Abstract:
mparison of the systemic bioavailability of mometasone furoate after oral inhalation from a mometasone furoate/formoterol fumarate metered-dose inhaler versus a mometasone furoate dry-powder inhaler in patients with chronic obstructive pulmonary disease Original Research (421) Total Article Views Authors: Kosoglou T, Hubbell J, Xuan F, Cutler DL, Meehan AG, Kantesaria B, Wittmer BA Published Date March 2013 Volume 2013:8 Pages 107 - 116 DOI: http://dx.doi.org/10.2147/COPD.S36592 Received: 01 August 2012 Accepted: 12 September 2012 Published: 07 March 2013 Teddy Kosoglou,1 James Hubbell,2 Fengjuan Xuan,3 David L Cutler,1 Alan G Meehan,4 Bhavna Kantesaria,5 Bret A Wittmer6, 1Clinical Pharmacology, 2Exploratory Drug Metabolism, 3Early Development Statistics, 4Medical Communications, 5Drug Metabolism/Pharmacokinetics, Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USA; 6Commonwealth Biomedical Research, LLC, Madisonville, KY, USA Dr Bret A Wittmer passed away on May 9, 2012. Background: Coadministration of mometasone furoate (MF) and formoterol fumarate (F) produces additive effects for improving symptoms and lung function and reduces exacerbations in patients with asthma and chronic obstructive pulmonary disease (COPD). The present study assessed the relative systemic exposure to MF and characterized the pharmacokinetics of MF and formoterol in patients with COPD. Methods: This was a single-center, randomized, open-label, multiple-dose, three-period, three-treatment crossover study. The following three treatments were self-administered by patients (n = 14) with moderate-to-severe COPD: MF 400 μg/F 10 μg via a metered-dose inhaler (MF/F MDI; DULERA /ZENHALE ) without a spacer device, MF/F MDI with a spacer, or MF 400 μg via a dry-powder inhaler (DPI; ASMANEX TWISTHALER ) twice daily for 5 days. Plasma samples for MF and formoterol assay were obtained predose and at prespecified time points after the last (morning) dose on day 5 of each period of the crossover. The geometric mean ratio (GMR) as a percent and the corresponding 90% confidence intervals (CI) were calculated for treatment comparisons. Results: Systemic MF exposure was lower (GMR 77%; 90% CI 58, 102) following administration by MF/F MDI compared to MF DPI. Additionally, least squares geometric mean systemic exposures of MF and formoterol were lower (GMR 72%; 90% CI 61, 84) and (GMR 62%; 90% CI 52, 74), respectively, following administration by MF/F MDI in conjunction with a spacer compared to MF/F MDI without a spacer. MF/F MDI had a similar adverse experience profile as that seen with MF DPI. All adverse experiences were either mild or moderate in severity; no serious adverse experience was reported. Conclusion: Systemic MF exposures were lower following administration by MF/F MDI compared with MF DPI. Additionally, systemic MF and formoterol exposures were lower following administration by MF/F MDI with a spacer versus without a spacer. The magnitude of these differences with respe

Abstract:
Background: This work aims at investigating the histology of
hippocampus formation as structural model of information processing. The study addressed
the question whether the pattern of cellular type distribution within
hippocampal fields could be used as support of information processing in the
hippocampus. Method: Pyramidal-shaped
neurons presenting both cytoplasm and nucleus outlined clearly were measured
systematically on brain slides, using a light microscope connected to a
microcomputer equipped with a scanner software for measuring particles. Morphological
types of cells were identified following class sizes and their distribution determined
through hippocampal fields. Results:
A battery of statistical tests: Sturges’ classification, class sizes distribution
around overall mean, Bartlett’s sphericity test, principal components analysis
(PCA) followed by correlations matrix analysis and ANOVA allowed two cellular
groups to be identified in the hippocampus: large and small pyramidal-shaped
cells. Conclusion: The results show
that sensory information processing in the hippocampus could be built on two
classes of pyramidal neurons that differed anatomically with probably different
physiological functions. The study suggests combination ensembles clustering
large and small pyramidal cells at different rates, as fundamental signaling
units of the hippocampus.

Abstract:
In systems such as block copolymer mesophases or physical gels formed by associating copolymers, the dynamical properties are often controlled by the extraction/association of a sticking group. We propose a description of the extraction/association process of a single sticker. The statistical physics of these associated systems is usually dominated by stretched brush-like regions. A sticker has to overcome a potential barrier both to penetrate the stretched structure or to escape a favorable region built by associated stickers. Our main result is that these barriers are crossed by tension fluctuations and that the corresponding processes are thus local with a friction independent of molecular weight. When the potential barriers are high, the (very stretched) equilibrium structures are not likely to develop on reasonable time scales. Stretched model systems may also be grown in situ from nuclei bearing initiating groups. These, irreversibly bound structures, are also briefly discussed.

