Biomechanics & remodeling of PGS-derived tissue engineered arteries

Issued as final reportNational Science Foundation (U.S.

Finite Element Modeling of the Posterior Eye in Microgravity

Microgravity experienced during spaceflight affects astronauts in various ways, including weakened muscles and loss of bone density. Recently, visual impairment and intracranial pressure (VIIP) syndrome has become a major concern for space missions lasting longer than 30 days. Astronauts suffering from VIIP syndrome have changes in ocular anatomical and visual impairment that persist after returning to earth. It is hypothesized that a cephalad fluid shift in microgravity may increase the intracranial pressure (ICP), which leads to an altered biomechanical environment of the posterior globe and optic nerve sheath (ONS).Currently, there is a lack of knowledge of how elevated ICP may lead to vision impairment and connective tissue changes in VIIP. Our goal was to develop a finite element model to simulate the acute effects of elevated ICP on the posterior eye and optic nerve sheath. We used a finite element (FE) analysis approach to understand the response of the lamina cribrosa and optic nerve to the elevations in ICP thought to occur in microgravity and to identify which tissue components have the greatest impact on strain experienced by optic nerve head tissues

Contractile force is enhanced in Aortas from pendrin null mice due to stimulation of angiotensin II-dependent signaling.

Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation

Association between benzodiazepine use and exacerbations and mortality in patients with asthma: a matched case-control and survival analysis using the United Kingdom Clinical Practice Research Datalink

Purpose: To investigate the association between the GABAergic drugs, benzodiazepines or zopiclone, and the occurrence of asthma exacerbations and subsequent mortality in a cohort of asthma patients. Methods: 105,747 patients without asthma exacerbation and 25,895 patients with exacerbated asthma were included. A nested case-control study probed the association between benzodiazepines or zopiclone and occurrence of asthma exacerbation (primary outcome) using conditional logistic regression. Cox regression was used to determine the association between the drugs and all-cause mortality in patients with recorded asthma exacerbation. Adjusted matched odds ratios (adj mOR), and adjusted hazard ratios (adj HR) with 95% confidence intervals (CI) are presented. Results: Current benzodiazepine use was associated with increased occurrence of asthma exacerbation (adj mOR 1.49; 1.15-1.93; P=0.001) as was current zopiclone use (adj mOR 1.59; 95% CI 1.37-1.85; P<0.001). In patients with an asthma exacerbation, current benzodiazepine use was associated with increased all-cause mortality during a median follow-up of 2 years (adj HR 2.78; 95% CI 1.26-6.12; P=0.011), and the association between zopiclone use and all-cause mortality showed borderline statistical significance (adj HR 1.58; 95% CI 0.98-2.54; P=0.058). Conclusion: Benzodiazepines and zopiclone may increase the likelihood of asthma exacerbation and benzodiazepines may also increase the likelihood of mortality following exacerbation. These data suggest that caution should be exercised when prescribing benzodiazepines to patients with asthma

Near-surface hydraulic conductivity of Northern Hemisphere glaciers

The hydrology of near‐surface glacier ice remains a neglected aspect of glacier hydrology despite its role in modulating meltwater delivery to downstream environments. To elucidate the hydrological characteristics of this near‐surface glacial weathering crust, we describe the design and operation of a capacitance‐based piezometer that enables rapid, economical deployment across multiple sites and provides an accurate, high‐resolution record of near‐surface water‐level fluctuations. Piezometers were employed at 10 northern hemisphere glaciers, and through the application of standard bail–recharge techniques, we derive hydraulic conductivity (K) values from 0.003 to 3.519 m day−1, with a mean of 0.185 ± 0.019 m day−1. These results are comparable to those obtained in other discrete studies of glacier near‐surface ice, and for firn, and indicate that the weathering crust represents a hydrologically inefficient aquifer. Hydraulic conductivity correlated positively with water table height but negatively with altitude and cumulative short‐wave radiation since the last synoptic period of either negative air temperatures or turbulent energy flux dominance. The large range of K observed suggests complex interactions between meteorological influences and differences arising from variability in ice structure and crystallography. Our data demonstrate a greater complexity of near‐surface ice hydrology than hitherto appreciated and support the notion that the weathering crust can regulate the supraglacial discharge response to melt production. The conductivities reported here, coupled with typical supraglacial channel spacing, suggest that meltwater can be retained within the weathering crust for at least several days. Not only does this have implications for the accuracy of predictive meltwater run‐off models, but we also argue for biogeochemical processes and transfers that are strongly conditioned by water residence time and the efficacy of the cascade of sediments, impurities, microbes, and nutrients to downstream ecosystems. Because continued atmospheric warming will incur rising snowline elevations and glacier thinning, the supraglacial hydrological system may assume greater importance in many mountainous regions, and consequently, detailing weathering crust hydraulics represents a research priority because the flow path it represents remains poorly constrained

Journeys from quantum optics to quantum technology

Sir Peter Knight is a pioneer in quantum optics which has now grown to an important branch of modern physics to study the foundations and applications of quantum physics. He is leading an effort to develop new technologies from quantum mechanics. In this collection of essays, we recall the time we were working with him as a postdoc or a PhD student and look at how the time with him has influenced our research

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky

Mechanically-induced remodeling of tissue engineered blood vessels

Issued as final reportUnited States. Dept. of Health and Human Service

Biomechanics and Remodeling in Native and Engineered Arteries

Presented on April 20, 2010 from 8:30 a.m.-9:30 a.m. at the Parker H. Petit Institute for Bioengineering & Bioscience (IBB), room 1128, Georgia Tech.Runtime: 53:17 minutesDespite advances over the past 25 years, a pressing clinical need remains to develop small diameter tissue engineered blood vessels (TEBV) with low thrombogenicity and immune responses, suitable mechanical properties, and a capacity to remodel to their environment. One promising technology for developing a TEBV is the self-assembly approach. This approach consists of culturing vascular cells to form sheets of cells and extracellular matrix, then rolling these sheets around a mandrel and culturing them to form a tubular structure. Sheets made from different cell types (e.g. SMCs versus fibroblasts) can be combined to produce heterogeneous vessels containing media-like and adventitia-like layers; vessels may also be seeded with endothelial cells to form a functional endothelium. This presentation reviews recent studies conducted in our lab that characterize the biomechanical properties of both native arteries and engineered tissues and the implications of these findings on defining appropriate design criteria for a coronary by-pass graft. Biomechanical testing and parameter estimation to characterize the mechanical behavior of the media-like and adventitia-like self assembly-derived TEBV are be presented and compared to TEBV constructed from competing tissue engineering strategies (e.g., collagen gels), as well as representative data from human coronary arteries taken from the literature. The predictive capability of the constitutive model is be demonstrated by comparing modeling predictions to experimental data from two-layer self assembly-derived TEBV. Finally, modeling results are presented to test novel fabrication strategies to control the mechanical behavior of self assembly-derived TEBV