Laser Applications to Chemical and Environmental Analysis: Introduction to the Feature Issue

This issue of Applied Optics features 16 papers describing chemical and environmental measurements made possible by lasers. Many of these contributions were presented at the Optical Society of America Topical Meeting on Laser Applications to Chemical and Environmental Analysis, held in Orlando, Florida, 9–11 March 1998.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86759/1/Sick33.pd

Predictions of airfoil aerodynamic performance degradation due to icing

An overview of NASA's ongoing efforts to develop an airfoil icing analysis capability is developed. An indication is given to the approaches being followed to calculate the water droplet trajectories past the airfoil, the buildup of ice on the airfoil, and the resultant changes in aerodynamic performance due to the leading edge ice accretion. Examples are given of current code capabilities/limitations through comparisons of predictions with experimental data gathered in various calibration/validation experiments. A brief discussion of future efforts to extend the analysis to handle three dimensional components is included

The development and evaluation of mini-GEMs: a short, focused, online e-learning videos in geriatric medicine

Mini Geriatric E-Learning Modules (Mini-GEMs) are short, focused, e-learning videos on geriatric medicine topics, hosted on YouTube, which are targeted at junior doctors working with older people. This study aimed to explore how these resources are accessed and used. The authors analyzed the viewing data from 22 videos published over the first 18 months of the Mini-GEM project. We conducted a focus group of U.K. junior doctors considering their experiences with Mini-GEMS. The Mini-GEMs were viewed 10,291 times over 18 months, equating to 38,435 minutes of total viewing time. The average viewing time for each video was 3.85 minutes. Learners valued the brevity and focused nature of the Mini-GEMs and reported that they watched them in a variety of settings to supplement clinical experiences and consolidate learning. Watching the videos led to an increase in self-reported confidence in managing older patients. Mini-GEMs can effectively disseminate clinical teaching material to a wide audience. The videos are valued by junior doctors due to their accessibility and ease of use

The Dynamics of Sustained Reentry in a Loop Model with Discrete Gap Junction Resistance

Dynamics of reentry are studied in a one dimensional loop of model cardiac cells with discrete intercellular gap junction resistance ($R$). Each cell is represented by a continuous cable with ionic current given by a modified Beeler-Reuter formulation. For $R$ below a limiting value, propagation is found to change from period-1 to quasi-periodic ($QP$) at a critical loop length ($L_{crit}$) that decreases with $R$. Quasi-periodic reentry exists from $L_{crit}$ to a minimum length ($L_{min}$) that is also shortening with $R$. The decrease of $L_{crit}(R)$ is not a simple scaling, but the bifurcation can still be predicted from the slope of the restitution curve giving the duration of the action potential as a function of the diastolic interval. However, the shape of the restitution curve changes with $R$.Comment: 6 pages, 7 figure

Approximate Bayesian Computation Reveals the Crucial Role of Oceanic Islands for the Assembly of Continental Biodiversity

The perceived low levels of genetic diversity, poor interspecific competitive and defensive ability, and loss of dispersal capacities of insular lineages have driven the view that oceanic islands are evolutionary dead ends. Focusing on the Atlantic bryophyte flora distributed across the archipelagos of the Azores, Madeira, the Canary Islands, Western Europe, and northwestern Africa, we used an integrative approach with species distribution modeling and population genetic analyses based on approximate Bayesian computation to determine whether this view applies to organisms with inherent high dispersal capacities. Genetic diversity was found to be higher in island than in continental populations, contributing to mounting evidence that, contrary to theoretical expectations, island populations are not necessarily genetically depauperate. Patterns of genetic variation among island and continental populations consistently fitted those simulated under a scenario of de novo foundation of continental populations from insular ancestors better than those expected if islands would represent a sink or a refugium of continental biodiversity. We, suggest that the northeastern Atlantic archipelagos have played a key role as a stepping stone for transoceanic migrants. Our results challenge the traditional notion that oceanic islands are the end of the colonization road and illustrate the significant role of oceanic islands as reservoirs of novel biodiversity for the assembly of continental flora

Decoherence of electron spin qubits in Si-based quantum computers

Direct phonon spin-lattice relaxation of an electron qubit bound by a donor impurity or quantum dot in SiGe heterostructures is investigated. The aim is to evaluate the importance of decoherence from this mechanism in several important solid-state quantum computer designs operating at low temperatures. We calculate the relaxation rate $1/T_1$ as a function of [100] uniaxial strain, temperature, magnetic field, and silicon/germanium content for Si:P bound electrons. The quantum dot potential is much smoother, leading to smaller splittings of the valley degeneracies. We have estimated these splittings in order to obtain upper bounds for the relaxation rate. In general, we find that the relaxation rate is strongly decreased by uniaxial compressive strain in a SiGe-Si-SiGe quantum well, making this strain an important positive design feature. Ge in high concentrations (particularly over 85%) increases the rate, making Si-rich materials preferable. We conclude that SiGe bound electron qubits must meet certain conditions to minimize decoherence but that spin-phonon relaxation does not rule out the solid-state implementation of error-tolerant quantum computing.Comment: 8 figures. To appear in PRB-July 2002. Revisions include: some references added/corrected, several typos fixed, a few things clarified. Nothing dramati

