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Sample records for product variational formulation

  1. Variational formulation of high performance finite elements: Parametrized variational principles

    NASA Technical Reports Server (NTRS)

    Felippa, Carlos A.; Militello, Carmello

    1991-01-01

    High performance elements are simple finite elements constructed to deliver engineering accuracy with coarse arbitrary grids. This is part of a series on the variational basis of high-performance elements, with emphasis on those constructed with the free formulation (FF) and assumed natural strain (ANS) methods. Parametrized variational principles that provide a foundation for the FF and ANS methods, as well as for a combination of both are presented.

  2. New Variational Formulations of Hybrid Stress Elements

    NASA Technical Reports Server (NTRS)

    Pian, T. H. H.; Sumihara, K.; Kang, D.

    1984-01-01

    In the variational formulations of finite elements by the Hu-Washizu and Hellinger-Reissner principles the stress equilibrium condition is maintained by the inclusion of internal displacements which function as the Lagrange multipliers for the constraints. These versions permit the use of natural coordinates and the relaxation of the equilibrium conditions and render considerable improvements in the assumed stress hybrid elements. These include the derivation of invariant hybrid elements which possess the ideal qualities such as minimum sensitivity to geometric distortions, minimum number of independent stress parameters, rank sufficient, and ability to represent constant strain states and bending moments. Another application is the formulation of semiLoof thin shell elements which can yield excellent results for many severe test cases because the rigid body nodes, the momentless membrane strains, and the inextensional bending modes are all represented.

  3. Variational formulations of guiding-center Vlasov-Maxwell theory

    NASA Astrophysics Data System (ADS)

    Brizard, Alain J.; Tronci, Cesare

    2016-06-01

    The variational formulations of guiding-center Vlasov-Maxwell theory based on Lagrange, Euler, and Euler-Poincaré variational principles are presented. Each variational principle yields a different approach to deriving guiding-center polarization and magnetization effects into the guiding-center Maxwell equations. The conservation laws of energy, momentum, and angular momentum are also derived by Noether method, where the guiding-center stress tensor is now shown to be explicitly symmetric.

  4. [Optimization of formulations for dietetic pastry products].

    PubMed

    Villarroel, M; Uquiche, E; Brito, G; Cancino, M

    2000-03-01

    Optimized formulations of dietetic pastry products such as cake and sponge cake premixes were formulated using the surface response methodology. % Emulsifier agent and baking time were the selected independent variables for cake, as well as % emulsifier agent % chlorinated flour the variables selected for sponge cake. Three different level of each variable summing up thirteen experimental formulae of each product were assessed to optimize the variables that could have some influence in the sensory characteristics of these dietetic products. The total sensory quality was determined for both dietetic products using the composite scoring test and a panel of 18 trained judges. Looking at the contour graphic and considering economic aspects the best combination of variables for cake formulation was 2% emulsifier agent and 48 minutes for baking time, With respect to sponge cake, the best combination was 6% emulsifier agent and 48% chlorinated flour. Shelf life studies showed that both dietetic formulations remained stable during storage conditions of 75 days at 30 degrees C. During this period, significant differences in sensory characteristics were not found (p < 0.05). Data of peroxide values were kept under the critical value reported for detection of organoleptic rancidity. Reported values of hedonic test showed that these dietetics pastry products had good acceptability, and open up marketing opportunities for new products with potential health benefits to consumers. PMID:11048573

  5. Variational formulation of a moment problem quantization method

    NASA Astrophysics Data System (ADS)

    Handy, Carlos R.; Maweu, John; Atterberry, Leticia Soto

    1996-03-01

    The eigenvalue moment method (EMM) has proven to be an effective technique for generating converging lower and upper bounds to the bosonic ground state energy of singular, strongly coupled, quantum systems. Application of EMM theory requires an appropriate linearization of the highly nonlinear Hankel-Hadamard (HH) moment determinant constraints for the (n+1)×(n+1) Hankel matrices Mn[u]≡M̂n0+∑i=1msM̂niu i), dependent on the missing moment variables {u(i)}≡u. We propose an alternate variational formulation utilizing the functions Det(Mn+1[u])/Det(Mn[u]), which we prove to be locally convex over the missing moment subset satisfying the HH positivity conditions Det(Mν[u])≳0, for ν≤n. Additional features of this variational formulation facilitate its application to important problems such as the octic, sextic, and quartic anharmonic oscillators.

  6. Variational formulation of macro-particle plasma simulation algorithms

    SciTech Connect

    Shadwick, B. A. Stamm, A. B.; Evstatiev, E. G.

    2014-05-15

    A variation formulation of macro-particle kinetic plasma models is discussed. In the electrostatic case, the use of symplectic integrators is investigated and found to offer advantages over typical generic methods. For the electromagnetic case, gauge invariance and momentum conservation are considered in detail. It is shown that, while the symmetries responsible for these conservation laws are broken in the presence of a spatial grid, the conservation laws hold in an average sense. The requirements for exact invariance are explored and it is shown that one viable option is to represent the potentials with a truncated Fourier basis.

  7. Immunoglobulin: production, mechanisms of action and formulations

    PubMed Central

    Novaretti, Marcia Cristina Zago; Dinardo, Carla Luana

    2011-01-01

    Human immunoglobulin (Ig) began to be applied in the clinical practice with the treatment of primary immunodeficiencies. Quickly, applications of Ig increased, as its anti-inflammatory and immunomodulatory functions were elucidated. Currently, Ig is the most commonly used blood product. Ig is obtained by processing plasma; methods, in particular, techniques to reduce plasma viral loads have been evolving over the years and include: pasteurization, solvent/ detergent treatment, caprylic acid treatment and nanofiltration. These methods contribute to increased safety and quality of blood products. The mechanisms of action of Ig not only involve the blockade of Fc receptors of phagocytes, but also control complement pathways, idiotype-anti-idiotype dimer formation, blockage of superantigen binding to T cells, inhibition of dendritic cells and stimulation of regulatory T cells (Tregs). There are several formulations of Ig available, each one with its own peculiar characteristics. In Brazil, there is stringent legislation regulating the quality of Ig. Only Ig products that completely fulfill the quality control criteria are released for use. These standards involve different tests from visual inspection to determination of anti-complementary activity. This paper will further review the history and current status of Ig, including its production and mechanisms of action. The formulations available in Brazil and also the criteria of quality control currently applied will be presented. PMID:23049343

  8. Partial differential equation transform — Variational formulation and Fourier analysis

    PubMed Central

    Wang, Yang; Wei, Guo-Wei; Yang, Siyang

    2011-01-01

    Nonlinear partial differential equation (PDE) models are established approaches for image/signal processing, data analysis and surface construction. Most previous geometric PDEs are utilized as low-pass filters which give rise to image trend information. In an earlier work, we introduced mode decomposition evolution equations (MoDEEs), which behave like high-pass filters and are able to systematically provide intrinsic mode functions (IMFs) of signals and images. Due to their tunable time-frequency localization and perfect reconstruction, the operation of MoDEEs is called a PDE transform. By appropriate selection of PDE transform parameters, we can tune IMFs into trends, edges, textures, noise etc., which can be further utilized in the secondary processing for various purposes. This work introduces the variational formulation, performs the Fourier analysis, and conducts biomedical and biological applications of the proposed PDE transform. The variational formulation offers an algorithm to incorporate two image functions and two sets of low-pass PDE operators in the total energy functional. Two low-pass PDE operators have different signs, leading to energy disparity, while a coupling term, acting as a relative fidelity of two image functions, is introduced to reduce the disparity of two energy components. We construct variational PDE transforms by using Euler-Lagrange equation and artificial time propagation. Fourier analysis of a simplified PDE transform is presented to shed light on the filter properties of high order PDE transforms. Such an analysis also offers insight on the parameter selection of the PDE transform. The proposed PDE transform algorithm is validated by numerous benchmark tests. In one selected challenging example, we illustrate the ability of PDE transform to separate two adjacent frequencies of sin(x) and sin(1.1x). Such an ability is due to PDE transform’s controllable frequency localization obtained by adjusting the order of PDEs. The

  9. Variation in captopril formulations in pharmacies across Canada

    PubMed Central

    Bhatt, Mihir Dipakkumar; Thomas, Jason E; Mondal, Tapas Kumar

    2011-01-01

    Captopril, an angiotensin-converting enzyme inhibitor used to manage congestive heart failure in the paediatric population, has limited data on efficacy and safety. Its variety of liquid formulations dispensed by different pharmacies poses a challenge in optimizing captopril dosing in patients. Fourteen tertiary paediatric centre pharmacies across Canada were contacted to decipher the type of captopril formulation they dispense, their recipe and the stability of each formulation. Of the 14 centres surveyed, four dispensed solid tablets, two dispensed either solid tablets or liquid formulations, and eight dispensed extemporaneously prepared liquid formulations. There was also great variety in the solutions used to prepare the liquid formulations. The bioequivalence of these preparations has not been studied. As a result, physicians cannot be certain about the effective dose of captopril. Uniformity is recommended among paediatric pharmacies in Canada when preparing medications such as captopril. Proper testing of the stability and bioequivalence of medications is recommended. PMID:22468132

  10. A variational formulation of constrained dislocation dynamics coupled with heat and vacancy diffusion

    NASA Astrophysics Data System (ADS)

    Po, Giacomo; Ghoniem, Nasr

    2014-05-01

    We present a formulation of the discrete Dislocation Dynamics (DD) method based on Onsager's variational principle. The motion of discrete dislocations is treated as a generalized irreversible flux associated with conjugate thermodynamic forces causing internal production of entropy. Intrinsic in the variational principle is the role of physical constraints that limit the choice of generalized fluxes. We leverage the concept of constrained maximization to introduce the requirement that dislocation climb must be sustained by the flux of vacancies into the dislocation core. The constrained variational approach results naturally in the coupling between plastic deformation induced by discrete dislocations, vacancy diffusion, and heat propagation in solid crystals. In particular, this coupling requires that dislocation velocity and chemical potential of vacancies at the dislocation core be found simultaneously. A new numerical formulation of DD that accounts for generalized constraints imposed on dislocations is presented, based on a network discretization of the dislocation configuration. Applications illustrate the significance of constrained motion of dislocations confined in channels and pillars, and the attainment of heterogeneous dislocation structures.

  11. Homogeneous catalyst formulations for methanol production

    DOEpatents

    Mahajan, Devinder; Sapienza, Richard S.; Slegeir, William A.; O'Hare, Thomas E.

    1991-02-12

    There is disclosed synthesis of CH.sub.3 OH from carbon monoxide and hydrogen using an extremely active homogeneous catalyst for methanol synthesis directly from synthesis gas. The catalyst operates preferably between 100.degree.-150.degree. C. and preferably at 100-150 psia synthesis gas to produce methanol. Use can be made of syngas mixtures which contain considerable quantities of other gases, such as nitrogen, methane or excess hydrogen. The catalyst is composed of two components: (a) a transition metal carbonyl complex and (b) an alkoxide component. In the simplest formulation, component (a) is a complex of nickel tetracarbonyl and component (b) is methoxide (CH.sub.3 O.sup.-), both being dissolved in a methanol solvent system. The presence of a co-solvent such as p-dioxane, THF, polyalcohols, ethers, hydrocarbons, and crown ethers accelerates the methanol synthesis reaction.

  12. Homogeneous catalyst formulations for methanol production

    DOEpatents

    Mahajan, Devinder; Sapienza, Richard S.; Slegeir, William A.; O'Hare, Thomas E.

    1990-01-01

    There is disclosed synthesis of CH.sub.3 OH from carbon monoxide and hydrogen using an extremely active homogeneous catalyst for methanol synthesis directly from synthesis gas. The catalyst operates preferably between 100.degree.-150.degree. C. and preferably at 100-150 psia synthesis gas to produce methanol. Use can be made of syngas mixtures which contain considerable quantities of other gases, such as nitrogen, methane or excess hydrogen. The catalyst is composed of two components: (a) a transition metal carbonyl complex and (b) an alkoxide component. In the simplest formulation, component (a) is a complex of nickel tetracarbonyl and component (b) is methoxide (CH.sub.3 O.sup.13 ), both being dissolved in a methanol solvent system. The presence of a co-solvent such as p-dioxane, THF, polyalcohols, ethers, hydrocarbons, and crown ethers accelerates the methanol synthesis reaction.

  13. A variational formulation for time-dependent climate models

    NASA Technical Reports Server (NTRS)

    Smith, G. L.

    1984-01-01

    A variational principle for time dependent diffusion problems is presented and is demonstrated by applying it to simple seasonal climate models. Two cases are treated. The first, a North-Coakley-type model with constant properties, is used as a tutorial example for the application of the technique. For the second case, heat capacity and thermal conductivity are considered to be latitude dependent in order to treat the effects of land/ocean distribution on the seasonal temperature distribution over the earth. The variational equations are derived and approximate analytical solutions are developed which delineate the influences of the physical asymmetries of the hemispheres in producing an asymmetric annual cycle.

  14. Variational formulation of covariant eikonal theory for vector waves

    SciTech Connect

    Kaufman, A.N.; Ye, H.; Hui, Y.

    1986-10-01

    The eikonal theory of wave propagation is developed by means of a Lorentz-covariant variational principle, involving functions defined on the natural eight-dimensional phase space of rays. The wave field is a four-vector representing the electromagnetic potential, while the medium is represented by an anisotropic, dispersive nonuniform dielectric tensor D/sup ..mu nu../(k,x). The eikonal expansion yields, to lowest order, the Hamiltonian ray equations, which define the Lagrangian manifold k(x), and the wave-action conservation law, which determines the wave-amplitude transport along the rays. The first-order contribution to the variational principle yields a concise expression for the transport of the polarization phase. The symmetry between k-space and x-space allows for a simple implementation of the Maslov transform, which avoids the difficulties of caustic singularities.

  15. Variational formulation for Black-Scholes equations in stochastic volatility models

    NASA Astrophysics Data System (ADS)

    Gyulov, Tihomir B.; Valkov, Radoslav L.

    2012-11-01

    In this note we prove existence and uniqueness of weak solutions to a boundary value problem arising from stochastic volatility models in financial mathematics. Our settings are variational in weighted Sobolev spaces. Nevertheless, as it will become apparent our variational formulation agrees well with the stochastic part of the problem.

  16. Variation in nutrients formulated and nutrients supplied on 5 California dairies.

    PubMed

    Rossow, H A; Aly, S S

    2013-01-01

    Computer models used in ration formulation assume that nutrients supplied by a ration formulation are the same as the nutrients presented in front of the cow in the final ration. Deviations in nutrients due to feed management effects such as dry matter changes (i.e., rain), loading, mixing, and delivery errors are assumed to not affect delivery of nutrients to the cow and her resulting milk production. To estimate how feed management affects nutrients supplied to the cow and milk production, and determine if nutrients can serve as indexes of feed management practices, weekly total mixed ration samples were collected and analyzed for 4 pens (close-up cows, fresh cows, high-milk-producing, and low-milk-producing cows, if available) for 7 to 12 wk on 5 commercial California dairies. Differences among nutrient analyses from these samples and nutrients from the formulated rations were analyzed by PROC MIXED of SAS (SAS Institute Inc., Cary, NC). Milk fat and milk protein percentages did not vary as much [coefficient of variation (CV) = 18 to 33%] as milk yield (kg; CV = 16 to 47 %) across all dairies and pens. Variability in nutrients delivered were highest for macronutrient fat (CV = 22%), lignin (CV = 15%), and ash (CV = 11%) percentages and micronutrients Fe (mg/kg; CV = 48%), Na (%; CV = 42%), and Zn (mg/kg; CV = 38%) for the milking pens across all dairies. Partitioning of the variability in random effects of nutrients delivered and intraclass correlation coefficients showed that variability in lignin percentage of TMR had the highest correlation with variability in milk yield and milk fat percentage, followed by fat and crude protein percentages. But, variability in ash, fat, and lignin percentages of total mixed ration had the highest correlation with variability in milk protein percentage. Therefore, lignin, fat, and ash may be the best indices of feed management to include effects of variability in nutrients on variability in milk yield, milk fat, and milk

  17. A variational justification of the assumed natural strain formulation of finite elements

    NASA Technical Reports Server (NTRS)

    Militello, Carmelo; Felippa, Carlos A.

    1991-01-01

    The objective is to study the assumed natural strain (ANS) formulation of finite elements from a variational standpoint. The study is based on two hybrid extensions of the Reissner-type functional that uses strains and displacements as independent fields. One of the forms is a genuine variational principle that contains an independent boundary traction field, whereas the other one represents a restricted variational principle. Two procedures for element level elimination of the strain field are discussed, and one of them is shown to be equivalent to the inclusion of incompatible displacement modes. Also, the 4-node C(exp 0) plate bending quadrilateral element is used to illustrate applications of this theory.

  18. On variational formulation of current drive problem in uniformly magnetized relativistic plasma

    NASA Astrophysics Data System (ADS)

    Hu, Y. M.; Hu, Y. J.

    2016-01-01

    A fully relativistic extension of the variational principle with the modified test function for the Spitzer function with momentum conservation in the electron-electron collision is investigated in uniformly magnetized plasma. The term of the momentum conserving constraint in Hirshman’s variational calculation is studied. The model developed is extended for arbitrary temperatures and covers exactly the asymptotic for u\\gg 1 when {{Z}\\text{eff}}\\gg 1 , and the results obtained are suited to facilitate the development of a rigorous variational formulation of current drive efficiency in tokamak plasma.

  19. Superconducting axisymmetric finite elements based on a gauged potential variational principle. Part 1: Formulation

    NASA Technical Reports Server (NTRS)

    Schuler, James J.; Felippa, Carlos A.

    1994-01-01

    The present work is part of a research program for the numerical simulation of electromagnetic (EM) fields within conventional Ginzburg-Landau (GL) superconductors. The final goal of this research is to formulate, develop and validate finite element (FE) models that can accurately capture electromagnetic thermal and material phase changes in a superconductor. The formulations presented here are for a time-independent Ginzburg-Landau superconductor and are derived from a potential-based variational principle. We develop an appropriate variational formulation of time-independent supercontivity for the general three-dimensional case and specialize it to the one-dimensional case. Also developed are expressions for the material-dependent parameters alpha and beta of GL theory and their dependence upon the temperature T. The one-dimensional formulation is then discretized for finite element purposes and the first variation of these equations is obtained. The resultant Euler equations contain nonlinear terms in the primary variables. To solve these equations, an incremental-iterative solution method is used. Expressions for the internal force vector, external force vector, loading vector and tangent stiffness matrix are therefore developed for use with the solution procedure.

  20. 7 CFR 1217.62 - Patents, copyrights, trademarks, inventions, product formulations, and publications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Patents, copyrights, trademarks, inventions, product... Promotion, Research, and Information § 1217.62 Patents, copyrights, trademarks, inventions, product formulations, and publications. Any patents, copyrights, trademarks, inventions, product formulations,...

  1. 7 CFR 1217.62 - Patents, copyrights, trademarks, inventions, product formulations, and publications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Patents, copyrights, trademarks, inventions, product... Promotion, Research, and Information § 1217.62 Patents, copyrights, trademarks, inventions, product formulations, and publications. Any patents, copyrights, trademarks, inventions, product formulations,...

  2. 7 CFR 1217.62 - Patents, copyrights, trademarks, inventions, product formulations, and publications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Patents, copyrights, trademarks, inventions, product... Promotion, Research, and Information § 1217.62 Patents, copyrights, trademarks, inventions, product formulations, and publications. Any patents, copyrights, trademarks, inventions, product formulations,...

  3. Hamiltonian magnetohydrodynamics: Helically symmetric formulation, Casimir invariants, and equilibrium variational principles

    SciTech Connect

    Andreussi, T.; Morrison, P. J.; Pegoraro, F.

    2012-05-15

    The noncanonical Hamiltonian formulation of magnetohydrodynamics (MHD) is used to construct variational principles for continuously symmetric equilibrium configurations of magnetized plasma, including flow. In particular, helical symmetry is considered, and results on axial and translational symmetries are retrieved as special cases of the helical configurations. The symmetry condition, which allows the description in terms of a magnetic flux function, is exploited to deduce a symmetric form of the noncanonical Poisson bracket of MHD. Casimir invariants are then obtained directly from the Poisson bracket. Equilibria are obtained from an energy-Casimir principle and reduced forms of this variational principle are obtained by the elimination of algebraic constraints.

  4. Variations on Slavnov's scalar product

    NASA Astrophysics Data System (ADS)

    Foda, O.; Wheeler, M.

    2012-10-01

    We consider the rational six-vertex model on an L× L lattice with domain wall boundary conditions and restrict N parallel-line rapidities, N ≤ L/2, to satisfy length- L XXX spin-1/2 chain Bethe equations. We show that the partition function is an ( L - 2 N )- parameter extension of Slavnov's scalar product of a Bethe eigenstate and a generic state, with N magnons each, on a length- L XXX spin-1/2 chain. Decoupling the extra parameters, we obtain a third determinant expression for the scalar product, where the first is due to Slavnov [1], and the second is due to Kostov and Matsuo [2]. We show that the new determinant is Casoratian, and consequently that tree-level {N}=4 SYM structure constants that are known to be determinants, remain determinants at 1-loop level.

  5. 7 CFR 1221.123 - Patents, copyrights, inventions, trademarks, information, publications, and product formulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Patents, copyrights, inventions, trademarks..., copyrights, inventions, trademarks, information, publications, and product formulations. (a) Any patents, copyrights, inventions, trademarks, information, publications, or product formulations developed through...

  6. 7 CFR 1221.123 - Patents, copyrights, inventions, trademarks, information, publications, and product formulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Patents, copyrights, inventions, trademarks..., copyrights, inventions, trademarks, information, publications, and product formulations. (a) Any patents, copyrights, inventions, trademarks, information, publications, or product formulations developed through...

  7. Generic development of topical dermatologic products: formulation development, process development, and testing of topical dermatologic products.

    PubMed

    Chang, Rong-Kun; Raw, Andre; Lionberger, Robert; Yu, Lawrence

    2013-01-01

    This review presents considerations which can be employed during the development of a semi-solid topical generic product. This includes a discussion on the implementation of quality by design concepts during development to ensure the generic drug product has similar desired quality attributes to the reference-listed drug (RLD) and ensure batch to batch consistency through commercial production. This encompasses the concept of reverse-engineering to copy the RLD as a strategy during product development to ensure qualitative (Q1) and quantitative (Q2) formulation similarity, as well as similarity in formulation microstructure (Q3). The concept of utilizing in vitro skin permeation studies as a tool to justify formulation differences between the test generic product and the RLD to ensure a successful pharmacodynamic or clinical endpoint bioequivalence study is discussed. The review concludes with a discussion on drug product evaluation and quality tests as well as in vivo bioequivalence studies. PMID:23054971

  8. Variational method for nonconservative field theories: Formulation and two PT-symmetric case examples

    NASA Astrophysics Data System (ADS)

    Kevrekidis, P. G.

    2014-01-01

    In a recent publication [5 Galley, Phys. Rev. Lett. 110, 174301 (2013), 10.1103/PhysRevLett.110.174301], Galley proposed an initial value problem formulation of Hamilton's principle that enables consideration of dissipative systems. Here we explore this formulation at the level of field theories with infinite degrees of freedom. In particular, we illustrate that it affords a previously unwarranted and appealing as well as broadly relevant possibility, namely, to generalize the popular collective coordinate or variational method to open systems, i.e., nonconservative ones. To showcase the relevance or validity of the method we explore two case examples from the timely area of PT-symmetric variants of field theories, in this case for a sine-Gordon and for a ϕ4 model.

  9. Mixed augmented variational formulation (MAVF) for lower hybrid full-wave calculations

    NASA Astrophysics Data System (ADS)

    Peysson, Y.; Roche, J. R.; Bertrand, P.; Chatenet, J.-H.; Kirsch, C.; Mokrani, A.; Labrunie, S.

    2009-11-01

    In the continuation of the works led in cylindrical geometry [2], a full toroidal description for an arbitrary poloidal cross-section of the plasma has been developed. For simulation purpose a mixed augmented variational formulation (MAVF), which is particularly well suited for solving Maxwell equations, is considered [4]. The discretization of the MAVF is carried out using Taylor-Hood P2-iso-P1 finite elements. This formulation provide a natural implementation for parallel processing, a particularly important aspect when simulations for plasmas of large size must be considered. Details on the specific application of the MAVF to the LH problem are presented, as well as the structure of the corresponding matrices. A first application to a realistic small tokamak configuration is considered.

  10. Alternative formulations of isotropic hardening for Mises materials, and associated variational inequalities

    NASA Astrophysics Data System (ADS)

    Gurtin, Morton E.; Reddy, B. Daya

    2009-07-01

    This work provides insight into aspects of classical Mises-Hill plasticity, its extension to the Aifantis theory of gradient plasticity, and the formulations of both theories as variational inequalities. Firstly, it is shown that the classical isotropic hardening rule, which is dissipative in nature, may equally well be characterized via a defect energy—and, what is striking, this energetically based hardening rule mimics dissipative behavior by describing loading processes that are irreversible. A second aspect concerns the equivalence between the conventional form of the flow rule and its formulation in terms of dissipation. This equivalence has been previously established using the tools of convex analysis (cf., e.g., Han and Reddy, Plasticity: mathematical theory and numerical analysis, Springer, New York, 1999)—in the current work this equivalence is derived directly from the constitutive equations and the specific form of the dissipation, without recourse to such machinery. Variational inequalities corresponding to the dissipative and energetic forms of the flow rule are derived; these inequalities involve only the displacement and plastic strain and are well suited to computational studies. Finally, it is shown that the framework developed for the classical theory is easily extended to incorporate the gradient-plasticity theory of Aifantis (Trans ASME J Eng Mater Technol 106:326-330, 1984).

  11. Production, acceptability and microbiological evaluation of weaning food formulations.

    PubMed

    Badau, M H; Jideani, I A; Nkama, I

    2006-06-01

    Weaning food formulations were produced from pearl millet cultivar (SOSAT C-88), cowpea and groundnut in the ratio of 70:20:10 and 5 per cent malt from six pearl millet cultivars (SOSAT C-88, ZANGO, EX-BORNO, ICMV IS 94206, GWAGWA, GB 8735) and one sorghum cultivar (ICSV III) were added to produce seven formulations plus the one without malt. Microbiological quality of eight weaning food formulations was evaluated. Twenty weaning mothers were used to determine the acceptability of gruels from the eight weaning food formulations using a nine-point hedonic scale. Addition of 5 per cent malt did not affect the microbial count of weaning food formulations. Saccharomyces cerevisiae, Klebsiella aerogenes and Aspergillus niger were found in all the weaning food formulations. Shigella and Salmonella were not encountered in this study. Addition of 5 per cent SOSAT C-88, ZANGO, EX-BORNO, ICMV-IS 94206 and GWAGWA malt improved the taste and texture of weaning food formulations. The population of micro-organisms isolated from weaning formulations was not high enough to produce effective dose. However, the need for processors of weaning foods to adopt strict hygiene practices cannot be overemphasized. PMID:16169859

  12. 7 CFR 1212.62 - Patents, copyrights, inventions, product formulations, and publications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, inventions, product formulations... Information Order Promotion, Research, and Information § 1212.62 Patents, copyrights, inventions, product... invention, any patents, copyrights, inventions, product formulations, or publications developed through...

  13. 7 CFR 1219.57 - Patents, copyrights, trademarks, publications, and product formulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research... development of such patent, copyright, trademark, invention, publication, or product formulation in a...

  14. A mathematical formulation for interface-based modular product design with geometric and weight constraints

    NASA Astrophysics Data System (ADS)

    Jung-Woon Yoo, John

    2016-06-01

    Since customer preferences change rapidly, there is a need for design processes with shorter product development cycles. Modularization plays a key role in achieving mass customization, which is crucial in today's competitive global market environments. Standardized interfaces among modularized parts have facilitated computational product design. To incorporate product size and weight constraints during computational design procedures, a mixed integer programming formulation is presented in this article. Product size and weight are two of the most important design parameters, as evidenced by recent smart-phone products. This article focuses on the integration of geometric, weight and interface constraints into the proposed mathematical formulation. The formulation generates the optimal selection of components for a target product, which satisfies geometric, weight and interface constraints. The formulation is verified through a case study and experiments are performed to demonstrate the performance of the formulation.

