A planned program of study and guidance for parents of acoustically handicapped children

Thesis (Ed.M.)--Boston Universit

Effect of HINS light on the contraction of fibroblast populated collagen lattices

High intensity narrow spectrum (HINS) light has been shown to have bactericidal effects on a range of medically important bacteria[1]. HINS technology could potentially be useful as a method for disinfecting medical implants, tissue engineered constructs and wounds. The fibroblast populated collagen lattice (FPCL) was used as an in vitro model to investigate the effect of HINS light on the wound contraction phase of wound healing

Efficient state initialization by a quantum spectral filtering algorithm

An algorithm that initializes a quantum register to a state with a specified energy range is given, corresponding to a quantum implementation of the celebrated Feit-Fleck method. This is performed by introducing a nondeterministic quantum implementation of a standard spectral filtering procedure combined with an apodization technique, allowing for accurate state initialization. It is shown that the implementation requires only two ancilla qubits. A lower bound for the total probability of success of this algorithm is derived, showing that this scheme can be realized using a finite, relatively low number of trials. Assuming the time evolution can be performed efficiently and using a trial state polynomially close to the desired states, it is demonstrated that the number of operations required scales polynomially with the number of qubits. Tradeoffs between accuracy and performance are demonstrated in a simple example: the harmonic oscillator. This algorithm would be useful for the initialization phase of the simulation of quantum systems on digital quantum computers.Comment: 12 pages, 4 figures, revised versio

Transient but not genetic loss of miR-451 attenuates the development of pulmonary arterial hypertension

<b>Rationale:</b> MicroRNAs are small non-coding RNAs involved in the regulation of gene expression and have recently been implicated in the development of pulmonary arterial hypertension (PAH). Previous work established that miR-451 is up-regulated in rodent models of PAH.<p></p> <b>Objectives:</b> The role of miR-451 in the pulmonary circulation is unknown. We therefore sought to assess the involvement of miR-451 in the development of pulmonary arterial hypertension.<p></p> <b>Methods:</b> Silencing of miR-451 was performed in vivo using miR-451 knockout mice and an antimiR targeting mature miR-451 in rats. Coupled with exposure to hypoxia, indices of pulmonary arterial hypertension were assessed. The effect of modulating miR-451 on human pulmonary artery smooth muscle cell proliferation and migration was analysed.<p></p> <b>Measurements and Main Results:</b> We observed a reduction in systolic right ventricular pressure in hypoxic rats pre-treated with antimiR-451 compared to hypoxia alone (47.7 ± 1.36mmHg and 56.0 ± 2.03mmHg respectively, p<0.01). In miR-451 knockout mice following exposure to chronic hypoxia, no significant differences were observed compared to wild type hypoxic mice. In vitro analysis demonstrated that over-expression of miR-451 in human pulmonary artery smooth muscle cells promoted migration under serum-free conditions. No effect on cellular proliferation was observed.<p></p> <b>Conclusions:</b> Transient inhibition of miR-451 attenuated the development of pulmonary arterial hypertension in hypoxia exposed rats. Genetic deletion of miR-451 had no beneficial effect on indices of pulmonary arterial hypertension, potentially due to pathway redundancy compensating for the loss of miR-451.<p></p&gt

Metformin reverses development of pulmonary hypertension via aromatase inhibition

Females are more susceptible to pulmonary arterial hypertension than males, although the reasons remain unclear. The hypoglycemic drug, metformin, is reported to have multiple actions, including the inhibition of aromatase and stimulation of AMP-activated protein kinase. Inhibition of aromatase using anastrazole is protective in experimental pulmonary hypertension but whether metformin attenuates pulmonary hypertension through this mechanism remains unknown. We investigated whether metformin affected aromatase activity and if it could reduce the development of pulmonary hypertension in the sugen 5416/hypoxic rat model. We also investigated its influence on proliferation in human pulmonary arterial smooth muscle cells. Metformin reversed right ventricular systolic pressure, right ventricular hypertrophy, and decreased pulmonary vascular remodeling in the rat. Furthermore, metformin increased rat lung AMP-activated protein kinase signaling, decreased lung and circulating estrogen levels, levels of aromatase, the estrogen metabolizing enzyme; cytochrome P450 1B1 and its transcription factor; the aryl hydrocarbon receptor. In human pulmonary arterial smooth muscle cells, metformin decreased proliferation and decreased estrogen synthesis by decreasing aromatase activity through the PII promoter site of Cyp19a1. Thus, we report for the first time that metformin can reverse pulmonary hypertension through inhibition of aromatase and estrogen synthesis in a manner likely to be mediated by AMP-activated protein kinase

