Modeling of complex chemical reactions and macromolecular orientation phenomena in confined geometries

The cooperative motion algorithm was applied on the molecular simulation of complex chemical reactions and macromolecular orientation phenomena in confined geometries. First, we investigated the case of equilibrium step-growth polymerization in lamellae, pores and droplets. In such systems, confinement was quantified as the area/volume ratio. Results showed that, as confinement increases, polymerization becomes slower and the average molecular weight (MW) at equilibrium decreases. This is caused by the sterical hindrance imposed by the walls since chain growth reactions in their close vicinity have less realization possibilities. For reactions inside droplets at surfaces, contact angles usually increased after polymerization to compensate conformation restrictions imposed by confinement upon growing chains. In a second investigation, we considered monodisperse and chemically inert chains and focused on the effect of confinement on chain orientation. Simulations of thin polymer films showed that chains are preferably oriented parallel to the surface. Orientation increases as MW increases or as film thickness d decreases, in qualitative agreement with experiments with low MW polystyrene. It is demonstrated that the orientation of simulated chains results from a size effect, being a function of the ratio between chain end-to-end distance and d. This study was complemented by experiments with thin films of pi-conjugated polymers like MEH-PPV. Anisotropic refractive index measurements were used to analyze chain orientation. With increasing MW, orientation is enhanced. However, for MEH-PPV, orientation does not depend on d even at thicknesses much larger than the chain contour length. This contradiction with simulations was discussed by considering additional causes for orientation, for instance the appearance of nematic-like ordering in polymer films. In another investigation, we simulated droplet evaporation at soluble surfaces and reproduced the formation of wells surrounded by ringlike deposits at the surface, as observed experimentally. In our simulations, swollen substrate particles migrate to the border of the droplet to minimize the contact between solvent and vacuum, which costs the most energy. Deposit formation in the beginning of evaporation results in pinning of the droplet. When polymer chains at the substrate surface have strong uniaxial orientation, the resulting pattern is no longer similar to a ring but to a pair of half-moons. In a final stage, as an extension for the model developed for polymerization in nanoreactors, we studied the effect of geometrical confinement on a hypothetical oscillating reaction following the mechanism of the so called periodically forced Brusselator. It was shown that a reaction which is chaotic in the bulk may be driven to periodicity by confinement and vice-versa, opening new perspectives for chaos control.

Right ventricular systolic function and cardiac resynchronization therapy

AIMS: The effect of cardiac resynchronization therapy (CRT) on right ventricular ejection fraction (RVEF) has not been well studied. Furthermore, it is unclear whether baseline RVEF influences response to CRT. To evaluate the acute and chronic effects of CRT on right ventricular systolic function, and to investigate whether baseline RVEF impacts response to CRT. METHODS AND RESULTS: Forty-four patients with a standard indication for CRT underwent radionuclide angiography at baseline and after at least 6 months' follow-up for measuring RVEF, right ventricular synchrony (using phase analysis), and left ventricular ejection fraction (LVEF). In addition, NYHA functional class and 6-min walking distance (6MWD) were evaluated. There were no significant acute changes in RVEF with CRT. After a mean follow-up of 9 +/- 5 months, RVEF was slightly improved (by 1.9 +/- 5.0% in absolute terms, P = 0.016), and to a lesser extent than LVEF (5.1 +/- 9.0%, P = 0.009 compared with RVEF). Right ventricular dyssynchrony was significantly improved at follow-up (P = 0.016). Patients with a baseline RVEF < or = 0.35 (n = 19) were less likely to improve in NYHA class (P = 0.016), and also tended to improve less in 6MWD and LVEF (P < 0.06). CONCLUSION: Cardiac resynchronization therapy has no acute effect on RVEF, and only slightly improves RVEF at follow-up. Patients with reduced RVEF at baseline were less likely to respond to CRT, indicating that right ventricular systolic dysfunction may play a role in patient selection.