  15. 7 CFR 1280.231 - Patents, copyrights, inventions, product formulations, and publications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Patents, copyrights, inventions, product formulations... Information Order Miscellaneous § 1280.231 Patents, copyrights, inventions, product formulations, and publications. (a) Any patents, copyrights, inventions or publications developed through the use of...

  16. 7 CFR 1280.231 - Patents, copyrights, inventions, product formulations, and publications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Patents, copyrights, inventions, product formulations... Information Order Miscellaneous § 1280.231 Patents, copyrights, inventions, product formulations, and publications. (a) Any patents, copyrights, inventions or publications developed through the use of...

  17. 7 CFR 1280.231 - Patents, copyrights, inventions, product formulations, and publications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Patents, copyrights, inventions, product formulations... Information Order Miscellaneous § 1280.231 Patents, copyrights, inventions, product formulations, and publications. (a) Any patents, copyrights, inventions or publications developed through the use of...

  18. 7 CFR 1280.231 - Patents, copyrights, inventions, product formulations, and publications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, inventions, product formulations... Information Order Miscellaneous § 1280.231 Patents, copyrights, inventions, product formulations, and publications. (a) Any patents, copyrights, inventions or publications developed through the use of...

  19. 7 CFR 1215.75 - Patents, copyrights, inventions, publications, and product formulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Patents, copyrights, inventions, publications, and..., and Consumer Information Order Miscellaneous § 1215.75 Patents, copyrights, inventions, publications, and product formulations. Any patents, copyrights, inventions, publications, or product...

  20. 7 CFR 1215.75 - Patents, copyrights, inventions, publications, and product formulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Patents, copyrights, inventions, publications, and..., and Consumer Information Order Miscellaneous § 1215.75 Patents, copyrights, inventions, publications, and product formulations. Any patents, copyrights, inventions, publications, or product...

  1. 7 CFR 1215.75 - Patents, copyrights, inventions, publications, and product formulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Patents, copyrights, inventions, publications, and..., and Consumer Information Order Miscellaneous § 1215.75 Patents, copyrights, inventions, publications, and product formulations. Any patents, copyrights, inventions, publications, or product...

  2. Proactive management of fermentation and formulation interactions to improve biocontrol product performance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The key components of biocontrol product development; discovery, fermentation, and formulation, are interactively linked to each other and ultimately, to product performance. The fermentation environment can be managed to maximize the quantity and quality of biomass and bioproducts produced which, ...

  3. 7 CFR 1215.75 - Patents, copyrights, inventions, publications, and product formulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, inventions, publications, and..., and Consumer Information Order Miscellaneous § 1215.75 Patents, copyrights, inventions, publications, and product formulations. Any patents, copyrights, inventions, publications, or product...

  4. Regularized formulation of the variational brittle fracture with unilateral contact: Numerical experiments

    NASA Astrophysics Data System (ADS)

    Amor, Hanen; Marigo, Jean-Jacques; Maurini, Corrado

    2009-08-01

    This paper presents a modified regularized formulation of the Ambrosio-Tortorelli type to introduce the crack non-interpenetration condition in the variational approach to fracture mechanics proposed by Francfort and Marigo [1998. Revisiting brittle fracture as an energy minimization problem. J. Mech. Phys. Solids 46 (8), 1319-1342]. We focus on the linear elastic case where the contact condition appears as a local unilateral constraint on the displacement jump at the crack surfaces. The regularized model is obtained by splitting the strain energy in a spherical and a deviatoric parts and accounting for the sign of the local volume change. The numerical implementation is based on a standard finite element discretization and on the adaptation of an alternate minimization algorithm used in previous works. The new regularization avoids crack interpenetration and predicts asymmetric results in traction and in compression. Even though we do not exhibit any gamma-convergence proof toward the desired limit behavior, we illustrate through several numerical case studies the pertinence of the new model in comparison to other approaches.

  5. Large eddy simulation models for incompressible magnetohydrodynamics derived from the variational multiscale formulation

    SciTech Connect

    Sondak, David; Oberai, Assad A.

    2012-10-15

    Novel large eddy simulation (LES) models are developed for incompressible magnetohydrodynamics (MHD). These models include the application of the variational multiscale formulation of LES to the equations of incompressible MHD. Additionally, a new residual-based eddy viscosity model is introduced for MHD. A mixed LES model that combines the strengths of both of these models is also derived. The new models result in a consistent numerical method that is relatively simple to implement. The need for a dynamic procedure in determining model coefficients is no longer required. The new LES models are tested on a decaying Taylor-Green vortex generalized to MHD and benchmarked against classical LES turbulence models. The LES simulations are run in a periodic box of size [-{pi}, {pi}]{sup 3} with 32 modes in each direction and are compared to a direct numerical simulation (DNS) with 512 modes in each direction. The new models are able to account for the essential MHD physics which is demonstrated via comparisons of energy spectra. We also compare the performance of our models to a DNS simulation by Pouquet et al.['The dynamics of unforced turbulence at high Reynolds number for Taylor-Green vortices generalized to MHD,' Geophys. Astrophys. Fluid Dyn. 104, 115-134 (2010)], for which the ratio of DNS modes to LES modes is 262:144.

  6. Theory on excitations of drift Alfvén waves by energetic particles. I. Variational formulation

    SciTech Connect

    Zonca, Fulvio; Chen, Liu

    2014-07-15

    A unified theoretical framework is presented for analyzing various branches of drift Alfvén waves and describing their linear and nonlinear behaviors, covering a wide range of spatial and temporal scales. Nonlinear gyrokinetic quasineutrality condition and vorticity equation, derived for drift Alfvén waves excited by energetic particles in fusion plasmas, are cast in integral form, which is generally variational in the linear limit; and the corresponding gyrokinetic energy principle is obtained. Well known forms of the kinetic energy principle are readily recovered from this general formulation. Furthermore, it is possible to demonstrate that the general fishbone like dispersion relation, obtained within the present theoretical framework, provides a unified description of drift Alfvén waves excited by energetic particles as either Alfvén eigenmodes or energetic particle modes. The advantage of the present approach stands in its capability of extracting underlying linear and nonlinear physics as well as spatial and temporal scales of the considered fluctuation spectrum. For these reasons, this unified theoretical framework can help understanding experimental observations as well as numerical simulation and analytic results with different levels of approximation. Examples and applications are given in Paper II [F. Zonca and L. Chen, “Theory on excitations of drift Alfvén waves by energetic particles. II. The general fishbone-like dispersion relation,” Phys. Plasmas 21, 072121 (2014)].

  7. Novel delivery system for natural products: Nano-curcumin formulations

    PubMed Central

    Rahimi, Hamid Reza; Nedaeinia, Reza; Sepehri Shamloo, Alireza; Nikdoust, Shima; Kazemi Oskuee, Reza

    2016-01-01

    Objective: Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer’s, inflammatory bowel disease (IBD), and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug. Materials and Methods: Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields): (“Curcumin” OR “Curcuma longa”) AND [(nanoparticles) OR (Nanomicelles) OR (micro emulsions) OR (liposome) OR (phospholipid). Results: Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially. Conclusion: These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions. PMID:27516979

  8. Variational formulation and stability analysis of a three dimensional superelastic model for shape memory alloys

    NASA Astrophysics Data System (ADS)

    Alessi, Roberto; Pham, Kim

    2016-02-01

    This paper presents a variational framework for the three-dimensional macroscopic modelling of superelastic shape memory alloys in an isothermal setting. Phase transformation is accounted through a unique second order tensorial internal variable, acting as the transformation strain. Postulating the total strain energy density as the sum of a free energy and a dissipated energy, the model depends on two material scalar functions of the norm of the transformation strain and a material scalar constant. Appropriate calibration of these material functions allows to render a wide range of constitutive behaviours including stress-softening and stress-hardening. The quasi-static evolution problem of a domain is formulated in terms of two physical principles based on the total energy of the system: a stability criterion, which selects the local minima of the total energy, and an energy balance condition, which ensures the consistency of the evolution of the total energy with respect to the external loadings. The local phase transformation laws in terms of Kuhn-Tucker relations are deduced from the first-order stability condition and the energy balance condition. The response of the model is illustrated with a numerical traction-torsion test performed on a thin-walled cylinder. Evolutions of homogeneous states are given for proportional and non-proportional loadings. Influence of the stress-hardening/softening properties on the evolution of the transformation domain is emphasized. Finally, in view of an identification process, the issue of stability of homogeneous states in a multi-dimensional setting is answered based on the study of second-order derivative of the total energy. Explicit necessary and sufficient conditions of stability are provided.

  9. Studies on application of annatto (Bixa orellena L.) dye formulations in dairy products.

    PubMed

    Sathiya Mala, Kripanand; Prabhakara Rao, Pamidighantam; Prabhavathy, Manda Babu; Satyanarayana, Akula

    2015-02-01

    Annatto is often used to add color to dairy products such as butter, cheese, or puddings. In India usage of annatto is restricted to butter and cheese, however there are no tailor made formulations available to obtain standardized colour shades for the products. Hence a study was initiated to develop the appropriate annatto dye formulations and level of application in few dairy products (butter, cheese, paneer, biscuit cream, icing cream). Dye extracted from annatto seeds was used for the preparation of water soluble potassium carbonate formulation (nor-bixin, 11.24 %), oil soluble formulation (1.35 % bixin) and an oil/water soluble propylene glycol formulation (PG formulation, 1.31 % bixin). Lovibond tintometer colour units of the commercial butter, cheese and biscuit cream samples were measured for standardizing the colour concentration in the experimental products. The present study evaluates the application and stability of these formulations in butter, cheese, paneer, biscuit cream, icing cream. The products were evaluated for stability of colour and bixin during storage period. The oil/water soluble propylene glycol formulation was found to be tailor-made for all the dairy products studied though the standardized levels varied between 3.75 and 5.0 mg/kg for butter, 3.75 mg/kg for cheese, 5.0-400 mg/kg for biscuit cream, 12.25 and 25 mg/kg for paneer, 5.0-500 mg/kg for icing cream. Increasing concentration in the range of 30-500 mg/kg yielded products with light cream to orange shades, useful for decorating cakes. The average recovery of bixin from the products immediately after processing was 90-98 %. Significant changes (P ≤ 0.05) were noticed in the colour units and recovery of bixin in all the products during storage of 6 months. PMID:25694700

  10. Understanding effect of formulation and manufacturing variables on the critical quality attributes of warfarin sodium product.

    PubMed

    Rahman, Ziyaur; Korang-Yeboah, Maxwell; Siddiqui, Akhtar; Mohammad, Adil; Khan, Mansoor A

    2015-11-10

    Warfarin sodium (WS) is a narrow therapeutic index drug and its product quality should be thoroughly understood and monitored in order to avoid clinical performance issues. This study was focused on understanding the effect of manufacturing and formulation variables on WS product critical quality attributes (CQAs). Eight formulations were developed with lactose monohydrate (LM) or lactose anhydrous (LA), and were either wet granulated or directly compressed. Formulations were granulated either with ethanol, isopropyl alcohol (IPA) and IPA-water mixture (50:50). Formulations were characterized for IPA, water content, hardness, disintegration time (DT), assay, dissolution and drug physical forms (scanning electron microscopy (SEM), near infrared chemical imaging (NIR-CI), X-ray powder diffraction (XRPD) and solid state nuclear magnetic resonance (ssNMR)), and performed accelerated stability studies at 40°C/75% RH for three days. The DT and dissolution of directly compressed formulations were faster than wet granulated formulations. This was due to phase transformation of crystalline drug into its amorphous form as indicated by SEM, NIR-CI, XRPD and ssNMR data which itself act as a binder. Similarly, LM showed faster disintegration and dissolution than LA containing formulations. Stability results indicated an increase in hardness and DT, and a decrease in dissolution rate and extent. This was due to phase transformation of the drug and consolidation with particles' bonding. In conclusion, the CQAs of WS product were significantly affected by manufacturing and formulation variables. PMID:26319638

  11. 7 CFR 1209.75 - Patents, copyrights, inventions, publications, and product formulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Patents, copyrights, inventions, publications, and..., Research, and Consumer Information Order Miscellaneous § 1209.75 Patents, copyrights, inventions, publications, and product formulations. Any patents, copyrights, inventions, publications, or...

  12. 7 CFR 63.501 - Patents, copyrights, inventions, trademarks, information, publications, and product formulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Patents, copyrights, inventions, trademarks... General Provisions Miscellaneous § 63.501 Patents, copyrights, inventions, trademarks, information, publications, and product formulations. Any patents, copyrights, inventions, trademarks,...

  13. 7 CFR 1209.75 - Patents, copyrights, inventions, publications, and product formulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Patents, copyrights, inventions, publications, and..., Research, and Consumer Information Order Miscellaneous § 1209.75 Patents, copyrights, inventions, publications, and product formulations. Any patents, copyrights, inventions, publications, or...

  14. 7 CFR 63.501 - Patents, copyrights, inventions, trademarks, information, publications, and product formulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Patents, copyrights, inventions, trademarks... General Provisions Miscellaneous § 63.501 Patents, copyrights, inventions, trademarks, information, publications, and product formulations. Any patents, copyrights, inventions, trademarks,...

  15. 7 CFR 63.501 - Patents, copyrights, inventions, trademarks, information, publications, and product formulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Patents, copyrights, inventions, trademarks... General Provisions Miscellaneous § 63.501 Patents, copyrights, inventions, trademarks, information, publications, and product formulations. Any patents, copyrights, inventions, trademarks,...

  16. 7 CFR 1209.75 - Patents, copyrights, inventions, publications, and product formulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Patents, copyrights, inventions, publications, and..., Research, and Consumer Information Order Miscellaneous § 1209.75 Patents, copyrights, inventions, publications, and product formulations. Any patents, copyrights, inventions, publications, or...

  17. 7 CFR 1209.75 - Patents, copyrights, inventions, publications, and product formulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, inventions, publications, and..., Research, and Consumer Information Order Miscellaneous § 1209.75 Patents, copyrights, inventions, publications, and product formulations. Any patents, copyrights, inventions, publications, or...

  18. A variational justification of the assumed natural strain formulation of finite elements. I - Variational principles. II - The C(0) four-node plate element

    NASA Technical Reports Server (NTRS)

    Militello, Carmelo; Felippa, Carlos A.

    1990-01-01

    The assumed natural strain formulation of finite elements is interpreted from a variational standpoint. The approach is based on hybrid extensions of the Reissner-type functional which uses the strains and displacements as independent fields. Consideration is restricted to linear elasticity. The four-node C(0) plate-bending quadrilateral is used as a specific example to illustrate the application of the present interpretation. A key finding is that any change in the strain-displacement interpolation from the variationally consistent interpolation must be associated in some way to the addition of incompatible displacement modes.

  19. Solvent effects in time-dependent self-consistent field methods. II. Variational formulations and analytical gradients

    DOE PAGESBeta

    Bjorgaard, J. A.; Velizhanin, K. A.; Tretiak, S.

    2015-08-06

    This study describes variational energy expressions and analytical excited state energy gradients for time-dependent self-consistent field methods with polarizable solvent effects. Linear response, vertical excitation, and state-specific solventmodels are examined. Enforcing a variational ground stateenergy expression in the state-specific model is found to reduce it to the vertical excitation model. Variational excited state energy expressions are then provided for the linear response and vertical excitation models and analytical gradients are formulated. Using semiempiricalmodel chemistry, the variational expressions are verified by numerical and analytical differentiation with respect to a static external electric field. Lastly, analytical gradients are further tested by performingmore » microcanonical excited state molecular dynamics with p-nitroaniline.« less

  20. Solvent effects in time-dependent self-consistent field methods. II. Variational formulations and analytical gradients

    SciTech Connect

    Bjorgaard, J. A.; Velizhanin, K. A.; Tretiak, S.

    2015-08-06

    This study describes variational energy expressions and analytical excited state energy gradients for time-dependent self-consistent field methods with polarizable solvent effects. Linear response, vertical excitation, and state-specific solventmodels are examined. Enforcing a variational ground stateenergy expression in the state-specific model is found to reduce it to the vertical excitation model. Variational excited state energy expressions are then provided for the linear response and vertical excitation models and analytical gradients are formulated. Using semiempiricalmodel chemistry, the variational expressions are verified by numerical and analytical differentiation with respect to a static external electric field. Lastly, analytical gradients are further tested by performing microcanonical excited state molecular dynamics with p-nitroaniline.

  1. High-performance liquid chromatographic determination of L-aspartyl-L-phenylalanine methyl ester in various food products and formulations.

    PubMed

    Fox, L; Anthony, G D; Lau, E P

    1976-09-01

    A simple, rapid, and specific high-performance liquid chromatographic (HPLC) procedure is described for the analysis of the chemical sweetener L-aspartyl-L-phenylalanine methyl ester (aspartame). Using a strong cation exchange column and pressures less than 1000 psig, an analysis can be performed in less than 15 min. The technique has been applied to a wide range of food products and formulations. No interferences were found in the samples studied. Recoveries are quantitative, and the coefficients of variation for replicate analyses are less than or equal to 2.5%. PMID:965327

  2. Variational finite element-tensor formulation for the large deflection random vibration of composite plates

    NASA Technical Reports Server (NTRS)

    Robinson, Jay H.

    1991-01-01

    A numerical integration routine is derived from a set of unified single step integration algorithms using a weighted satisfaction of the equilibrium equation governing the large deflection random response of laminated composite plates. The equilibrium equation is derived using a constant matrix large deflection finite-element formulation. In-plane inertia terms are considered in the formulation, however, rotary inertia terms are assumed negligible. Probability density, spectral density and autocorrelation functions of the maximum displacement and strain responses are presented for three acoustic excitation levels. Classical thin plate boundary conditions and pseudo white noise excitation are used in this investigation.

  3. Zinc oxide as a new antimicrobial preservative of topical products: interactions with common formulation ingredients.

    PubMed

    Pasquet, Julia; Chevalier, Yves; Couval, Emmanuelle; Bouvier, Dominique; Bolzinger, Marie-Alexandrine

    2015-02-01

    Zinc oxide (ZnO) appears as a promising preservative for pharmaceutical or cosmetic formulations. The other ingredients of the formulations may have specific interactions with ZnO that alter its antimicrobial properties. The influence of common formulation excipients on the antimicrobial efficacy of ZnO has been investigated in simple model systems and in typical topical products containing a complex formulation. A wide variety of formulation excipients have been investigated for their interactions with ZnO: antioxidants, chelating agents, electrolytes, titanium dioxide pigment. The antimicrobial activity of ZnO against Escherichia coli was partially inhibited by NaCl and MgSO4 salts. A synergistic influence of uncoated titanium dioxide has been observed. The interference effects of antioxidants and chelating agents were quite specific. The interactions of these substances with ZnO particles and with the soluble species released by ZnO were discussed so as to reach scientific guidelines for the choice of the ingredients. The preservative efficacy of ZnO was assessed by challenge testing in three different formulations: an oil-in-water emulsion; a water-in-oil emulsion and a dry powder. The addition of ZnO in complex formulations significantly improved the microbiological quality of the products, in spite of the presence of other ingredients that modulate the antimicrobial activity. PMID:25527211

  4. Lean production of taste improved lipidic sodium benzoate formulations.

    PubMed

    Eckert, C; Pein, M; Breitkreutz, J

    2014-10-01

    Sodium benzoate is a highly soluble orphan drug with unpleasant taste and high daily dose. The aim of this study was to develop a child appropriate, individually dosable, and taste masked dosage form utilizing lipids in melt granulation process and tableting. A saliva resistant coated lipid granule produced by extrusion served as reference product. Low melting hard fat was found to be appropriate as lipid binder in high-shear granulation. The resulting granules were compressed to minitablets without addition of other excipients. Compression to 2mm minitablets decreased the dissolved API amount within the first 2 min of dissolution from 33% to 23%. The Euclidean distances, calculated from electronic tongue measurements, were reduced, indicating an improved taste. The reference product showed a lag time in dissolution, which is desirable for taste masking. Although a lag time was not achieved for the lipidic minitablets, drug release in various food materials was reduced to 2%, assuming a suitable taste masking for oral sodium benzoate administration. PMID:24859305

  5. Formulation and Storage of Platelet-Rich Plasma Homemade Product

    PubMed Central

    Giraudo, Laurent; Veran, Julie; Magalon, Jeremy; Coudreuse, Jean-Marie; Magalon, Guy; Dubois, Christophe; Serratrice, Nicolas; Dignat-George, Françoise; Sabatier, Florence

    2012-01-01

    Abstract The platelet-rich plasma (PRP) is an autologous biotherapy based on platelet-healing properties. Here, we developed a simple and reproducible PRP purification protocol based on two successive centrifugations. We evaluated different centrifugation speeds and time-storage durations on the platelet quantity and quality. Sterility and stability of our PRP homemade product were also performed. We prepared PRP from 54 healthy volunteers. We tested activation state, reactivity, and stability of platelets by flow cytometry using basal and adenosine diphosphate (ADP)-induced P-selectin expression markers; growth factor release after platelet activation by an enzyme-linked immunosorbent assay (ELISA); platelet aggregation capacity by aggregrometry assays; clot formation and retraction by thromboelastography; and platelet morphology by ultrastructural analysis. About 130 and 250 g successive speed centrifugations further concentrated platelets while preserving their bioactivity during 6 h (after that, platelet functions were significantly altered). In these conditions, we obtained a highly concentrated pure PRP product (with a low leukocyte count) suitable to study platelet properties. To avoid the loss of efficacy, we recommend injecting PRP under 3 h after preparation. PMID:23516671

  6. Alternative methods of processing bio-feedstocks in formulated consumer product design

    PubMed Central

    Peremezhney, Nicolai; Jacob, Philipp-Maximilian; Lapkin, Alexei

    2014-01-01

    In this work new methods of processing bio-feedstocks in the formulated consumer products industry are discussed. Our current approach to formulated products design is based on heuristic knowledge of formulators that allows selecting individual compounds from a library of available materials with known properties. We speculate that most of the compounds (or functions) that make up the product to be designed can potentially be obtained from a few bio-sources. In this case, it may be possible to design a sequence of transformations required to convert feedstocks into products with desired properties, analogous to a metabolic pathway of a complex organism. We conceptualize some novel approaches to processing bio-feedstocks with the aim of bypassing the step of a fixed library of ingredients. Two approaches are brought forward: one making use of knowledge-based expert systems and the other making use of applications of metabolic engineering and dynamic combinatorial chemistry. PMID:24860803

  7. Alternative methods of processing bio-feedstocks in formulated consumer product design

    NASA Astrophysics Data System (ADS)

    Peremezhney, Nicolai; Jacob, Philipp-Maximilian; Lapkin, Alexei

    2014-05-01

    In this work new methods of processing bio-feedstocks in the formulated consumer products industry are discussed. Our current approach to formulated products design is based on heuristic knowledge of formulators that allows selecting individual compounds from a library of available materials with known properties. We speculate that most of the compounds (or functions) that make up the product to be designed can potentially be obtained from a few bio-sources. In this case, it may be possible to design a sequence of transformations required to convert feedstocks into products with desired properties, analogous to a metabolic pathway of a complex organism. We conceptualize some novel approaches to processing bio-feedstocks with the aim of bypassing the step of a fixed library of ingredients. Two approaches are brought forward: one making use of knowledge-based expert systems and the other making use of applications of metabolic engineering and dynamic combinatorial chemistry.

  8. ALTERNATIVE FORMULATIONS TO REDUCE CFC USE IN U.S. EXEMPTED AND EXCLUSED AEROSOL PRODUCTS

    EPA Science Inventory

    The report examines products exempted and excluded from those affected by the 1978 ban on the use of chlorofluorocarbons (CFCs) as aerosol propellants, the present consumption of CFCs still utilized for these products in the U.S., and alternative formulations which may be used to...

  9. ALTERNATIVE FORMULATIONS TO REDUCE CFC USE IN U.S. EXEMPTED AND EXCLUDED AEROSOL PRODUCTS

    EPA Science Inventory

    The report examines products exempted and excluded from those affected by the 1978 ban on the use of chlorofluorocarbons (CFCs) as aerosol propellants, the present consumption of CFCs still utilized for these products in the U.S., and alternative formulations which may be used to...

  10. Challenging the requirement for chronic fish toxicity studies on formulated plant protection products.

    PubMed

    Creton, Stuart; Douglas, Mark; Wheeler, James R; Hutchinson, Thomas H

    2010-11-30

    Ecotoxicity testing of pesticide active ingredients and formulated plant protection products (PPPs) prior to their commercial use is required by authorities around the world. Such studies are important for the conduct of risk assessments to protect wildlife and the environment, but they should only be conducted when their use is scientifically justified. One test of questionable scientific merit is the chronic fish toxicity test when conducted with formulated PPPs, which is a potential requirement under European legislation: chronic exposure to the formulated product per se rarely occurs in the environment and therefore it is generally not possible to use the data from chronic formulation studies in a meaningful risk assessment. A recent survey of European crop protection companies to explore the scientific merits and regulatory drivers for chronic fish toxicity studies has shown that current practice in deciding on the need for chronic fish toxicity testing of formulated PPPs varies substantially between companies. The most commonly cited reason for conducting such studies was solely to meet regulatory requirements. We conclude that chronic formulation testing is rarely if ever scientifically justified, and recommend that the forthcoming revision of the EU Aquatic Toxicology Guidance Document takes account of this by including a requirement that justification must be provided for conducting the test, rather than the current situation where the onus is on the registrant to provide a justification for not conducting the test. PMID:20832457

  11. Variational formulation of hybrid problems for fully 3-D transonic flow with shocks in rotor

    NASA Technical Reports Server (NTRS)

    Liu, Gao-Lian

    1991-01-01

    Based on previous research, the unified variable domain variational theory of hybrid problems for rotor flow is extended to fully 3-D transonic rotor flow with shocks, unifying and generalizing the direct and inverse problems. Three variational principles (VP) families were established. All unknown boundaries and flow discontinuities (such as shocks, free trailing vortex sheets) are successfully handled via functional variations with variable domain, converting almost all boundary and interface conditions, including the Rankine Hugoniot shock relations, into natural ones. This theory provides a series of novel ways for blade design or modification and a rigorous theoretical basis for finite element applications and also constitutes an important part of the optimal design theory of rotor bladings. Numerical solutions to subsonic flow by finite elements with self-adapting nodes given in Refs., show good agreement with experimental results.

  12. Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols.

    PubMed

    Flora, Jason W; Meruva, Naren; Huang, Chorng B; Wilkinson, Celeste T; Ballentine, Regina; Smith, Donna C; Werley, Michael S; McKinney, Willie J

    2016-02-01

    E-cigarettes are gaining popularity in the U.S. as well as in other global markets. Currently, limited published analytical data characterizing e-cigarette formulations (e-liquids) and aerosols exist. While FDA has not published a harmful and potentially harmful constituent (HPHC) list for e-cigarettes, the HPHC list for currently regulated tobacco products may be useful to analytically characterize e-cigarette aerosols. For example, most e-cigarette formulations contain propylene glycol and glycerin, which may produce aldehydes when heated. In addition, nicotine-related chemicals have been previously reported as potential e-cigarette formulation impurities. This study determined e-liquid formulation impurities and potentially harmful chemicals in aerosols of select commercial MarkTen(®) e-cigarettes manufactured by NuMark LLC. The potential hazard of the identified formulation impurities and aerosol chemicals was also estimated. E-cigarettes were machine puffed (4-s duration, 55-mL volume, 30-s intervals) to battery exhaustion to maximize aerosol collection. Aerosols analyzed for carbonyls were collected in 20-puff increments to account for analyte instability. Tobacco specific nitrosamines were measured at levels observed in pharmaceutical grade nicotine. Nicotine-related impurities in the e-cigarette formulations were below the identification and qualification thresholds proposed in ICH Guideline Q3B(R2). Levels of potentially harmful chemicals detected in the aerosols were determined to be below published occupational exposure limits. PMID:26617410

  13. 7 CFR 1219.57 - Patents, copyrights, trademarks, publications, and product formulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Patents, copyrights, trademarks, publications, and..., and Information Order Budgets, Expenses, and Assessments § 1219.57 Patents, copyrights, trademarks, publications, and product formulations. (a) Any patents, copyrights, trademarks, inventions,...

