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PARSAFE: computer program for safety assessment and optimization of parenteral nutrition formulations based on chemical speciation analysis.

Instability arising from the formation of precipitates and lipid emulsion aggregates is common in parenteral nutrition formulations due to the concentration- and pH-dependent incompatibility of some of the vital ingredients. Previously, the boundaries between stability and instability could only be established through the use of laborious and expensive empirical methods. The predictive technique with the concept of chemical speciation (based on the analysis of many competitive thermodynamic equilibriums) has been adapted for use with parenteral fluids so that these detrimental events may now be avoided. A comprehensive computer program, PARSAFE ((C) 1991. Sponsors interested in this program should contact D.R.W.) has been developed for this purpose. PARSAFE encompasses chemical-speciation techniques and contains a large data base of commonly used intravenous fluid constituents together with the appropriate thermodynamic equilibrium constants describing their interactions so that stability prediction may be readily achieved in hospital pharmacy laboratories. We review the relevant physical chemistry required for the successful implementation of PARSAFE and outline the audit trails involved in the development of the predictive model.

Algorithms↗

Linear quadrupoles with added hexapole fields.

Linear quadrupoles with added hexapole fields are described. The shifts in ion oscillation frequency caused by the addition of a hexapole field are calculated within the effective potential model. Methods to construct linear quadrupoles with added hexapole fields with exact electrode geometries and with round rods are discussed. A quadrupole with added hexapole field can be constructed with round rods by rotating two rods (say the y rods) towards an x rod. Computer simulations are used to investigate the possibility of mass analysis with quadrupoles with added hexapole fields. We find that a quadrupole with an added hexapole field in the range 2-12% can provide mass analysis provided the dc is applied with the correct polarity and value. When a rod set is constructed with round rods, other multipoles in the potential degrade the peak shape, resolution and transmission. The largest of these after the quadrupole and hexapole are a dipole and octopole term. With round rod sets, the peak shape can be improved by using different diameters for the x and y rod pairs to minimize the octopole term in the potential and by injecting ions at the field center where the dipole term is zero. Calculations of the boundaries of the stability diagram for this case show the boundaries move out, relative to those of a pure quadrupole field, but remain sharp.

Journal Article↗

Effects of time-delayed feedback on chaotic oscillators.

We study the effects of time-delayed feedback on chaotic systems where the delay time is both fixed (static case) and varying (dynamic case) in time. For the static case, typical phase coherent and incoherent chaotic oscillators are investigated. Detailed phase diagrams are investigated in the parameter space of feedback gain ( K ) and delay time ( tau ). Linear stability analysis, by assuming the time-delayed perturbation, varies as e(lambdat) where lambda is the eigenvalue, gives the boundaries of the stability islands and critical feedback gains ( K(c) ) for both Rössler oscillators and Lorenz oscillators. We also found that the stability island are found when the delay time is about tau= (n+ 1 / 2 ) T , where n is an integer and T is the average period of the chaotic oscillator. It is shown that these analytical predictions agree well with the numerical results. For the dynamic case, we investigate Rössler oscillator with periodically modulated delay time. Stability regimes are found for parameter space of feedback gain and modulation frequency in which it was impossible to be stabilized for a fixed delay time. We also trace the detailed routes to the stability near the island boundaries for both cases by investigating bifurcation diagrams.

Journal Article↗

Stability of atmospheric CO2 levels across the Triassic/Jurassic boundary.

The Triassic/Jurassic boundary, 208 million years ago, is associated with widespread extinctions in both the marine and terrestrial biota. The cause of these extinctions has been widely attributed to the eruption of flood basalts of the Central Atlantic Magmatic Province. This volcanic event is thought to have released significant amounts of CO2 into the atmosphere, which could have led to catastrophic greenhouse warming, but the evidence for CO2-induced extinction remains equivocal. Here we present the carbon isotope compositions of pedogenic calcite from palaeosol formations, spanning a 20-Myr period across the Triassic/Jurassic boundary. Using a standard diffusion model, we interpret these isotopic data to represent a rise in atmospheric CO2 concentrations of about 250 p.p.m. across the boundary, as compared with previous estimates of a 2,000-4,000 p.p.m. increase. The relative stability of atmospheric CO2 across this boundary suggests that environmental degradation and extinctions during the Early Jurassic were not caused by volcanic outgassing of CO2. Other volcanic effects-such as the release of atmospheric aerosols or tectonically driven sea-level change-may have been responsible for this event.