Hydrogel-based engineered skeletal muscle grafts normalize heart function early after myocardial infarction

Tissue engineering represents an attractive approach for the treatment of congestive heart failure. The influence of the differentiation of myogenic graft for functional recovery is not defined. We engineered a biodegradable skeletal muscle graft (ESMG) tissue and investigated its functional effect after implantation on the epicardium of an infarcted heart segment. ESMGs were synthesized by mixing collagen (2 mg/mL), Matrigel (2 mg/mL), and rat skeletal muscle cells (10(6)). Qualitative and quantitative aspects of ESMGs were optimized. Two weeks following coronary ligation, the animals were randomized in three groups: ESMG glued to the epicardial surface with fibrin (ESMG, n = 7), fibrin alone (fibrin, n = 5), or sham operation (sham, n = 4). Echocardiography, histology, and immunostaining were performed 4 weeks later. A cohesive three-dimensional tissular structure formed in vitro within 1 week. Myoblasts differentiated into randomly oriented myotubes. Four weeks postimplantation, ESMGs were vascularized and invaded by granulation tissue. Mean fractional shortening (FS) was, however, significantly increased in the ESMG group as compared with preimplantation values (42 +/- 6 vs. 33 +/- 5%, P < 0.05) and reached the values of controlled noninfarcted animals (control, n = 5; 45 +/- 3%; not significant). Pre- and postimplantation FS did not change over these 4 weeks in the sham group and the fibrin-treated animals. This study showed that it is possible to improve systolic heart function following myocardial infarction through implantation of differentiated muscle fibers seeded on a gel-type scaffold despite a low rate of survival.

Air pollution during pregnancy and lung function in newborns: a birth cohort study

Post-natal exposure to air pollution is associated with diminished lung growth during school age. The current authors aimed to determine whether pre-natal exposure to air pollution is associated with lung function changes in the newborn. In a prospective birth cohort of 241 healthy term-born neonates, tidal breathing, lung volume, ventilation inhomogeneity and exhaled nitric oxide (eNO) were measured during unsedated sleep at age 5 weeks. Maternal exposure to particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)), nitrogen dioxide (NO(2)) and ozone (O(3)), and distance to major roads were estimated during pregnancy. The association between these exposures and lung function was assessed using linear regression. Minute ventilation was higher in infants with higher pre-natal PM(10) exposure (24.9 mL x min(-1) per microg x m(-3) PM(10)). The eNO was increased in infants with higher pre-natal NO(2) exposure (0.98 ppb per microg x m(-3) NO(2)). Post-natal exposure to air pollution did not modify these findings. No association was found for pre-natal exposure to O(3) and lung function parameters. The present results suggest that pre-natal exposure to air pollution might be associated with higher respiratory need and airway inflammation in newborns. Such alterations during early lung development may be important regarding long-term respiratory morbidity.

Vertebroplasty: experimental characterization of polymethylmethacrylate bone cement spreading as a function of viscosity, bone porosity, and flow rate

STUDY DESIGN: This is an experimental study on an artificial vertebra model and human cadaveric spine. OBJECTIVE: Characterization of polymethylmethacrylate (PMMA) bone cement distribution in the vertebral body as a function of cement viscosity, bone porosity, and injection speed. Identification of relevant parameters for improved cement flow predictability and leak prevention in vertebroplasty. SUMMARY OF BACKGROUND DATA: Vertebroplasty is an efficient procedure to treat vertebral fractures and stabilize osteoporotic bone in the spine. Severe complications result from bone cement leakage into the spinal canal or the vascular system. Cement viscosity has been identified as an important parameter for leak prevention but the influence of bone structure and injection speed remain obscure. METHODS: An artificial vertebra model based on open porous aluminum foam was used to simulate bone of known porosity. Fifty-six vertebroplasties with 4 different starting viscosity levels and 2 different injection speeds were performed on artificial vertebrae of 3 different porosities. A validation on a human cadaveric spine was executed. The experiments were radiographically monitored and the shape of the cement clouds quantitatively described with the 2 indicators circularity and mean cement spreading distance. RESULTS: An increase in circularity and a decrease in mean cement spreading distance was observed with increasing viscosity, with the most striking change occurring between 50 and 100 Pas. Larger pores resulted in significantly reduced circularity and increased mean cement spreading distance whereas the effect of injection speed on the 2 indicators was not significant. CONCLUSION: Viscosity is the key factor for reducing the risk of PMMA cement leakage and it should be adapted to the degree of osteoporosis encountered in each patient. It may be advisable to opt for a higher starting viscosity but to inject the material at a faster rate.