  14. 7 CFR 1218.56 - Patents, copyrights, trademarks, information, publications, and product formulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Patents, copyrights, trademarks, information, publications, and product formulations. 1218.56 Section 1218.56 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF...

  15. 7 CFR 63.501 - Patents, copyrights, inventions, trademarks, information, publications, and product formulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Patents, copyrights, inventions, trademarks, information, publications, and product formulations. 63.501 Section 63.501 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE...

  16. 7 CFR 1215.75 - Patents, copyrights, inventions, publications, and product formulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Patents, copyrights, inventions, publications, and product formulations. 1215.75 Section 1215.75 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN...

  17. 7 CFR 1219.57 - Patents, copyrights, trademarks, publications, and product formulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, trademarks, publications, and..., and Information Order Budgets, Expenses, and Assessments § 1219.57 Patents, copyrights, trademarks, publications, and product formulations. (a) Any patents, copyrights, trademarks, inventions,...

  18. 7 CFR 1221.123 - Patents, copyrights, inventions, trademarks, information, publications, and product formulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Patents, copyrights, inventions, trademarks, information, publications, and product formulations. 1221.123 Section 1221.123 Agriculture Regulations of the... Promotion, Research, and Information Order Promotion, Research, and Information § 1221.123...

  19. The Production System's Formulation of Relative Clause Structures: Evidence from Polish

    ERIC Educational Resources Information Center

    McDaniel, Dana; Lech, Dorota

    2003-01-01

    In this study, we focused on the formulation of relative clauses with preposition and genitive pied-piping. Thirty child (5;9 to 8;4) and 30 adult Polish speakers were given an elicited production task and a grammaticality judgment task. Almost all of the children accepted preposition pied-piping, but only half of them produced it. We suggest that…

  20. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

    PubMed

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R

    2014-07-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single

  1. The Regional Ocean Modeling System (ROMS) 4-dimensional variational data assimilation systems . Part I - System overview and formulation

    NASA Astrophysics Data System (ADS)

    Moore, Andrew M.; Arango, Hernan G.; Broquet, Gregoire; Powell, Brian S.; Weaver, Anthony T.; Zavala-Garay, Javier

    2011-10-01

    The Regional Ocean Modeling System (ROMS) is one of the few community ocean general circulation models for which a 4-dimensional variational data assimilation (4D-Var) capability has been developed. The ROMS 4D-Var capability is unique in that three variants of 4D-Var are supported: a primal formulation of incremental strong constraint 4D-Var (I4D-Var), a dual formulation based on a physical-space statistical analysis system (4D-PSAS), and a dual formulation representer-based variant of 4D-Var (R4D-Var). In each case, ROMS is used in conjunction with available observations to identify a best estimate of the ocean circulation based on a set of a priori hypotheses about errors in the initial conditions, boundary conditions, surface forcing, and errors in the model in the case of 4D-PSAS and R4D-Var. In the primal formulation of I4D-Var the search for the best circulation estimate is performed in the full space of the model control vector, while for the dual formulations of 4D-PSAS and R4D-Var only the sub-space of linear functions of the model state vector spanned by the observations (i.e. the dual space) is searched. In oceanographic applications, the number of observations is typically much less than the dimension of the model control vector, so there are clear advantages to limiting the search to the space spanned by the observations. In the case of 4D-PSAS and R4D-Var, the strong constraint assumption (i.e. that the model is error free) can be relaxed leading to the so-called weak constraint formulation. This paper describes the three aforementioned variants of 4D-Var as they are implemented in ROMS. Critical components that are common to each approach are conjugate gradient descent, preconditioning, and error covariance models, which are also described. Finally, several powerful 4D-Var diagnostic tools are discussed, namely computation of posterior errors, eigenvector analysis of the posterior error covariance, observation impact, and observation sensitivity.

  2. Sensitivity of secondary production and export flux to choice of trophic transfer formulation in marine ecosystem models

    NASA Astrophysics Data System (ADS)

    Anderson, Thomas R.; Hessen, Dag O.; Mitra, Aditee; Mayor, Daniel J.; Yool, Andrew

    2013-09-01

    The performance of four contemporary formulations describing trophic transfer, which have strongly contrasting assumptions as regards the way that consumer growth is calculated as a function of food C:N ratio and in the fate of non-limiting substrates, was compared in two settings: a simple steady-state ecosystem model and a 3D biogeochemical general circulation model. Considerable variation was seen in predictions for primary production, transfer to higher trophic levels and export to the ocean interior. The physiological basis of the various assumptions underpinning the chosen formulations is open to question. Assumptions include Liebig-style limitation of growth, strict homeostasis in zooplankton biomass, and whether excess C and N are released by voiding in faecal pellets or via respiration/excretion post-absorption by the gut. Deciding upon the most appropriate means of formulating trophic transfer is not straightforward because, despite advances in ecological stoichiometry, the physiological mechanisms underlying these phenomena remain incompletely understood. Nevertheless, worrying inconsistencies are evident in the way in which fundamental transfer processes are justified and parameterised in the current generation of marine ecosystem models, manifested in the resulting simulations of ocean biogeochemistry. Our work highlights the need for modellers to revisit and appraise the equations and parameter values used to describe trophic transfer in marine ecosystem models.

  3. Variational Formulation of Particle Algorithms for Kinetic E&M Plasma Simulations

    NASA Astrophysics Data System (ADS)

    Stamm, Alexander; Shadwick, Bradley; Evstatiev, Evstati

    2013-10-01

    A rigorous variational method was used to derive a self-consistent set of equations of motion from a discretized Lagrangian to study kinetic plasmas. Discretization of the Lagrangian was performed by reduction of the phase-space distribution function to a collection of finite-sized macro-particles of arbitrary shape and discretization of field quantities onto a spatial grid. The equations of motion were then obtained by demanding the action be stationary. This approach may be used in both lab frame and moving window coordinates, which improve computational efficiency when modeling laser-plasma interactions. The primary advantage of the variational approach is preservation of Lagrangian symmetries, which in our case leads to energy conservation and avoids difficulties with grid heating. Additionally, this approach decouples particle size from grid spacing and relaxes restrictions on particle shape, leading to a decrease in numerical noise. The variational approach also guarantees consistent ordering and is amiable to higher order methods in both space and time. Simulations conducted with the new equations of motion demonstrate the desired energy conservation and a decrease in numerical noise. This work was supported by the U.S. Department of Education grant P200A090156 and by the U.S. Department of Energy under Contract No. DE-FG02-08ER55000.

  4. Current perspectives on stability of protein drug products during formulation, fill and finish operations.

    PubMed

    Rathore, Nitin; Rajan, Rahul S

    2008-01-01

    Commercialization of protein-based therapeutics is a challenging task in part due to the difficulties in maintaining protein solutions safe and efficacious throughout the drug product development process, storage, transportation and patient administration. Bulk drug substance goes through a series of formulation, fill and finish operations to provide the final dosage form in the desired formulation and container or delivery device. Different process parameters during each of these operations can affect the purity, activity and efficacy of the final product. Common protein degradation pathways and the various physical and chemical factors that can induce such reactions have been extensively studied for years. This review presents an overview of the various formulation-fill-finish operations with a focus on processing steps and conditions that can impact product quality. Various manufacturing operations including bulk freeze-thaw, formulation, filtration, filling, lyophilization, inspection, labeling, packaging, storage, transport and delivery have been reviewed. The article highlights our present day understanding of protein instability issues during biopharmaceutical manufacturing and provides guidance on process considerations that can help alleviate these concerns. PMID:18484778

  5. A Variational Formulation for the Finite Element Analysis of Sound Wave Propagation in a Spherical Shell

    NASA Technical Reports Server (NTRS)

    Lebiedzik, Catherine

    1995-01-01

    Development of design tools to furnish optimal acoustic environments for lightweight aircraft demands the ability to simulate the acoustic system on a workstation. In order to form an effective mathematical model of the phenomena at hand, we have begun by studying the propagation of acoustic waves inside closed spherical shells. Using a fully-coupled fluid-structure interaction model based upon variational principles, we have written a finite element analysis program and are in the process of examining several test cases. Future investigations are planned to increase model accuracy by incorporating non-linear and viscous effects.

  6. Final Report on the “ New Directions in the Variational Multiscale Formulation of Large Eddy Simulation of Turbulence”

    SciTech Connect

    Assad A. Oberai

    2007-07-13

    The work performed as part of this grant may be described in the context of developing numerical methods for solving an abstract, nonlinear variational problem for which the straightforward Galerkin approximation on a space of reasonable dimension is inaccurate. Target applications include flows with turbulence and systems with shocks. With this in mind, an alternate finite dimensional problem is proposed in which a model term (with unknown parameters) is added to the Galerkin approximation to improve its performance. We have developed new formulations for this model term especially for turbulent flows and for systems with shocks. We have also developed a dynamic approach for evaluating the parameters that appear in this model term. We have conducted several numerical studies to confirm the usefulness of the proposed approach.

  7. Multi-variate joint PDF for non-Gaussianities: exact formulation and generic approximations

    SciTech Connect

    Verde, Licia; Jimenez, Raul; Alvarez-Gaume, Luis; Heavens, Alan F.; Matarrese, Sabino E-mail: raul.jimenez@icc.ub.edu E-mail: a.heavens@imperial.ac.uk

    2013-06-01

    We provide an exact expression for the multi-variate joint probability distribution function of non-Gaussian fields primordially arising from local transformations of a Gaussian field. This kind of non-Gaussianity is generated in many models of inflation. We apply our expression to the non-Gaussianity estimation from Cosmic Microwave Background maps and the halo mass function where we obtain analytical expressions. We also provide analytic approximations and their range of validity. For the Cosmic Microwave Background we give a fast way to compute the PDF which is valid up to more than 7σ for f{sub NL} values (both true and sampled) not ruled out by current observations, which consists of expressing the PDF as a combination of bispectrum and trispectrum of the temperature maps. The resulting expression is valid for any kind of non-Gaussianity and is not limited to the local type. The above results may serve as the basis for a fully Bayesian analysis of the non-Gaussianity parameter.

  8. Multi-variate joint PDF for non-Gaussianities: exact formulation and generic approximations

    NASA Astrophysics Data System (ADS)

    Verde, Licia; Jimenez, Raul; Alvarez-Gaume, Luis; Heavens, Alan F.; Matarrese, Sabino

    2013-06-01

    We provide an exact expression for the multi-variate joint probability distribution function of non-Gaussian fields primordially arising from local transformations of a Gaussian field. This kind of non-Gaussianity is generated in many models of inflation. We apply our expression to the non-Gaussianity estimation from Cosmic Microwave Background maps and the halo mass function where we obtain analytical expressions. We also provide analytic approximations and their range of validity. For the Cosmic Microwave Background we give a fast way to compute the PDF which is valid up to more than 7σ for fNL values (both true and sampled) not ruled out by current observations, which consists of expressing the PDF as a combination of bispectrum and trispectrum of the temperature maps. The resulting expression is valid for any kind of non-Gaussianity and is not limited to the local type. The above results may serve as the basis for a fully Bayesian analysis of the non-Gaussianity parameter.

  9. Formulation and process factors influencing product quality and in vitro performance of ophthalmic ointments.

    PubMed

    Xu, Xiaoming; Al-Ghabeish, Manar; Rahman, Ziyaur; Krishnaiah, Yellela S R; Yerlikaya, Firat; Yang, Yang; Manda, Prashanth; Hunt, Robert L; Khan, Mansoor A

    2015-09-30

    Owing to its unique anatomical and physiological functions, ocular surface presents special challenges for both design and performance evaluation of the ophthalmic ointment drug products formulated with a variety of bases. The current investigation was carried out to understand and identify the appropriate in vitro methods suitable for quality and performance evaluation of ophthalmic ointment, and to study the effect of formulation and process variables on its critical quality attributes (CQA). The evaluated critical formulation variables include API initial size, drug percentage, and mineral oil percentage while the critical process parameters include mixing rate, temperature, time and cooling rate. The investigated quality and performance attributes include drug assay, content uniformity, API particle size in ointment, rheological characteristics, in vitro drug release and in vitro transcorneal drug permeation. Using design of experiments (DoE) as well as a novel principle component analysis approach, five of the quality and performance attributes (API particle size, storage modulus of ointment, high shear viscosity of ointment, in vitro drug release constant and in vitro transcorneal drug permeation rate constant) were found to be highly influenced by the formulation, in particular the strength of API, and to a lesser degree by processing variables. Correlating the ocular physiology with the physicochemical characteristics of acyclovir ophthalmic ointment suggested that in vitro quality metrics could be a valuable predictor of its in vivo performance. PMID:26231106

  10. Sources of variation in developmental language disorders: evidence from eye-tracking studies of sentence production

    PubMed Central

    Norbury, Courtenay Frazier

    2014-01-01

    Skilled sentence production involves distinct stages of message conceptualization (deciding what to talk about) and message formulation (deciding how to talk about it). Eye-movement paradigms provide a mechanism for observing how speakers accomplish these aspects of production in real time. These methods have recently been applied to children with autism spectrum disorder (ASD) and specific language impairment (LI) in an effort to reveal qualitative differences between groups in sentence production processes. Findings support a multiple-deficit account in which language production is influenced not only by lexical and syntactic constraints, but also by variation in attention control, inhibition and social competence. Thus, children with ASD are especially vulnerable to atypical patterns of visual inspection and verbal utterance. The potential to influence attentional focus and prime appropriate language structures are considered as a mechanism for facilitating language adaptation and learning. PMID:24324237

  11. Ultrasonic characterization of the fat source and composition of formulated dry-cured meat products.

    PubMed

    Jimenez, Edith Corona; García-Pérez, Jose Vicente; Canillas, Sonia Ventanas; Fort, Jose Javier Benedito

    2014-06-01

    The aim of this work was to test the feasibility of using ultrasonic measurements to estimate the fat content and identify the fat sources used in formulated dry-cured pork meat products. For that purpose, dry-cured sausages were prepared using different fat sources (two Iberian pork backfats, Iberian lard, and sunflower oil) and contents (fat content from 3% to 17% wet basis) and characterized by measuring the ultrasonic velocity (at 2 degrees C, 6 degrees C, 10 degrees C, 15 degrees C, 20 degrees C, and 25 degrees C), fatty acid profile, thermal behavior, and composition. The fatty acid composition affected the melting behavior of the sausages, which also involved different ultrasonic velocities, depending on the fat source used for the sausage formulation. Significant (p < 0.05) linear relationships were established between the ultrasonic velocity and the percentage of melted fat, by means of which the sausage batches were differentiated according to the fat source used. The ultrasonic velocity temperature dependence allowed the determination of the fat content (explained variance 96.1%) by measuring the ultrasonic velocity in the dry-cured sausages at 2 degrees C and 25 degrees C and using a semi-empirical equation. Therefore, the ultrasonic measurements could be considered as a reliable tool for the characterization and differentiation of formulated dry-cured meat products with different fat sources and contents. PMID:23751543

  12. Talc based exopolysaccharides formulation enhancing growth and production of Hellianthus annuus under saline conditions.

    PubMed

    Tewari, S; Arora, K

    2014-01-01

    Stress tolerating strain of Pseudomonas aeruginosa PF07 possessing plant growth promoting activity was screened for the production of exopolysaccharides (EPS). EPS production was monitored in the cell free culture supernatant (CFCS) and extracted EPS was further purified by thin layer chromatography. EPS producing cells were taken to design talc based formulation and its efficacy was checked on oilseed crop sunflower (Hellianthus annuus), under in vivo saline conditions (soil irrigated with 125 mM of saline water). Application of bioformulation significantly enhanced the yield and growth attributes of the plant in comparison to control (untreated seeds) under stress and non—stress conditions. Germination rate, plant length, dry weight and seed weight increased remarkably. The above findings suggest the application and benefits of utilizing EPS formulation in boosting early seedling emergence, enhancing plant growth parameters, increasing seed weight and mitigating stress in saline affected regions. Such bioformulation may enhance RAS/RT (Root Adhering Soil to Root Tissue ratio), texture of the soil, increase porosity, improve uptake of nutrients, and hence may be considered as commercially important formulation for renovation of stressed sites and enhancing plant growth. PMID:25535716

  13. Omega-3 Fatty Acid Formulations in Cardiovascular Disease: Dietary Supplements are Not Substitutes for Prescription Products.

    PubMed

    Fialkow, Jonathan

    2016-08-01

    Omega-3 fatty acid products are available as prescription formulations (icosapent ethyl, omega-3-acid ethyl esters, omega-3-acid ethyl esters A, omega-3-carboxylic acids) and dietary supplements (predominantly fish oils). Most dietary supplements and all but one prescription formulation contain mixtures of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Products containing both EPA and DHA may raise low-density lipoprotein cholesterol (LDL-C). In clinical trials, the EPA-only prescription product, icosapent ethyl, did not raise LDL-C compared with placebo. To correct a common misconception, it is important to note that omega-3 fatty acid dietary supplements are not US FDA-approved over-the-counter drugs and are not required to demonstrate safety and efficacy prior to marketing. Conversely, prescription products are supported by extensive clinical safety and efficacy investigations required for FDA approval and have active and ongoing safety monitoring programs. While omega-3 fatty acid dietary supplements may have a place in the supplementation of diet, they generally contain lower levels of EPA and DHA than prescription products and are not approved or intended to treat disease. Perhaps due to the lack of regulation of dietary supplements, EPA and DHA levels may vary widely within and between brands, and products may also contain unwanted cholesterol or fats or potentially harmful components, including toxins and oxidized fatty acids. Accordingly, omega-3 fatty acid dietary supplements should not be substituted for prescription products. Similarly, prescription products containing DHA and EPA should not be substituted for the EPA-only prescription product, as DHA may raise LDL-C and thereby complicate the management of patients with dyslipidemia. PMID:27138439

  14. Optimization of a fermented soy product formulation with a kefir culture and fiber using a simplex-centroid mixture design.

    PubMed

    Baú, Tahis Regina; Garcia, Sandra; Ida, Elza Iouko

    2013-12-01

    The objective of this work was to optimize a fermented soy product formulation with kefir and soy, oat and wheat fibers and to evaluate the fiber and product characteristics. A simplex-centroid mixture design was used for the optimization. Soymilk, soy, oat and wheat fiber mixtures, sucrose and anti-foaming agent were used for the formulation, followed by thermal treatment, cooling and the addition of flavoring. Fermentation was performed at 25 °C with a kefir culture until a pH of 4.5 was obtained. The products were cooled, homogenized and stored for analysis. From the mathematical models and variables response surface and desirability an optimal fermented product was formulated containing 3% (w/w) soy fiber. Compared with the other formulations, soy fermented product with 3% soy fiber had the best acidity, viscosity, syneresis, firmness and Lactococcus lactis count. PMID:23876105

  15. A variational formulation for vibro-acoustic analysis of a panel backed by an irregularly-bounded cavity

    NASA Astrophysics Data System (ADS)

    Xie, Xiang; Zheng, Hui; Qu, Yegao

    2016-07-01

    A weak form variational based method is developed to study the vibro-acoustic responses of coupled structural-acoustic system consisting of an irregular acoustic cavity with general wall impedance and a flexible panel subjected to arbitrary edge-supporting conditions. The structural and acoustical models of the coupled system are formulated on the basis of a modified variational method combined with multi-segment partitioning strategy. Meanwhile, the continuity constraints on the sub-segment interfaces are further incorporated into the system stiffness matrix by means of least-squares weighted residual method. Orthogonal polynomials, such as Chebyshev polynomials of the first kind, are employed as the wholly admissible unknown displacement and sound pressure field variables functions for separate components without meshing, and hence mapping the irregular physical domain into a square spectral domain is necessary. The effects of weighted parameter together with the number of truncated polynomial terms and divided partitions on the accuracy of present theoretical solutions are investigated. It is observed that applying this methodology, accurate and efficient predictions can be obtained for various types of coupled panel-cavity problems; and in weak or strong coupling cases for a panel surrounded by a light or heavy fluid, the inherent principle of velocity continuity on the panel-cavity contacting interface can all be handled satisfactorily. Key parametric studies concerning the influences of the geometrical properties as well as impedance boundary are performed. Finally, by performing the vibro-acoustic analyses of 3D car-like coupled miniature, we demonstrate that the present method seems to be an excellent way to obtain accurate mid-frequency solution with an acceptable CPU time.

  16. Relative toxicities of formulated glycol aircraft deicers and pure glycol products to duckweed (Lemna minor)

    SciTech Connect

    DuFresne, D.L.; Pillard, D.A.

    1995-12-31

    Ethylene and propylene glycol deicers are commonly used at airports in the US and other countries to both remove snow and ice from aircraft, and to retard the accumulation of those materials. Snow and ice often pile up at airports during the winter and are then flushed into the storm sewer system during warmer temperatures or rainfall. Some of this water containing deicers may enter waterbodies without prior treatment, While previous studies have investigated the effects of deicers on aquatic animals and algae, data are not available on the effects on aquatic macrophytes, Glycol deicers were obtained in the formulated mixtures used on aircraft; pure ethylene and propylene glycol were obtained from Sigma{reg_sign}. Duckweed (Lemna minor) fronds were exposed to various concentrations of pure and formulated glycol mixtures. The number of fronds at test termination and chlorophyll concentration (measured using a spectrophotometer) were the measured endpoints. Based upon glycol concentration, the formulated products were more toxic than the pure material. These results are consistent with results seen in other animal and plant studies.

  17. A full variational calculation based on a tensor product decomposition

    NASA Astrophysics Data System (ADS)

    Senese, Frederick A.; Beattie, Christopher A.; Schug, John C.; Viers, Jimmy W.; Watson, Layne T.

    1989-08-01

    A new direct full variational approach exploits a tensor (Kronecker) product decomposition of the Hamiltonian. Explicit assembly and storage of the Hamiltonian matrix is avoided by using the Kronecker product structure to form matrix-vector products directly from the molecular integrals. Computation-intensive integral transformations and formula tapes are unnecessary. The wavefunction is expanded in terms of spin-free primitive kets rather than Slater determinants or configuration state functions, and the expansion is equivalent to a full configuration interaction expansion. The approach suggests compact storage schemes and algorithms which are naturally suited to parallel and pipelined machines.

  18. A Tensor Product Formulation of Strassen's Matrix Multiplication Algorithm with Memory Reduction

    DOE PAGESBeta

    Kumar, B.; Huang, C. -H.; Sadayappan, P.; Johnson, R. W.

    1995-01-01

    In this article, we present a program generation strategy of Strassen's matrix multiplication algorithm using a programming methodology based on tensor product formulas. In this methodology, block recursive programs such as the fast Fourier Transforms and Strassen's matrix multiplication algorithm are expressed as algebraic formulas involving tensor products and other matrix operations. Such formulas can be systematically translated to high-performance parallel/vector codes for various architectures. In this article, we present a nonrecursive implementation of Strassen's algorithm for shared memory vector processors such as the Cray Y-MP. A previous implementation of Strassen's algorithm synthesized from tensor product formulas required workingmore » storage of size O(7 n ) for multiplying 2 n × 2 n matrices. We present a modified formulation in which the working storage requirement is reduced to O(4 n ). The modified formulation exhibits sufficient parallelism for efficient implementation on a shared memory multiprocessor. Performance results on a Cray Y-MP8/64 are presented.« less

  19. Validation of radiolabeling of drug formulations for aerosol deposition assessment of orally inhaled products.

    PubMed

    Devadason, Sunalene G; Chan, Hak-Kim; Haeussermann, Sabine; Kietzig, Claudius; Kuehl, Philip J; Newman, Stephen; Sommerer, Knut; Taylor, Glyn

    2012-12-01

    Radiolabeling of inhaler formulations for imaging studies is an indirect method of determining lung deposition and regional distribution of drug in human subjects. Hence, ensuring that the radiotracer and drug exhibit similar aerodynamic characteristics when aerosolized, and that addition of the radiotracer has not significantly altered the characteristics of the formulation, are critical steps in the development of a radiolabeling method. The validation phase should occur during development of the radiolabeling method, prior to commencement of in vivo studies. The validation process involves characterization of the aerodynamic particle size distribution (APSD) of drug in the reference formulation, and of both drug and radiotracer in the radiolabeled formulation, using multistage cascade impaction. We propose the adoption of acceptance criteria similar to those recommended by the EMA and ISAM/IPAC-RS for determination of therapeutic equivalence of orally inhaled products: (a) if only total lung deposition is being quantified, the fine particle fraction ratio of both radiolabeled drug and radiotracer to that of the reference drug should fall between 0.85 and 1.18, and (b) if regional lung deposition (e.g., outer and inner lung regions) is to be quantified, the ratio of both radiolabeled drug and radiotracer to reference drug on each impactor stage or group of stages should fall between 0.85 and 1.18. If impactor stages are grouped together, at least four separate groups should be provided. In addition, while conducting in vivo studies, measurement of the APSD of the inhaler used on each study day is recommended to check its suitability for use in man. PMID:23215848

  20. Anti-inflammatory effects of natural product formulations on murine dendritic cells.

    PubMed

    Miller, Andrea K; Benson, Jenna M; Muanza, Dave N; Smith, Jerry R; Shepherd, David M

    2011-03-01

    The popularity and availability of herbal extracts has increased dramatically over the last decade, providing an inexpensive manner of self-medication. Although the efficacy of individual extracts is currently being studied intensively, research regarding complex mixtures is limited. Therefore, we evaluated the effects of three complex formulations, including BRC-301, a polyherbal extract; BRC-304, a mixture of vitamins, minerals, antioxidant enzymes, botanical extracts, and carotenoids; and BRC-306, a proprietary blend of Uncaria tomentosa (cat's claw) and Phytolens(®) on murine dendritic cells (DCs). We hypothesized that these formulations would decrease the inflammatory responsiveness and innate function of DCs. In order to address this hypothesis, we evaluated the effects of BRC-301, BRC-304, and BRC-306 on DC2.4 cells and assessed the effects of BRC-301 on bone marrow-derived DCs (bmDCs). Lipopolysaccharide (LPS) stimulation of DC2.4 cells and bmDCs induced production of nitric oxide (NO), TNF-α, and IL-6, a response that was modulated by concomitant treatment with non-cytotoxic concentrations of BRC-301. In contrast, only the production of NOor IL-6 by LPS-activated DC2.4 cells was affected by BRC-304 or BRC-306, respectively. Flow cytometric evaluation following concurrent BRC-301 and LPS treatment revealed an increased relative expression of CD11c, CD86, and CD54 on bmDCs and an increased frequency of bmDCs expressing MHC II. Finally, BRC-301 enhanced the uptake of fluorescein isothiocyanate-conjugated ovalbumin by bmDCs. Taken together, these results suggest that these commercially available formulations modulate the innate responsiveness of murine DCs and may enhance their ability to initiate T cell-mediated immunity. PMID:21399725

  1. Can low-dose combination products for inhalation be formulated in single crystalline particles?

    PubMed

    Kumon, Michiko; Kwok, Philip Chi Lip; Adi, Handoko; Heng, Desmond; Chan, Hak-Kim

    2010-04-16

    This study aims to produce and test the performance of novel crystalline respirable particles containing two low-dose active ingredients and mannitol. This technique overcomes the usual requirement of blending with lactose carriers in formulating combination inhalation products. Ternary powders were produced by co-spray drying solutions containing an inhaled corticosteroid (ICS), a long-acting beta2-agonist (LABA), and mannitol as a crystalline excipient. Two formulations comprising widely used ICS and LABA were studied: budesonide/formoterol fumarate dihydrate/mannitol (B/F/M-SD) and fluticasone propionate/salmeterol xinafoate/mannitol (F/S/M-SD). Various physicochemical properties of the powders were analyzed. Aerosol performance was evaluated by dispersing each powder from an Aerolizer at 60 and 100 L/min into a Next Generation Impactor. We obtained partially hollow spherical particles (volume median diameters of 2 microm) with drug-enriched surfaces. Both formulations contained alpha-mannitol, and the ICSs were crystalline. The content of each drug component in the powder was found to conform to the theoretical dose. The ternary powders generated high fine particle fractions (>50% of the loaded dose), with concomitant drug deposition on the impactor stages. The aerosol performance of B/F/M-SD was maintained after storage over silica gel at 22 degrees C for 11 weeks. In conclusion, co-spray dried particles of ICS/LABA/M-SD were largely crystalline, stable and showed excellent aerosol performance. They may provide an attractive alternative strategy to develop combination products without lactose blends. PMID:20172026

  2. Microvesicle formulations used in topical drugs and cosmetics affect product efficiency, performance and allergenicity.

