Fabricating microfluidic devices in polymers for bioanalytica applications

The research presented in this document focuses on the fabrication, characterization and application of microfluidic systems fabricated in poly(methyl methacrylate) (PMMA) with the emphasis focused on the fabrication processing steps. Microfluidic devices were produced in PMMA using X-ray lithography. The fabrication methods investigated were sacrificial mask, polyimide membrane mask and embossing techniques. PMMA microfluidic devices fabricated using X-ray lithography were characterized using scanning electron microscopy (SEM) and optical microscopy, while analytical techniques such as electroosmotic flow determination, separations, and fluorescent microscopy were used to characterize fluid transport in these devices. A novel method for the heat annealing of PMMA to PMMA to create a closed system is described. Characterization of this technique was carried out by optical microscopy and scanning electron microscopy. The manufacturing techniques utilized in producing mold inserts for hot embossing and injection molding is discussed as well. Both the mold insert and devices produced from the inserts were characterized using scanning electron microscopy. Devices produced can be used to perform a number of analytical techniques including single molecule detection and fluorescence lifetime monitoring. The primary goal of this research was to develop molding tools consisting of high-aspect-ratio microstructures using robust and reproducible processing steps

Dynamic wormholes

A new framework is proposed for general dynamic wormholes, unifying them with black holes. Both are generically defined locally by outer trapping horizons, temporal for wormholes and spatial or null for black and white holes. Thus wormhole horizons are two-way traversible, while black-hole and white-hole horizons are only one-way traversible. It follows from the Einstein equation that the null energy condition is violated everywhere on a generic wormhole horizon. It is suggested that quantum inequalities constraining negative energy break down at such horizons. Wormhole dynamics can be developed as for black-hole dynamics, including a reversed second law and a first law involving a definition of wormhole surface gravity. Since the causal nature of a horizon can change, being spatial under positive energy and temporal under sufficient negative energy, black holes and wormholes are interconvertible. In particular, if a wormhole's negative-energy source fails, it may collapse into a black hole. Conversely, irradiating a black-hole horizon with negative energy could convert it into a wormhole horizon. This also suggests a possible final state of black-hole evaporation: a stationary wormhole. The new framework allows a fully dynamical description of the operation of a wormhole for practical transport, including the back-reaction of the transported matter on the wormhole. As an example of a matter model, a Klein-Gordon field with negative gravitational coupling is a source for a static wormhole of Morris & Thorne.Comment: 5 revtex pages, 4 eps figures. Minor change which did not reach publisher

Pharmaceutical induction of ApoE secretion by multipotent mesenchymal stromal cells (MSCs)

<p>Abstract</p> <p>Background</p> <p>Apolipoprotein E (ApoE) is a molecular scavenger in the blood and brain. Aberrant function of the molecule causes formation of protein and lipid deposits or "plaques" that characterize Alzheimer's disease (AD) and atherosclerosis. There are three human isoforms of ApoE designated ε2, ε3, and ε4. Each isoform differentially affects the structure and function of the protein and thus the development of disease. Homozygosity for ApoE ε4 is associated with atherosclerosis and Alzheimer's disease whereas ApoE ε2 and ε3 tend to be protective. Furthermore, the ε2 form may cause forms of hyperlipoproteinemia. Therefore, introduction of ApoE ε3 may be beneficial to patients that are susceptible to or suffering from these diseases. Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) are adult progenitor cells found in numerous tissues. They are easily expanded in culture and engraft into host tissues when administered appropriately. Furthermore, MSCs are immunosuppressive and have been reported to engraft as allogeneic transplants. In our previous study, mouse MSCs (mMSCs) were implanted into the brains of ApoE null mice, resulting in production of small amounts of ApoE in the brain and attenuation of cognitive deficits. Therefore human MSCs (hMSCs) are a promising vector for the administration of ApoE ε3 in humans.</p> <p>Results</p> <p>Unlike mMSCs, hMSCs were found not to express ApoE in culture; therefore a molecular screen was performed for compounds that induce expression. PPARγ agonists, neural stem cell conditioned medium, osteo-inductive media, dexamethasone, and adipo-inductive media (AIM) were tested. Of the conditions tested, only AIM or dexamethasone induced sustained secretion of ApoE in MSCs and the duration of secretion was only limited by the length of time MSCs could be sustained in culture. Upon withdrawal of the inductive stimuli, the ApoE secretion persisted for a further 14 days.</p> <p>Conclusion</p> <p>The data demonstrated that pre-treatment and perhaps co-administration of MSCs homozygous for ApoE ε3 and dexamethasone may represent a novel therapy for severe instances of AD, atherosclerosis and other ApoE-related diseases.</p

