Altered breathing mechanics and ventilatory response during exercise in children born extremely preterm.

BACKGROUND: Extreme preterm birth confers risk of long-term impairments in lung function and exercise capacity. There are limited data on the factors contributing to exercise limitation following extreme preterm birth. This study examined respiratory mechanics and ventilatory response during exercise in a large cohort of children born extremely preterm (EP). METHODS: This cohort study included children 8-12 years of age who were born EP (≤28 weeks gestation) between 1997 and 2004 and treated in a large regionalised neonatal intensive care unit in western Canada. EP children were divided into no/mild bronchopulmonary dysplasia (BPD) (ie, supplementary oxygen or ventilation ceased before 36 weeks gestational age; n=53) and moderate/severe BPD (ie, continued supplementary oxygen or ventilation at 36 weeks gestational age; n=50). Age-matched control children (n=65) were born at full term. All children attempted lung function and cardiopulmonary exercise testing measurements. RESULTS: Compared with control children, EP children had lower airway flows and diffusion capacity but preserved total lung capacity. Children with moderate/severe BPD had evidence of gas trapping relative to other groups. The mean difference in exercise capacity (as measured by oxygen uptake (VO2)% predicted) in children with moderate/severe BPD was -18±5% and -14±5.0% below children with no/mild BPD and control children, respectively. Children with moderate/severe BPD demonstrated a potentiated ventilatory response and greater prevalence of expiratory flow limitation during exercise compared with other groups. Resting lung function did not correlate with exercise capacity. CONCLUSIONS: Expiratory flow limitation and an exaggerated ventilatory response contribute to respiratory limitation to exercise in children born EP with moderate/severe BPD.

Adsorption of Surface-Modified Silica Nanoparticles to the Interface of Melt Poly(lactic acid) and Supercritical Carbon Dioxide.

With the purpose of fabricating polymer nanocomposite foams and preventing coalescence in foaming processes, the interfacial tension of poly(lactic acid) (PLA)-silica composites is investigated in this work. Synthesized silica nanoparticles (SNs) with a CO2-philic surface modification are used as the dispersed nanoparticles. Interfacial tension is a key parameter in processing of polymer foams since it directly affects the final foam properties, such as cell size and cell density. Interfacial tension of silica-containing PLA and supercritical carbon dioxide (CO2) is measured using axisymmetric drop shape analysis profile (ADSA-P) pendant drop method at high pressures and high temperatures. The interfacial tension between PLA and supercritical CO2 is observed to decrease as a result of the nanoparticles' adsorption to the interface. These results indicate that the reduction in interfacial tension with increasing silica content significantly deviates from a linear trend; there is a minimum at 2 wt % loading of the SNs and then the interfacial tension curve reaches a plateau. Contact angle measurements show an affinity of the SNs for the polymer-supercritical CO2 interface, and these obtained results are used to calculate the binding energy of the nanoparticles to the PLA/CO2 interface. In addition to interfacial properties, the adsorption of silica nanoparticles at the interface is also studied in detail with scanning electron microscopy.

Assessing crop N status of fertigated vegetable crops using plant and soil monitoring techniques.