    PubMed

    Madsen, Jakob Torp; Andersen, Klaus Ejner

    2010-01-01

    Attempts to improve the formulations of topical products are continuing processes (ie, to increase cosmetic performance, enhance effects, and protect ingredients from degradation). The development of micro- and nanovesicular systems has led to the marketing of topical drugs and cosmetics that use these technologies. Several articles have reported improved clinical efficacy by the encapsulation of pharmaceuticals in vesicular systems, and the numbers of publications and patents are rising. Some vesicular systems may deliver the drug deeper in the skin as compared to conventional vehicles, or even make transdermal delivery more efficient for a number of drugs. Vesicular systems may also allow a more precise drug delivery to the site of action (ie, the hair follicles) and thereby minimize the applied drug concentration, reducing potential side effects. On the other hand, this may increase the risk of other side effects. Few case reports have suggested that microvesicle formulations may affect the allergenicity of topical products. This article gives an overview of the current knowledge about the topical use of microvesicular systems and the dermatoallergologic aspects. PMID:20920408

  3. Formulation of Gammaoryzanol-Loaded Nanoparticles for Potential Application in Fortifying Food Products

    PubMed Central

    Ghaderi, Serveh; Ghanbarzadeh, Saeed; Mohammadhassani, Zahra; Hamishehkar, Hamed

    2014-01-01

    Purpose: The field of nanoparticle delivery systems for nutrients and nutraceuticals with poor water solubility has attracted a great attention during the last decades. Methods: Ethyl cellulose (EC) based GO-loaded nanoparticles were prepared by solvent evaporation method. The effects of formulation parameters on nanoparticle size, encapsulation efficiency (EE%) and loading efficiency (LE%) were investigated. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) techniques were used to investigate the crystalline behavior of GO and EC after the preparation of nanoparticles. Stability of the prepared nanoparticle was investigated during five weeks of storage. Results: Particle sizes of all formulation were in the range of 70-100 nm with narrow size distribution. Increase in the time of sonication from 1 to 5 minutes decreased the particle size. However, the mean particle size was increased when the sonication time increased from 5 to 7 minutes. The results showed that in the same concentration of PVA, increasing the ratio of EC:GO led to an increase in the GO encapsulation efficiency and decrease in loading efficiency. During five weeks, the mean diameter and size distribution indexes (SPAN values) of nanoparticles did not show significant changes. DSC and XRD studies indicated that crystallinity of GO was decreased in nanoparticles. Conclusion: EC based nanoparticles are promising carriers for addition of GO as a water insoluble antioxidant to fortify liquid food products without any change in quality of products. PMID:25671188

  4. An Improved Formulation of Hybrid Model Predictive Control With Application to Production-Inventory Systems.

    PubMed

    Nandola, Naresh N; Rivera, Daniel E

    2013-01-01

    We consider an improved model predictive control (MPC) formulation for linear hybrid systems described by mixed logical dynamical (MLD) models. The algorithm relies on a multiple-degree-of-freedom parametrization that enables the user to adjust the speed of setpoint tracking, measured disturbance rejection and unmeasured disturbance rejection independently in the closed-loop system. Consequently, controller tuning is more flexible and intuitive than relying on objective function weights (such as move suppression) traditionally used in MPC schemes. The controller formulation is motivated by the needs of non-traditional control applications that are suitably described by hybrid production-inventory systems. Two applications are considered in this paper: adaptive, time-varying interventions in behavioral health, and inventory management in supply chains under conditions of limited capacity. In the adaptive intervention application, a hypothetical intervention inspired by the Fast Track program, a real-life preventive intervention for reducing conduct disorder in at-risk children, is examined. In the inventory management application, the ability of the algorithm to judiciously alter production capacity under conditions of varying demand is presented. These case studies demonstrate that MPC for hybrid systems can be tuned for desired performance under demanding conditions involving noise and uncertainty. PMID:24348004

  5. Cognitive Modeling of Individual Variation in Reference Production and Comprehension

    PubMed Central

    Hendriks, Petra

    2016-01-01

    A challenge for most theoretical and computational accounts of linguistic reference is the observation that language users vary considerably in their referential choices. Part of the variation observed among and within language users and across tasks may be explained from variation in the cognitive resources available to speakers and listeners. This paper presents a computational model of reference production and comprehension developed within the cognitive architecture ACT-R. Through simulations with this ACT-R model, it is investigated how cognitive constraints interact with linguistic constraints and features of the linguistic discourse in speakers’ production and listeners’ comprehension of referring expressions in specific tasks, and how this interaction may give rise to variation in referential choice. The ACT-R model of reference explains and predicts variation among language users in their referential choices as a result of individual and task-related differences in processing speed and working memory capacity. Because of limitations in their cognitive capacities, speakers sometimes underspecify or overspecify their referring expressions, and listeners sometimes choose incorrect referents or are overly liberal in their interpretation of referring expressions. PMID:27092101

  6. Variations in Physicochemical Properties of a Traditional Mercury-Based Nanopowder Formulation: Need for Standard Manufacturing Practices

    PubMed Central

    Kamath, S. U.; Pemiah, B.; Rajan, K. S.; Krishnaswamy, S.; Sethuraman, S.; Krishnan, U. M.

    2014-01-01

    Rasasindura is a mercury-based nanopowder synthesized using natural products through mechanothermal processing. It has been used in the Ayurvedic system of medicine since time immemorial for various therapeutic purposes such as rejuvenation, treatment of syphilis and in genital disorders. Rasasindura is said to be composed of mercury, sulphur and organic moieties derived from the decoction of plant extracts used during its synthesis. There is little scientific understanding of the preparation process so far. Though metallic mercury is incorporated deliberately for therapeutic purposes, it certainly raises toxicity concerns. The lack of gold standards in manufacturing of such drugs leads to a variation in the chemical composition of the final product. The objective of the present study was to assess the physicochemical properties of Rasasindura samples of different batches purchased from different manufacturers and assess the extent of deviation and gauge its impact on human health. Modern characterization techniques were employed to analyze particle size and morphology, surface area, zeta potential, elemental composition, crystallinity, thermal stability and degradation. Average particle size of the samples observed through scanning electron microscope ranged from 5-100 nm. Mercury content was found to be between 84 and 89% from elemental analysis. Despite batch-to-batch and manufacturer-to-manufacturer variations in the physicochemical properties, all the samples contained mercury in the form of HgS. These differences in the physicochemical properties may ultimately impact its biological outcome. PMID:25593382

  7. Oral tacrolimus oil formulations for enhanced lymphatic delivery and efficient inhibition of T-cell's interleukin-2 production.

    PubMed

    Yoshida, Takayuki; Nakanishi, Kiyo; Yoshioka, Tatsunobu; Tsutsui, Yuuki; Maeda, Atsushi; Kondo, Hiromu; Sako, Kazuhiro

    2016-03-01

    Oral oil formulations have been reported to deliver drugs into the lymph. Lymphatic delivery of immunomodulatory drugs can more efficiently expose the drugs to T-cells in lymph, consequently induce higher efficacy and lower side effects. In this study, effects of tacrolimus oral oil formulations on drug blood exposure, and on inhibition of T-cell's interleukin-2 (IL-2) production were investigated in rats. Oil formulations (sunflower oil, cacao butter, medium chain triglyceride, and palm oil) dissolving tacrolimus showed lower drug blood concentration than a solid dispersion formulation (SDF). The sunflower oil, and cacao butter formulations suppressed drug blood exposure to 50% of the SDF, and inhibited T-cell's IL-2 production similar to the SDF. In vitro digestion tests indicated that slower digestion of the oils might reduce amount and rate of tacrolimus blood absorption. The cacao butter formulations showed 3.0 times more rapid tacrolimus absorption to lymphatic fluid than the SDF. Ratio of the rate constants of absorption into lymph to that into blood was higher in oil formulations (15 times in cacao butter, 15 times sunflower oil, and 3.5 times palm oil) than in the SDF. These results indicated that the oral oil formulations might be suitable for reduced tacrolimus blood concentration for low systemic side effects, and keep high lymph concentration for high efficacy in organ transplantation patients. PMID:26748381

  8. Formulation of criteria for pollution control on cement products produced from solid wastes in China.

    PubMed

    Yang, Yufei; Huang, Qifei; Yang, Yu; Huang, Zechun; Wang, Qi

    2011-08-01

    The process of producing cement products from solid waste can increase the level of pollutants in the cement products. Therefore, it is very important to establish a pollution control standard for cement products to protect the environment and human health. This paper presents acceptance limits for the availability of heavy metals in cement products which have been produced from solid wastes and explains how the limits have been calculated. The approach and method used to formulate these criteria were based on EN 12920. The typical exposure scenarios used in this paper involve concrete being used for drinking water supply pipelines and concrete pavements and are based on an analysis of typical applications of cement in China, and the potential for contact with water. The parameters of a tank test which was based on NEN 7375 were set in accordance with the environmental conditions of typical scenarios in China. Mechanisms controlling the release of heavy metals in concrete and a model for that release were obtained using the leaching test. Finally, based on acceptance criteria for drinking water and groundwater quality in China, limit values for the availability of heavy metals in concrete were calculated. PMID:21514989

  9. Variations of cosmogenic radionuclide production rates along the meteorite orbits

    NASA Astrophysics Data System (ADS)

    Alexeev, V. A.; Laubenstein, M.; Povinec, P. P.; Ustinova, G. K.

    2015-08-01

    Cosmogenic radionuclides produced by galactic cosmic rays (GCR) in meteorites during their motion in space are natural detectors of the GCR intensity and variations along the meteorite orbits. On the basis of measured and calculated contents of cosmogenic radionuclides in the freshly fallen Chelyabinsk and Košice chondrites some peculiarities of generation of cosmogenic radionuclides of different half-lives in the chondrites of different orbits and dates of fall onto the Earth are demonstrated. Dependence of production rates of the radionuclides on the GCR variations in the heliosphere is analyzed. Using radionuclides with different half-lives it is possible to compare the average GCR intensity over various time periods. The measurement and theoretical analysis of cosmogenic radionuclides in consecutively fallen chondrites provide a unique information on the space-time continuum of the cosmogenic radionuclide production rates and their variations over a long time scale, which could be useful in correlative analyses of processes in the heliosphere. Some applications of cosmogenic radionuclide depth distribution in chondrites for estimation of their pre-atmospheric sizes are illustrated.

  10. Variational formulation and numerical accuracy of a quantitative phase-field model for binary alloy solidification with two-sided diffusion.

    PubMed

    Ohno, Munekazu; Takaki, Tomohiro; Shibuta, Yasushi

    2016-01-01

    We present the variational formulation of a quantitative phase-field model for isothermal low-speed solidification in a binary dilute alloy with diffusion in the solid. In the present formulation, cross-coupling terms between the phase field and composition field, including the so-called antitrapping current, naturally arise in the time evolution equations. One of the essential ingredients in the present formulation is the utilization of tensor diffusivity instead of scalar diffusivity. In an asymptotic analysis, it is shown that the correct mapping between the present variational model and a free-boundary problem for alloy solidification with an arbitrary value of solid diffusivity is successfully achieved in the thin-interface limit due to the cross-coupling terms and tensor diffusivity. Furthermore, we investigate the numerical performance of the variational model and also its nonvariational versions by carrying out two-dimensional simulations of free dendritic growth. The nonvariational model with tensor diffusivity shows excellent convergence of results with respect to the interface thickness. PMID:26871136

  11. Variational formulation and numerical accuracy of a quantitative phase-field model for binary alloy solidification with two-sided diffusion

    NASA Astrophysics Data System (ADS)

    Ohno, Munekazu; Takaki, Tomohiro; Shibuta, Yasushi

    2016-01-01

    We present the variational formulation of a quantitative phase-field model for isothermal low-speed solidification in a binary dilute alloy with diffusion in the solid. In the present formulation, cross-coupling terms between the phase field and composition field, including the so-called antitrapping current, naturally arise in the time evolution equations. One of the essential ingredients in the present formulation is the utilization of tensor diffusivity instead of scalar diffusivity. In an asymptotic analysis, it is shown that the correct mapping between the present variational model and a free-boundary problem for alloy solidification with an arbitrary value of solid diffusivity is successfully achieved in the thin-interface limit due to the cross-coupling terms and tensor diffusivity. Furthermore, we investigate the numerical performance of the variational model and also its nonvariational versions by carrying out two-dimensional simulations of free dendritic growth. The nonvariational model with tensor diffusivity shows excellent convergence of results with respect to the interface thickness.

  12. Centennial Scale Variations in Lake Productivity Linked to Solar Activity

    NASA Astrophysics Data System (ADS)

    Englebrecht, A.; Bhattacharyya, S.; Guilderson, T. P.; Ingram, L.; Byrne, R.

    2012-12-01

    Solar variations on both decadal and centennial timescales have been associated with climate phenomena (van Loon et al., 2004; Hodell et al., 2001; White et al., 1997). The energy received by the Earth at the peak of the solar cycle increases by <0.1%; so the question has remained of how this could be amplified to produce an observable climate response. Recent modeling shows that the response of the Earth's climate system to the 11-year solar cycle may be amplified through stratosphere and ocean feedbacks and has the potential to impact climate variability on a multidecadal to centennial timescales (Meehl et al., 2009). Here, we report a 1000-year record of changes in the stratigraphy and carbon isotope composition of varved lake sediment from Isla Isabela (22°N, 106°W) in the subtropical northeast Pacific. Stable carbon isotopes and carbonate stratigraphy can be used to infer surface productivity in the lake. Our analysis shows variations in primary productivity on centennial timescales and suggests that solar activity may be an important component of Pacific climate variability. A possible response during solar maxima acts to keep the eastern equatorial Pacific cooler and drier than usual, producing conditions similar to a La Niña event. In the region around Isla Isabela peak solar years were characterized by decreased surface temperatures and suppressed precipitation (Meehl et al., 2009), which enhance productivity at Isabela (Kienel et al. 2011). In the future, we plan to analyze the data using advanced time series analysis techniques like the wavelets together with techniques to handle irregularly spaced time series data. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-571672

  13. Herbicidal activity of formulated sorgoleone, a natural product of sorghum root exudate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The allelochemical, sorgoleone, a major component of the hydrophobic root exudates of Sorghum bicolor, was formulated as a wettable powder [WP] and evaluated as a natural herbicide on several weed and crop species under different growth conditions. Formulated sorgoleone suppressed germination and ...

  14. Effect of fermentation media on the production, efficacy and storage stability of Metarhizium brunneum microsclerotia formulated as a prototype granule

    Technology Transfer Automated Retrieval System (TEKTRAN)

    New liquid fermentation techniques for the production of the bioinsecticidal fungus Metarhizium brunneum strain F-52 have resulted in the formation of microsclerotia (MS), a compact, melonized-hyphal structure capable of surviving desiccation and formulation as dry granules. When rehydrated, these M...

  15. ESTIMATION OF THE RATE OF VOC EMISSIONS FROM SOLVENT-BASED INDOOR COATING MATERIALS BASED ON PRODUCT FORMULATION

    EPA Science Inventory

    Two computational methods are proposed for estimation of the emission rate of volatile organic compounds (VOCs) from solvent-based indoor coating materials based on the knowledge of product formulation. The first method utilizes two previously developed mass transfer models with ...

  16. The role of dissipation and defect energy in variational formulations of problems in strain-gradient plasticity. Part 2: single-crystal plasticity

    NASA Astrophysics Data System (ADS)

    Reddy, B. D.

    2011-11-01

    Variational formulations are constructed for rate-independent problems in small-deformation single-crystal strain-gradient plasticity. The framework, based on that of Gurtin (J Mech Phys Solids 50: 5-32, 2002), makes use of the flow rule expressed in terms of the dissipation function. Provision is made for energetic and dissipative microstresses. Both recoverable and non-recoverable defect energies are incorporated into the variational framework. The recoverable energies include those that depend smoothly on the slip gradients, the Burgers tensor, or on the dislocation densities (Gurtin et al. J Mech Phys Solids 55:1853-1878, 2007), as well as an energy proposed by Ohno and Okumura (J Mech Phys Solids 55:1879-1898, 2007), which leads to excellent agreement with experimental results, and which is positively homogeneous and therefore not differentiable at zero slip gradient. Furthermore, the variational formulation accommodates a non-recoverable energy due to Ohno et al. (Int J Mod Phys B 22:5937-5942, 2008), which is also positively homogeneous, and a function of the accumulated dislocation density. Conditions for the existence and uniqueness of solutions are established for the various examples of defect energy, with or without the presence of hardening or slip resistance.

  17. Variational Monte Carlo simulations using tensor-product projected states

    NASA Astrophysics Data System (ADS)

    Sikora, Olga; Chang, Hsueh-Wen; Chou, Chung-Pin; Pollmann, Frank; Kao, Ying-Jer

    2015-04-01

    We propose an efficient numerical method, which combines the advantages of recently developed tensor-network based methods and standard trial wave functions, to study the ground-state properties of quantum many-body systems. In this approach, we apply a projector in the form of a tensor-product operator to an input wave function, such as a Jastrow-type or Hartree-Fock wave function, and optimize the tensor elements via variational Monte Carlo. The entanglement already contained in the input wave function can considerably reduce the bond dimensions compared to the regular tensor-product state representation. In particular, this allows us to also represent states that do not obey the area law of entanglement entropy. In addition, for fermionic systems, the fermion sign structure can be encoded in the input wave function. We show that the optimized states provide good approximations of the ground-state energy and correlation functions in the cases of two-dimensional bosonic and fermonic systems.

  18. Melatonin production in healthy infants: evidence for seasonal variations.

    PubMed

    Sivan, Y; Laudon, M; Tauman, R; Zisapel, N

    2001-01-01

    The objective of this study was to determine the normal range of nocturnal urinary excretion of the major melatonin metabolite, 6-sulfatoxymelatonin (6SMT) in a large sample of healthy full-term infants (8 and 16 wk old) and assess whether the endogenous production of melatonin changes with season. 6SMT was assessed in urine samples extracted from disposable diapers removed from full-term, 8- (n = 317) and 16-wk-old (n = 93) infants over the nocturnal period (19:00-08:00 h). In addition, 6SMT was assessed in 8-wk-old (n = 35) healthy infants over the entire 24-h period. 6SMT was determined by an ELISA assay. 6SMT excretion at 8 wk of age exhibited diurnal variations with (mean +/- SD) 61 +/- 18% of the daily production excreted during the nocturnal period regardless of season. The nocturnal 6SMT values in the entire cohort (at 8 as well as 16 wk of age) were found to significantly depart from normal distribution (Kolmogorov-Smirnov test). A normal distribution was obtained using a natural base logarithmic (ln) transformation of the data. The normal range (2.5-97.5 percentile of the ln 6SMT excretion per night) was thus defined as 4.66-8.64 (106-5646 ng/night) for 8-wk-old and 5.19-9.67 (180-15,820 ng/night) for 16-wk-old infants. A significant effect of the month of birth on 6SMT production at the age of 8 wk was found (ANOVA, p < 0.002) with maximal levels produced by infants born in June (summer solstice) and minimal excretion in infants born in December (winter solstice). Short-photoperiod-born infants excreted on average about threefold less 6SMT compared with long-photoperiod-born infants (t test, p = 0. 01). The seasonal variations were no longer present at 16 wk of age. No effect of breast-feeding at the time of sampling on seasonality of 6SMT was found. Normal ranges for the nocturnal urinary excretion of 6SMT in full-term infants at 8 and 16 wk of age are defined. This enables the evaluation of nocturnal 6SMT excretion as a prognostic and diagnostic factor

  19. Formulation and solution of the delayed gamma dose rate problem using the concept of effective delayed gamma production cross section

    SciTech Connect

    Liew, S.L.; Ku, L.P.

    1989-06-01

    With appropriate approximations, the delayed gamma dose rate problem can be formulated in terms of the effective delayed gamma production cross section. The coupled neutron-delayed-gamma transport equations then take the same form as the coupled neutron-prompt-gamma transport equations and they can, therefore, be solved directly in the same manner. This eliminates the need for the tedious and error prone flux coupling step in conventional calculations. Mathematical formulation and solution algorithms are derived. The advantages of this method are illustrated by an example of its application in the solution of a practical design problem. 62 refs., 10 figs., 1 tab.

  20. A probabilistic model framework for evaluating year-to-year variation in crop productivity

    NASA Astrophysics Data System (ADS)

    Yokozawa, M.; Iizumi, T.; Tao, F.

    2008-12-01

    Most models describing the relation between crop productivity and weather condition have so far been focused on mean changes of crop yield. For keeping stable food supply against abnormal weather as well as climate change, evaluating the year-to-year variations in crop productivity rather than the mean changes is more essential. We here propose a new framework of probabilistic model based on Bayesian inference and Monte Carlo simulation. As an example, we firstly introduce a model on paddy rice production in Japan. It is called PRYSBI (Process- based Regional rice Yield Simulator with Bayesian Inference; Iizumi et al., 2008). The model structure is the same as that of SIMRIW, which was developed and used widely in Japan. The model includes three sub- models describing phenological development, biomass accumulation and maturing of rice crop. These processes are formulated to include response nature of rice plant to weather condition. This model inherently was developed to predict rice growth and yield at plot paddy scale. We applied it to evaluate the large scale rice production with keeping the same model structure. Alternatively, we assumed the parameters as stochastic variables. In order to let the model catch up actual yield at larger scale, model parameters were determined based on agricultural statistical data of each prefecture of Japan together with weather data averaged over the region. The posterior probability distribution functions (PDFs) of parameters included in the model were obtained using Bayesian inference. The MCMC (Markov Chain Monte Carlo) algorithm was conducted to numerically solve the Bayesian theorem. For evaluating the year-to-year changes in rice growth/yield under this framework, we firstly iterate simulations with set of parameter values sampled from the estimated posterior PDF of each parameter and then take the ensemble mean weighted with the posterior PDFs. We will also present another example for maize productivity in China. The

  1. Subvisible Particle Content, Formulation, and Dose of an Erythropoietin Peptide Mimetic Product Are Associated With Severe Adverse Postmarketing Events.

    PubMed

    Kotarek, Joseph; Stuart, Christine; De Paoli, Silvia H; Simak, Jan; Lin, Tsai-Lien; Gao, Yamei; Ovanesov, Mikhail; Liang, Yideng; Scott, Dorothy; Brown, Janice; Bai, Yun; Metcalfe, Dean D; Marszal, Ewa; Ragheb, Jack A

    2016-03-01

    Peginesatide (Omontys(®); Affymax, Inc., Cupertino, CA) was voluntarily withdrawn from the market less than a year after the product launch. Although clinical trials had demonstrated the drug to be safe and efficacious, 49 cases of anaphylaxis, including 7 fatalities, were reported not long after market introduction. Commercialization was initiated with a multiuse vial presentation, which differs in formulation from the single-use vial presentation used in phase 3 studies. Standard physical and chemical testing did not indicate any deviation from product specifications in either formulation. However, an analysis of subvisible particulates using nanoparticle tracking analysis and flow imaging revealed a significantly higher concentration of subvisible particles in the multiuse vial presentation linked to the hypersensitivity cases. Although it is unknown whether the elevated particulate content is causally related to these serious adverse events, this report illustrates the utility of characterizing subvisible particulates not captured by conventional light obscuration. PMID:26886324

  2. Lexical or Syntactic Control of Sentence Formulation? Structural Generalizations from Idiom Production

    ERIC Educational Resources Information Center

    Konopka, Agnieszka E; Bock, Kathryn

    2009-01-01

    To compare abstract structural and lexicalist accounts of syntactic processes in sentence formulation, we examined the effectiveness of nonidiomatic and idiomatic phrasal verbs in inducing structural generalizations. Three experiments made use of a syntactic priming paradigm in which participants recalled sentences they had read in rapid serial…

  3. Controlling the simultaneous production of laccase and lignin peroxidase from Streptomyces cinnamomensis by medium formulation

    PubMed Central

    2012-01-01

    Background Use of crude ligninase of bacterial origin is one of the most promising ways to improve the practical biodegradation of lignocellulosic biomass. However, lignin is composed of diverse monolignols with different abundance levels in different plant biomass and requires different proportions of ligninase to realize efficient degradation. To improve activity and reduce cost, the simultaneous submerged fermentation of laccase and lignin peroxidase (LiP) from a new bacterial strain, Streptomyces cinnamomensis, was studied by adopting formulation design, principal component analysis, regression analysis and unconstrained mathematical programming. Results The activities of laccase and LiP from S. cinnamomensis cultured with the optimal medium formulations were improved to be five to eight folders of their initial activities, and the measured laccase:LiP activity ratios reached 0.1, 0.4 and 1.7 when cultured on medium with formulations designed to produce laccase:LiP complexes with theoretical laccase:LiP activity ratios of 0.05 to 0.1, 0.5 to 1 and 1.1 to 2. Conclusion Both the laccase and LiP activities and also the activity ratio of laccase to LiP could be controlled by the medium formulation as designed. Using a crude laccase-LiP complex with a specially designed laccase:LiP activity ratio has the potential to improve the degradation of various plant lignins composed of diverse monolignols with different abundance levels. PMID:22429569

  4. Climate Variations and Alaska Tundra Vegetation Productivity Declines in Spring

    NASA Astrophysics Data System (ADS)

    Bhatt, U. S.; Walker, D. A.; Bieniek, P.; Raynolds, M. K.; Epstein, H. E.; Comiso, J. C.; Pinzon, J. E.; Tucker, C. J.

    2015-12-01

    While sea ice has continued to decline, vegetation productivity increases have declined particularly during spring in Alaska as well as many parts of the Arctic tundra. To understand the processes behind these features we investigate spring climate variations that includes temperature, circulation patterns, and snow cover to determine how these may be contributing to spring browning. This study employs remotely sensed weekly 25-km sea ice concentration, weekly surface temperature, and bi-weekly NDVI from 1982 to 2014. Maximum NDVI (MaxNDVI, Maximum Normalized Difference Vegetation Index), Time Integrated NDVI (TI-NDVI), Summer Warmth Index (SWI, sum of degree months above freezing during May-August), atmospheric reanalysis data, dynamically downscaled climate data, meteorological station data, and snow water equivalent (GlobSnow, assimilated snow data set). We analyzed the data for the full period (1982-2014) and for two sub-periods (1982-1998 and 1999-2014), which were chosen based on the declining Alaska SWI since 1998. MaxNDVI has increased from 1982-2014 over most of the Arctic but has declined from 1999 to 2014 southwest Alaska. TI-NDVI has trends that are similar to those for MaxNDVI for the full period but display widespread declines over the 1999-2014 period. Therefore, as the MaxNDVI has continued to increase overall for the Arctic, TI-NDVI has been declining since 1999 and these declines are particularly noteworthy during spring in Alaska. Spring declines in Alaska have been linked to increased spring snow cover that can delay greenup (Bieniek et al. 2015) but recent ground observations suggest that after an initial warming and greening, late season freezing temperature are damaging the plants. The late season freezing temperature hypothesis will be explored with meteorological climate/weather data sets for Alaska tundra regions. References P.A. Bieniek, US Bhatt, DA Walker, MK Raynolds, JC Comiso, HE Epstein, JE Pinzon, CJ Tucker, RL Thoman, H Tran, N M

  5. Stated product formulation preferences for HIV pre-exposure prophylaxis among women in the VOICE-D (MTN-003D) study

    PubMed Central

    Luecke, Ellen H; Cheng, Helen; Woeber, Kubashni; Nakyanzi, Teopista; Mudekunye-Mahaka, Imelda C; van der Straten, Ariane

    2016-01-01

    Introduction The effectiveness of HIV pre-exposure prophylaxis (PrEP) requires consistent and correct product use, thus a deeper understanding of women's stated product formulation preferences, and the correlates of those preferences, can help guide future research. VOICE-D (MTN-003D), a qualitative ancillary study conducted after the VOICE trial, retrospectively explored participants’ tablet and gel use, as well as their preferences for other potential PrEP product formulations. Methods We conducted an analysis of quantitative and qualitative data from VOICE-D participants. During in-depth interviews, women were presented with pictures and descriptions of eight potential PrEP product formulations, including the oral tablet and vaginal gel tested in VOICE, and asked to discuss which product formulations they would prefer to use and why. Seven of the original product formulations displayed were combined into preferred product formulation categories based on exploratory factor and latent class analyses. We examined demographic and behavioural correlates of these preferred product formulation categories. In-depth interviews with participants were conducted, coded, and analysed for themes related to product preference. Results Of the 68 female participants who completed in-depth interviews (22 South Africa, 24 Zimbabwe, 22 Uganda), median age was 28 (range 21–41), 81% were HIV negative, and 49% were married or living with a partner. Four preferred product formulation categories were identified via exploratory factor analysis: 1) oral tablets; 2) vaginal gel; 3) injectable, implant, or vaginal ring; and 4) vaginal film or suppository. A majority of women (81%) expressed a preference for product formulations included in category 3. Characteristics significantly associated with each preferred product category differed. Attributes described by participants as being important in a preferred product formulation included duration of activity, ease of use, route of

  6. A palette of fine-scale eddy viscosity and residual-based models for variational multiscale formulations of turbulence

    NASA Astrophysics Data System (ADS)

    Oberai, Assad A.; Hughes, Thomas J. R.