The long arm of time pressure at work: Cognitive failure and commuting near-accidents

This study tests whether cognitive failures mediate effects of work-related time pressure and time control on commuting accidents and near-accidents. Participants were 83 employees (56% female) who each commuted between their regular place of residence and place of work using vehicles. The Workplace Cognitive Failure Scale (WCFS) asked for the frequency of failure in memory function, failure in attention regulation, and failure in action execution. Time pressure and time control at work were assessed by the Instrument for Stress Oriented Task Analysis (ISTA). Commuting accidents in the last 12 months were reported by 10% of participants, and half of the sample reported commuting near-accidents in the last 4 weeks. Cognitive failure significantly mediated the influence of time pressure at work on near-accidents even when age, gender, neuroticism, conscientiousness, commuting duration, commuting distance, and time pressure during commuting were controlled for. Time control was negatively related to cognitive failure and neuroticism, but no association with commuting accidents or near-accidents was found. Time pressure at work is likely to increase cognitive load. Time pressure might, therefore, increase cognitive failures during work and also during commuting. Hence, time pressure at work can decrease commuting safety. The result suggests a reduction of time pressure at work should improve commuting safety.

Biodiversity and Ecosystem Function in the Gulf of Maine: Pattern and Role of Zooplankton and Pelagic Nekton

This paper forms part of a broader overview of biodiversity of marine life in the Gulf of Maine area (GoMA), facilitated by the GoMA Census of Marine Life program. It synthesizes current data on species diversity of zooplankton and pelagic nekton, including compilation of observed species and descriptions of seasonal, regional and cross-shelf diversity patterns. Zooplankton diversity in the GoMA is characterized by spatial differences in community composition among the neritic environment, the coastal shelf, and deep offshore waters. Copepod diversity increased with depth on the Scotian Shelf. On the coastal shelf of the western Gulf of Maine, the number of higher-level taxonomic groups declined with distance from shore, reflecting more nearshore meroplankton. Copepod diversity increased in late summer, and interdecadal diversity shifts were observed, including a period of higher diversity in the 1990s. Changes in species diversity were greatest on interannual scales, intermediate on seasonal scales, and smallest across regions, in contrast to abundance patterns, suggesting that zooplankton diversity may be a more sensitive indicator of ecosystem response to interannual climate variation than zooplankton abundance. Local factors such as bathymetry, proximity of the coast, and advection probably drive zooplankton and pelagic nekton diversity patterns in the GoMA, while ocean-basin-scale diversity patterns probably contribute to the increase in diversity at the Scotian Shelf break, a zone of mixing between the cold-temperate community of the shelf and the warm-water community offshore. Pressing research needs include establishment of a comprehensive system for observing change in zooplankton and pelagic nekton diversity, enhanced observations of "underknown'' but important functional components of the ecosystem, population and metapopulation studies, and development of analytical modeling tools to enhance understanding of diversity patterns and drivers. Ultimately, sustained observations and modeling analysis of biodiversity must be effectively communicated to managers and incorporated into ecosystem approaches for management of GoMA living marine resources.

Role of phosphatidylethanolamine in the function and assembly of phenylalanine-specific permease of Escherichia coli

Transmembrane segments of polytopic membrane proteins once inserted are generally considered stably oriented due to the large free energy barrier for topological reorientation of adjacent extra-membrane domains. However, proper topology and function of the polytopic membrane protein lactose permease (LacY) of Escherichia coli is dependent on the membrane phospholipid composition revealing topological dynamics of transmembrane domains (Bogdanov, M., Heacock, P. N., and Dowhan, W. (2002) EMBO J. 21, 2107–2116). The high affinity phenylalanine permease PheP shares many topological similarities with LacY. In this study, mutant E. coli cells lacking phosphatidylethanolamine (PE) as a membrane component were used to evaluate the role of PE in the function and assembly of PheP. Active transport of phenylalanine by cells lacking PE was severely inhibited (both Vmax and Km were altered), whereas the PheP protein level in membranes was unaffected. Cysteine residues were introduced into predicted periplasmic or cytoplasmic segments of cysteine-less PheP, and the topology of the protein was explored using a membrane-impermeable thiol-specific biotinylated probe. Based on the biotinylation patterns of PheP in whole cells, the N-terminus and adjoining transmembrane hairpin of PheP adopted an inverted topological orientation in PE-lacking cells. Introduction of PE following the assembly of PheP triggered a reorientation of the N-terminus and adjacent hairpin to their native orientation associated with regain of wild type transport function. These results coupled with the results for LacY support a specific role for membrane lipid composition in determining topological organization and function of membrane proteins. Several other secondary symporters are compromised for activity in PE-lacking cells suggesting that lipid-assisted topogenesis is a general property of such transporters. The reversible orientation of these secondary transport proteins in response to a change of phospholipid composition might be a result of inherent conformational flexibility necessary for transport function or during protein assembly. ^