HPLC Plasma Assay of a Novel Anti-MRSA Compound, Kaempferol-3-O-Alpha-L-(2 \u27\u27,3 \u27\u27-di-p-coumaroyl)rhamnoside, from Sycamore Leaves

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious pathogen that is resistant to current antibiotic therapy. Thus, there is an urgent need for novel antimicrobial agents that can effectively combat these new strains of drug-resistant superbugs . Recently, fractionation of an extract from Platanus occidentalis (American sycamore) leaves produced an active kaempferol molecule, 3-O-alpha-L-(2 ,3 -di-p-coumaroyl)rhamnoside (KCR), in four isomeric forms; all four isomers exhibit potent anti-MRSA activity. In order to further the preclinical development of KCR as a new antibiotic class, we developed and validated a simple analytical method for assaying KCR plasma concentration. Because KCR will be developed as a new drug, although comprising four stereoisomers, the analytical method was devised to assay the total amount of all four isomers. In the present work, both a plasma processing procedure and an HPLC method have been developed and validated. Mouse plasma containing KCR was first treated with ethanol and then centrifuged. The supernatant was dried, suspended in ethanol, centrifuged, and the supernatant was injected into an HPLC system comprising a Waters C18, a mobile phase composing methanol, acetonitrile, and trifluoroacetic acid and monitored at 313 nm. The method was validated by parameters including a good linear correlation, a limit of quantification of 0.27 μg/mL, and high accuracy. In summary, this method allows a rapid analysis of KCR in the plasma samples for pharmacokinetics studies

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype

Diesel exhaust particulate induces pulmonary and systemic inflammation in rats without impairing endothelial function ex vivo or in vivo

<p>Abstract</p> <p>Background</p> <p>Inhalation of diesel exhaust impairs vascular function in man, by a mechanism that has yet to be fully established. We hypothesised that pulmonary exposure to diesel exhaust particles (DEP) would cause endothelial dysfunction in rats as a consequence of pulmonary and systemic inflammation.</p> <p>Methods</p> <p>Wistar rats were exposed to DEP (0.5 mg) or saline vehicle by intratracheal instillation and hind-limb blood flow, blood pressure and heart rate were monitored <it>in situ </it>6 or 24 h after exposure. Vascular function was tested by administration of the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) <it>in vivo </it>and <it>ex vivo </it>in isolated rings of thoracic aorta, femoral and mesenteric artery from DEP exposed rats. Bronchoalveolar lavage fluid (BALF) and blood plasma were collected to assess pulmonary (cell differentials, protein levels & interleukin-6 (IL-6)) and systemic (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP)) inflammation, respectively.</p> <p>Results</p> <p>DEP instillation increased cell counts, total protein and IL-6 in BALF 6 h after exposure, while levels of IL-6 and TNFα were only raised in blood 24 h after DEP exposure. DEP had no effect on the increased hind-limb blood flow induced by ACh <it>in vivo </it>at 6 or 24 h. However, responses to SNP were impaired at both time points. In contrast, <it>ex vivo </it>responses to ACh and SNP were unaltered in arteries isolated from rats exposed to DEP.</p> <p>Conclusions</p> <p>Exposure of rats to DEP induces both pulmonary and systemic inflammation, but does not modify endothelium-dependent vasodilatation. Other mechanisms <it>in vivo </it>limit dilator responses to SNP and these require further investigation.</p

The Australian multiple sclerosis (MS) immunotherapy study: A prospective, multicentre study of drug utilisation using the MSBase platform

To prospectively characterise treatment persistence and predictors of treatment discontinuation in an Australian relapsing-remitting multiple sclerosis (RRMS) population. Tertiary MS treatment centres participating in the MSBase registry prospectively assessed treatment utilisation, persistence, predictors of treatment discontinuation and switch rates. Multivariable survival analyses were used to compare treatment persistence between drugs and to identify predictors of treatment discontinuation. 1113 RRMS patients were studied. Patients persisted on their first disease-modifying therapy (DMT) for a median of 2.5 years. Treatment persistence on GA was shorter than on all IFN&beta; products (p&lt;0.03). Younger age at treatment initiation and higher EDSS were predictive of DMT discontinuation. Patients persisted on subsequent DMTs, for 2.3 years. Patients receiving natalizumab (NAT) as a subsequent DMT persisted longer on treatment than those on IFN&beta; or GA (p&lt;0.000). The primary reason for treatment discontinuation for any drug class was poor tolerability. Annualised switch or cessation rates were 9.5&ndash;12.5% for individual IFN&beta; products, 11.6% for GA and 4.4% for NAT. This multicentre MS cohort study is the first to directly compare treatment persistence on IFN&beta; and GA to NAT. We report that treatment persistence in our Australian RRMS population is short, although patients receiving IFN&beta; as a first DMT persisted longer on treatment than those on GA. Additionally, patients receiving NAT as a subsequent DMT were more likely to persist on treatment than those switched to IFN&beta; or GA. EDSS and age at DMT initiation were predictive of DMT discontinuation. Treatment intolerance was the principal reason for treatment cessation