Journal Article↗

Structure of [110] tilt grain boundaries in zirconia bicrystals.

Cubic stabilized zirconia bicrystals with [110] symmetric tilt grain boundaries were fabricated by diffusion bonding of two single crystals with the composition of ZrO2-9.6mol%Y2O3. The structures of symmetric tilt small angle grain boundary and two types of symmetric tilt sigma3 grain boundaries with different grain boundary planes were observed by transmission electron microscopy (TEM). High-resolution transmission electron microscopy (HREM) observations clarified that the [110] small angle tilt grain boundary consists of periodic array of b = a/2[110] type edge dislocations. This result is consistent with Frank's dislocation model for small angle grain boundary. HREM observation also revealed that the 70.5 degrees sigma3 grain boundary shows atomically coherent grain boundary structure with the boundary plane of [111], while the 109.5 degrees sigma3 grain boundary accompanies grain boundary facets taking [111]/[115] asymmetric grain boundary plane. Because of the very low surface energy of [111] plane and/or high lattice matching of [111] and [115] type planes, the grain boundary faceting may be preferred in spite of increasing grain boundary area to about 6%. TEM-energy-dispersive X-ray spectroscopy (EDS) analyses were performed on both sigma3 grain boundaries, and the segregation of yttrium ions to the boundaries was detected in both cases. The amount of segregation is about the same in both sigma3 boundaries. It can be concluded that the segregation of yttrium ions to sigma3 grain boundary exists in cubic zirconia.

Journal Article↗

Organizational development of a university-based interdisciplinary health promotion project.

PURPOSE: To analyze the organizational development and implementation of an interdisciplinary health promotion project at the University of New Mexico. The effort involved three academic units in a 3-year externally funded project to institutionalize health promotion curricula in the respective schools and to develop a wellness-oriented service for students, faculty, and staff. METHODS: The open systems theory was used as a framework to analyze the organizational and role issues that emerged from the data collected through interviews, staff surveys, and document review. The analysis is summarized by five thematic questions: (1) How did the project's vision affect its development? (2) How was leadership enacted, and with what effect? (3) What were the organizational issues for the staff? (4) What were the interdisciplinary dilemmas? (5) What was instituted or changed as a result of the project? RESULTS: The analysis uncovered a series of interpersonal and organizational dilemmas involving the nature of the organizational environment, the character of interdisciplinary work, leadership, boundaries of group membership, and the structuring of a unified vision. CONCLUSIONS: Future projects should consider the strength and stability of the boundary spanners, the resource context, and the role of a unified vision for new and organizationally linked units as key issues in facilitating and sustaining change.

Health Plan Implementation↗

Simplified methods for pKa and acid pH-dependent stability estimation in proteins: removing dielectric and counterion boundaries.

Much computational research aimed at understanding ionizable group interactions in proteins has focused on numerical solutions of the Poisson-Boltzmann (PB) equation, incorporating protein exclusion zones for solvent and counterions in a continuum model. Poor agreement with measured pKas and pH-dependent stabilities for a (protein, solvent) relative dielectric boundary of (4,80) has lead to the adoption of an intermediate (20,80) boundary. It is now shown that a simple Debye-Huckel (DH) calculation, removing both the low dielectric and counterion exclusion regions associated with protein, is equally effective in general pKa calculations. However, a broad-based discrepancy to measured pH-dependent stabilities is maintained in the absence of ionizable group interactions in the unfolded state. A simple model is introduced for these interactions, with a significantly improved match to experiment that suggests a potential utility in predicting and analyzing the acid pH-dependence of protein stability. The methods are applied to the relative pH-dependent stabilities of the pore-forming domains of colicins A and N. The results relate generally to the well-known preponderance of surface ionizable groups with solvent-mediated interactions. Although numerical PB solutions do not currently have a significant advantage for overall pKa estimations, development based on consideration of microscopic solvation energetics in tandem with the continuum model could combine the large deltapKas of a subset of ionizable groups with the overall robustness of the DH model.