    2016-04-01

    We explore a general family of eddy viscosity models for the large-eddy simulation of turbulence within the framework of the Variational Multiscale Method. Our investigation encompasses various fine-scale eddy viscosities and coarse-scale residual-based constructs. We delineate the domain of parameter space in which physically and mathematically suitable models exist, and identify several sub-families of potentially useful models that are either entirely new or extend previously proposed ones. We also combine classical modeling ideas, that lead to turbulent kinetic energy evolution equations, with the residual-based approach to derive a new residual-driven, one-equation dynamic model.

  7. Variational formulation of oscillating fluid clusters and oscillator-like classification. II. Numerical study of pinned liquid clusters

    NASA Astrophysics Data System (ADS)

    Kurzeja, Patrick S.; Steeb, Holger

    2014-04-01

    A numerical study of pinned, oscillating water clusters is presented. Two main models represent a liquid bridge between the walls of two particles and a water column enclosed in a slender pore channel, respectively. Variations include material properties (density, viscosity, surface tension, contact angle) and geometric properties (volume, slenderness, winding, interfacial areas). They are initially based on water clusters in 1 mm pore-space, which are weakly damped at eigenfrequencies around a few hundred Hz. Stiffness and damping are characterized by eigenfrequency and damping coefficient of an equivalent 1-dim. harmonic-oscillator model. Finally, frequency dependence of the dynamical properties is demonstrated. The comprehensive quantitative analysis extends and explains relationships between geometric and material properties and the response to harmonic stimulation. Furthermore, interpolation functions of characteristic dynamic properties are provided for use in multiphase theories. The frequency dependence of cluster stiffness and damping was proven and of limited influence on the stimulation of two typical, weakly damped liquid clusters.

  8. Historical variation of structural novelty in a natural product library.

    PubMed

    Kong, De-Xin; Guo, Ming-Yue; Xiao, Zhi-Hong; Chen, Ling-Ling; Zhang, Hong-Yu

    2011-11-01

    To evaluate the potential of natural products as novel structure suppliers, a historical analysis was performed on the structural novelty of a natural product library, viz., the Chapman & Hall/CRC Dictionary of Natural Products. The results show that although the unexplored natural product universe is still ample, it is more and more difficult to find novel agents from nature, with the discovery probability of novel structures and scaffolds being lower than 50% in the near future, which mainly results from the intrinsic redundancy of natural products and, thus, is unlikely to be reversed merely through technical progresses. PMID:22083910

  9. Interactions between the stratum corneum and topically applied products: regulatory, instrumental and formulation issues with focus on moisturizers.

    PubMed

    Lodén, M

    2014-09-01

    Virtually everyone in Europe will use at least one cosmetic product every day. The extensive use of cosmetics and results from measurements of quality of life in patients with skin diseases demonstrate the importance of a healthy skin. The skin is not only a barrier against desiccation and intrusion of harmful materials, but also an organ of social communication, where dry, scaly, rough stratum corneum is unappealing to touch, inducing anxiety and depression. Knowledge about the skin biochemistry and the use of noninvasive instruments facilitate the development of topical products and quantification of their effects. The presentation of the products and mode of action determine the regulatory demands and the approval process, as they can fall into different regulatory entities, such as cosmetics, medicinal products, medical devices and as other chemical products. The majority of the topical products on the market are regulated as cosmetics. For example, facial skin care and daily moisturizing routines are frequently used. However, despite visible relief of dryness symptoms, some products are reported to result in deterioration of the skin barrier function. New clinical outcomes show important clinical differences between formulations and the relapse of eczema. In a worst case scenario, treatment with a moisturizing cream may increase the risks of eczema and asthma. In the present overview, product presentations and mode of actions are reflected against the regulatory demands in Europe. The regulations are continuously revisited and new guidelines are being implemented, such as the new cosmetic regulation with advice on testing and responsible marketing. PMID:25040916

  10. Quality by design in formulation and process development for a freeze-dried, small molecule parenteral product: a case study.

    PubMed

    Mockus, Linas N; Paul, Timothy W; Pease, Nathan A; Harper, Nancy J; Basu, Prabir K; Oslos, Elizabeth A; Sacha, Gregory A; Kuu, Wei Y; Hardwick, Lisa M; Karty, Jacquelyn J; Pikal, Michael J; Hee, Eun; Khan, Mansoor A; Nail, Steven L

    2011-01-01

    A case study has been developed to illustrate one way of incorporating a Quality by Design approach into formulation and process development for a small molecule, freeze-dried parenteral product. Sodium ethacrynate was chosen as the model compound. Principal degradation products of sodium ethacrynate result from hydrolysis of the unsaturated ketone in aqueous solution, and dimer formation from a Diels-Alder condensation in the freeze-dried solid state. When the drug crystallizes in a frozen solution, the eutectic melting temperature is above -5°C. Crystallization in the frozen system is affected by pH in the range of pH 6-8 and buffer concentration in the range of 5-50 mM, where higher pH and lower buffer concentration favor crystallization. Physical state of the drug is critical to solid state stability, given the relative instability of amorphous drug. Stability was shown to vary considerably over the ranges of pH and buffer concentration examined, and vial-to-vial variability in degree of crystallinity is a potential concern. The formulation design space was constructed in terms of pH and drug concentration, and assuming a constant 5 mM concentration of buffer. The process design space is constructed to take into account limitations on the process imposed by the product and by equipment capability. PMID:21932931

  11. Glacial cycles drive variations in the production of oceanic crust

    NASA Astrophysics Data System (ADS)

    Crowley, John W.; Katz, Richard F.; Huybers, Peter; Langmuir, Charles H.; Park, Sung-Hyun

    2015-03-01

    Glacial cycles redistribute water between oceans and continents, causing pressure changes in the upper mantle, with consequences for the melting of Earth’s interior. Using Plio-Pleistocene sea-level variations as a forcing function, theoretical models of mid-ocean ridge dynamics that include melt transport predict temporal variations in crustal thickness of hundreds of meters. New bathymetry from the Australian-Antarctic ridge shows statistically significant spectral energy near the Milankovitch periods of 23, 41, and 100 thousand years, which is consistent with model predictions. These results suggest that abyssal hills, one of the most common bathymetric features on Earth, record the magmatic response to changes in sea level. The models and data support a link between glacial cycles at the surface and mantle melting at depth, recorded in the bathymetric fabric of the sea floor.

  12. Glacial cycles drive variations in the production of oceanic crust.

    PubMed

    Crowley, John W; Katz, Richard F; Huybers, Peter; Langmuir, Charles H; Park, Sung-Hyun

    2015-03-13

    Glacial cycles redistribute water between oceans and continents, causing pressure changes in the upper mantle, with consequences for the melting of Earth's interior. Using Plio-Pleistocene sea-level variations as a forcing function, theoretical models of mid-ocean ridge dynamics that include melt transport predict temporal variations in crustal thickness of hundreds of meters. New bathymetry from the Australian-Antarctic ridge shows statistically significant spectral energy near the Milankovitch periods of 23, 41, and 100 thousand years, which is consistent with model predictions. These results suggest that abyssal hills, one of the most common bathymetric features on Earth, record the magmatic response to changes in sea level. The models and data support a link between glacial cycles at the surface and mantle melting at depth, recorded in the bathymetric fabric of the sea floor. PMID:25766231

  13. Glacial cycles drive variations in the production of oceanic crust

    NASA Astrophysics Data System (ADS)

    Katz, R. F.; Crowley, J. W.; Langmuir, C. H.

    2012-12-01

    Glacial cycles redistribute water between the oceans and continents, causing long-wavelength changes of static pressure in the upper mantle. Previous work has shown that subaerial, glaciated volcanoes respond to these changes with variation in eruption rates (Jull & McKenzie 1996, Huybers & Langmuir 2009), and has suggested that the magmatic flux at mid-ocean ridges may vary with changes in sea-level (Huybers & Langmuir 2009, Lund & Asimow 2011). The latter is speculative, however, because previous theory has assumed highly simplified melt transport and neglected the dependence of the ridge thermal structure on spreading rate. Moreover, it remains a challenge to connect model predictions of variations arising from sea-level change with sea-floor observations. Here we present results from a theoretical model of a mid-ocean ridge based on conservation of mass, momentum, energy, and composition for two phases (magma & mantle) and two thermodynamic components (enriched & depleted) (Katz 2008, 2010). The model is driven by imposed variations in the static pressure within the mantle. We consider both the geochemically inferred record of past sea-level variation, as well as simpler harmonic and instantaneous variations. The output of these models is compared with observations of bathymetry at ridges that are undisturbed by off-axis volcanism. The comparison is preliminary but suggests that some abyssal hills on the sea-floor are, at least in part, the result of glacial cycles. To understand the simulation results in more detail, we develop analytical solutions for a reduced-complexity model. This model is derived according to the idea that the melting induced by sea-level changes can be thought of as a small perturbation to a steady-state system. We obtain a Green's function solution for crustal thickness as a function of sea-level change with the associated dependencies on geophysical parameters of the magma/mantle system. We show that this solution captures much of the

  14. Climatic change controls productivity variation in global grasslands

    PubMed Central

    Gao, Qingzhu; Zhu, Wenquan; Schwartz, Mark W.; Ganjurjav, Hasbagan; Wan, Yunfan; Qin, Xiaobo; Ma, Xin; Williamson, Matthew A.; Li, Yue

    2016-01-01

    Detection and identification of the impacts of climate change on ecosystems have been core issues in climate change research in recent years. In this study, we compared average annual values of the normalized difference vegetation index (NDVI) with theoretical net primary productivity (NPP) values based on temperature and precipitation to determine the effect of historic climate change on global grassland productivity from 1982 to 2011. Comparison of trends in actual productivity (NDVI) with climate-induced potential productivity showed that the trends in average productivity in nearly 40% of global grassland areas have been significantly affected by climate change. The contribution of climate change to variability in grassland productivity was 15.2–71.2% during 1982–2011. Climate change contributed significantly to long-term trends in grassland productivity mainly in North America, central Eurasia, central Africa, and Oceania; these regions will be more sensitive to future climate change impacts. The impacts of climate change on variability in grassland productivity were greater in the Western Hemisphere than the Eastern Hemisphere. Confirmation of the observed trends requires long-term controlled experiments and multi-model ensembles to reduce uncertainties and explain mechanisms. PMID:27243565

  15. Climatic change controls productivity variation in global grasslands.

    PubMed

    Gao, Qingzhu; Zhu, Wenquan; Schwartz, Mark W; Ganjurjav, Hasbagan; Wan, Yunfan; Qin, Xiaobo; Ma, Xin; Williamson, Matthew A; Li, Yue

    2016-01-01

    Detection and identification of the impacts of climate change on ecosystems have been core issues in climate change research in recent years. In this study, we compared average annual values of the normalized difference vegetation index (NDVI) with theoretical net primary productivity (NPP) values based on temperature and precipitation to determine the effect of historic climate change on global grassland productivity from 1982 to 2011. Comparison of trends in actual productivity (NDVI) with climate-induced potential productivity showed that the trends in average productivity in nearly 40% of global grassland areas have been significantly affected by climate change. The contribution of climate change to variability in grassland productivity was 15.2-71.2% during 1982-2011. Climate change contributed significantly to long-term trends in grassland productivity mainly in North America, central Eurasia, central Africa, and Oceania; these regions will be more sensitive to future climate change impacts. The impacts of climate change on variability in grassland productivity were greater in the Western Hemisphere than the Eastern Hemisphere. Confirmation of the observed trends requires long-term controlled experiments and multi-model ensembles to reduce uncertainties and explain mechanisms. PMID:27243565

  16. Climatic change controls productivity variation in global grasslands

    NASA Astrophysics Data System (ADS)

    Gao, Qingzhu; Zhu, Wenquan; Schwartz, Mark W.; Ganjurjav, Hasbagan; Wan, Yunfan; Qin, Xiaobo; Ma, Xin; Williamson, Matthew A.; Li, Yue

    2016-05-01

    Detection and identification of the impacts of climate change on ecosystems have been core issues in climate change research in recent years. In this study, we compared average annual values of the normalized difference vegetation index (NDVI) with theoretical net primary productivity (NPP) values based on temperature and precipitation to determine the effect of historic climate change on global grassland productivity from 1982 to 2011. Comparison of trends in actual productivity (NDVI) with climate-induced potential productivity showed that the trends in average productivity in nearly 40% of global grassland areas have been significantly affected by climate change. The contribution of climate change to variability in grassland productivity was 15.2–71.2% during 1982–2011. Climate change contributed significantly to long-term trends in grassland productivity mainly in North America, central Eurasia, central Africa, and Oceania; these regions will be more sensitive to future climate change impacts. The impacts of climate change on variability in grassland productivity were greater in the Western Hemisphere than the Eastern Hemisphere. Confirmation of the observed trends requires long-term controlled experiments and multi-model ensembles to reduce uncertainties and explain mechanisms.

  17. Interannual Variation in Phytoplankton Primary Production at a Global Scale

    NASA Technical Reports Server (NTRS)

    Rousseaux, Cecile Severine; Gregg, Watson W.

    2013-01-01

    We used the NASA Ocean Biogeochemical Model (NOBM) combined with remote sensing data via assimilation to evaluate the contribution of four phytoplankton groups to the total primary production. First, we assessed the contribution of each phytoplankton groups to the total primary production at a global scale for the period 1998-2011. Globally, diatoms contributed the most to the total phytoplankton production ((is)approximately 50%, the equivalent of 20 PgC·y1). Coccolithophores and chlorophytes each contributed approximately 20% ((is) approximately 7 PgC·y1) of the total primary production and cyanobacteria represented about 10% ((is) approximately 4 PgC·y1) of the total primary production. Primary production by diatoms was highest in the high latitudes ((is) greater than 40 deg) and in major upwelling systems (Equatorial Pacific and Benguela system). We then assessed interannual variability of this group-specific primary production over the period 1998-2011. Globally the annual relative contribution of each phytoplankton groups to the total primary production varied by maximum 4% (1-2 PgC·y1). We assessed the effects of climate variability on group-specific primary production using global (i.e., Multivariate El Niño Index, MEI) and "regional" climate indices (e.g., Southern Annular Mode (SAM), Pacific Decadal Oscillation (PDO) and North Atlantic Oscillation (NAO)). Most interannual variability occurred in the Equatorial Pacific and was associated with climate variability as indicated by significant correlation (p (is) less than 0.05) between the MEI and the group-specific primary production from all groups except coccolithophores. In the Atlantic, climate variability as indicated by NAO was significantly correlated to the primary production of 2 out of the 4 groups in the North Central Atlantic (diatoms/cyanobacteria) and in the North Atlantic (chlorophytes and coccolithophores). We found that climate variability as indicated by SAM had only a limited effect

  18. Napping-Ultra Flash Profile as a Tool for Category Identification and Subsequent Model System Formulation of Caramel Corn Products.

    PubMed

    Mayhew, Emily; Schmidt, Shelly; Lee, Soo-Yeun

    2016-07-01

    In a novel approach to formulation, the flash descriptive profiling technique Napping-Ultra Flash Profile (Napping-UFP) was used to characterize a wide range of commercial caramel corn products. The objectives were to identify product categories, develop model systems based on product categories, and correlate analytical parameters with sensory terms generated through the Napping-UFP exercise. In one 2 h session, 12 panelists participated in 4 Napping-UFP exercises, describing and grouping, on a 43×56 cm paper sheet, 12 commercial caramel corn samples by degree of similarity, globally and in terms of aroma-by-mouth, texture, and taste. The coordinates of each sample's placement on the paper sheet and descriptive terms generated by the panelists were used to conduct Multiple Factor Analysis (MFA) and hierarchical clustering of the samples. Strong trends in the clustering of samples across the 4 Napping-UFP exercises resulted in the determination of 3 overarching types of commercial caramel corn: "small-scale dark" (typified by burnt, rich caramel corn), "large-scale light" (typified by light and buttery caramel corn), and "large-scale dark" (typified by sweet and molasses-like caramel corn). Representative samples that best exemplified the properties of each category were used as guides in the formulation of 3 model systems that represent the spread of commercial caramel corn products. Analytical testing of the commercial products, including aw measurement, moisture content determination, and thermal characterization via differential scanning calorimetry, were conducted and results related to sensory descriptors using Spearman's correlation. PMID:27249670

  19. Proactive Management of Fermentation and Formulation Interactions to Improve Biocontrol Product Performance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The key components of biocontrol product development—discovery, fermentation, and formulation—are interactively linked to each other and ultimately to product performance. To identify biocontrol agents suited for commercial development, our discovery programs utilize a cumulative ranking system tha...

  20. Vanadium(V) and -(IV) complexes of anionic polysaccharides: Controlled release pharmaceutical formulations and models of vanadium biotransformation products.

    PubMed

    Kremer, Lauren E; McLeod, Andrew I; Aitken, Jade B; Levina, Aviva; Lay, Peter A

    2015-06-01

    Uncontrolled reactions in biological media are a main obstacle for clinical translation of V-based anti-diabetic or anti-cancer pro-drugs. We investigated the use of controlled-release pharmaceutical formulations to ameliorate this issue with a series of V(V) and (IV) complexes of anionic polysaccharides. Carboxymethyl cellulose, xanthan gum, or alginic acid formulations were prepared by the reactions of [VO4](3-) with one or two molar equivalents of biological reductants, L-ascorbic acid (AA) or L-cysteine (Cys), in the presence of excess polysaccharide at pH~7 or pH~4. XANES studies with the use of a previously developed library of model V(V), V(IV) and V(III) complexes showed that reactions in the presence of AA led mostly to the mixtures of five- and six-coordinate V(IV) species, while the reactions in the presence of Cys led predominantly to the mixtures of five- and six-coordinate V(V) species. The XANES spectra of some of these samples closely matched those reported previously for [VO4](3-) biotransformation products in isolated blood plasma, red blood cells, or cultured adipocytes, which supports the hypothesis that modified polysaccharides are major binders of V(V) and V(IV) in biological systems. Studies by EPR spectroscopy suggested predominant V(IV)-carboxylato binding in complexes with polysaccharides. One of the isolated products (a V(IV)-alginato complex) showed selective release of low-molecular-mass V species at pH~8, but not at pH~2, which makes it a promising lead for the development of V-containing formulations for oral administration that are stable in the stomach, but release the active ingredient in the intestines. PMID:25958254

  1. Formulation of a Traditionally Used Polyherbal Product for Burn Healing and HPTLC Fingerprinting of Its Phenolic Contents

    PubMed Central

    Fahimi, Shirin; Mortazavi, Seyed Alireza; Abdollahi, Mohammad; Hajimehdipoor, Homa

    2016-01-01

    Nowadays, plants have been considered as powerful agents for treatment of disorders regarding to their traditional use. In Iranian Traditional Medicine (ITM), plants have a special role in the treatment of various diseases. Burns with their devastating outcomes have been discussed in ITM as well. In the present study, a polyherbal ointment (PHO), retrieved from ITM, was formulated for burn healing and it’s HPTLC fingerprint was prepared. Aqueous extracts of Malva sylvestris and Solanum nigrum leaves and oily extract of Rosa damascena petals (4.85%, 4.85% and 33%, respectively) were added to white beeswax, eucerin and white petrolatum as ointment base. In addition to the microbiological tests, physical stability and rheological behavior of the product were assessed. Fingerprinting of phytochemical constituents of PHO was performed by using silica gel plates and toluene: ethyl acetate: acetic acid (60:40:1) and ethyl acetate: formic acid: acetic acid: water (100:11:11:10) as mobile phases. The results showed that PHO was stable towards physical changes and successfully passed microbiological tests. Moreover, PHO exhibited plastic behavior which is in favor of a topical burn product. In addition, HPTLC fingerprinting of PHO demonstrated the presence of several phenolic constituents corresponding to the plant extracts. Regarding to the role of phenolic compounds in wound healing process, PHO could be an appropriate candidate for burn healing with respect to its traditional use in ITM. Moreover, HPTLC fingerprinting could be utilized as an applicable method for quality control of the prepared formulation. PMID:27610150

  2. Formulation of a Traditionally Used Polyherbal Product for Burn Healing and HPTLC Fingerprinting of Its Phenolic Contents.

    PubMed

    Fahimi, Shirin; Mortazavi, Seyed Alireza; Abdollahi, Mohammad; Hajimehdipoor, Homa

    2016-01-01

    Nowadays, plants have been considered as powerful agents for treatment of disorders regarding to their traditional use. In Iranian Traditional Medicine (ITM), plants have a special role in the treatment of various diseases. Burns with their devastating outcomes have been discussed in ITM as well. In the present study, a polyherbal ointment (PHO), retrieved from ITM, was formulated for burn healing and it's HPTLC fingerprint was prepared. Aqueous extracts of Malva sylvestris and Solanum nigrum leaves and oily extract of Rosa damascena petals (4.85%, 4.85% and 33%, respectively) were added to white beeswax, eucerin and white petrolatum as ointment base. In addition to the microbiological tests, physical stability and rheological behavior of the product were assessed. Fingerprinting of phytochemical constituents of PHO was performed by using silica gel plates and toluene: ethyl acetate: acetic acid (60:40:1) and ethyl acetate: formic acid: acetic acid: water (100:11:11:10) as mobile phases. The results showed that PHO was stable towards physical changes and successfully passed microbiological tests. Moreover, PHO exhibited plastic behavior which is in favor of a topical burn product. In addition, HPTLC fingerprinting of PHO demonstrated the presence of several phenolic constituents corresponding to the plant extracts. Regarding to the role of phenolic compounds in wound healing process, PHO could be an appropriate candidate for burn healing with respect to its traditional use in ITM. Moreover, HPTLC fingerprinting could be utilized as an applicable method for quality control of the prepared formulation. PMID:27610150

  3. A novel in situ hydrophobic ion paring (HIP) formulation strategy for clinical product selection of a nanoparticle drug delivery system.

    PubMed

    Song, Young Ho; Shin, Eyoung; Wang, Hong; Nolan, Jim; Low, Susan; Parsons, Donald; Zale, Stephen; Ashton, Susan; Ashford, Marianne; Ali, Mir; Thrasher, Daniel; Boylan, Nicholas; Troiano, Greg

    2016-05-10

    preclinical efficacy and tolerability data were generated for the pamoic acid lead formulation, which has been selected for evaluation in a Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT 02579226). This work clearly demonstrates the importance of assessing a wide range of drug release rates during formulation screening as a critical step for new drug product development, and how utilizing hydrophobic ion pairing enabled this promising nanoparticle formulation to proceed into clinical development. PMID:27001894

  4. Finding temporal variations of tectonic uplift rate through inversion of long profiles of rivers: Formulation, algorithm, and application to tilted blocks in the western Basin and Range

    NASA Astrophysics Data System (ADS)

    Goren, L.; Fox, M.; Willett, S.

    2012-12-01

    A major forcing agent responsible for the evolution of fluvial landscapes is the rate of tectonic uplift. Recently, a growing body of evidence has shown that temporal changes in uplift rate affect the longitudinal profiles of rivers by introducing variations of river steepness and migrating knickpoints. An important and challenging question is thus whether and how the inverse problem may be solved, i.e. can tectonic uplift rates, U, be extracted reliably from the longitudinal profiles of rivers? A well-established formulation relates the change of landscape elevation through time to tectonic uplift rate and to erosion rate, which is described as a power law function of the upstream drainage area, Am, and the local slope, Sn, where m and n are positive exponents. In this work, we present a close form integral solution to the above formulation for the linear case, where n=1. The integral solution is formulated as an inverse problem and used to extract U/K as a function of K-scaled time, where K, the erodibility, depends on geological and climatic conditions. The inversion algorithm is unexpectedly simple and computationally efficient. We apply the inversion procedure to several tilted blocks in the western Basin and Range area that form part of the eastern California shear zone. The blocks are bounded by faults, and we analyze rivers that drain toward fault segments with significant dip-slip component. Each group of rivers draining to a particular fault segment is treated separately, in order to resolve the independent uplift history of each of the tilted blocks. For each group of rivers, we first demonstrate that n=1 is a suitable assumption, and we constrain the best-fit value of m, which is found to be similar for the different tilted blocks. Then, we simultaneously invert the rivers' long profiles of each group to find the tectonic uplift history of its block. This represents the time dependent dip-slip component of velocity along the normal fault that bounds the

  5. Effect of fermentation media on the production, efficacy, and storage stability of Metarhizium brunneum microsclerotia formulated as a prototype granule.

    PubMed

    Behle, Robert W; Jackson, Mark A

    2014-04-01

    New liquid fermentation techniques for the production of the bioinsecticidal fungus Metarhizium brunneum strain F-52 have resulted in the formation of microsclerotia (MS), a compact, melonized-hyphal structure capable of surviving desiccation and formulation as dry granules. When rehydrated, these MS granules germinate to produce conidia that can infect susceptible insects. Fermentation media containing cottonseed or soy flours as nitrogen sources and formulated at two carbon to nitrogen ratios (C:N), 30:1 or 50:1, were evaluated forproduction of microsclerotia. Dry MS granule samples were compared for storage stability based on conidia production, and insecticidal activity against larvae of the lesser mealworm, Alphitobius diaperinus (Panzer), using a potting soil bioassay. Cottonseed and soy flours were equivalent for production, MS granule viability, and insecticidal activity. Fermentation media containing higher nitrogen concentrations (30:1 C:N) resulted in greater biomass accumulation and greater production of conidia from granules regardless of the nitrogen source. MS granules made with M. brunneum cultures grown in media with 30:1 C:N produced 8.5 x 10(9) conidia per gram of granules after 8-d incubation, significantly higher than MS granules made using fungus produced using 50:1 C:N media (5.5 x 10(9) conidia per gram dry MS granules). The LC50 for larval mortality was 8.05 x 10(5) conidia per cup, equivalent to applications of 94 or 147 microg granules per cup for granules made from high and low nitrogen media, respectively. Measurements of water activity were not significantly different among granule samples (0.28-0.29) even though granules made from high nitrogen media had higher moisture content (> 5.2%) compared with granules made from low nitrogen media (< 4.6%). Higher initial conidial production was reflected in longer storage stability at 25 degrees C, with half-lives estimated at 3.7 and 1.7 wk for 30:1 and 50:1 C:N ratios, respectively. These

  6. Advanced stable lipid-based formulations for a patient-centric product design.

    PubMed

    Becker, Karin; Saurugger, Eva-Maria; Kienberger, Diana; Lopes, Diogo; Haack, Detlev; Köberle, Martin; Stehr, Michael; Lochmann, Dirk; Zimmer, Andreas; Salar-Behzadi, Sharareh

    2016-01-30

    Multiparticulate dosage forms are a recent strategy to meet the special needs of children, elderly people and patients suffering from dysphagia. Our study presents a novel and cost-efficient approach for the manufacturing of a taste-masked multiparticulate system with a stable immediate release profile by applying lipid-based excipients in a solvent-free hot melt coating process. The thermosensitive N-acetylcysteine (N-ac) was used as model drug and hot-melt coated with a mixture of tripalmitin and polysorbate 65. A predictive in vitro method for the evaluation of the taste masking efficiency was developed based on the deprotonation of the carboxyl group of N-ac and the decline of pH, responsible for the unpleasant sour taste of the compound. The method was confirmed using in vivo studies. Differential scanning calorimetry and X-ray scattering experiments revealed polymorphic transformation and its dependency on transformation time, temperature and emulsifier concentration. During the process, the coating was transformed almost completely into the stable β-polymorph, leading to an unaltered dissolution profile during storage. A statistical design was conducted that revealed the critical process parameters affecting the taste masking efficiency and drug release. This study shows the successful application of solvent-free hot-melt coating in the development of a taste-masked and stable formulation. PMID:26621689

  7. The austral peregrine falcon: Color variation, productivity, and pesticides

    USGS Publications Warehouse

    Ellis, D.H.