The impact of flooding on road transport:A depth-disruption function

Transport networks underpin economic activity by enabling the movement of goods and people. During extreme weather events transport infrastructure can be directly or indirectly damaged, posing a threat to human safety, and causing significant disruption and associated economic and social impacts. Flooding, especially as a result of intense precipitation, is the predominant cause of weather-related disruption to the transport sector. Existing approaches to assess the disruptive impact of flooding on road transport fail to capture the interactions between floodwater and the transport system, typically assuming a road is fully operational or fully blocked, which is not supported by observations. In this paper we develop a relationship between depth of standing water and vehicle speed. The function that describes this relationship has been constructed by fitting a curve to video analysis supplemented by a range of quantitative data that has be extracted from existing studies and other safety literature. The proposed relationship is a good fit to the observed data, with an R-squared of 0.95. The significance of this work is that it is simple to incorporate our function into existing transport models to produce better estimates of flood induced delays and we demonstrate this with an example from the 28"sup"th"/sup" June 2012 flood in Newcastle upon Tyne, UK. Document type: Articl

A resonant chain of four transiting, sub-Neptune planets

Surveys have revealed many multi-planet systems containing super-Earths and Neptunes in orbits of a few days to a few months. There is debate whether in situ assembly or inward migration is the dominant mechanism of the formation of such planetary systems. Simulations suggest that migration creates tightly packed systems with planets whose orbital periods may be expressed as ratios of small integers (resonances), often in a many-planet series (chain). In the hundreds of multi-planet systems of sub-Neptunes, more planet pairs are observed near resonances than would generally be expected, but no individual system has hitherto been identified that must have been formed by migration. Proximity to resonance enables the detection of planets perturbing each other. Here we report transit timing variations of the four planets in the Kepler-223 system, model these variations as resonant-angle librations, and compute the long-term stability of the resonant chain. The architecture of Kepler-223 is too finely tuned to have been formed by scattering, and our numerical simulations demonstrate that its properties are natural outcomes of the migration hypothesis. Similar systems could be destabilized by any of several mechanisms, contributing to the observed orbital-period distribution, where many planets are not in resonances. Planetesimal interactions in particular are thought to be responsible for establishing the current orbits of the four giant planets in the Solar System by disrupting a theoretical initial resonant chain similar to that observed in Kepler-223

Transit Timing Observations from Kepler: III. Confirmation of 4 Multiple Planet Systems by a Fourier-Domain Study of Anti-correlated Transit Timing Variations

We present a method to confirm the planetary nature of objects in systems with multiple transiting exoplanet candidates. This method involves a Fourier-Domain analysis of the deviations in the transit times from a constant period that result from dynamical interactions within the system. The combination of observed anti-correlations in the transit times and mass constraints from dynamical stability allow us to claim the discovery of four planetary systems Kepler-25, Kepler-26, Kepler-27, and Kepler-28, containing eight planets and one additional planet candidate.Comment: Accepted to MNRA

How reliable are knee kinematics and kinetics during side-cutting manoeuvres?