Bacterial Proteins↗

Cell intercalation during notochord development in Xenopus laevis.

Morphometric data from scanning electron micrographs (SEM) of cells in intact embryos and high-resolution time-lapse recordings of cell behavior in cultured explants were used to analyze the cellular events underlying the morphogenesis of the notochord during gastrulation and neurulation of Xenopus laevis. The notochord becomes longer, narrower, and thicker as it changes its shape and arrangement and as more cells are added at the posterior end. The events of notochord development fall into three phases. In the first phase, occurring in the late gastrula, the cells of the notochord become distinct from those of the somitic mesoderm on either side. Boundaries form between the two tissues, as motile activity at the boundary is replaced by stabilizing lamelliform protrusions in the plane of the boundary. In the second phase, spanning the late gastrula and early neurula, cell intercalation causes the notochord to narrow, thicken, and lengthen. Its cells elongate and align mediolaterally as they rearrange. Both protrusive activity and its effectiveness are biased: the anterioposterior (AP) margins of the cells advance and retract but produce much less translocation than the more active left and right ends. The cell surfaces composing the lateral boundaries of the notochord remain inactive. In the last phase, lasting from the mid- to late neurula stage, the increasingly flattened cells spread at all their interior margins, transforming the notochord into a cylindrical structure resembling a stack of pizza slices. The notochord is also lengthened by the addition of cells to its posterior end from the circumblastoporal ring of mesoderm. Our results show that directional cell movements underlie cell intercalation and raise specific questions about the cell polarity, contact behavior, and mechanics underlying these movements. They also demonstrate that the notochord is built by several distinct but carefully coordinated processes, each working within a well-defined geometric and mechanical environment.

Animals↗

Arnold's method for asymptotic stability of steady inviscid incompressible flow through a fixed domain with permeable boundary.

The flow of an ideal fluid in a domain with a permeable boundary may be asymptotically stable. Here the permeability means that the fluid can flow into and out of the domain through some parts of the boundary. This permeability is a principal reason for the asymptotic stability. Indeed, the well-known conservation laws make the asymptotic stability of an inviscid flow impossible, if the usual no flux condition on a rigid wall (or on a free boundary) is employed. We study the stability problem using the direct Lyapunov method in the Arnold's form. We prove the linear and nonlinear Lyapunov stability of a two-dimensional flow through a domain with a permeable boundary under Arnold's conditions. Under certain additional conditions, we amplify the linear result and prove the exponential decay of small disturbances. Here we employ the plan of the proof of the Barbashin-Krasovskiy theorem, established originally only for systems with a finite number of degrees of freedom. (c) 2002 American Institute of Physics.

Journal Article↗

Quadrupole mass filters with octopole fields.

The performance of quadrupole mass filters with added octopole fields in the range 2.0-4.0% has been investigated. The added fields are much greater than those normally added to conventional rod sets by mechanical tolerances or construction errors. Quadrupole rod sets with added octopole fields were constructed with round rods by making one pair of rods greater in diameter than the other pair. For positive ions, resolution at half height of only about 200 is possible if the negative direct current (dc) output of the quadrupole power supply is connected to the smaller rods. If the positive dc output of the quadrupole power supply is connected to the smaller rods, the resolution improves dramatically; a resolution at half height of 5800 has been observed with a rod set with 2.6% added octopole field. For negative ions the best resolution is obtained with the polarity of the dc reversed, i.e. with the negative dc applied to the smaller rods. These findings are unexpected in view of the literature that argues that to obtain high mass resolution with quadrupole mass filters, higher order multipoles must be kept as small as possible. Numerical simulations of peak shapes agree qualitatively with experiments. Simulation of the boundaries of the first stability region for positive ions shows that when the positive dc is applied to the smaller rods, the addition of a 2.0% octopole field causes the boundaries to shift slightly but the boundaries are well defined, and the tip of the stability region remains sharp. When the positive dc is applied to the larger rods, the boundaries of the stability region move out and become diffuse. For instruments that require a rod set that can be used both as a linear trap and a mass filter, these rod sets may offer improved trap performance while still being capable of providing conventional mass analysis.

Journal Article↗

Salt effects on the phase behavior, structure, and rheology of chromonic liquid crystals.