Evaluation of crop N status will assist optimal N management of intensive vegetable production. Simple procedures for monitoring crop N status such as petiole sap [NO 3--N], leaf N content and soil solution [NO 3-] were evaluated with indeterminate tomato and muskmelon. Their sensitivity to assess crop N status throughout each crop was evaluated using linear regression analysis against nitrogen nutrition index (NNI) and crop N content. NNI is the ratio between the actual and the critical crop N contents (critical N content is the minimum N content necessary to achieve maximum growth), and is an established indicator of crop N status. Nutrient solutions with four different N concentrations (treatments N1-N4) were applied throughout each crop. Average applied N concentrations were 1, 5, 13 and 22 mmol L-1 in tomato, and 2, 7, 13 and 21 mmol L-1 in muskmelon. Respective rates of N were 23, 147, 421 and 672 kg N ha-1 in tomato, and 28, 124, 245 and 380 kg N ha-1 in muskmelon. For each N treatment in each crop, petiole sap [NO 3--N] was relatively constant throughout the crop. During both crops, there were very significant (P < 0.001) linear relationships between both petiole sap [NO 3--N] and leaf N content with NNI and with crop N content. In indeterminate tomato, petiole sap [NO 3--N] was very strongly linearly related to NNI (R2 = 0.88-0.95, P < 0.001) with very similar slope and intercept values on all dates. Very similar relationships were obtained from published data of processing tomato. A single linear regression (R2 = 0.77, P < 0.001) described the relationship between sap [NO 3--N] and NNI for both indeterminate and processing tomato, each grown under very different conditions. A single sap [NO 3--N] sufficiency value of 1050 mg N L-1 was subsequently derived for optimal crop N nutrition (at NNI = 1) of tomato grown under different conditions. In muskmelon, petiole sap [NO 3--N] was strongly linearly related to NNI (R2 = 0.75 - 0.88, P < 0.001) with very similar slope and intercept values for much of the crop (44-72 DAT, days after transplanting). A single linear relationship between sap [NO 3--N] and NNI (R2 = 0.77, P < 0.001) was derived for this period, but sap sufficiency values could not be derived for muskmelon as NNI values were >1. Relationships between petiole sap [NO 3--N] with crop N content, and leaf N content with both NNI and crop N content had variable slopes and intercept values during the indeterminate tomato and the muskmelon crops. Soil solution [NO 3-] in the root zone was not a sensitive indicator of crop N status. Of the three systems examined for monitoring crop/soil N status, petiole sap [NO 3--N] is suggested to be the most useful because of its sensitivity to crop N status and because it can be rapidly analysed on the farm.

The self-assembly of particles with isotropic interactions.

A generic field-theoretic model for the self-assembly of particles with isotropic interactions, motivated by ideas in DNA-mediated colloidal assembly, is presented. A simplest possible system of colloids in explicit solvent is examined to determine the ability of non-connected particles to form complex nanometre or micron scale equilibrium structures in the absence of confounding kinetic effects. It is found that non-trivial morphologies are possible and that, for this effectively one component system, these parallel the phases of diblock copolymer melts for certain parameter choices, despite the absence of connectivity or packing frustration in the model. An explanation for the morphological similarity between these architecturally disparate systems is given. For other parameter choices, it is found that meta-stable and defected phases become more common, and that similarity with block copolymer morphologies decreases.

MR spectroscopy measurement of the diffusion of dimethyl sulfoxide in articular cartilage and comparison to theoretical predictions.

UNLABELLED: Cartilage cryopreservation requires optimal loading of protective solutes, most commonly dimethyl sulfoxide (DMSO), to maximize chondrocyte survival. Previously, diffusion models have been used to predict the distribution of solutes in tissue samples, but the accuracy of spatiotemporal predictions of these models have not been validated with empirical studies and remains unknown. OBJECTIVE: In this study, magnetic resonance spectroscopic imaging was used to measure the spatial and temporal changes in DMSO and water concentrations in porcine articular cartilage plugs, throughout 1 h of solute loading. DESIGN: A custom NMR spectroscopic imaging pulse sequence provided water and DMSO concentration images with an in-plane spatial resolution of 135 µm and a temporal resolution of 150 s, repeated for 60 min throughout DMSO loading. Delayed gadolinium-enhanced magnetic resonance of cartilage (d-GEMRIC) imaging provided fixed charge density and spin-density imaging provided water density images prior to DMSO loading. RESULTS: The measured spatial and temporal distribution of DMSO in three different samples was compared to independent predictions of Fick's law and the modified triphasic biomechanical model by Abazari et al. (2011) with the empirical data more closely agreeing with the triphasic model. CONCLUSION: Dynamic NMR spectroscopic imaging can measure spatial and temporal changes in water and cryoprotectant concentrations in articular cartilage. The modified triphasic model predictions for the interstitial distribution of DMSO were confirmed and its advantage over the predictions by Fick's law model, which is commonly used in the literature of cryobiology, was demonstrated.