The dust environment of comet 67P/Churyumov-Gerasimenko from Rosetta OSIRIS and VLT observations in the 4.5 to 2.9 AU heliocentric distance range inbound

Context. The ESA Rosetta spacecraft, currently orbiting around cornet 67P/Churyumov-Gerasimenko, has already provided in situ measurements of the dust grain properties from several instruments, particularly OSIRIS and GIADA. We propose adding value to those measurements by combining them with ground-based observations of the dust tail to monitor the overall, time-dependent dust-production rate and size distribution. Aims. To constrain the dust grain properties, we take Rosetta OSIRIS and GIADA results into account, and combine OSIRIS data during the approach phase (from late April to early June 2014) with a large data set of ground-based images that were acquired with the ESO Very Large Telescope (VLT) from February to November 2014. Methods. A Monte Carlo dust tail code, which has already been used to characterise the dust environments of several comets and active asteroids, has been applied to retrieve the dust parameters. Key properties of the grains (density, velocity, and size distribution) were obtained from. Rosetta observations: these parameters were used as input of the code to considerably reduce the number of free parameters. In this way, the overall dust mass-loss rate and its dependence on the heliocentric distance could be obtained accurately. Results. The dust parameters derived from the inner coma measurements by OSIRIS and GIADA and from distant imaging using VLT data are consistent, except for the power index of the size-distribution function, which is alpha = -3, instead of alpha = -2, for grains smaller than 1 mm. This is possibly linked to the presence of fluffy aggregates in the coma. The onset of cometary activity occurs at approximately 4.3 AU, with a dust production rate of 0.5 kg/s, increasing up to 15 kg/s at 2.9 AU. This implies a dust-to-gas mass ratio varying between 3.8 and 6.5 for the best-fit model when combined with water-production rates from the MIRO experiment.

Structure function and Multifractal spectrum applied to Digital Elevation Model

A Digital Elevation Model (DEM) provides the information basis used for many geographic applications such as topographic and geomorphologic studies, landscape through GIS (Geographic Information Systems) among others. The DEM capacity to represent Earth?s surface depends on the surface roughness and the resolution used. Each DEM pixel depends on the scale used characterized by two variables: resolution and extension of the area studied. DEMs can vary in resolution and accuracy by the production method, although there are statistical characteristics that keep constant or very similar in a wide range of scales. Based on this property, several techniques have been applied to characterize DEM through multiscale analysis directly related to fractal geometry: multifractal spectrum and the structure function. The comparison of the results by both methods is discussed. The study area is represented by a 1024 x 1024 data matrix obtained from a DEM with a resolution of 10 x 10 m each point, which correspond with a region known as ?Monte de El Pardo? a property of Spanish National Heritage (Patrimonio Nacional Español) of 15820 Ha located to a short distance from the center of Madrid. Manzanares River goes through this area from North to South. In the southern area a reservoir is found with a capacity of 43 hm3, with an altitude of 603.3 m till 632 m when it is at the highest capacity. In the middle of the reservoir the minimum altitude of this area is achieved.