    1985-01-01

    The austral peregrine falcon (Falco peregrinus cassini) was studied in the Andean foot- hills and across the Patagonian steppe from November to December 1981. The birds under study (18 pairs) were reproducing at or near normal (pre-DDT) levels for other races. Pesticide residues, while elevated, were well below the values associated with reproductive failure in other populations. With one exception, eggshells were not abnormally thin. The peregrine falcon in Patagonia exhibits extreme color variation. Pallid birds are nearly pure white below (light cream as juveniles), whereas normally pigmented birds are black-crowned and conspicuously barred with black ventrally. Rare individuals of the Normal Phase display black heads, broad black ventral barring, and warm reddish-brown ventral background coloration.

  8. UNDERSTANDING PRODUCTIVITY VARIATION ON UN-IRRIGATED CLAYPAN SOILS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A high clay-content argillic horizon occurring 10 to 100 cm below the surface restricts soil water movement and reduces nutrient efficiency of claypan soils, which affect soil quality related to production and environmental buffering. The objective of this study was to determine the impacts of long-...

  9. Use of diets formulated for summer water temperatures in pond production of hybrid striped bass

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated water temperatures are common in hybrid striped bass or Sunshine bass (HSB; Morone chrysops x M. saxatilis) production ponds during summer months in the southern US. Median daily water temperatures often exceed 30 C from June through September. This experiment was conducted to extend and re...

  10. Product formulations using recycled tire crumb rubber. Final report/project accomplishments summary

    SciTech Connect

    Lula, J.W.; Bohnert, G.W.

    1998-02-01

    The objective of this project was to combine crumb rubber and synthetic fiber obtained from scrap tires with thermoplastic polymers and convert these materials into commercially useful, high-value products. A specific goal was to use these materials for roofing, while remaining cognizance of other potential applications.

  11. Adverse drug reaction labelling for atomoxetine, methylphenidate and modafinil: comparison of product information for oral formulations in Australia, Denmark and the United States.

    PubMed

    Aagaard, Lise; Hansen, Ebba Holme

    2013-07-01

    Medical product information contains information about efficacy and safety for marketed pharmaceuticals. Three studies have compared safety labelling for different therapeutic categories in different countries and detected large variations in a number of reported adverse drug reactions (ADRs). The rapid increase in use of medications for treatment of ADHD symptoms has created concern due to lack of information about effects from long-term use. The aim of this study was to compare ADR information in product information (PI)/summary of product characteristics (SPC) for oral formulations of atomoxetine, methylphenidate and modafinil marketed by the same pharmaceutical companies in Australia, Denmark and the United States. Discrepancies in listed ADRs were defined as types of ADRs (system organ class) not listed in all countries. For ADRs where discrepancies were detected, we extracted information about study design (clinical trials, spontaneous report). Discrepancies in ADR labelling for the medications were found across the three countries. A total of 75 ADR categories were listed for atomoxetine and 80% of these were listed in all three countries. For methylphenidate, totally 101 ADR categories and for modafinil 115 ADR categories were listed. For both substances approximately 60% of listed ADRs were found in all three countries. Discrepancies were primarily detected for ADRs information based on clinical trials. For methylphenidate, many ADRs labelled in Australia and Denmark were not mentioned in PIs issued in the United States. In conclusion, information about possible ADRs associated with the use of a specific product should be made available worldwide, as the prescriber information about medicines' safety profile should not depend on the country in which the medication is licensed. PMID:23914751

  12. PR notice 87-6. Notice to manufacturers, formulators, procedures, and registrants of pesticide products

    SciTech Connect

    Not Available

    1987-05-01

    The document is one in the series of Pesticide Regulatory Notices, usually called PR Notices, which supplement the laws and regulations governing pesticide regulation in the US. These notices clarify, interpret and explain regulatory requirements and policies. They are directed at pesticide registrants and other parties interested in detailed procedures of regulation. This notice announces certain policies designed to reduce the potential for adverse effects from the use of pesticide products containing toxic inert ingredients. The agency is encouraging the use of the least toxic inert ingredient available and requiring the development of data necessary to determine the conditions of safe use of products containing toxic inert ingredients. In support of these policies, the Agency has categorized inert ingredients according to toxicity.

  13. Coherent States for Kronecker Products of Non Compact Groups: Formulation and Applications

    NASA Technical Reports Server (NTRS)

    Bambah, Bindu A.; Agarwal, Girish S.

    1996-01-01

    We introduce and study the properties of a class of coherent states for the group SU(1,1) X SU(1,1) and derive explicit expressions for these using the Clebsch-Gordan algebra for the SU(1,1) group. We restrict ourselves to the discrete series representations of SU(1,1). These are the generalization of the 'Barut Girardello' coherent states to the Kronecker Product of two non-compact groups. The resolution of the identity and the analytic phase space representation of these states is presented. This phase space representation is based on the basis of products of 'pair coherent states' rather than the standard number state canonical basis. We discuss the utility of the resulting 'bi-pair coherent states' in the context of four-mode interactions in quantum optics.

  14. Geographical variation in sound production in the anemonefish Amphiprion akallopisos

    PubMed Central

    Parmentier, E; Lagardère, J.P; Vandewalle, P; Fine, M.L

    2005-01-01

    Because of pelagic-larval dispersal, coral-reef fishes are distributed widely with minimal genetic differentiation between populations. Amphiprion akallopisos, a clownfish that uses sound production to defend its anemone territory, has a wide but disjunct distribution in the Indian Ocean. We compared sounds produced by these fishes from populations in Madagascar and Indonesia, a distance of 6500 km. Differentiation of agonistic calls into distinct types indicates a complexity not previously recorded in fishes' acoustic communication. Moreover, various acoustic parameters, including peak frequency, pulse duration, number of peaks per pulse, differed between the two populations. The geographic comparison is the first to demonstrate ‘dialects’ in a marine fish species, and these differences in sound parameters suggest genetic divergence between these two populations. These results highlight the possible approach for investigating the role of sounds in fish behaviour in reproductive divergence and speciation. PMID:16087425

  15. Liquid phase low temperature method for production of methanol from synthesis gas and catalyst formulations therefor

    DOEpatents

    Mahajan, Devinder

    2005-07-26

    The invention provides a homogenous catalyst for the production of methanol from purified synthesis gas at low temperature and low pressure which includes a transition metal capable of forming transition metal complexes with coordinating ligands and an alkoxide, the catalyst dissolved in a methanol solvent system, provided the transition metal complex is not transition metal carbonyl. The coordinating ligands can be selected from the group consisting of N-donor ligands, P-donor ligands, O-donor ligands, C-donor ligands, halogens and mixtures thereof.

  16. Optimization of corn, rice and buckwheat formulations for gluten-free wafer production.

    PubMed

    Dogan, Ismail Sait; Yildiz, Onder; Meral, Raciye

    2016-07-01

    Gluten-free baked products for celiac sufferers are essential for healthy living. Cereals having gluten such as wheat and rye must be removed from the diet for the clinical and histological improvement. The variety of gluten-free foods should be offered for the sufferers. In the study, gluten-free wafer formulas were optimized using corn, rice and buckwheat flours, xanthan and guar gum blend as an alternative product for celiac sufferers. Wafer sheet attributes and textural properties were investigated. Considering all wafer sheet properties in gluten-free formulas, better results were obtained by using 163.5% water, 0.5% guar and 0.1% xanthan in corn formula; 173.3% water, 0.45% guar and 0.15% xanthan gum in rice formula; 176% water, 0.1% guar and 0.5% xanthan gum in buckwheat formula. Average desirability values in gluten-free formulas were between 0.86 and 0.91 indicating they had similar visual and textural profiles to control sheet made with wheat flour. PMID:26446284

  17. Variation of distortion product otoacoustic emissions with furosemide injection.

    PubMed

    Mills, D M; Rubel, E W

    1994-06-15

    Cochlear function was monitored in adult gerbils using distortion product otoacoustic emissions (DPOAE) during intraperitoneal injection of furosemide. All stimulus parameters were varied independently over a wide range, the stimulus frequencies f1 and f2 from 1 to 16 kHz, and the stimulus levels L1 and L2 from 20 to 80 dB SPL. The observed emissions at 2f1-f2 and 3f1-2f2 could be considered to be made up of two distinct components: (1) an 'active' source which depended in a complex way on the stimulus frequencies and levels, which was dominant at low and moderate stimulus levels, and which, by definition, was eliminated by sufficient furosemide intoxication; and (2) a 'passive' source which was essentially the same at all frequencies, with a level dependence given approximately by a simple power law distribution. The change from the active to the passive source was usually accompanied by an abrupt shift in emission phase angle. A simple summation model was shown to account for the observed form of this transition. The amount of the decrease in 2f1-f2 emission amplitude after furosemide injection was approximately independent of frequency and consistent for the middle frequency ratios and intensity levels (f2/f1 approximately equal to 1.3, L1 x L2 approximately equal to 55 x 50 dB SPL). It was concluded that the combination of DPOAE with furosemide injection can usefully be employed as a probe of active cochlear mechanics. PMID:7928730

  18. Effect of fertilizer formulation and bioaugmentation on biodegradation and leaching of crude oils and refined products in soils.

    PubMed

    Coulon, F; Brassington, K J; Bazin, R; Linnet, P E; Thomas, K A; Mitchell, T R; Lethbridge, G; Smith, J W N; Pollarda, S J T

    2012-09-01

    The effects of soil characteristics and oil types as well as the efficacy of two fertilizer formulations and three bioaugmentation packages in improving the bioremediation of oil-contaminated soils were assessed as a means of ex situ treatment selection and optimization through seven laboratory microcosm studies. The influence of bioremediation on leaching of oil from the soil was also investigated. The studies demonstrated the benefits ofbiostimulation to overcome nutrient limitation, as most of the soils were nutrient depleted. The application of both liquid and pelleted slow-release N and P fertilizers increased both the hydrocarbon biodegradation rates (by a factor of 1.4 to 2.9) and the percentage of hydrocarbon mass degraded (by > 30% after 12 weeks and 80% after 37 weeks), when compared with the unamended soils. Slow-release fertilizers can be particularly useful when multiple liquid applications are not practical or cost-effective. Bioaugmentation products containing inoculum plus fertilizer also increased biodegradation by 20% to 37% compared with unamended biotic controls; however, there was no clear evidence of additional benefits due to the inocula, compared with fertilizer alone. Therefore biostimulation is seen as the most cost-effective bioremediation strategy for contaminated soils with the levels of crude oil and refined products used in this study. However, site-specific considerations remain essential for establishing the treatability of oil-contaminated soils. PMID:23240181

  19. Centennial-scale variations in diatom productivity off Peru over the last 3000 years

    NASA Astrophysics Data System (ADS)

    Fleury, Sophie; Crosta, Xavier; Schneider, Ralph; Blanz, Thomas; Ther, Olivier; Martinez, Philippe; Kim, Jung-Hyun

    2016-04-01

    The Peruvian coastal upwelling is one of the most productive systems in the global ocean, with important impacts on the carbon cycle. Primary productivity there displays strong variations at the inter-annual to decadal timescales. However, down-core investigations rarely reach sufficient temporal resolution to assess the response of productivity to climatic variations at these timescales beyond the instrumental and historical periods. We here analyzed diatom assemblages, sea-surface temperatures, nitrogen and organic carbon contents on a laminated sediment core from the Peruvian continental shelf to trace variations in regional productivity over the last 3000 years. Our record provides evidence for different climatic and oceanic conditions with more humid and less productive conditions older than 2500 Cal years BP and drier and more productive conditions younger than 2500 Cal years BP. The last 2500 years also present much stronger centennial-scale variability with the occurrence of six intervals with higher total diatom abundances and stronger percentages in upwelling-related diatom species, representative of intensified productivity, congruent to lower percentages in benthic diatoms, indicative of reduced rainfall. These six periods were synchronous to intervals of enhanced Walker circulation, suggesting a strong imprint of the Pacific zonal circulation on productivity variations off Peru. Our record also demonstrates that SSTs did not vary in phase with productivity, arguing against the idea of regional SSTs controlled by the upwelling intensity, but were rather in agreement to SST records off southern Chile, suggesting that Peruvian SSTs variations were largely controlled by oceanic currents at southern high latitudes.

  20. Variation in tobacco and mainstream smoke toxicant yields from selected commercial cigarette products.

    PubMed

    Eldridge, A; Betson, T R; Gama, M Vinicius; McAdam, K

    2015-04-01

    There is a drive toward the mandated lowering and reporting of selected toxicants in tobacco smoke. Several studies have quantified the mainstream cigarette emissions of toxicants, providing benchmark levels. Few, however, have examined how measured toxicant levels within a single product vary over time due to natural variation in the tobacco, manufacturing and measurement. In a single centre analysis, key toxicants were measured in the tobacco blend and smoke of 3R4F reference cigarette and three commercial products, each sampled monthly for 10 months. For most analytes, monthly variation was low (coefficient of variation <15%); but higher (⩾ 20%) for some compounds present at low (ppb) levels. Reporting toxicant emissions as a ratio to nicotine increased the monthly variation of the 9 analytes proposed for mandated lowering, by 1-2 percentage points. Variation in toxicant levels was generally 1.5-1.7-fold higher in commercial cigarettes compared with 3R4F over the 10-month period, but increased up to 3.5-fold for analytes measured at ppb level. The potential error (2CV) associated with single-point-in-time sampling averaged ∼ 20%. Together, these data demonstrate that measurement of emissions from commercial cigarettes is associated with considerable variation for low-level toxicants. This variation would increase if the analyses were conducted in more than one laboratory. PMID:25620723

  1. Widening the envelope of UK HLW vitrification - Experimental studies with high waste loadings and new product formulations on a full scale non-active vitrification plant

    SciTech Connect

    Short, R.; Gribble, N.; Riley, A.

    2008-07-01

    The Vitrification Test Rig is a full scale waste vitrification plant that processes non-radioactive liquid HLW simulants based on the active waste streams produced by the reprocessing plants in the UK. Previous work on the rig has primarily concerned increasing the operational envelopes for the active waste vitrification plants at Sellafield to accommodate higher throughputs of Blended waste streams, higher waste oxide incorporation rates in the vitrified products, and the incorporation of legacy waste streams from early reactor commissioning and reprocessing operations at Sellafield. Recent operations have focussed on four main areas; dilute liquid feeds, very high Magnox waste stream incorporation levels, alternative base glass formulations and providing an operational envelope for 28 %w/w Magnox waste vitrification. This paper details the work performed and the major findings of that work. In summary: The VTR has been successfully used to determine operational envelopes and product quality for several HLW feed variations that will allow WVP to increase overall plant throughput via increased waste loading in canisters, increased HLW feed rates or a combination of both. The VTR has also demonstrated the ability to go to waste incorporations, feed rates and glass compositions that are currently beyond WVP specified limits, but that are feasible for future vitrification regimes. In addition, the VTR has trialled dilute feeds similar to those that are likely to be received by WVP in the future and the data obtained from these experiments will allow WVP to prepare adequately for the high throughput challenge of such feeds. Furthermore, new equipment has been trialled on the VTR in water feed mode to determine its suitability and operational limitations for WVP. Future operations will, in the short term, be concerned with increasing the throughput of WVP and are likely to focus on HLW decommissioning operations waste streams in the longer term. (authors)

  2. Enhanced ethanol production from pomelo peel waste by integrated hydrothermal treatment, multienzyme formulation, and fed-batch operation.

    PubMed

    Huang, Renliang; Cao, Ming; Guo, Hong; Qi, Wei; Su, Rongxin; He, Zhimin

    2014-05-21

    Pomelo peel is an abundant pectin-rich biomass waste in China and has the potential to serve as a source of fuels and chemicals. This study reports a promising way to deal with pomelo peel waste and to utilize it as raw material for ethanol production via simultaneous saccharification and fermentation (SSF). An integrated strategy, incorporating hydrothermal treatment, multienzyme formulation, and fed-batch operation, was further developed to enhance the ethanol production. The results show that hydrothermal treatment (120 °C, 15 min) could significantly reduce the use of cellulase (from 7 to 3.8 FPU g(-1)) and pectinase (from 20 to 10 U g(-1)). A multienzyme complex, which consists of cellulase, pectinase, β-glucosidase, and xylanase, was also proven to be effective to improve the hydrolysis of pretreated pomelo peel, leading to higher concentrations of fermentative sugars (36 vs 14 g L(-1)) and galacturonic acid (23 vs 9 g L(-1)) than those with the use of a single enzyme. Furthermore, to increase the final ethanol concentration, fed-batch operation by adding fresh substrate was employed in the SSF process. A final solid loading of 25% (w/v), which is achieved by adding 15% fresh substrate to the SSF system at an initial solid loading of 10%, produced 36 g L(-1) ethanol product in good yield (73.5%). The ethanol concentration is about 1.73-fold that at the maximum solid loading of 14% for batch operation, whereas both of them have a closed ethanol yield. The results indicate that the use of the fed-batch mode could alleviate the decrease in ethanol yield at high solid loading, which is caused by significant mass transfer limitation and increased inhibition of toxic compounds in the SSF process. The integrated strategy demonstrated in this work could open a new avenue for dealing with pectin-rich biomass wastes and utilization of the wastes to produce ethanol. PMID:24802243

  3. LC-MS method for the simultaneous determination of six glucocorticoids in pharmaceutical formulations and counterfeit cosmetic products.

    PubMed

    Fiori, Jessica; Andrisano, Vincenza

    2014-03-01

    A screening method based on liquid chromatography-electrospray mass spectrometry for the simultaneous determination of six corticosteroids (betamethasone 17-valerate BM 17-V, beclomethasone BC, beclomethasone dipropionate BCDP, methylprednisolone MP, budesonide BD, flunisolide FN) was developed in order to control their illegal use in cosmetic and natural products. Indeed, despite corticosteroids are banned in cosmetics, counterfeit products might be present on the market, representing a health hazard. Therefore, effective analytical methods are required to rapidly screen over the counter products in health care shops for counterfeit corticosteroids. The analytical method involves the employment of a Waters Synergy C18 column (150mm×2.0mm I.D.) by using the following mobile phase: A (0.1% formic acid in acetonitrile), B (0.1% formic acid in water) in a linear gradient (from A-B 25:75, v/v to A-B 95:5, v/v in 30min) at the flow rate of 0.3mL/min. The detection was performed with an ion trap (IT) mass spectrometer in positive polarity, total ion current (TIC) and tandem mass modalities for qualitative purpose; single ion monitoring (SIM) mode was used for quantitative analysis on the ESI generated most abundant ion for each steroid. The method was fully validated in terms of precision, detection and quantification limits, linearity, recovery, and it was applied to the identification and quantification of corticosteroids in pharmaceutical formulations and cosmetic products. The mean recovery of BM 17-V, BC, BCDP, MP, BD and FN were found to be 101.3, 101.5, 98.8, 98.9, 98.1, 99.0%, respectively. Limits of quantitation (LOQ) were comprised in the range 29-95ng/mL. To the best of our knowledge, for the first time this mix of glucocorticoids were simultaneously determined in cosmetic products by using a fully validated method. BMV, in its two isomeric forms BM 17-V and BM 21-V, was found to be illegally present in one cream sample (A) with the total concentration level

  4. Eye irritation of low-irritant cosmetic formulations: correlation of in vitro results with clinical data and product composition.

    PubMed

    Debbasch, Caroline; Ebenhahn, Catherine; Dami, Nadia; Pericoi, Marc; Van den Berghe, Christine; Cottin, Martine; Nohynek, Gerhard J

    2005-01-01

    Alternative methods to the Draize eye irritation test, such as the hen's egg test-chorioallantoic membrane (HET-CAM) or the bovine corneal opacity and permeability (BCOP) tests, are currently used to evaluate the irritant potential of cosmetic or consumer products. Although, for strong irritants, the results of these tests correlate well with those of the Draize test, they appear to be less suited to identify mild irritants. In order to improve the sensitivity of alternative eye irritation tests, we developed a novel method that uses a human corneal epithelial cell line (CEPI), and the endpoints of cytotoxicity and IL-8 release. Twelve make-up removers were assessed by the HET-CAM, BCOP and CEPI tests, as well as in a clinical in-use test under ophthalmological control after their application to the external eye lid. In addition, we investigated the impact of osmolality and raw material composition on in vitro and clinical results and compared the in vitro results with those of clinical studies. Overall, although HET-CAM results were unrelated to eye discomfort and adverse clinical signs, they correlated mainly with the presence and concentration of surfactants in the test articles. BCOP scores were unrelated to clinical signs, but related mainly to glycol and sodium lactate content and concentration in the test articles. Cytotoxicity in CEPI mainly correlated with presence and concentrations of surfactants, and IL-8 release to clinical signs and/or glycol and sodium lactate concentrations. Overall, IL-8 release appeared to be the most sensitive and reliable endpoint to predict human eye tolerance to mildly irritant products. Although our results suggest that the IL-8 assay appears to be a promising screen for borderline-irritant formulations, further experiments are required to confirm and validate these preliminary results. PMID:15582208

  5. Scale-up of industrial biodiesel production to 40 m(3) using a liquid lipase formulation.

    PubMed

    Price, Jason; Nordblad, Mathias; Martel, Hannah H; Chrabas, Brent; Wang, Huali; Nielsen, Per Munk; Woodley, John M

    2016-08-01

    In this work, we demonstrate the scale-up from an 80 L fed-batch scale to 40 m(3) along with the design of a 4 m(3) continuous process for enzymatic biodiesel production catalyzed by NS-40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot plant data for the transesterification of used cooking oil and brown grease, we propose a method applying first order integral analysis to fed-batch data based on either the bound glycerol or free fatty acid content in the oil. This method greatly simplifies the modeling process and gives an indication of the effect of mixing at the various scales (80 L to 40 m(3) ) along with the prediction of the residence time needed to reach a desired conversion in a CSTR. Suitable process metrics reflecting commercial performance such as the reaction time, enzyme efficiency, and reactor productivity were evaluated for both the fed-batch and CSTR cases. Given similar operating conditions, the CSTR operation on average, has a reaction time which is 1.3 times greater than the fed-batch operation. We also showed how the process metrics can be used to quickly estimate the selling price of the enzyme. Assuming a biodiesel selling price of 0.6 USD/kg and a one-time use of the enzyme (0.1% (w/woil ) enzyme dosage); the enzyme can then be sold for 30 USD/kg which ensures that that the enzyme cost is not more than 5% of the biodiesel revenue. Biotechnol. Bioeng. 2016;113: 1719-1728. © 2016 Wiley Periodicals, Inc. PMID:26806356

  6. Robust SMO methodology for exposure tool and mask variations in high volume production

    NASA Astrophysics Data System (ADS)

    Hashimoto, Takaki; Kai, Yasunobu; Masukawa, Kazuyuki; Nojima, Shigeki; Kotani, Toshiya

    2013-04-01

    A robust source mask optimization (RSMO) methodology has been developed for the first time to decrease variations of critical dimension (CD) and overlay displacement on wafer caused by extremely complex exposure tools and mask patterns. The RSMO methodology takes into account exposure tool variations of source shape, aberrations and mask as well as dose and focus to get source shapes and mask patterns robust to the exposure tool variations. A comparison between the conventional SMO and the new RSMO found that the RSMO improved the edge placement error (EPE) and displacement sensitivity to coma and astigmatism aberrations by 14% and 40%, respectively. Interestingly, even a greatly-simplified source from the RSMO provides totally smaller EPE than uselessly complex source shape from the conventional SMO. Thus, the RSMO methodology is much more effective for semiconductor products with high volume production.

  7. Comparative genomics reveals multiple causes of variation in mycotoxin production among Fusarium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Collectively, species of Fusarium produce a structurally diverse array of mycotoxins and other secondary metabolites (SMs), but individual species contribute to only a fraction of this diversity. To elucidate causes of variation in SM production among species, we are examining the distribution and e...

  8. An Application of Variational Theory to an Integrated Walrasian Model of Exchange, Consumption and Production

    NASA Astrophysics Data System (ADS)

    Donato, M. B.; Milasi, M.; Vitanza, C.

    2010-09-01

    An existence result of a Walrasian equilibrium for an integrated model of exchange, consumption and production is obtained. The equilibrium model is characterized in terms of a suitable generalized quasi-variational inequality; so the existence result comes from an original technique which takes into account tools of convex and set-valued analysis.

  9. High individual variation in pheromone production by tree-killing bark beetles (Coleoptera: Curculionidae: Scolytinae)

    NASA Astrophysics Data System (ADS)

    Pureswaran, Deepa S.; Sullivan, Brian T.; Ayres, Matthew P.

    2008-01-01

    Aggregation via pheromone signalling is essential for tree-killing bark beetles to overcome tree defenses and reproduce within hosts. Pheromone production is a trait that is linked to fitness, so high individual variation is paradoxical. One explanation is that the technique of measuring static pheromone pools overestimates true variation among individuals. An alternative hypothesis is that aggregation behaviour dilutes the contribution of individuals to the trait under selection and reduces the efficacy of natural selection on pheromone production by individuals. We compared pheromone measurements from traditional hindgut extractions of female southern pine beetles with those obtained by aerating individuals till they died. Aerations showed greater total pheromone production than hindgut extractions, but coefficients of variation (CV) remained high (60-182%) regardless of collection technique. This leaves the puzzle of high variation unresolved. A novel but simple explanation emerges from considering bark beetle aggregation behaviour. The phenotype visible to natural selection is the collective pheromone plume from hundreds of colonisers. The influence of a single beetle on this plume is enhanced by high variation among individuals but constrained by large group sizes. We estimated the average contribution of an individual to the pheromone plume across a range of aggregation sizes and showed that large aggregation sizes typical in mass attacks limit the potential of natural selection because each individual has so little effect on the overall plume. Genetic variation in pheromone production could accumulate via mutation and recombination, despite strong effects of the pheromone plume on the fitness of individuals within the aggregation. Thus, aggregation behaviour, by limiting the efficacy of natural selection, can allow the persistence of extreme phenotypes in nature.

  10. Longitudinal and depth variation of bacterioplankton productivity and related factors in a temperate estuary

    NASA Astrophysics Data System (ADS)

    Peierls, Benjamin L.; Paerl, Hans W.

    2011-11-01

    Bacterioplankton productivity (BP) spatial variation was investigated in relation to potential resources, including primary productivity and dissolved organic matter, in the micro-tidal Neuse River-Pamlico Sound estuarine system, North Carolina, USA. Estuarine BP was predicted to correlate with the trophic gradient, decreasing along the salinity gradient in parallel with the decrease in organic matter and primary productivity. This prediction was tested over four years at spatial scales ranging from kilometers to meters along the riverine axis and with depth. The general pattern of BP across the salinity gradient was unimodal and matched the phytoplankton patterns in peak location and variability. Peak locations varied with discharge, especially in 2003 when above average discharge moved peaks downstream. Spatial coherence of BP with other variables was much less at short time scales. The effect of temperature, nutrients, and phytoplankton on BP varied by location, especially fresh versus brackish stations, although only temperature explained more than 20% of the BP variation. Depth variation of BP was as great as longitudinal variation and bottom samples were often higher than surface. BP was strongly correlated with particulate organic carbon at the pycnocline and bottom, highlighting the importance of particulate matter as a resource. Station-averaged BP and phytoplankton data corresponded well with two published meta-analyses, although the offset of the freshwater station suggested longitudinal differences in community composition or resource availability.