Real-time 3-dimensional echocardiography provides new insight into mechanisms of tricuspid valve regurgitation in patients with hypoplastic left heart syndrome.

BACKGROUND: Tricuspid regurgitation in hypoplastic left heart syndrome has an impact on outcome, but its mechanisms remain unclear. METHODS AND RESULTS: Real-time 3-dimensional echocardiography was performed in 35 patients with hypoplastic left heart syndrome (age, 1 month to 10 years; 10 after first-stage Norwood, 12 after superior cavopulmonary shunt, 13 after Fontan). From the 3-dimensional data set, we marked the annulus in systole and diastole. At mid systole, we marked the location of the papillary muscle tip and point of chordal attachment to the leaflet. We traced the surfaces of the tricuspid valve leaflets and measured the volume of leaflet prolapse, tethering, annular and septal leaflet areas, and papillary muscle position. Seventeen patients had moderate tricuspid regurgitation (prolapse, 7; tethered leaflets, 7) and 18 mild (prolapse, 0; tethered leaflets, 7). Multiple linear regression analysis revealed that moderate tricuspid regurgitation is associated with leaflet tethering and prolapse; that in hypoplastic left heart syndrome with tethered leaflets, the papillary muscle is displaced laterally and the tricuspid annulus is more planar; and that enlargement of the annulus at mid systole, small septal leaflet area, and age affect the degree of prolapse. CONCLUSIONS: In hypoplastic left heart syndrome, moderate tricuspid regurgitation may be associated with increasing age, geometrical changes of the annulus, leaflet prolapse, lateral papillary muscle displacement, and subsequent leaflet tethering, as well as a smaller septal leaflet.

Origin of change in molecular-weight dependence for polymer surface tension.

Self-consistent-field theory is used to reproduce the behavior of polymer surface tension with molecular-weight for both lower and higher molecular-weight polymers. The change in behavior of the surface tension between these two regimes is shown to be due to the almost total exclusion of polymer from the nonpolymer bulk phase. The predicted two regime surface tension behavior with molecular-weight and the exclusion explanation are shown to be valid for a range of different polymer compressibilities.

Effect of temperature and pressure on surface tension of polystyrene in supercritical carbon dioxide.

The surface tension of polymers in a supercritical fluid is one of the most important physicochemical parameters in many engineering processes, such as microcellular foaming where the surface tension between a polymer melt and a fluid is a principal factor in determining cell nucleation and growth. This paper presents experimental results of the surface tension of polystyrene in supercritical carbon dioxide, together with theoretical calculations for a corresponding system. The surface tension is determined by Axisymmetric Drop Shape Analysis-Profile (ADSA-P), where a high pressure and temperature cell is designed and constructed to facilitate the formation of a pendent drop of polystyrene melt. Self-consistent field theory (SCFT) calculations are applied to simulate the surface tension of a corresponding system, and good qualitative agreement with experiment is obtained. The physical mechanisms for three main experimental trends are explained by using SCFT, and none of the explanations quantitatively depend on the configurational entropy of the polymer constituents. These calculations therefore rationalize the use of simple liquid models for the quantitative prediction of surface tensions of polymers. As pressure and temperature increase, the surface tension of polystyrene decreases. A linear relationship is found between surface tension and temperature, and between surface tension and pressure; the slope of surface tension change with temperature is dependent on pressure.

Predicting nonpolymeric materials structure with real-space self-consistent field theory.