Serotonin signaling through the 5-HT1B receptor and NADPH oxidase 1 in pulmonary arterial hypertension

Objective: Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesise that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 anti-oxidant systems, promoting vascular injury. Approach and Results: HPASMCs from controls and PAH patients, and PASMCs from Nox1-/- mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT1B receptor and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing (SERT+) female mice, a model of pulmonary hypertension (PH). We confirmed serotonin increased superoxide and H2O2 production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and peroxiredoxin-SO3H and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated, and dependent on c-Src, 5-HT1B receptor and the serotonin transporter in PAH-hPASMCs. Proliferation and extracellular matrix remodeling were exaggerated in PAH-hPASMCs and dependent on 5-HT1B receptor signaling and Nox1, confirmed in PASMCs from Nox1-/- mice. In SERT+ mice, SB216641, a 5-HT1B receptor antagonist, prevented development of PH in a ROS-dependent manner. Conclusions: Serotonin can induce c-Src-regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins, activation of redox-sensitive signaling pathways in hPASMCs; associated with mitogenic responses. 5-HT1B receptors contribute to experimental PH by inducing lung ROS production. Our results suggest 5-HT1B receptor-dependent c-Src-Nox1-pathways contribute to vascular remodeling in PAH

Laser drilling of via micro-holes in single-crystal semiconductor substrates using a 1070 nm fibre laser with millisecond pulse widths

Micro-machining of semiconductors is relevant to fabrication challenges within the semiconductor industry. For via holes for solar cells, laser drilling potentially avoids deep plasma etching which requires sophisticated equipment and corrosive, high purity gases. Other applications include backside loading of cold atoms into atom chips and ion traps for quantum physics research, for which holes through the semiconductor substrate are needed. Laser drilling, exploiting the melt ejection material removal mechanism, is used industrially for drilling hard to machine materials such as superalloys. Lasers of the kind used in this work typically form holes with diameters of 100’s of microns and depths of a few millimetres in metals. Laser drilling of semiconductors typically uses short pulses of UV or long wavelength IR to achieve holes as small as 50 microns. A combination of material processes occurs including laser absorption, heating, melting, vaporization with vapour and dust particle ejection and resolidification. An investigation using materials with different fundamental material parameters allows the suitability of any given laser for the processing of semiconductors to be determined. We report results on the characterization of via holes drilled using a 2000 W maximum power 1070 nm fibre laser with 1-20 ms pulses using single crystal silicon, gallium arsenide and sapphire. Holes were characterised in cross-section and plan view. Significantly, relatively long pulses were effective even for wide bandgap substrates which are nominally transparent at 1070 nm. Examination of drilled samples revealed holes had been successfully generated in all materials via melt ejection

Investigation of Boundary Conditions for Flexible Multibody Spacecraft Dynamics

In support of both the Space Shuttle and International Space Station programs, a set of generic multibody dynamics algorithms integrated within the Trick simulation environment have addressed the variety of on-orbit manipulator simulation requirements for engineering analysis, procedures development and crew familiarization/training at the NASA Johnson Space Center (JSC). Enhancements to these dynamics algorithms are now being driven by a new set of Constellation program requirements for flexible multibody spacecraft simulation. One particular issue that has been discussed within the NASA community is the assumption of cantilever-type flexible body boundary conditions. This assumption has been commonly utilized within manipulator multibody dynamics formulations as it simplifies the computation of relative motion for articulated flexible topologies. Moreover, its use for modeling of space-based manipulators such as the Shuttle Remote Manipulator System (SRMS) and Space Station Remote Manipulator System (SSRMS) has been extensively validated against flight data. For more general flexible spacecraft applications, however, the assumption of cantilever-type boundary conditions may not be sufficient. This paper describes the boundary condition assumptions that were used in the original formulation, demonstrates that this formulation can be augmented to accommodate systems in which the assumption of cantilever boundary conditions no longer applies, and verifies the approach through comparison with an independent model previously validated against experimental hardware test data from a spacecraft flexible dynamics emulator

Successful elimination of factor VIII inhibitor using cyclosporin A

No abstract available