On the Mahalanobis Distance Classification Criterion for Multidimensional Normal Distributions

Many existing engineering works model the statistical characteristics of the entities under study as normal distributions. These models are eventually used for decision making, requiring in practice the definition of the classification region corresponding to the desired confidence level. Surprisingly enough, however, a great amount of computer vision works using multidimensional normal models leave unspecified or fail to establish correct confidence regions due to misconceptions on the features of Gaussian functions or to wrong analogies with the unidimensional case. The resulting regions incur in deviations that can be unacceptable in high-dimensional models. Here we provide a comprehensive derivation of the optimal confidence regions for multivariate normal distributions of arbitrary dimensionality. To this end, firstly we derive the condition for region optimality of general continuous multidimensional distributions, and then we apply it to the widespread case of the normal probability density function. The obtained results are used to analyze the confidence error incurred by previous works related to vision research, showing that deviations caused by wrong regions may turn into unacceptable as dimensionality increases. To support the theoretical analysis, a quantitative example in the context of moving object detection by means of background modeling is given.

Effect of substrate-target distance and sputtering pressure in the synthesis of AlN thin films

In this work, we analyze the influence of the processing pressure and the substrate–target distance on the synthesis by reactive sputtering of c-axis oriented polycrystalline aluminum nitride thin films deposited on Si(100) wafers. The crystalline quality of AlN has been characterized by high-resolution X-ray diffraction (HR-XRD). The films exhibited a very high degree of c-axis orientation especially when a low process pressure was used. After growth, residual stress measurements obtained indirectly from radius of curvature measurements of the wafer prior and after deposition are also provided. Two different techniques are used to determine the curvature—an optically levered laser beam and a method based on X-ray diffraction. There is a transition from compressive to tensile stress at a processing pressure around 2 mTorr. The transition occurs at different pressures for thin films of different thickness. The degree of c-axis orientation was not affected by the target–substrate distance as it was varied in between 30 and 70 mm.

A new similarity function for generalized trapezoidal fuzzy numbers

Numerous authors have proposed functions to quantify the degree of similarity between two fuzzy numbers using various descriptive parameters, such as the geometric distance, the distance between the centers of gravity or the perimeter. However, these similarity functions have drawback for specific situations. We propose a new similarity measure for generalized trapezoidal fuzzy numbers aimed at overcoming such drawbacks. This new measure accounts for the distance between the centers of gravity and the geometric distance but also incorporates a new term based on the shared area between the fuzzy numbers. The proposed measure is compared against other measures in the literature.

Single-pair fluorescence resonance energy transfer on freely diffusing molecules: Observation of Förster distance dependence and subpopulations

Photon bursts from single diffusing donor-acceptor labeled macromolecules were used to measure intramolecular distances and identify subpopulations of freely diffusing macromolecules in a heterogeneous ensemble. By using DNA as a rigid spacer, a series of constructs with varying intramolecular donor-acceptor spacings were used to measure the mean and distribution width of fluorescence resonance energy transfer (FRET) efficiencies as a function of distance. The mean single-pair FRET efficiencies qualitatively follow the distance dependence predicted by Förster theory. Possible contributions to the widths of the FRET efficiency distributions are discussed, and potential applications in the study of biopolymer conformational dynamics are suggested. The ability to measure intramolecular (and intermolecular) distances for single molecules implies the ability to distinguish and monitor subpopulations of molecules in a mixture with different distances or conformational states. This is demonstrated by monitoring substrate and product subpopulations before and after a restriction endonuclease cleavage reaction. Distance measurements at single-molecule resolution also should facilitate the study of complex reactions such as biopolymer folding. To this end, the denaturation of a DNA hairpin was examined by using single-pair FRET.

Long-distance transcriptional enhancement by the histone acetyltransferase PCAF

Enhancers are defined by their ability to stimulate gene activity from remote sites and their requirement for promoter-proximal upstream activators to activate transcription. Here we demonstrate that recruitment of the p300/CBP-associated factor PCAF to a reporter gene is sufficient to stimulate promoter activity. The PCAF-mediated stimulation of transcription from either a distant or promoter-proximal position depends on the presence of an upstream activator (Sp1). These data suggest that acetyltransferase activity may be a primary component of enhancer function, and that recruitment of polymerase and enhancement of transcription are separable. Transcriptional activation by PCAF requires both its acetyltransferase activity and an additional activity within its N terminus. We also show that the simian virus 40 enhancer and PCAF itself are sufficient to counteract Mad-mediated repression. These results are compatible with recent models in which gene activity is regulated by the competition between deacetylase-mediated repression and enhancer-mediated recruitment of acetyltransferases.