Polymer self-consistent field theory of the Edwards-Helfand kind is the state-of-the-art method for predicting the morphologies of block copolymer materials. The methodology of block copolymer self-consistent field theory is transported to classical density functional theory such that a wide range of self-consistent field theory tools can be applied to completely nonpolymeric materials, such as liquid crystal, molecular, or colloidal systems. This allows for the prediction of structure in nonpolymeric condensed matter systems without any prior knowledge of the possible phases, using calculations that take a fraction of the time needed for simulations. The approach is applied to a simple interaction site density functional theory representing adsorbed nitrogen molecules, and plastic crystal as well as herringbone phases are found in the phase diagram.

Concentrations of extracellular free zinc (pZn)e in the central nervous system during simple anesthetization, ischemia and reperfusion.

"Free Zn2+" (rapidly exchangeable Zn2+) is stored along with glutamate in the presynaptic terminals of specific specialized (gluzinergic) cerebrocortical neurons. This synaptically releasable Zn2+ has been recognized as a potent modulator of glutamatergic transmission and as a key toxin in excitotoxic neuronal injury. Surprisingly (despite abundant work on bound zinc), neither the baseline concentration of free Zn2+ in the brain nor the presumed co-release of free Zn2+ and glutamate has ever been directly observed in the intact brain in vivo. Here, we show for the first time in dialysates of rat and rabbit brain and human CSF samples from lumbar punctures that: (i) the resting or "tonic" level of free Zn2+ signal in the extracellular fluid of the rat, rabbit and human being is approximately 19 nM (95% range: 5-25 nM). This concentration is 15,000-fold lower than the "300 microM" concentration which is often used as the "physiological" concentration of free zinc for stimulating neural tissue. (ii) During ischemia and reperfusion in the rabbit, free zinc and glutamate are (as has often been presumed) released together into the extracellular fluid. (iii) Unexpectedly, Zn2+ is also released alone (without glutamate) at a variable concentration for several hours during the reperfusion aftermath following ischemia. The source(s) of this latter prolonged release of Zn2+ is/are presumed to be non-synaptic and is/are now under investigation. We conclude that both Zn2+ and glutamate signaling occur in excitotoxicity, perhaps by two (or more) different release mechanisms.

Improved convergence in block copolymer self-consistent field theory by Anderson mixing.

A modification to real space polymeric self-consistent field theory algorithms that greatly improves the convergence properties is presented. The method is based on Anderson mixing [D. G. Anderson, J. Assoc. Comput. Mach. 12, 547 (1965)], and each iteration computed takes negligibly longer to perform than with other methods, but the number of iterations required to reach a high accuracy solution is greatly reduced. No a priori knowledge of possible phases is required to apply this method. We apply our approach to a standard diblock copolymer melt, and demonstrate iteration reductions of more than a factor of 5 in some cases.

Elastic moduli of multiblock copolymers in the lamellar phase.

We study the linear elastic response of multiblock copolymer melts in the lamellar phase, where the molecules are composed of tethered symmetric AB diblock copolymers. We use a self-consistent field theory method, and introduce a real space approach to calculate the tensile and shear moduli as a function of block number. The former is found to be in qualitative agreement with experiment. We find that the increase in bridging fraction with block number, that follows the increase in modulus, is not responsible for the increase in modulus. It is demonstrated that the change in modulus is due to an increase in mixing of repulsive A and B monomers. Under extension, this increase originates from a widening of the interface, and more molecules pulled free of the interface. Under compression, only the second of these two processes acts to increase the modulus.

Ordering mechanisms in triblock copolymers.

The ordering mechanisms for an ABC triblock copolymer system are studied using self-consistent field theory. We find a two-phase mechanism, similar to what has been suggested experimentally (two-step mechanism). Analysis of free energy components shows that the two-phase process comes about through a competition between stretching energy and interfacial energy. The mechanism is found to be sufficiently robust so as to make it potentially useful for device applications.

Fluorescent zinc indicators for neurobiology.