Chromonic liquid crystals are formed by the addition of aromatic molecules such as disodium chromoglycate (cromolyn) to water. In this study, we investigate the addition of salts to the lyotropic nematic phase of cromolyn aqueous solutions. The addition of sodium and potassium salts shifts the isotropic-nematic phase boundary upward by more than 10 degrees C, so that samples that were isotropic at room temperature are transformed into nematic phases. Salt effects are predominantly dictated by the cation, not the anion, and appear to differ based on cation size. In contrast to small, hydrated cations like sodium, large, weakly hydrated cations such as tetraethylammonium and tetrabutylammonium shift the phase boundary downward, thus stabilizing the isotropic phase at the expense of the nematic one. The phase behavior results are highly correlated with viscosity measurements, with an upward shift in the phase boundary correlating with an increase in solution viscosity and vice versa. We also probe the microstructure in cromolyn-salt solutions, both indirectly by small-angle neutron scattering (SANS) and directly by cryo-transmission electron microscopy (cryo-TEM). The cryo-TEM images show the presence of rodlike aggregates that possibly undergo a higher order aggregation into bundles in the presence of salt.

Cromolyn Sodium↗

[Effect of physical training on postural control of elderly].

BACKGROUND: Preservation of balance in the elderly is fundamental to maintaining functional independence. Balance impairments have a tremendous impact on health care costs and quality of life. Fall prevention programs are an important health strategy, consequently there is a general need to develop effective and practical exercise programs that improve balance in the elderly. OBJECTIVE: To explore whether stability can be improved through exercise in inactive old subjects and to determine whether specific balance training proves to be more beneficial to retaining balance than strength training. METHODS: A randomized controlled study was conducted with 42 healthy elderly individuals. They were randomly allocated to three groups: Balance training (BT), Isometric training (IT) and Control (CG) received no intervention; each group consisted of 14 members. "Static" and "dynamic" postural stability were evaluated for seven postural conditions in upright standing before and immediately after 3 months of intervention using a force platform, and an isokinetic dynamometer used to determine whether the training improved muscle strength. RESULTS: The BT group significantly improved their forward-backward stability limits (maximal body lean) post intervention compared with other groups. Plantar and dorsiflexion isometric strength remained the same in all groups. No significant improvement was found in COP based measures in upright standing in all study groups, apart from the BT group that significantly improved parameters in performance with eyes open and during standing on a foam. BT subjects improved their self-confidence post intervention in 64.2%, while IT subjects improved in only 35.7%. CONCLUSIONS: Balance exercises appear to improve balance in the elderly, especially extending the boundaries of their stability a more dynamic component of balance. However it remains to be determined whether the lack of difference between groups in COP measures in upright standing ("static balance") was due to the short period of intervention, small sample size, unchallenged exercise regime or due to the inability of elderly individuals to improve their sway in upright standing.

Aged↗

On the effect of an applied magnetic field on the shear-induced pattern formation in nematic polymer liquid crystals.

The effect of an applied magnetic field and of the boundaries on the stability of the shear flow of nematic polymer liquid crystals of the tumbling type with respect to the formation of the transient spatially periodic patterns that appears after the start-up of shearing is studied. The unidirectional shear of a nematic director initially uniformly oriented orthogonally to the sample plane and with strong anchoring is considered. The magnetic field is applied orthogonally to the sample plane or in the same direction of the flow. For a given value of the Ericksen number of the flow a critical value of the magnetic-to-viscous energy ratio shows up above which the uniform flow is stable. When the influence of the boundaries may be neglected, an internal Ericksen number that stays constant in a given material is considered such that the wavelength of the periodic pattern is a self-adjusted length. An internal generalized Ericksen number is defined such that it is a universal function of the magnetic-to-viscous energy ratio.

Journal Article↗

Contribution to the physicochemical rationale for the caries reducing effect of fluoride.

