Biophysical modelling of a drosophila photoreceptor

It remains unclear how visual information is co-processed by different layers of neurons in the retina. In particular, relatively little is known how retina translates vast environmental light changes into neural responses of limited range. We began examining this question in a bottom-up way in a relatively simple °y eye. To gain understanding of how complex bio-molecular interactions govern the conversion of light input into voltage output (phototransduction), we are building a biophysical model of the Drosophila R1-R6 photoreceptor. Our model, which relates molecular dynamics of the underlying biochemical reactions to external light input, attempts to capture the molecular dynamics of phototransduction gain control in a quantitative way

Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD

Dirkje S Postma,1 Nicolas Roche,2 Gene Colice,3 Elliot Israel,4 Richard J Martin,5 Willem MC van Aalderen,6 Jonathan Grigg,7 Anne Burden,8 Elizabeth V Hillyer,8 Julie von Ziegenweidt,8 Gokul Gopalan,9 David Price8,10 1University of Groningen, Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, Groningen, the Netherlands; 2Respiratory and Intensive Care Medicine, Cochin Hospital Group, APHP, Paris-Descartes University (EA2511), Paris, France; 3Pulmonary, Critical Care and Respiratory Services, Washington Hospital Center and George Washington University School of Medicine, Washington DC, USA; 4Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 5Department of Medicine, National Jewish Health, Denver, CO, USA; 6Dept of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital AMC, Amsterdam, the Netherlands; 7Blizard Institute, Queen Mary University London, London, UK; 8Research in Real Life, Ltd, Cambridge, UK; 9Respiratory, Global Scientific Affairs, Teva Pharmaceuticals, Frazer, PA, USA; 10Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK Purpose: Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD), which is currently treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD) grades 2–4. This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone) and larger-particle ICS (fluticasone) in primary care patients with COPD. Patients and methods: Smokers and ex-smokers with COPD ≥40 years old initiating or stepping-up their dose of extrafine beclomethasone or fluticasone were matched 1:1 for demographic characteristics, index prescription year, concomitant therapies, and disease severity during 1 baseline year. During 2 subsequent years, we evaluated treatment change and COPD exacerbations, defined as emergency care/hospitalization for COPD, acute oral corticosteroids, or antibiotics for lower respiratory tract infection. Results: Mean patient age was 67 years, 57%–60% being male. For both initiation (n=334:334) and step-up (n=189:189) patients, exacerbation rates were comparable between extrafine beclomethasone and fluticasone cohorts during the 2 year outcome period. Odds of treatment stability (no exacerbation or treatment change) were significantly greater for patients initiating extrafine beclomethasone compared with fluticasone (adjusted odds ratio 2.50; 95% confidence interval, 1.32–4.73). Median ICS dose exposure during 2 outcome years was significantly lower (P<0.001) for extrafine beclomethasone than fluticasone cohorts (315 µg/day versus 436 µg/day for initiation, 438 µg/day versus 534 µg/day for step-up patients). Conclusion: We observed that small-particle ICS at significantly lower doses had comparable effects on exacerbation rates as larger-particle ICS at higher doses, whereas initiation of small-particle ICS was associated with better odds of treatment stability during 2-years' follow-up. Keywords: COPD exacerbation, extrafine particle, matched cohort analysis, real life, small airway

Sneutrino condensate as a candidate for the hot big bang cosmology

If inflationary paradigm is correct, then it must create conditions for the hot big bang model with all observed matter, baryons and the seed perturbations for the structure formation. In this paper we propose a scenario where the inflaton energy density is dumped into the bulk in a brane world setup, and all the required physical conditions are created by the right handed neutrino sector within supersymmetry. The scalar component of the right handed Majorana neutrino is responsible for generating the scale invariant fluctuations in the cosmic microwave background radiation, reheating the Universe at a temperature~$T_{rh}\leq 10^{9}$ GeV, and finally generating the lepton/baryon asymmetry, $n_{B}/s\sim 10^{-10}$, with no lepton/baryon isocurvature fluctuations.Comment: 19 pages, 3 figures. Some discussion on neutrino masses and baryogenesis, and other small changes adde

Curvaton Potential Terms, Scale-Dependent Perturbation Spectra and Chaotic Initial Conditions

The curvaton scenario predicts an almost scale-invariant spectrum of perturbations in most inflation models. We consider the possibility that renormalisable phi^4 or Planck scale-suppressed non-renormalisable curvaton potential terms may result in an observable deviation from scale-invariance. We show that if the curvaton initially has a large amplitude and if the total number of e-foldings of inflation is less than about 300 then a running blue perturbation spectrum with an observable deviation from scale-invariance is likely. D-term inflation is considered as an example with a potentially low total number of e-foldings of inflation. A secondary role for the curvaton, in which it drives a period of chaotic inflation leading to D-term or other flat potential inflation from an initially chaotic state, is suggested.Comment: 12 pages LaTeX, minor corrections, to be published in JCA

Interference effects in electronic transport through metallic single-wall carbon nanotubes

In a recent paper Liang {\it et al.} [Nature {\bf 411}, 665 (2001)] showed experimentally, that metallic nanotubes, strongly coupled to external electrodes, may act as coherent molecular waveguides for electronic transport. The experimental results were supported by theoretical analysis based on the scattering matrix approach. In this paper we analyze theoretically this problem using a real-space approach, which makes it possible to control quality of interface contacts. Electronic structure of the nanotube is taken into account within the tight-binding model. External electrodes and the central part (sample) are assumed to be made of carbon nanotubes, while the contacts between electrodes and the sample are modeled by appropriate on-site (diagonal) and hopping (off-diagonal) parameters. Conductance is calculated by the Green function technique combined with the Landauer formalism. In the plots displaying conductance {\it vs.} bias and gate voltages, we have found typical diamond structure patterns, similar to those observed experimentally. In certain cases, however, we have found new features in the patterns, like a double-diamond sub-structure.Comment: 15 pages, 4 figures. To apear in Phys. Rev.