Mounting evidence indicates that zinc has multiple roles in cell biology, viz. as a part of metalloenzyme catalytic sites, as a structural component of gene regulatory proteins, and (like calcium) as a free signal ion, particularly in the cortex of the brain. While most Zn(II) in the brain is tightly bound, such that free Zn(II) levels extracellularly and intracellularly are likely to be picomolar, a subset of glutamatergic neurons possess weakly bound zinc in presynaptic boutons which is released at micromolar levels in response to a variety of stimuli. Key to further progress in understanding the multiple roles of zinc will be the availability of fluorescent indicator systems that will permit quantitative determination and imaging of zinc fluxes and levels over a broad concentration range both intracellularly and extracellularly using fluorescence microscopy. Towards that end, we have compared a variety of fluorescent indicators for their sensitivity to Zn(II) and Cu(II), selectivity for Zn(II) in the presence of potential interferents such as Ca(II) or Mg(II), and potential for quantitative imaging. The commercially available probes Fura-2, Mag-Fura-5, Newport Green DCF, and FuraZin-1 were compared with the carbonic anhydrase-based indicator systems for selectivity and sensitivity. In addition, intracellular levels of Zn following excitotoxic insult were determined by single pixel fluorescence lifetime microscopy of Newport Green DCF, and extracellular levels of free zinc following stimulus of rat hippocampal slices were determined ratiometrically with a carbonic anhydrase-based indicator system. These results suggest that zinc ion at high nM to microM levels can be accurately quantitated by FuraZin-1 ratiometrically or by Newport Green DCF by fluorescence lifetime; and at levels down to pM by intensity ratio, lifetime, or polarization using carbonic anhydrase-based systems.

Management factors affecting ammonia volatilization from land-applied cattle slurry in the Mid-Atlantic USA.

Ammonia (NH3) volatilization commonly causes a substantial loss of crop-available N from surface-applied cattle slurry. Field studies were conducted with small wind tunnels to assess the effect of management factors on NH3 volatilization. Two studies compared NH3 volatilization from grass sward and bare soil. The average total NH3 loss was 1.5 times greater from slurry applied to grass sward. Two studies examined the effect of slurry dry matter (DM) content on NH3 loss under hot, summer conditions in Maryland, USA. Slurry DM contents were between 54 and 134 g kg(-1). Dry matter content did not affect total NH3 loss, but did influence the time course of NH3 loss. Higher DM content slurries had relatively higher rates of NH3 volatilization during the first 12 to 24 h, but lower rates thereafter. Under the hot conditions, the higher DM content slurries appeared to dry and crust more rapidly causing smaller rates of NH3 volatilization after 12 to 24 h, which offset the earlier positive effects of DM content on NH3 volatilization. Three studies compared immediate incorporation with different tillage implements. Total NH3 loss from unincorporated slurry was 45% of applied slurry NH4+-N, while losses following immediate incorporation with a moldboard plow, tandem-disk harrow, or chisel plow were, respectively, 0 to 3, 2 to 8, and 8 to 12%. These ground cover and DM content data can be used to improve predictions of NH3 loss under specific farming conditions. The immediate incorporation data demonstrate management practices that can reduce NH3 volatilization, which can improve slurry N utilization in crop-forage production.

Foundations for blockbuster drugs in federally sponsored research.

'Blockbuster' drugs, which are widely prescribed and improve the health of millions, often originate in fundamental laboratory research. An important example of such drugs are the cholesterol-lowering drugs called 'statins', including Zocor, Pravachol, and Lipitor, which millions of people take in the U.S. every year. This short paper outlines the direct and indirect contributions of federally sponsored research to the development of these important drugs.

Commissioning and quality assurance for MLC-based IMRT.