The effect of fluoride on the stability of apatites containing Na+ and CO3(2)- ions is described qualitatively. Also the boundaries of the apatite stability field in the quasi-septary system CaO - P2O5 - H2O - Na2O - CO2 - NaF - MX are presented. At these boundaries brushite (or monetite), octocalciumphosphate, calcite and calcium fluoride can become stable solid phases. As a consequence, certain mechanisms for the caries reducing effect of fluoride gain probability over other proposed mechanisms. First, it is likely that endemic fluoride yields more fully mineralized enamel which in turn results in a lower initial rate of the caries process. Second, after eruption the mineral in the tooth superficial layer is bound to accumulate fluoride on the surface of its crystals. This causes a slower rate of the crystal surface dissolution at that site and, hence, a thicker and denser intact superficial layer over the lesion. Finally, the formation of a precipitate of fluorhydroxyapatite and perhaps also of calcium fluoride is promoted in the plaque during cycles of metabolic activity. Subsequent dissolution of the CaF2 and transformation of the fluorhydroxyapatite sets free Ca+ and F- ions. Both of these ions promote the remineralization of the lesion during periods of metabolic rest whereby brushite or monetite are transformed back into apatite.

Apatites↗

Functional mapping of the translation-dependent instability element of yeast MATalpha1 mRNA.

The determinants of mRNA stability include specific cis-acting destabilizing sequences located within mRNA coding and noncoding regions. We have developed an approach for mapping coding-region instability sequences in unstable yeast mRNAs that exploits the link between mRNA translation and turnover and the dependence of nonsense-mediated mRNA decay on the activity of the UPF1 gene product. This approach, which involves the systematic insertion of in-frame translational termination codons into the coding sequence of a gene of interest in a upf1delta strain, differs significantly from conventional methods for mapping cis-acting elements in that it causes minimal perturbations to overall mRNA structure. Using the previously characterized MATalpha1 mRNA as a model, we have accurately localized its 65-nucleotide instability element (IE) within the protein coding region. Termination of translation 5' to this element stabilized the MATalpha1 mRNA two- to threefold relative to wild-type transcripts. Translation through the element was sufficient to restore an unstable decay phenotype, while internal termination resulted in different extents of mRNA stabilization dependent on the precise location of ribosome stalling. Detailed mutagenesis of the element's rare-codon/AU-rich sequence boundary revealed that the destabilizing activity of the MATalpha1 IE is observed when the terminal codon of the element's rare-codon interval is translated. This region of stability transition corresponds precisely to a MATalpha1 IE sequence previously shown to be complementary to 18S rRNA. Deletion of three nucleotides 3' to this sequence shifted the stability boundary one codon 5' to its wild-type location. Conversely, constructs containing an additional three nucleotides at this same location shifted the transition downstream by an equivalent sequence distance. Our results suggest a model in which the triggering of MATalpha1 mRNA destabilization results from establishment of an interaction between translating ribosomes and a downstream sequence element. Furthermore, our data provide direct molecular evidence for a relationship between mRNA turnover and mRNA translation.

Alleles↗

Influence of janusin and tenascin on growth cone behavior in vitro.

Janusin and tenascin are glia-derived, structurally related, extracellular matrix glycoproteins of the J1 family that are expressed in vivo at times and in locations where active neurite outgrowth occurs, but also when the formation or stabilization of cytoarchitectonic boundaries appears to be in operation. To resolve this apparent functional dichotomy, we have studied the behavioral response of growth cones, growing in culture on the permissive substrate laminin to janusin and tenascin, by video time lapse microscopy. When janusin and tenascin were offered as sharp substrate boundaries, dorsal root ganglion (DRG) and retinal ganglion neuron growth cones avoided growing on these molecules, but were not induced to collapse. On the other hand, when janusin and tenascin were offered, in a mixture with laminin, as uniform substrates, DRG growth cones displayed a collapsed morphology and were able to advance at a faster rate than on laminin alone. In contrast, the outgrowth of retinal ganglion neuron growth cones was completely inhibited under these conditions, underscoring a cell type specificity in the response of growth cones to these molecules. Using several monoclonal antibodies binding to distinct epitopes on the tenascin molecule, we have identified two domains responsible for growth cone repulsion, on epidermal growth factor (EGF)-like repeats 3-5 and fibronectin type III homologous repeats 4 and 5. These domains are different from the one previously recognized to be involved in neurite outgrowth on a uniform tenascin substrate. We conclude that both molecules may promote or retard growth cone advance, depending on the spatial expression pattern and the neuronal cell type.

Animals↗