Improved Aircraft Acoustic Technology and its Effect on Airport Community Noise Impact

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Evaluating the Environmental Performance of the U.S. Next Generation Air Transportation System

The environmental impacts of several possible U.S. Next Generation Air Transportation scenarios have been quantitatively evaluated for noise, air-quality, fuel-efficiency, and CO2 impacts. Three principal findings have emerged. (1) 2025 traffic levels about 30% higher than 2006 are obtained by increasing traffic according to FAA projections while also limiting traffic at each airport using reasonable ratios of demand to capacity. NextGen operational capabilities alone enable attainment of an additional 10-15% more flights beyond that 2025 baseline level with negligible additional noise, air-quality, and fuel-efficiency impacts. (2) The addition of advanced engine and airframe technologies provides substantial additional reductions in noise and air-quality impacts, and further improves fuel efficiency. 2025 environmental goals based on projected system-wide improvement rates of about 1% per year for noise and fuel-efficiency (an air-quality goal is not yet formulated) are achieved using this new vehicle technology. (3) Overall air-transport "product", as measured by total flown distance or total payload distance, increases by about 50% relative to 2006, but total fuel consumption and CO2 production increase by only about 40% using NextGen operational capabilities. With the addition of advanced engine/airframe technologies, the increase in total fuel consumption and CO2 production can be reduced to about 30%

Using decision analysis: connecting "classroom" and "field"

This paper reports on the findings of a small-scale research project investigating the views of social work students on the use of decision analysis. After giving the context of the research, the article reports on what was found when students, who had just completed a Decision Making and Risk module, were asked for their opinions on the component parts of decision analysis, its use as a practice tool and their attitudes to using it on placement. The research found that the respondents in general took a critical and supportive stance towards the use of decision analysis in social work and, with extra teaching and a positive approach from their practice assessor, would be happy to use decision analysis. When the same group of students completed a follow-up questionnaire on a placement recall day, half of them had thought about using decision analysis but only three had gone on to discuss this with their practice assessors. Some issues in relation to connecting 'classroom' and 'field' are identified and the paper concludes that a number of further steps would be necessary to realise the potential of decision analysis to help students be more systematic and analytical in their approach to decision makin

Sustained Expression with Partial Correction of Neutrophil Defects 5 Years After Intramuscular rAAV1 Gene Therapy for Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency is a common monogenic disorder resulting in emphysema, which is currently treated with weekly infusions of protein replacement. We previously reported achieving plasma wild-type (M) AAT concentrations at 2.5-3.8% of the therapeutic level at 1 year after intramuscular (IM) administration of 6×1012vg/kg of a recombinant adeno-associated virus serotype 1 (rAAV1)-AAT vector in AAT-deficient patients, with an associated regulatory T cell (Treg) response to AAV1 capsid epitopes in the absence of any exogenous immune suppression. Here, we report sustained expression at greater than 2% of the therapeutic level for 5 years after one-time treatment with rAAV1-AAT in an AAT-deficient patient from that study, with partial correction of neutrophil defects previously reported in AAT-deficient patients. There was also evidence of an active Treg response (FoxP3+, Helios+) and an exhausted cytotoxic T cell response (PD-1+, LAG-3+) to AAV1 capsid. These findings suggest that muscle-based AAT gene replacement is toleragenic and that very stable levels of M AAT may exert beneficial effects at lower concentrations than previously anticipated

The Tribology of Sliding Elastic Media

The tribology of a sliding elastic continuum in contact with a disordered substrate is investigated analytically and numerically via a bead-spring model. The deterministic dynamics of this system exhibits a depinning transition at a finite driving force, with complex spatial-temporal dynamics including stick-slip events of all sizes. These behaviors can be understood completely by mapping the system to the well-known problem of a directed-path in {\em higher-dimensional } random media.Comment: Uuencode file: 4 pages, small changes in the previous versio

5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from years 1-5 in these same patients without any additional recombinant adeno-associated virus serotype-1 alpha-1 antitrypsin vector administration. In addition, we observed partial correction of disease-associated neutrophil defects, including neutrophil elastase inhibition, markers of degranulation, and membrane-bound anti-neutrophil antibodies. There was also evidence of an active T regulatory cell response (similar to the 1 year data) and an exhausted cytotoxic T cell response to adeno-associated virus serotype-1 capsid. These findings suggest that muscle-based alpha-1 antitrypsin gene replacement is tolerogenic and that stable levels of M-AAT may exert beneficial neutrophil effects at lower concentrations than previously anticipated

Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results

Recombinant adeno-associated virus (rAAV) vectors offer promise for the gene therapy of α(1)-antitrypsin (AAT) deficiency. In our prior trial, an rAAV vector expressing human AAT (rAAV1-CB-hAAT) provided sustained, vector-derived AAT expression for \u3e1 year. In the current phase 2 clinical trial, this same vector, produced by a herpes simplex virus complementation method, was administered to nine AAT-deficient individuals by intramuscular injection at doses of 6.0×10(11), 1.9×10(12), and 6.0×10(12) vector genomes/kg (n=3 subjects/dose). Vector-derived expression of normal (M-type) AAT in serum was dose dependent, peaked on day 30, and persisted for at least 90 days. Vector administration was well tolerated, with only mild injection site reactions and no serious adverse events. Serum creatine kinase was transiently elevated on day 30 in five of six subjects in the two higher dose groups and normalized by day 45. As expected, all subjects developed anti-AAV antibodies and interferon-γ enzyme-linked immunospot responses to AAV peptides, and no subjects developed antibodies to AAT. One subject in the mid-dose group developed T cell responses to a single AAT peptide unassociated with any clinical effects. Muscle biopsies obtained on day 90 showed strong immunostaining for AAT and moderate to marked inflammatory cell infiltrates composed primarily of CD3-reactive T lymphocytes that were primarily of the CD8(+) subtype. These results support the feasibility and safety of AAV gene therapy for AAT deficiency, and indicate that serum levels of vector-derived normal human AAT \u3e20 μg/ml can be achieved. However, further improvements in the design or delivery of rAAV-AAT vectors will be required to achieve therapeutic target serum AAT concentrations

Academic freedom: in justification of a universal ideal

This paper examines the justification for, and benefits of, academic freedom to academics, students, universities and the world at large. The paper surveys the development of the concept of academic freedom within Europe, more especially the impact of the reforms at the University of Berlin instigated by Wilhelm von Humboldt. Following from this, the paper examines the reasons why the various facets of academic freedom are important and why the principle should continue to be supported

Static and Dynamic Properties of Inhomogeneous Elastic Media on Disordered Substrate

The pinning of an inhomogeneous elastic medium by a disordered substrate is studied analytically and numerically. The static and dynamic properties of a $D$-dimensional system are shown to be equivalent to those of the well known problem of a $D$-dimensional random manifold embedded in $(D+D)$-dimensions. The analogy is found to be very robust, applicable to a wide range of elastic media, including those which are amorphous or nearly-periodic, with local or nonlocal elasticity. Also demonstrated explicitly is the equivalence between the dynamic depinning transition obtained at a constant driving force, and the self-organized, near-critical behavior obtained by a (small) constant velocity drive.Comment: 20 pages, RevTeX. Related (p)reprints also available at http://matisse.ucsd.edu/~hwa/pub.htm

Search for CP Violation in the Decay Z -> b (b bar) g

About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, ${\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab}$ and $h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}$, limits of \hat{h}_b < 0.59$and$h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st