  11. A thermodynamic interpretation of Budyko and L'vovich formulations of annual water balance: Proportionality Hypothesis and maximum entropy production

    NASA Astrophysics Data System (ADS)

    Wang, Dingbao; Zhao, Jianshi; Tang, Yin; Sivapalan, Murugesu

    2015-04-01

    The paper forms part of the search for a thermodynamic explanation for the empirical Budyko Curve, addressing a long-standing research question in hydrology. Here this issue is pursued by invoking the Proportionality Hypothesis underpinning the Soil Conservation Service (SCS) curve number method widely used for estimating direct runoff at the event scale. In this case, the Proportionality Hypothesis posits that the ratio of continuing abstraction to its potential value is equal to the ratio of direct runoff to its potential value. Recently, the validity of the Proportionality Hypothesis has been extended to the partitioning of precipitation into runoff and evaporation at the annual time scale as well. In this case, the Proportionality Hypothesis dictates that the ratio of continuing evaporation to its potential value is equal to the ratio of runoff to its potential value. The Budyko Curve could then be seen as the straightforward outcome of the application of the Proportionality Hypothesis to estimate mean annual water balance. In this paper, we go further and demonstrate that the Proportionality Hypothesis itself can be seen as a result of the application of the thermodynamic principle of Maximum Entropy Production (MEP). In this way, we demonstrate a possible thermodynamic basis for the Proportionality Hypothesis, and consequently for the Budyko Curve. As a further extension, the L'vovich formulation for the two-stage partitioning of annual precipitation is also demonstrated to be a result of MEP: one for the competition between soil wetting and fast flow during the first stage; another for the competition between evaporation and base flow during the second stage.

  12. 40 CFR 152.43 - Alternate formulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Registration Procedures § 152.43 Alternate formulations... label text of the alternate formulation product must be identical to that of the basic formulation....

  13. 40 CFR 152.43 - Alternate formulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Registration Procedures § 152.43 Alternate formulations... label text of the alternate formulation product must be identical to that of the basic formulation....

  14. Modelling natural grass production and its spatio-temporal variations in a semiarid Mediterranean watershed

    NASA Astrophysics Data System (ADS)

    Schnabel, Susanne; Lozano-Parra, Javier; Maneta-López, Marco

    2014-05-01

    Natural grasses are found in semiarid rangelands with disperse tree cover of part of the Iberian Peninsula and constitute a resource with high ecologic and economic value worth, being an important source of food for livestock, playing a significant role in the hydrologic cycle, controlling the soil thermal regime, and are a key factor in reducing soil erosion and degradation. However, increasing pressure on the resources, changes in land use as well as possible climate variations threaten the sustainability of natural grasses. Despite of their importance, the spatio-temporal variations of pasture production over whole watersheds are poorly known. In this sense, previous studies by other authors have indicated its dependence on a balance of positive and negative effects brought about by the main limiting factors: water, light, nutrients and space. Nevertheless, the specific weight of each factor is not clear because they are highly variable due to climate characteristics and the structure of these agroforestry systems. We have used a physical spatially-distributed ecohydrologic model to investigate the specific weight of factors that contribute to pasture production in a semiarid watershed of 99.5 ha in western Spain. This model couples a two layer (canopy and understory) vertical local closure energy balance scheme, a hydrologic model and a carbon uptake and vegetation growth component, and it was run using a synthetic daily climate dataset generated by a stochastic weather generator, which reproduced the range of climatic variations observed under mediterranean current climate. The modelling results reproduced satisfactorily the seasonality effects of climate as precipitation and temperatures, as well as annual and inter-annual variations of pasture production. Spatial variations of pasture production were largely controlled by topographic and tree effects, showing medium-low values depending of considered areas. These low values require introduction of feed to

  15. Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product

    PubMed Central

    2013-01-01

    Background Existence of anti-malarial generic drugs with low bioavailability marketed on sub-Saharan Africa raises a concern on patients achieving therapeutic concentrations after intake of such products. This work compared bioavailability of one generic tablet formulation with innovator’s product. Both were fixed dose combination tablet formulations containing artemether and lumefantrine. Methodology The study was conducted in Dar Es Salaam, Tanzania, in which a survey of the most abundant generic containing artemether-lumefantrine tablet formulation was carried out in retail pharmacies. The most widely available generic (Artefan®, Ajanta Pharma Ltd, Maharashtra, India) was sampled for bioavailability comparison with Coartem® (Novartis Pharma, Basel, Switzerland) - the innovator’s product. A randomized, two-treatment cross-over study was conducted in 18 healthy Tanzanian black male volunteers. Each volunteer received Artefan® (test) and Coartem® (as reference) formulation separated by 42 days of drug-free washout period. Serial blood samples were collected up to 168 hours after oral administration of a single dose of each treatment. Quantitation of lumefantrine plasma levels was done using HPLC with UV detection. Bioequivalence of the two products was assessed in accordance with the US Food and Drug Authority (FDA) guidelines. Results The most widely available generic in pharmacies was Artefan® from India. All eighteen enrolled volunteers completed the study and both test and reference tablet formulations were well tolerated. It was possible to quantify lumefantrine alone, therefore, the pharmacokinetic parameters reported herein are for lumefantrine. The geometric mean ratios for Cmax, AUC0-t and AUC0-∞ were 84% in all cases and within FDA recommended bioequivalence limits of 80% – 125%, but the 90% confidence intervals were outside FDA recommended limits (CI 49–143%, 53 - 137%, 52 - 135% respectively). There were no statistical significant

  16. Decadal variations of Pacific North Equatorial Current bifurcation from multiple ocean products

    NASA Astrophysics Data System (ADS)

    Zhai, Fangguo; Wang, Qingye; Wang, Fujun; Hu, Dunxin

    2014-02-01

    In this study, we examine the decadal variations of the Pacific North Equatorial Current (NEC) bifurcation latitude (NBL) averaged over upper 100 m and underlying dynamics over the past six decades using 11 ocean products, including seven kinds of ocean reanalyzes based on ocean data assimilation systems, two kinds of numerical simulations without assimilating observations and two kinds of objective analyzes based on in situ observations only. During the period of 1954-2007, the multiproduct mean of decadal NBL anomalies shows maxima around 1965/1966, 1980/1981, 1995/1996, and 2003/2004, and minima around 1958, 1971/1972, 1986/1987, and 2000/2001, respectively. The NBL decadal variations are related to the first Empirical Orthogonal Function mode of decadal anomalies of sea surface height (SSH) in the northwestern tropical Pacific Ocean, which shows spatially coherent variation over the whole region and explains most of the total variance. Further regression and composite analyzes indicate that northerly/southerly NBL corresponds to negative/positive SSH anomalies and cyclonic/anticyclonic gyre anomalies in the northwestern tropical Pacific Ocean. These decadal circulation variations and thus the decadal NBL variations are governed mostly by the first two vertical modes and attribute the most to the first baroclinic mode. The NBL decadal variation is highly positively correlated with the tropical Pacific decadal variability (TPDV) around the zero time lag. With a lead of about half the decadal cycle the NBL displays closer but negative relationship to TPDV in four ocean products, possibly manifesting the dynamical role of the circulation in the northwestern tropical Pacific in the phase-shifting of TPDV.

  17. Characterization, Genetic Variation, and Combining Ability of Maize Traits Relevant to the Production of Cellulosic Ethanol

    SciTech Connect

    Lorenz, A. J.; Coors, J. G.; de Leon, N.; Wolfrum, E. J.; Hames, B. R.; Sluiter, A. D.; Weimer, P. J.

    2009-01-01

    Maize (Zea mays L.) stover has been identified as an important feedstock for the production of cellulosic ethanol. Our objectives were to measure hybrid effect and combining ability patterns of traits related to cellulosic ethanol production, determine if germplasm and mutations used for silage production would also be beneficial for feedstock production, and examine relationships between traits that are relevant to selective breeding. We evaluated grain hybrids, germplasm bred for silage production, brown-midrib hybrids, and a leafy hybrid. Yield and composition traits were measured in four environments. There was a 53% difference in stover yield between commercial grain hybrids that were equivalent for other production-related traits. Silage germplasm may be useful for increasing stover yield and reducing lignin concentration. We found much more variation among hybrids than either in vitro ruminal fermentability or polysaccharide concentration. Correlations between traits were mostly favorable or nonexistent. Our results suggest that utilizing standing genetic variation of maize in breeding programs could substantially increase the amount of biofuels produced from stover per unit area of land.

  18. Formulation techniques for nanofluids.

    PubMed

    Rivera-Solorio, Carlos I; Payán-Rodríguez, Luis A; García-Cuéllar, Alejandro J; Ramón-Raygoza, E D; L Cadena-de-la-Peña, Natalia; Medina-Carreón, David

    2013-11-01

    Fluids with suspended nanoparticles, commonly known as nanofluids, may be formulated to improve the thermal performance of industrial heat transfer systems and applications. Nanofluids may show enhanced thermal and electrical properties such as thermal conductivity, viscosity, heat transfer coefficient, dielectric strength, etc. However, stability problems may arise as nanoparticles usually have the tendency to agglomerate and sediment producing deterioration in the increment of these properties. In this review, we discuss patents that report advances in the formulation of nanofluids including: production methods, selection of components (nanoparticles, base fluid and surfactants), their chemical compositions and morphologies, and characterization techniques. Finally, current and future directions in the development of nanofluid formulation are discussed. PMID:24330043

  19. Reactive decontamination formulation

    DOEpatents

    Giletto, Anthony; White, William; Cisar, Alan J.; Hitchens, G. Duncan; Fyffe, James

    2003-05-27

    The present invention provides a universal decontamination formulation and method for detoxifying chemical warfare agents (CWA's) and biological warfare agents (BWA's) without producing any toxic by-products, as well as, decontaminating surfaces that have come into contact with these agents. The formulation includes a sorbent material or gel, a peroxide source, a peroxide activator, and a compound containing a mixture of KHSO.sub.5, KHSO.sub.4 and K.sub.2 SO.sub.4. The formulation is self-decontaminating and once dried can easily be wiped from the surface being decontaminated. A method for decontaminating a surface exposed to chemical or biological agents is also disclosed.

  20. Seasonal variation of chemical composition and biomethane production from the brown seaweed Ascophyllum nodosum.

    PubMed

    Tabassum, Muhammad Rizwan; Xia, Ao; Murphy, Jerry D

    2016-09-01

    Ascophyllum nodosum, an abundant Irish brown seaweed, shows significant seasonal variation in chemical composition and biogas production. The polyphenol content is shown to be a more important factor in biogas production than ash content. High polyphenol content in summer months adversely affected biogas production; suggesting two potential harvest dates, March and October. A. nodosum harvested in October showed a relatively low level of polyphenols (2% of TS) and ash (23% of volatile solids), and exhibited a specific methane yield of 215LCH4kgVS(-1), which was 44% of theoretical yield. The highest yield per wet weight of 47m(3)CH4t(-1) was achieved in October, which is 2.9 times higher than the lowest value (16m(3)CH4t(-1)), obtained in December. The gross energy yield of A. nodosum based on the optimal biogas production can achieve 116GJha(-1)yr(-1) in October. PMID:27240238

  1. Submerged Culture of a Mycelial Formulation of a Bioherbicidal Strain of Myrothecium verrucaria with Mitigated Mycotoxin Production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A mycelial formulation of the fungus Myrothecium verrucaria (IMI 361390) was shown to be highly efficacious in controlling the exotic invasive weed kudzu. The mycelium can be rapidly (48 h) produced in several media including soy flour-cornmeal medium. HPLC analyses revealed that the mycelial formu...

  2. Variation in the pulmonary hypertensive responsiveness of broilers to lipopolysaccharide and innate variation in nitric oxide production by mononuclear cells.

    PubMed

    Bowen, O T; Wideman, R F; Anthony, N B; Erf, G F

    2006-08-01

    Variability among broilers in their pulmonary hypertensive (PH) responsiveness to lipopolysaccharide (LPS) appears to reflect innate variation in the types or proportions of vasodilators and vasoconstrictors released by leukocytes and endothelial cells. Two experiments were designed to evaluate possible correlations between the PH responsiveness to LPS in vivo and the quantities of nitric oxide (NO; a potent pulmonary vasodilator) produced by mononuclear cells in vitro. In Experiment 1, blood samples were collected from male broilers from a base population (control group) and from survivors of a 60% lethal dose i.v. injection of cellulose microparticles (MP survivor group). In Experiment 2, blood samples were collected from male broilers from a relaxed line and from lines known to be susceptible or resistant to pulmonary hypertension syndrome. Peripheral mononuclear cells (PMNC) from each blood sample were cultured at 2 million cells per well, remained unstimulated, or were stimulated with LPS to elicit the expression of inducible NO synthase, and the 24-h production of NO was measured. In both experiments, unstimulated PMNC cultures did not produce consistently detectable levels of NO, whereas LPS-stimulated cultures produced quantities of NO that varied widely among individuals. Nitric oxide production by cultured PMNC also was evaluated by flow cytometry, demonstrating that LPS-stimulated PMNC produced substantially more NO than did unstimulated cells in all of the groups evaluated. Moreover, NO-producing PMNC were identified to be monocytes. The same broilers from which PMNC had been isolated were catheterized subsequently to record pulmonary arterial pressure, LPS was injected i.v. to assess the amplitudes of peak and postpeak PH responses, then N(omega)-nitro-L-arginine methyl ester was injected to inhibit ongoing NO production. In Experiment 1, the amplitude of the peak and postpeak PH responses to LPS were correlated with the quantity of NO produced by LPS

  3. Uncertainties in the production of p nuclei in massive stars obtained from Monte Carlo variations

    NASA Astrophysics Data System (ADS)

    Rauscher, T.; Nishimura, N.; Hirschi, R.; Cescutti, G.; Murphy, A. St. J.; Heger, A.

    2016-09-01

    Nuclear data uncertainties in the production of p nuclei in massive stars have been quantified in a Monte Carlo procedure. Bespoke temperature-dependent uncertainties were assigned to different types of reactions involving nuclei from Fe to Bi. Their simultaneous impact was studied in postprocessing explosive trajectories for three different stellar models. It was found that the grid of mass zones in the model of a 25 M⊙ star, which is widely used for investigations of p nucleosynthesis, is too crude to properly resolve the detailed temperature changes required for describing the production of p nuclei. Using models with finer grids for 15 M⊙ and 25 M⊙ stars with initial solar metallicity, it was found that most of the production uncertainties introduced by nuclear reaction uncertainties are smaller than a factor of two. Since a large number of rates were varied at the same time in the Monte Carlo procedure, possible cancellation effects of several uncertainties could be taken into account. Key rates were identified for each p nucleus, which provide the dominant contribution to the production uncertainty. These key rates were found by examining correlations between rate variations and resulting abundance changes. This method is superior to studying flow patterns, especially when the flows are complex, and to individual, sequential variation of a few rates.

  4. Ion Implantation Angle Variation to Device Performance and the Control in Production

    SciTech Connect

    Zhao, Z.Y.; Hendrix, D.; Wu, L.Y.; Cusson, B.K.

    2003-08-26

    As the device features get smaller and aspect ratios of photoresist openings get steeper, shadowing effect has more impact on the performance of devices. Many of the traditional 7 deg. tilt implants have progressed to 0 deg. implants. But shadowing may still occur if the tilt angle deviates from normal direction. Some implants, such as halo implants, demand even more stringent angle control to reduce device performance variation. The demand for implant angle control and monitoring thus becomes more obvious and important. However, statistical process control (SPC) cannot be done on shadowing effect without special test structures. Channeling, on the other hand, provides good sensitivity in regard to implant angle changes. It is the authors' intention to introduce channeling implant in different channels to monitor the implant angle variation. The incoming <100> silicon wafers have a cut-angle spec of +/- 1.0 deg. This poses a difficulty if one wants to control the implant angle's accuracy within +/- 0.5 deg. Other measures have to be taken to ensure the consistency of test wafers and to have prompt diagnosis feedback when needed. This paper will discuss the effect of implant tilt angle on device parameters and how to control the angle variation in production. Correlations of implant tilt angle variation to ThermaWave, sheet resistance (Rs), Secondary Ion Mass Spectrometry (SIMS) and device parameters will be covered with certain implant conditions.

  5. Ion Implantation Angle Variation to Device Performance and the Control in Production

    NASA Astrophysics Data System (ADS)

    Zhao, Z. Y.; Hendrix, D.; Wu, L. Y.; Cusson, B. K.

    2003-08-01

    As the device features get smaller and aspect ratios of photoresist openings get steeper, shadowing effect has more impact on the performance of devices. Many of the traditional 7° tilt implants have progressed to 0° implants. But shadowing may still occur if the tilt angle deviates from normal direction. Some implants, such as halo implants, demand even more stringent angle control to reduce device performance variation. The demand for implant angle control and monitoring thus becomes more obvious and important. However, statistical process control (SPC) cannot be done on shadowing effect without special test structures. Channeling, on the other hand, provides good sensitivity in regard to implant angle changes. It is the authors' intention to introduce channeling implant in different channels to monitor the implant angle variation. The incoming <100> silicon wafers have a cut-angle spec of +/- 1.0°. This poses a difficulty if one wants to control the implant angle's accuracy within +/- 0.5°. Other measures have to be taken to ensure the consistency of test wafers and to have prompt diagnosis feedback when needed. This paper will discuss the effect of implant tilt angle on device parameters and how to control the angle variation in production. Correlations of implant tilt angle variation to ThermaWave™, sheet resistance (Rs), Secondary Ion Mass Spectrometry (SIMS) and device parameters will be covered with certain implant conditions.

  6. Cross-language comparisons of contextual variation in the production and perception of vowels

    NASA Astrophysics Data System (ADS)

    Strange, Winifred

    2005-04-01

    In the last two decades, a considerable amount of research has investigated second-language (L2) learners problems with perception and production of non-native vowels. Most studies have been conducted using stimuli in which the vowels are produced and presented in simple, citation-form (lists) monosyllabic or disyllabic utterances. In my laboratory, we have investigated the spectral (static/dynamic formant patterns) and temporal (syllable duration) variation in vowel productions as a function of speech-style (list/sentence utterances), speaking rate (normal/rapid), sentence focus (narrow focus/post-focus) and phonetic context (voicing/place of surrounding consonants). Data will be presented for a set of languages that include large and small vowel inventories, stress-, syllable-, and mora-timed prosody, and that vary in the phonological/phonetic function of vowel length, diphthongization, and palatalization. Results show language-specific patterns of contextual variation that affect the cross-language acoustic similarity of vowels. Research on cross-language patterns of perceived phonetic similarity by naive listeners suggests that listener's knowledge of native language (L1) patterns of contextual variation influences their L1/L2 similarity judgments and subsequently, their discrimination of L2 contrasts. Implications of these findings for assessing L2 learners perception of vowels and for developing laboratory training procedures to improve L2 vowel perception will be discussed. [Work supported by NIDCD.

  7. Inter- and intra-annual variations of clumping index derived from the MODIS BRDF product

    NASA Astrophysics Data System (ADS)

    He, Liming; Liu, Jane; Chen, Jing M.; Croft, Holly; Wang, Rong; Sprintsin, Michael; Zheng, Ting; Ryu, Youngryel; Pisek, Jan; Gonsamo, Alemu; Deng, Feng; Zhang, Yongqin

    2016-02-01

    Clumping index quantifies the level of foliage aggregation, relative to a random distribution, and is a key structural parameter of plant canopies and is widely used in ecological and meteorological models. In this study, the inter- and intra-annual variations in clumping index values, derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) BRDF product, are investigated at six forest sites, including conifer forests, a mixed deciduous forest and an oak-savanna system. We find that the clumping index displays large seasonal variation, particularly for the deciduous sites, with the magnitude in clumping index values at each site comparable on an intra-annual basis, and the seasonality of clumping index well captured after noise removal. For broadleaved and mixed forest sites, minimum clumping index values are usually found during the season when leaf area index is at its maximum. The magnitude of MODIS clumping index is validated by ground data collected from 17 sites. Validation shows that the MODIS clumping index can explain 75% of variance in measured values (bias = 0.03 and rmse = 0.08), although with a narrower amplitude in variation. This study suggests that the MODIS BRDF product has the potential to produce good seasonal trajectories of clumping index values, but with an improved estimation of background reflectance.

  8. Advanced protein formulations

    PubMed Central

    Wang, Wei

    2015-01-01

    It is well recognized that protein product development is far more challenging than that for small-molecule drugs. The major challenges include inherent sensitivity to different types of stresses during the drug product manufacturing process, high rate of physical and chemical degradation during long-term storage, and enhanced aggregation and/or viscosity at high protein concentrations. In the past decade, many novel formulation concepts and technologies have been or are being developed to address these product development challenges for proteins. These concepts and technologies include use of uncommon/combination of formulation stabilizers, conjugation or fusion with potential stabilizers, site-specific mutagenesis, and preparation of nontraditional types of dosage forms—semiaqueous solutions, nonfreeze-dried solid formulations, suspensions, and other emerging concepts. No one technology appears to be mature, ideal, and/or adequate to address all the challenges. These gaps will likely remain in the foreseeable future and need significant efforts for ultimate resolution. PMID:25858529

  9. Strain variation in microalgal lipid production during mixotrophic growth with glycerol.

    PubMed

    Paranjape, Kiran; Leite, Gustavo B; Hallenbeck, Patrick C

    2016-03-01

    Algal cultivation at high latitudes is challenged by the relatively low annual solar flux. One possible scenario to overcome this limitation is the use of mixotrophic growth to potentially boost biomass and lipid production. Here the effect of glycerol addition on the growth and lipid production by twelve indigenous microalgae was examined. The results show that there is considerable strain dependent variation in the maximum growth rate under mixotrophic conditions with the addition of glycerol causing in some cases up to a 2.4-fold increase in growth rate and a up to a 1.9-fold increase in biomass. In addition, glycerol increased total lipid production 40-60% in some strains. These results also show the value in screening culture collections for desired traits independent of strain identification since here one (PCH02) of the five Chlorella strains showed a large increase in lipid with glycerol. PMID:26773947

  10. Roller compaction, granulation and capsule product dissolution of drug formulations containing a lactose or mannitol filler, starch, and talc.

    PubMed

    Chang, Chialu Kevin; Alvarez-Nunez, Fernando A; Rinella, Joseph V; Magnusson, Lars-Erik; Sueda, Katsuhiko

    2008-01-01

    This study investigated the influence of excipient composition to the roller compaction and granulation characteristics of pharmaceutical formulations that were comprised of a spray-dried filler (lactose monohydrate or mannitol), pregelatinized starch, talc, magnesium stearate (1% w/w) and a ductile active pharmaceutical ingredient (25% w/w) using a mixed-level factorial design. The main and interaction effects of formulation variables (i.e., filler type, starch content, and talc content) to the response factors (i.e., solid fraction and tensile strength of ribbons, particle size, compressibility and flow of granules) were analyzed using multi-linear stepwise regression analysis. Experimental results indicated that roller compacted ribbons of both lactose and mannitol formulations had similar tensile strength. However, resulting lactose-based granules were finer than the mannitol-based granules because of the brittleness of lactose compared to mannitol. Due to the poor compressiblility of starch, increasing starch content in the formulation from 0% to 20% w/w led to reduction in ribbon solid fraction by 10%, ribbon tensile strength by 60%, and granule size by 30%. Granules containing lactose or more starch showed less cohesive flow than granules containing mannitol and less starch. Increasing talc content from 0% to 5% w/w had little effect to most physical properties of ribbons and granules while the flow of mannitol-based granules was found improved. Finally, it was observed that stored at 40 degrees C/75% RH over 12 weeks, gelatin capsules containing lactose-based granules had reduced dissolution rates due to pellicle formation inside capsule shells, while capsules containing mannitol-based granules remained immediate dissolution without noticeable pellicle formation. PMID:18459052

  11. The steady-state serum concentration of genistein aglycone is affected by formulation: a bioequivalence study of bone products.

    PubMed

    Bitto, Alessandra; Burnett, Bruce P; Polito, Francesca; Russo, Silvia; D'Anna, Rosario; Pillai, Lakshmi; Squadrito, Francesco; Altavilla, Domenica; Levy, Robert M

    2013-01-01

    An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μ g molybdenum, 250 μ g boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs. Total serum genistein, after β -glucuronidase/sulfatase digestion, was measured by time-resolved fluorometric assay. Maximal time (Tmax), concentration (Cmax), half-life (T1/2), and area under the curve (AUC) were determined for genistein in each formulation. Fosteum and the Squadrito study formulation were equivalent for genistein Tmax (2 hrs), Cmax (0.7 μM), T1/2 (18 ± 6.9 versus 21 ± 4.9 hrs), and AUC (9221 ± 413 versus 9818 ± 1370 ng·hr/mL). The OTC supplement's synthetically derived genistein, however, showed altered Tmax (6 hrs), Cmax (0.57 μ M), T1/2 (8.3 ± 1.9 hrs), and AUC (6474 ± 287 ng·hr/mL). Differences in uptake may be due to multiple ingredients in the OTC supplement which interfere with genistein absorption. PMID:23484100

  12. Contemporary formulation and distribution practices for cold-filled acid products: Australian industry survey and modeling of published pathogen inactivation data.

    PubMed

    Chapman, B; Scurrah, K J; Ross, T

    2010-05-01

    A survey of 12 Australian manufacturers indicated that mild-tasting acids and preservatives are used to partially replace acetic acid in cold-filled acid dressings and sauces. In contrast to traditional ambient temperature distribution practices, some manufacturers indicated that they supply the food service sector with cold-filled acid products prechilled for incorporation into ready-to-eat foods. The Comité des Industries des Mayonnaises et Sauces Condimentaires de la Communauté Economique Européenne (CIMSCEE) Code, a formulation guideline used by the industry to predict the safety of cold-filled acid formulations with respect to Salmonella enterica and Escherichia coli, does not extend to the use of acids and preservatives other than acetic acid nor does it consider the effects of chill distribution. We found insufficient data in the published literature to comprehensively model the response of S. enterica and E. coli to all of the predictor variables (i.e., pH, acetic acid, NaCl, sugars, other acids, preservatives, and storage temperature) of relevance for contemporary cold-filled acid products in Australia. In particular, we noted a lack of inactivation data for S. enterica at aqueous-phase NaCl concentrations of >3% (wt/wt). However, our simple models clearly identified pH and 1/absolute temperature of storage as the most important variables generally determining inactivation. To develop robust models to predict the effect of contemporary formulation and storage variables on product safety, additional empirical data are required. Until such models are available, our results support challenge testing of cold-filled acid products to ascertain their safety, as suggested by the CIMSCEE, but suggest consideration of challenging with both E. coli and S. enterica at incubation temperatures relevant to intended product distribution temperatures. PMID:20501041

  13. SEBAL For Detecting Spatial Variation Of Water Productivity For Wheat In The Yaqui Valley, Mexico

    NASA Astrophysics Data System (ADS)

    Zwart, S. J.; Bastiaanssen, W. G. M.; Garatuza-Payan, J.; Watts, C. J.

    2006-08-01

    Although the use of water productivity is gaining importance for evaluating good management practices, there is no standardized framework that aids the calculations. A methodology has been developed to quantify spatial variation of crop yield, evapotranspiration (ET) and water productivity (WPET) using the SEBAL algorithm and high and low resolution satellite images. SEBAL estimated ET was validated over a wheat dominated area in the Yaqui Valley, Mexico and proved to be accurate. Estimated average wheat yields of 5.5 ton ha-1 were well within the range of measured yields reported in the literature. Area average WPET was 1.37 kg m-3 and could be considered high compared to other irrigated systems around the world It is concluded that the proposed methodology is accurate and that better knowledge of the spatial variation of WP provides valuable information for regional water managers to seek local solutions for boosting the productivity of agricultural water use by means of sharing and exchanging good management practices.

  14. Case study of polychlorinated naphthalene emissions and factors influencing emission variations in secondary aluminum production.