INTRODUCTION: Side-cutting tasks are commonly used in dynamic assessment of ACL injury risk, but only limited information is available concerning the reliability of knee loading parameters. The aim of this study was to investigate the reliability of side-cutting data with additional focus on modelling approaches and task execution variables. METHODS: Each subject (n=8) attended six testing sessions conducted by two observers. Kinematic and kinetic data of 45° side-cutting tasks was collected. Inter-trial, inter-session, inter-observer variability and observer/trial ratios were calculated at every time-point of normalised stance, for data derived from two modelling approaches. Variation in task execution variables was regressed against that of temporal profiles of relevant knee data using one-dimensional statistical parametric mapping. RESULTS: Variability in knee kinematics was consistently low across the time-series waveform (≤5°), but knee kinetic variability was high (31.8, 24.1 and 16.9Nm for sagittal, frontal and transverse planes, respectively) in the weight acceptance phase of the side-cutting task. Calculations conveyed consistently moderate-to-good measurement reliability. Inverse kinematic modelling reduced the variability in sagittal (∼6Nm) and frontal planes (∼10Nm) compared to direct kinematic modelling. Variation in task execution variables did not explain any knee data variability. CONCLUSION: Side-cutting data appears to be reliably measured, however high knee moment variability exhibited in all planes, particularly in the early stance phase, suggests cautious interpretation towards ACL injury mechanics. Such variability may be inherent to the dynamic nature of the side-cutting task or experimental issues not yet known

Kepler-16: A Transiting Circumbinary Planet

We report the detection of a planet whose orbit surrounds a pair of low-mass stars. Data from the Kepler spacecraft reveal transits of the planet across both stars, in addition to the mutual eclipses of the stars, giving precise constraints on the absolute dimensions of all three bodies. The planet is comparable to Saturn in mass and size, and is on a nearly circular 229-day orbit around its two parent stars. The eclipsing stars are 20% and 69% as massive as the sun, and have an eccentric 41-day orbit. The motions of all three bodies are confined to within 0.5 degree of a single plane, suggesting that the planet formed within a circumbinary disk.Comment: Science, in press; for supplemental material see http://www.sciencemag.org/content/suppl/2011/09/14/333.6049.1602.DC1/1210923.Doyle.SOM.pd

Discovery of a Third Transiting Planet in the Kepler-47 Circumbinary System

Of the nine confirmed transiting circumbinary planet systems, only Kepler-47 is known to contain more than one planet. Kepler-47 b (the "inner planet") has an orbital period of 49.5 days and a radius of about 3 R⊕. Kepler-47 c (the "outer planet") has an orbital period of 303.2 days and a radius of about 4.7 R⊕. Here we report the discovery of a third planet, Kepler-47 d (the "middle planet"), which has an orbital period of 187.4 days and a radius of about 7 R⊕. The presence of the middle planet allows us to place much better constraints on the masses of all three planets, where the 1σranges are less than 26 M⊕, between 7–43 M⊕, and between 2–5 M⊕ for the inner, middle, and outer planets, respectively. The middle and outer planets have low bulk densities, with ρ_(middle) < 0.68 g cm^(−3) and ρ_(outer) < 0.26 g cm^(−3) at the 1σ level. The two outer planets are "tightly packed," assuming the nominal masses, meaning no other planet could stably orbit between them. All of the orbits have low eccentricities and are nearly coplanar, disfavoring violent scattering scenarios and suggesting gentle migration in the protoplanetary disk

Kepler-21b: A 1.6REarth Planet Transiting the Bright Oscillating F Subgiant Star HD 179070

We present Kepler observations of the bright (V=8.3), oscillating star HD 179070. The observations show transit-like events which reveal that the star is orbited every 2.8 days by a small, 1.6 R_Earth object. Seismic studies of HD 179070 using short cadence Kepler observations show that HD 179070 has a frequencypower spectrum consistent with solar-like oscillations that are acoustic p-modes. Asteroseismic analysis provides robust values for the mass and radius of HD 179070, 1.34{\pm}0.06 M{\circ} and 1.86{\pm}0.04 R{\circ} respectively, as well as yielding an age of 2.84{\pm}0.34 Gyr for this F5 subgiant. Together with ground-based follow-up observations, analysis of the Kepler light curves and image data, and blend scenario models, we conservatively show at the >99.7% confidence level (3{\sigma}) that the transit event is caused by a 1.64{\pm}0.04 R_Earth exoplanet in a 2.785755{\pm}0.000032 day orbit. The exoplanet is only 0.04 AU away from the star and our spectroscopic observations provide an upper limit to its mass of ~10 M_Earth (2-{\sigma}). HD 179070 is the brightest exoplanet host star yet discovered by Kepler.Comment: Accepted to Ap