Abstract:
Predation risk describes the energetic cost an animal suffers when making a trade off between maximizing energy intake and minimizing threats to its survival. We tested whether Andean condors (Vultur gryphus) influenced the foraging behaviors of a top predator in Patagonia, the puma (Puma concolor), in ways comparable to direct risks of predation for prey to address three questions: 1) Do condors exact a foraging cost on pumas?; 2) If so, do pumas exhibit behaviors indicative of these risks?; and 3) Do pumas display predictable behaviors associated with prey species foraging in risky environments? Using GPS location data, we located 433 kill sites of 9 pumas and quantified their kill rates. Based upon time pumas spent at a carcass, we quantified handling time. Pumas abandoned >10% of edible meat at 133 of 266 large carcasses after a single night, and did so most often in open grasslands where their carcasses were easily detected by condors. Our data suggested that condors exacted foraging costs on pumas by significantly decreasing puma handling times at carcasses, and that pumas increased their kill rates by 50% relative to those reported for North America to compensate for these losses. Finally, we determined that the relative risks of detection and associated harassment by condors, rather than prey densities, explained puma “giving up times” (GUTs) across structurally variable risk classes in the study area, and that, like many prey species, pumas disproportionately hunted in high-risk, high-resource reward areas.

Abstract:
The problem of ring formation in solutions of cylindrical micelles is reinvestigated theoretically, taking into account a finite bending rigidity of the self-assembled linear objects. Transitions between three regimes are found when the scission energy is sufficiently large. At very low densities only spherical and very short, rod-like micelles form. Beyond a critical density, mainly rings but also rod-like chains appear in (virtually) fixed relative amounts. Above a second transition both the length of the linear chains and the relative amount of material taken up by them increase rapidly with increasing concentration. The mass accumulated into long, semi-flexible worms then overwhelms that in rings. The ring-dominated regime is very narrow for semi-flexible chains, confirming that the presence of rings may be difficult to observe in many micellar systems, and indeed disappears completely for sufficiently low scission energy and/or large persistence length.

Abstract:
A coarse-grained simulation model eliminates microscopic degrees of freedom and represents a polymer by a simplified structure. A priori, two classes of coarse-grained models may be distinguished: those which are designed for a specific polymer and reflect the underlying atomistic details to some extent, and those which retain only the most basic features of a polymer chain (chain connectivity, short-range excluded-volume interactions, etc.). In this review we mainly focus on the second class of generic polymer models, while the first class of specific coarse-grained models is only touched upon briefly.

Abstract:
We describe a new continuum approach to the modelling of stress propagation in static granular media, focussing on the conical sandpile created from a point source. We argue that the stress continuity equations should be closed by means of scale-free, local constitutive relations between different components of the stress tensor, encoding the construction history of the pile: this history determines the organization of the grains, and thereby the local relationship between stresses. Our preferred model FPA (Fixed Principle Axes) assumes that the eigendirections (but not the eigenvalues) of the stress tensor are determined forever when a material element is first buried. Stresses propagate along a nested set of archlike structures within the medium; the results are in good quantitative agreement with published experimental data. The FPA model is one of a larger class, called OSL (Oriented Stress Linearity) models, in which the direction of the characteristics for stress propagation are fixed at burial. We speculate on the connection between these characteristics and the stress paths observed microscopically.

Abstract:
Focusing on isotropic elastic networks we propose a novel simple-average expression $G(t) = \mu_A - h(t)$ for the computational determination of the shear-stress relaxation modulus $G(t)$ of a classical elastic solid or fluid and its equilibrium modulus $\G_{eq} = \lim_{t \to \infty} G(t)$. Here, $\mu_A = G(0)$ characterizes the shear transformation of the system at $t=0$ and $h(t)$ the (rescaled) mean-square displacement of the instantaneous shear stress $\hat{\tau}(t)$ as a function of time $t$. While investigating sampling time effects we also discuss the related expressions in terms of shear-stress autocorrelation functions. We argue finally that our key relation may be readily adapted for more general linear response functions.

Abstract:
We revisit the relation between the shear stress relaxation modulus $G(t)$, computed at finite shear strain $0 < \gamma \ll 1$, and the shear stress autocorrelation functions $C(t)|_{\gamma}$ and $C(t)|_{\tau}$ computed, respectively, at imposed strain $\gamma$ and mean stress $\tau$. Focusing on permanent isotropic spring networks it is shown theoretically and computationally that in general $G(t) = C(t)|_{\tau} = C(t)|_{\gamma} + G_{eq}$ for $t > 0$ with $G_{eq}$ being the static equilibrium shear modulus. $G(t)$ and $C(t)|_{\gamma}$ thus must become different for solids and it is impossible to obtain $G_{eq}$ alone from $C(t)|_{\gamma}$ as often assumed. We comment briefly on self-assembled transient networks where $G_{eq}(f)$ must vanish for a finite scission-recombination frequency $f$. We argue that $G(t) = C(t)|_{\tau} = C(t)|_{\gamma}$ should reveal an intermediate plateau set by the shear modulus $G_{eq}(f=0)$ of the quenched network.

Abstract:
In this paper, two new electronically tunable filter configurations are proposed. The proposed filters operate current-mode (CM), voltage-mode (VM), transimpedance-mode (TIM) and transadmittance-mode (TAM). The first configuration realizes second-order VM band-pass and TAM high-pass filter characteristics from the same configuration. The second one realizes second-order TIM band-pass and CM low-pass filter characteristics from the same configuration. They also use minimum number of electronic components (two capacitors and one active component namely; current controlled current difference transconductance amplifier). The workability of the proposed structures has been demonstrated by simulation results.