The commissioning and quality assurance (QA) associated with the implementation of linear accelerator multileaf collimator (MLC)-based intensity-modulated radiation therapy (IMRT) at the University of Nebraska Medical Center are described. Our MLC-based IMRT is implemented using the PRIMUS linear accelerator interface through the IMPAC record and verification system to the CORVUS treatment planning system. The "step-and-shoot" technique is used for this MLC-based IMRT. Commissioning process requires the verification of predefined parameters available on the CORVUS and the collection of some machine data. The machine data required are output factor in air and output factor in phantom, and percent depth dose for a number of field sizes. In addition, inplane and crossplane dose profiles of 4 x 4 cm and 20 x 20 cm field sizes and diagonal dose profiles of a large field size have to be measured. Validation of connectivity and dose model includes the use of uniform intensity bar strips, triangular-shaped nonuniform intensity bar strip, and N-shaped target. QA procedure follows the recommendation of the AAPM Task Group No. 40 report. In addition, the leaf position accuracy and reproducibility of the MLC should be checked at regular intervals. The dose validation is implemented through the hybrid plan where the patient beam parameters are applied to a flat phantom. Independent dose calculation method is used to confirm the dose delivery plan and data input to the CORVUS.

Predicting the mesophases of copolymer-nanoparticle composites.

The interactions between mesophase-forming copolymers and nanoscopic particles can lead to highly organized hybrid materials. The morphology of such composites depends not only on the characteristics of the copolymers, but also on the features of the nanoparticles. To explore this vast parameter space and predict the mesophases of the hybrids, we have developed a mean field theory for mixtures of soft, flexible chains and hard spheres. Applied to diblock-nanoparticle mixtures, the theory predicts ordered phases where particles and diblocks self-assemble into spatially periodic structures. The method can be applied to other copolymer-particle mixtures and can be used to design novel composite architectures.

Loss of vesicular zinc and appearance of perikaryal zinc after seizures induced by pilocarpine.

The condition of status epilepticus induced by systemic administration of kainic acid (KA) causes an apparent translocation of vesicular zinc from presynaptic boutons into postsynaptic neurons. The accumulation of zinc in the somata has been identified as a contributing cause of neuronal injury. We show here that another form of status epilepticus, induced by administration of the muscarinic agonist pilocarpine, produces changes in zinc that are essentially the same as those produced by the kainic acid-induced seizures. Moreover, neurons that develop zinc staining after pilocarpine seizures are the same that shown degenerative changes. This result suggests that the loss of zinc from presynaptic boutons and the appearance of zinc in postsynaptic somata may both occur in seizures per se, regardless of etiology.

Commissioning of Peacock System for intensity-modulated radiation therapy.

The Peacock System was introduced to perform tomographic intensity-modulated radiation therapy (IMRT). Commissioning of the Peacock System included the alignment of the multileaf intensity-modulating collimator (MIMiC) to the beam axis, the alignment of the RTA device for immobilization, and checking the integrity of the CRANE for indexing the treatment couch. In addition, the secondary jaw settings, couch step size, and transmission through the leaves were determined. The dosimetric data required for the CORVUS planning system were divided into linear accelerator-specific and MIMiC-specific. The linear accelerator-specific dosimetric data were relative output in air, relative output in phantom, percent depth dose for a range of field sizes, and diagonal dose profiles for a large field size. The MIMiC-specific dosimetric data were the in-plane and cross-plane dose profiles of a small and a large field size to derive the penumbra fit. For each treatment unit, the Beam Utility software requires the data be entered into the CORVUS planning system in modular forms. These modules were treatment unit information, angle definition, configuration, gantry and couch angles range, dosimetry, results, and verification plans. After the appropriate machine data were entered, CORVUS created a dose model. The dose model was used to create known simple dose distribution for evaluation using the verification tools of the CORVUS. The planned doses for phantoms were confirmed using an ion chamber for point dose measurement and film for relative dose measurement. The planning system calibration factor was initially set at 1.0 and will be changed after data on clinical cases are acquired. The treatment unit was released for clinical use after the approval icon was checked in the verification plans module.