Identifying the curvaton within MSSM

We consider inflaton couplings to MSSM flat directions and the thermalization of the inflaton decay products, taking into account gauge symmetry breaking due to flat direction condensates. We then search for a suitable curvaton candidate among the flat directions, requiring an early thermally induced start for the flat direction oscillations to facilitate the necessary curvaton energy density dominance. We demonstrate that the supersymmetry breaking $A$-term is crucial for achieving a successful curvaton scenario. Among the many possible candidates, we identify the ${\bf u_1dd}$ flat direction as a viable MSSM curvaton.Comment: 9 pages. Discussion on the evaporation of condensate added, final version published in JCA

Control of spin in quantum dots with non-Fermi liquid correlations

Spin effects in the transport properties of a quantum dot with spin-charge separation are investigated. It is found that the non-linear transport spectra are dominated by spin dynamics. Strong spin polarization effects are observed in a magnetic field. They can be controlled by varying gate and bias voltages. Complete polarization is stable against interactions. When polarization is not complete, it is power-law enhanced by non-Fermi liquid effects.Comment: 4 pages, 4 figure

Hooge's Constant of Carbon Nanotube Field Effect Transistors

The 1/f noise in individual semiconducting carbon nanotubes (s-CNT) in a field effect transistor configuration has been measured in ultra-high vacuum and following exposure to air. The amplitude of the normalized current spectral noise density is independent of source-drain current, indicating the noise is due to mobility rather than number fluctuations. Hooge's constant for s-CNT is found to be 9.3 plus minus 0.4x10^-3. The magnitude of the 1/f noise is substantially degreased by exposing the devices to air

Biomarker Discovery In Chronic Obstructive Pulmonary Disease (COPD) Using Epithelial Lining Fluid:A Proteomic Approach

RATIONALE Chronic Obstructive Pulmonary Disease (COPD) is the third most frequent disease worldwide with increasing mortality. Cigarette smoking is the principle risk factor and 15-20% of smokers develop COPD. Epithelial Lining Fluid (ELF) covers the internal part of the airways and can be collected during bronchoscopy. ELF appears to be well-suited for proteomic analysis, since it contains a higher concentration of proteins (150-300 μg /mL) than other lung fluids and can be obtained from different locations of the lungs. No comprehensive proteomic analysis of human ELF has been performed to date, which makes ELF a highly interesting fluid for biomarker discovery in COPD. AIM To discover proteins that change in abundance in ELF from COPD patients versus healthy controls using a quantitative proteomics approach. METHODS The ELF proteome from COPD patients and healthy controls was studied by 1D polyacrylamide gel electrophoresis in the presence of SDS followed by in-gel tryptic digestion to establish the methodology and assess the feasibility of such an approach. Approximately 40 gel slices were obtained from each lane of the gel (corresponding to one patient). Digested samples were analyzed by nanoChip-LC-MS/MS using an ion trap. We performed a quantitative pilot study of ELF from 4 COPD patients and 4 healthy controls (table 1) to test for statistically significant differences in protein levels. ELF samples were digested by trypsin, labeled with stable isotope-containing reagents (iTRAQ®, 8-plex) and processed by strong cation-exchange chromatography followed by nanoLC-MS/MS. In order to validate the results, a second quantitative analysis of an independent sample set (4 COPD vs 4 healthy) using the same methodological approach was done. RESULTS The 1D electrophoretic approach resulted in more than 300 identified proteins. Most of the identified proteins were present in both COPD and healthy samples, although some proteins were only identified either in healthy control or in COPD samples. The quantitative studies showed that a number of proteins was significantly different between ELF of COPD patients and controls, including 4 up-regulated proteins in common in both studies. CONCLUSIONS This is the first study in ELF of COPD patients and healthy controls in which such a large number of proteins has been identified. The obtained results show the feasibility of this proteomic approach and the possibility to discover proteins that are differentially expressed in ELF of COPD patients and controls. We are currently validating these proteins further by western blot and immunohistochemistry

Basins of attraction of a nonlinear nanomechanical resonator

We present an experiment that systematically probes the basins of attraction of two fixed points of a nonlinear nanomechanical resonator and maps them out with high resolution. We observe a separatrix which progressively alters shape for varying drive strength and changes the relative areas of the two basins of attraction. The observed separatrix is blurred due to ambient fluctuations, including residual noise in the drive system, which cause uncertainty in the preparation of an initial state close to the separatrix. We find a good agreement between the experimentally mapped and theoretically calculated basins of attraction