahmen bewertet