    PubMed

    Jiang, Xiaoxu; Liu, Guorui; Wang, Mei; Liu, Wenbin; Tang, Chen; Li, Li; Zheng, Minghui

    2015-04-01

    Secondary aluminum production has been recognized as an important source of polychlorinated naphthalenes (PCNs). Large variations in PCN emissions as the smelting process proceeds have not been determined. In this study, solid and gaseous discharges, including fly ash, slag, and stack gas samples collected from four secondary smelting plants during different smelting stages were analyzed for PCNs. The average emission factor of ∑(1-8)PCNs to air was calculated to be 17.4 mg t(-1), with a range of 4.3-29.5 mg t(-1). The average emission factors of ∑(1-8)PCNs from fly ash and slag were 55.5 ng t(-1) and 0.13 ng t(-1), respectively. The derived emission factors may enable a more accurate estimation of annual emissions and a more comprehensive knowledge of the distribution of PCNs emitted from secondary aluminum production. The emission levels and characteristics of PCNs during different smelting stages were compared. Possible factors, including the organic impurities from aluminum scrap, fuel, and chloride additives, which could contribute to variations in PCN emissions and characteristics were discussed. These results may provide useful information for developing better control strategies for reducing PCN emissions in secondary aluminum production. PMID:25637821

  15. Recent geographic variations in terrestrial carbon cycle based on new production efficiency model

    NASA Astrophysics Data System (ADS)

    Sasai, T.; Ichii, K.; Yamaguchi, Y.

    2003-12-01

    The terrestrial carbon budget must be understood more accurately for the prediction of future changes in climate and carbon cycle. The goal of this study is to estimate spatial and temporal patterns of the carbon fluxes more accurately using the newly developed terrestrial biosphere model and satellite data. Our model consists of terrestrial carbon cycle and hydrology submodels. An advantage is a new approach in the LUE (Light Use Efficiency) concept, which calculates temperature and water stress factor in LUE model from a photosynthetic model and stomatal conductance formulation. In carbon cycle model, GPP is calculated from the LUE concept and satellite-based fPAR dataset. The soil carbon cycle model is based on CENTURY model with optimized water and temperature factor. Hydrological submodel is based on BIOME3, calculating ET is used by Penman-Monteith method. The model was run for 18 years (1982-1999) on a global scale, and we simulated the geographic distributions of the terrestrial carbon fluxes. We have checked simulated vegetation growth limiting factor with stress factor of MODIS NPP algorithm. Large differences were found in the northern mid and high latitude forests because soil moisture stress is not incorporated into MODIS NPP algorithm. Although responses of stress factors in MODIS NPP algorithm are mostly similar to our theoretically based one, our model works well in the soil moisture limited regions. Global total NPP was estimated at 61.7GtC/yr, and total NEP variations are strongly related with ENSO. Validation using measured values from the GPPDI database showed that our NPP estimation was within a reasonable range. The temporal patterns of the terrestrial carbon flux showed that NPP increased in the northern middle/high latitudes, central Africa, and India. In contrast, NPP decreased in the south Amazon region, the middle latitudes of the southern hemisphere, a part of North America, and Southeast Asia. Sensitivity analysis indicated that NPP

  16. Formation Sequences of Iron Minerals in the Acidic Alteration Products and Variation of Hydrothermal Fluid Conditions

    NASA Astrophysics Data System (ADS)

    Isobe, H.; Yoshizawa, M.

    2008-12-01

    Iron minerals have important role in environmental issues not only on the Earth but also other terrestrial planets. Iron mineral species related to alteration products of primary minerals with surface or subsurface fluids are characterized by temperature, acidity and redox conditions of the fluids. We can see various iron- bearing alteration products in alteration products around fumaroles in geothermal/volcanic areas. In this study, zonal structures of iron minerals in alteration products of the geothermal area are observed to elucidate temporal and spatial variation of hydrothermal fluids. Alteration of the pyroxene-amphibole andesite of Garan-dake volcano, Oita, Japan occurs by the acidic hydrothermal fluid to form cristobalite leaching out elements other than Si. Hand specimens with unaltered or weakly altered core and cristobalite crust show various sequences of layers. XRD analysis revealed that the alteration degree is represented by abundance of cristobalite. Intermediately altered layers are characterized by occurrence including alunite, pyrite, kaolinite, goethite and hematite. A specimen with reddish brown core surrounded by cristobalite-rich white crust has brown colored layers at the boundary of core and the crust. Reddish core is characterized by occurrence of crystalline hematite by XRD. Another hand specimen has light gray core, which represents reduced conditions, and white cristobalite crust with light brown and reddish brown layers of ferric iron minerals between the core and the crust. On the other hand, hornblende crystals, typical ferrous iron-bearing mineral of the host rock, are well preserved in some samples with strongly decolorized cristobalite-rich groundmass. Hydrothermal alteration experiments of iron-rich basaltic material shows iron mineral species depend on acidity and temperature of the fluid. Oxidation states of the iron-bearing mineral species are strongly influenced by the acidity and redox conditions. Variations of alteration

  17. Prediction of seasonal climate-induced variations in global food production

    NASA Astrophysics Data System (ADS)

    Iizumi, Toshichika; Sakuma, Hirofumi; Yokozawa, Masayuki; Luo, Jing-Jia; Challinor, Andrew J.; Brown, Molly E.; Sakurai, Gen; Yamagata, Toshio

    2013-10-01

    Consumers, including the poor in many countries, are increasingly dependent on food imports and are thus exposed to variations in yields, production and export prices in the major food-producing regions of the world. National governments and commercial entities are therefore paying increased attention to the cropping forecasts of important food-exporting countries as well as to their own domestic food production. Given the increased volatility of food markets and the rising incidence of climatic extremes affecting food production, food price spikes may increase in prevalence in future years. Here we present a global assessment of the reliability of crop failure hindcasts for major crops at two lead times derived by linking ensemble seasonal climatic forecasts with statistical crop models. We found that moderate-to-marked yield loss over a substantial percentage (26-33%) of the harvested area of these crops is reliably predictable if climatic forecasts are near perfect. However, only rice and wheat production are reliably predictable at three months before the harvest using within-season hindcasts. The reliabilities of estimates varied substantially by crop--rice and wheat yields were the most predictable, followed by soybean and maize. The reasons for variation in the reliability of the estimates included the differences in crop sensitivity to the climate and the technology used by the crop-producing regions. Our findings reveal that the use of seasonal climatic forecasts to predict crop failures will be useful for monitoring global food production and will encourage the adaptation of food systems toclimatic extremes.

  18. Variation of the reactivity of solids near the interface reagent-product of the topochemical reaction

    NASA Astrophysics Data System (ADS)

    Boldyrev, V. V.; Lomovsky, O. I.; Zaikova, T. O.; Gavrilov, E. F.

    1984-01-01

    During the topochemical decomposition of ammonium perchlorate and copper hypophosphite an enhanced acid concentration occurs near the reagent-product interface. Concentration profiles of the acid were observed after the treatment of the partially decomposed crystals by indicator solution and by microphotometry. Profiles exhibit the diffusive characteristics. The diffusion coefficient is 10 -10 cm 2/sec for ammonium perchlorate and 10 -9 cm 2/sec for copper hypophosphite at 20°C. It is concluded that the variation of the reactivity near the interface is due to the enhanced acid concentration.

  19. Global Precipitation Variations and Long-term Changes Derived from the GPCP Monthly Product

    NASA Technical Reports Server (NTRS)

    Adler, Robert F.; Gu, Guojun; Huffman, George; Curtis, Scott

    2005-01-01

    Global and large regional rainfall variations and possible long-term changes are examined using the 25-year (1979-2004) monthly dataset from the Global Precipitation Climatology Project (GPCP). The emphasis is to discriminate among the variations due to ENSO, volcanic events and possible long-term changes. Although the global change of precipitation in the data set is near zero, the data set does indicate an upward trend (0.13 mm/day/25yr) and a downward trend (-0.06 mm/day/25yr) over tropical oceans and lands (25S-25N), respectively. This corresponds to a 4% increase (ocean) and 2% decrease (land) during this time period. Techniques are applied to attempt to eliminate variations due to ENSO and major volcanic eruptions. The impact of the two major volcanic eruptions over the past 25 years is estimated to be about a 5% reduction in tropical rainfall. The modified data set (with ENSO and volcano effect removed) retains the same approximate change slopes, but with reduced variance leading to significance tests with results in the 90-95% range. Inter-comparisons between the GPCP, SSWI (1988-2004), and TRMM (1998-2004) rainfall products are made to increase or decrease confidence in the changes seen in the GPCP analysis.

  20. Interannual variation in climate-potential net primary productivity relationships in differing ecosystems of California

    SciTech Connect

    Koch, G.W.; Randerson, J.T. )

    1994-06-01

    The seasonality and interannual variation in potential net primary production (NPP) were examined in differing vegetation types in California over three years of contrasting precipitation using co-registered maps of climate, vegetation, and 1km biweekly NDVI derived from high resolution satellite AVHRR data. Differences in seasonality of the vegetation types (annual grassland, chamise chaparral, deciduous oak woodland, and evergreen oak) were clearly evident and corresponded well to patterns observed in field studies. In years and locations having high precipitation the annual peak in NDVI occurred later in all vegetation classes. The annual sum of biweekly NDVI was correlated with annual precipitation in all vegetation types, although the slopes and intercepts of the regressions differed among types. Annual grassland showed the largest increase in sumNDVI per unit increase in total precipitation and most of the variation in grassland sumNDVI was explained by variation in autumn precipitation. In general the ratio of sumNDVI to annual precipitation was dependent on the temporal distribution of precipitation with respect to the long-term average pattern. Published relationships between precipitation and NPP were used to develop equations relating annual NDVI sum to NPP.

  1. The Steady-State Serum Concentration of Genistein Aglycone Is Affected by Formulation: A Bioequivalence Study of Bone Products

    PubMed Central

    Bitto, Alessandra; Burnett, Bruce P.; Polito, Francesca; Russo, Silvia; D'Anna, Rosario; Pillai, Lakshmi; Squadrito, Francesco; Altavilla, Domenica; Levy, Robert M.

    2013-01-01

    An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μg molybdenum, 250 μg boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs. Total serum genistein, after β-glucuronidase/sulfatase digestion, was measured by time-resolved fluorometric assay. Maximal time (Tmax), concentration (Cmax), half-life (T1/2), and area under the curve (AUC) were determined for genistein in each formulation. Fosteum and the Squadrito study formulation were equivalent for genistein Tmax (2 hrs), Cmax (0.7 μM), T1/2 (18 ± 6.9 versus 21 ± 4.9 hrs), and AUC (9221 ± 413 versus 9818 ± 1370 ng·hr/mL). The OTC supplement's synthetically derived genistein, however, showed altered Tmax (6 hrs), Cmax (0.57 μM), T1/2 (8.3 ± 1.9 hrs), and AUC (6474 ± 287 ng·hr/mL). Differences in uptake may be due to multiple ingredients in the OTC supplement which interfere with genistein absorption. PMID:23484100

  2. Nitric oxide production by haemocytes from Mytilus galloprovincialis shows seasonal variations.

    PubMed

    Novas, Ana; Barcia, Ramiro; Ramos-Martínez, Juan Ignacio

    2007-10-01

    Nitric oxide (NO) has been identified as an important physiological modulator, with evidence of its role as a signalling molecule throughout the whole phylogenetic scale. In marine molluscs, it intervenes in processes related to the immune function of haemocytes. The presented results indicate that basal NO production by haemocytes of Mytilus galloprovincialis shows seasonal variations, with summer values statistically higher than those of winter. The presence of IL-2 increased NO production in winter. In summer, incubating the haemocytes with TNF-alpha for 6h slightly increased NO production. LPS, TGF-beta1 or PDGF did not induce significant effects on NO production by the haemocytes. Immunoblotting experiments detected two proteins that bind to vertebrate iNOS and eNOS antibodies, with different seasonal expression: the protein that binds to anti-iNOS antibody was expressed throughout the year, whereas the anti-eNOS antibody bound with a protein that was only detected in winter. IL-2 is suggested to start a signalling system dependent on the seasonal presence of winter protein. Such a system would activate the enzyme, thus favouring the higher NO production detected in winter. PMID:17574865

  3. Localizing the Holy Grail: Glacial/interglacial variations in atmospheric CO2 and oceanic deepwater production

    NASA Astrophysics Data System (ADS)

    Zeebe, R. E.

    2003-04-01

    The 'Holy Grail' of glacial/interglacial CO_2 research is to identify the major driver for variations in atmospheric CO_2 on this time scale. A simple mechanism has hitherto remained elusive. I use an entirely new approach to the problem, namely a global vertical advection-diffusion balance of tracers in the ocean which shows that the ocean's deepwater production (DWP) is the sought-after physical mechanism. The model adequately reproduces modern pCO_2 and vertical profiles of temperature, ΣCO_2, Alkalinity, PO_4, and O_2 in the ocean. Based on recently advanced compelling evidence for reduced glacial DWP, the model will then be shown to explain the glacial pCO_2 of 200~μatm. over a full glacial/interglacial transition (20~ky), model results excellently reproduce the observed temporal evolution of atmospheric CO_2 and deep ocean CaCO_3 saturation. The mechanism also explains the remarkable correlation between Antarctic temperature and CO_2 as recorded in ice cores. The ocean's deepwater production rate is hence identified as the dominant driver of glacial/interglacial CO_2 variations through its effect on the vertical distribution of heat and elements in the sea, initially set into motion in the Southern Hemisphere.

  4. Relative bioavailability of commercial ampicillin formulations in man

    PubMed Central

    Mayersohn, M.; Endrenyi, L.

    1973-01-01

    The relative bioavailability of three commercial ampicillin products was examined in 12 human subjects using a crossover experimental design. Based upon the areas under the ampicillin plasma concentration-time curves after the oral administration of 250 mg. ampicillin and using an analysis of variance technique no statistically significant differences were found between the products examined. These findings are in contrast to those of a recent report and appear to be explained by formulation differences. These relatively minor differences in formulation reflect the importance of formulation variables in providing efficient drug therapy. The intrasubject variation associated with several of these products is quite marked and is consistent with the incomplete and erratic absorption of this antibiotic in man. PMID:4758871

  5. The Challenge of Peat Substitution in Organic Seedling Production: Optimization of Growing Media Formulation through Mixture Design and Response Surface Analysis

    PubMed Central

    Ceglie, Francesco Giovanni; Bustamante, Maria Angeles; Ben Amara, Mouna; Tittarelli, Fabio

    2015-01-01

    Peat replacement is an increasing demand in containerized and transplant production, due to the environmental constraints associated to peat use. However, despite the wide information concerning the use of alternative materials as substrates, it is very complex to establish the best materials and mixtures. This work evaluates the use of mixture design and surface response methodology in a peat substitution experiment using two alternative materials (green compost and palm fibre trunk waste) for transplant production of tomato (Lycopersicon esculentum Mill.); melon, (Cucumis melo L.); and lettuce (Lactuca sativa L.) in organic farming conditions. In general, the substrates showed suitable properties for their use in seedling production, showing the best plant response the mixture of 20% green compost, 39% palm fibre and 31% peat. The mixture design and applied response surface methodology has shown to be an useful approach to optimize substrate formulations in peat substitution experiments to standardize plant responses. PMID:26070163

  6. FORMULATIONS OF BIOPESTICIDES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Formulation development is one of many steps required for commercialization of biological pesticides and holds the promise to bridge the gap between production of the active agent and use by consumers. A biological pesticide begins with discovery of an agent capable of controlling a pest. Active a...

  7. Quality by Design Approaches to Formulation Robustness-An Antibody Case Study.

    PubMed

    Wurth, Christine; Demeule, Barthelemy; Mahler, Hanns-Christian; Adler, Michael

    2016-05-01

    The International Conference on Harmonization Q8 (R2) includes a requirement that "Critical formulation attributes and process parameters are generally identified through an assessment of the extent to which their variation can impact the quality of the drug product," that is, the need to assess the robustness of a formulation. In this article, a quality-by-design-based definition of a "robust formulation" for a biopharmaceutical product is proposed and illustrated with a case study. A multivariate formulation robustness study was performed for a selected formulation of a monoclonal antibody to demonstrate acceptable quality at the target composition as well as at the edges of the allowable composition ranges and fulfillment of the end-of-shelf-life stability requirements of 36 months at the intended storage temperature (2°C-8°C). Extrapolation of 24 months' formulation robustness data to end of shelf life showed that the MAb formulation was robust within the claimed formulation composition ranges. Based on this case study, we propose that a formulation can be claimed as "robust" if all drug substance and drug product critical quality attributes remain within their respective end-of-shelf-life critical quality attribute-acceptance criteria throughout the entire claimed formulation composition range. PMID:27001536

  8. Concentrated protein body product derived from rice endosperm as an oral tolerogen for allergen-specific immunotherapy--a new mucosal vaccine formulation against Japanese cedar pollen allergy.

    PubMed

    Wakasa, Yuhya; Takagi, Hidenori; Watanabe, Nobumasa; Kitamura, Noriko; Fujiwara, Yoshihiro; Ogo, Yuko; Hayashi, Shimpei; Yang, Lijun; Ohta, Masaru; Thet Tin, Wai Wai; Sekikawa, Kenji; Takano, Makoto; Ozawa, Kenjirou; Hiroi, Takachika; Takaiwa, Fumio

    2015-01-01

    The endoplasmic reticulum-derived type-I protein body (PB-I) from rice endosperm cells is an ideal candidate formulation for the oral delivery of bioencapsulated peptides as tolerogens for allergen-specific immunotherapy. In the present study, PBs containing the deconstructed Japanese cedar pollen allergens Cryptomeria japonica 1 (Cry j 1) and Cry j 2 were concentrated by treatment with thermostable α-amylase at 90°C to remove the starch from milled rice powder, which resulted in a 12.5-fold reduction of dry weight compared to the starting material. The modified Cry j 1 and Cry j 2 antigens in this concentrated PB product were more resistant to enzymatic digestion than those in the milled seed powder despite the absence of intact cell wall and starch, and remained stable for at least 10 months at room temperature without detectable loss or degradation. The high resistance of these allergens could be attributed to changes in protein physicochemical properties induced by the high temperature concentration process, as suggested by the decreased solubility of the antigens and seed proteins in PBs in step-wise-extraction experiments. Confocal microscopy showed that the morphology of antigen-containing PB-Is was preserved in the concentrated PB product. The concentrated PB product induced specific immune tolerance against Cry j 1 and Cry j 2 in mice when orally administered, supporting its potential use as a novel oral tolerogen formulation. PMID:25774686

  9. Concentrated Protein Body Product Derived from Rice Endosperm as an Oral Tolerogen for Allergen-Specific Immunotherapy—A New Mucosal Vaccine Formulation against Japanese Cedar Pollen Allergy

    PubMed Central

    Wakasa, Yuhya; Takagi, Hidenori; Watanabe, Nobumasa; Kitamura, Noriko; Fujiwara, Yoshihiro; Ogo, Yuko; Hayashi, Shimpei; Yang, Lijun; Ohta, Masaru; Thet Tin, Wai Wai; Sekikawa, Kenji; Takano, Makoto; Ozawa, Kenjirou; Hiroi, Takachika; Takaiwa, Fumio

    2015-01-01

    The endoplasmic reticulum-derived type-I protein body (PB-I) from rice endosperm cells is an ideal candidate formulation for the oral delivery of bioencapsulated peptides as tolerogens for allergen-specific immunotherapy. In the present study, PBs containing the deconstructed Japanese cedar pollen allergens Cryptomeria japonica 1 (Cry j 1) and Cry j 2 were concentrated by treatment with thermostable α-amylase at 90°C to remove the starch from milled rice powder, which resulted in a 12.5-fold reduction of dry weight compared to the starting material. The modified Cry j 1 and Cry j 2 antigens in this concentrated PB product were more resistant to enzymatic digestion than those in the milled seed powder despite the absence of intact cell wall and starch, and remained stable for at least 10 months at room temperature without detectable loss or degradation. The high resistance of these allergens could be attributed to changes in protein physicochemical properties induced by the high temperature concentration process, as suggested by the decreased solubility of the antigens and seed proteins in PBs in step-wise-extraction experiments. Confocal microscopy showed that the morphology of antigen-containing PB-Is was preserved in the concentrated PB product. The concentrated PB product induced specific immune tolerance against Cry j 1 and Cry j 2 in mice when orally administered, supporting its potential use as a novel oral tolerogen formulation. PMID:25774686

  10. Variation Trend and Driving Factors of Greenhouse Gas Emissions from Chinese Magnesium Production.

    PubMed

    Gao, Feng; Liu, Yu; Nie, Zuo-Ren; Gong, Xianzheng; Wang, Zhihong

    2015-11-01

    As the largest magnesium producer in the world, China is facing a great challenge of greenhouse gas (GHG) emissions reduction. In this paper, the variation trend and driving factors of GHG emissions from Chinese magnesium production were evaluated and the measures of technology and policy for effectively mitigating GHG emissions were provided. First, the energy-related and process-oriented GHG inventory is compiled for magnesium production in China. Then, the driving forces for the changes of the energy-related emission were analyzed by the method of Logarithmic Mean Divisia Index (LMDI) decomposition. Results demonstrated that Chinese magnesium output from 2003 to 2013 increased by 125%, whereas GHG emissions only increased by 16%. The emissions caused by the fuels consumption decline most significantly (from 28.4 to 6.6 t CO2eq/t Mg) among all the emission sources. The energy intensity and the energy structure were the main offsetting factors for the increase of GHG emissions, while the scale of production and the international market demand were the main contributors for the total increase. Considering the improvement of technology application and more stringent policy measures, the annual GHG emissions from Chinese primary magnesium production will be controlled within 22 million tons by 2020. PMID:26458120

  11. The global pediatric antiretroviral market: analyses of product availability and utilization reveal challenges for development of pediatric formulations and HIV/AIDS treatment in children

    PubMed Central

    2010-01-01

    Background Important advances in the development and production of quality-certified pediatric antiretroviral (ARV) formulations have recently been made despite significant market disincentives for manufacturers. This progress resulted from lobbying and innovative interventions from HIV/AIDS activists, civil society organizations, and international organizations. Research on uptake and dispersion of these improved products across countries and international organizations has not been conducted but is needed to inform next steps towards improving child health. Methods We used information from the World Health Organization Prequalification Programme and the United States Food and Drug Administration to describe trends in quality-certification of pediatric formulations and used 7,989 donor-funded, pediatric ARV purchase transactions from 2002-2009 to measure uptake and dispersion of new pediatric ARV formulations across countries and programs. Prices for new pediatric ARV formulations were compared to alternative dosage forms. Results Fewer ARV options exist for HIV/AIDS treatment in children than adults. Before 2005, most pediatric ARVs were produced by innovator companies in single-component solid and liquid forms. Five 2-in1 and four 3-in-1 generic pediatric fixed-dose combinations (FDCs) in solid and dispersible forms have been quality-certified since 2005. Most (67%) of these were produced by one quality-certified manufacturer. Uptake of new pediatric FDCs outside of UNITAID is low. UNITAID accounted for 97-100% of 2008-2009 market volume. In total, 33 and 34 countries reported solid or dispersible FDC purchases in 2008 and 2009, respectively, but most purchases were made through UNITAID. Only three Global Fund country recipients reported purchase of these FDCs in 2008. Prices for pediatric FDCs were considerably lower than liquids but typically higher than half of an adult FDC. Conclusion Pediatric ARV markets are more fragile than adult markets. Ensuring a long

  12. Prediction of Seasonal Climate-induced Variations in Global Food Production

    NASA Technical Reports Server (NTRS)

    Iizumi, Toshichika; Sakuma, Hirofumi; Yokozawa, Masayuki; Luo, Jing-Jia; Challinor, Andrew J.; Brown, Molly E.; Sakurai, Gen; Yamagata, Toshio

    2013-01-01

    Consumers, including the poor in many countries, are increasingly dependent on food imports and are therefore exposed to variations in yields, production, and export prices in the major food-producing regions of the world. National governments and commercial entities are paying increased attention to the cropping forecasts of major food-exporting countries as well as to their own domestic food production. Given the increased volatility of food markets and the rising incidence of climatic extremes affecting food production, food price spikes may increase in prevalence in future years. Here we present a global assessment of the reliability of crop failure hindcasts for major crops at two lead times derived by linking ensemble seasonal climatic forecasts with statistical crop models. We assessed the reliability of hindcasts (i.e., retrospective forecasts for the past) of crop yield loss relative to the previous year for two lead times. Pre-season yield predictions employ climatic forecasts and have lead times of approximately 3 to 5 months for providing information regarding variations in yields for the coming cropping season. Within-season yield predictions use climatic forecasts with lead times of 1 to 3 months. Pre-season predictions can be of value to national governments and commercial concerns, complemented by subsequent updates from within-season predictions. The latter incorporate information on the most recent climatic data for the upcoming period of reproductive growth. In addition to such predictions, hindcasts using observations from satellites were performed to demonstrate the upper limit of the reliability of crop forecasting.

  13. Modifications ofAOAC Official Method 999.15 to improve the quantitation of vitamin K1 in complex formulated nutritional products.

    PubMed

    Delmonte, Pierluigi; Barrientos, Steven; Rader, Jeanne I

    2013-01-01

    Vitamin K1 (phylloquinone) occurs in foods in relatively low concentrations. It is synthesized for addition to formulated nutritional products (infant formulas, medical foods, and adult nutritional products). In recent years, nutritional products formulated with free amino acids and partially hydrolyzed proteins have been introduced in the market. Schimpf et al. demonstrated that the current AOAC Official Method 999.15 for determination of vitamin K in milk and infant formula is not adequate to quantitatively extract vitamin K1 from such products. We developed a modification of AOAC 999.15 for the analysis of vitamin K1 in these products that provides quantitative extraction by increasing the sample size, volume of extraction solvents, time of liquid/liquid partitioning, and order of the addition of solvents. This modified procedure showed extraction efficiency comparable to that of the original AOAC 999.15 procedure for analyzing infant formula matrixes and to the modified procedure of Schimpf et al. for the analysis of samples containing limited amounts of free amino acids andlor partially hydrolyzed proteins. Extraction efficiency increased more than 10% using the modified extraction procedure for samples containing higher amounts of these components. The chromatographic separation was improved by using a Dionex Acclaim triacontanol-bonded C30 column (250 x 3.0 mm id, 3 pm particle size) maintained at 15 degrees C, with acetonitrile-methanol (50 + 50, v/v) mobile phase at a flow rate of 0.5 mL/min, which provided baseline separation of the cis and trans isomers of vitamin K1 from each other and from other compounds contained in the sample extracts. PMID:23513963

  14. [Variation trends of natural vegetation net primary productivity in China under climate change scenario].

    PubMed

    Zhao, Dong-sheng; Wu, Shao-hong; Yin, Yun-he

    2011-04-01

    Based on the widely used Lund-Potsdam-Jena Dynamic Global Vegetation Model (LPJ) for climate change study, and according to the features of natural environment in China, the operation mechanism of the model was adjusted, and the parameters were modified. With the modified LPJ model and taking 1961-1990 as baseline period, the responses of natural vegetation net primary productivity (NPP) in China to climate change in 1991-2080 were simulated under the Special Report on Emissions Scenarios (SRES) B2 scenario. In 1961-1990, the total NPP of natural vegetation in China was about 3.06 Pg C a(-1); in 1961-2080, the total NPP showed a fluctuant decreasing trend, with an accelerated decreasing rate. Under the condition of slight precipitation change, the increase of mean air temperature would have definite adverse impact on the NPP. Spatially, the NPP decreased from southeast coast to northwest inland, and this pattern would have less variation under climate change. In eastern China with higher NPP, especially in Northeast China, east of North China, and Loess Plateau, the NPP would mainly have a decreasing trend; while in western China with lower NPP, especially in the Tibetan Plateau and Tarim Basin, the NPP would be increased. With the intensive climate change, such a variation trend of NPP would be more obvious. PMID:21774310

  15. Relevance of variation in use of terminology to define generic pharmaceutical products.

    PubMed

    Fonseca, Elize Massard da

    2015-02-01

    The World Health Organization (WHO) promotes the use of generic drug policies to foster competition in the pharmaceutical sector, reduce drug prices, and increase access to therapeutic drugs. However, little is known about how countries implement these policies. This article describes different terminology adopted by national regulatory authorities to define generic versus proprietary drug products in developing countries, including those in Latin America, and challenges that arise in their application of WHO guidelines, such as labeling issues. The author concludes that variation in generics terminology in these countries is a result of institutional context (i.e., the public sector setting as well as the body of laws and regulations that exists in the country) and policy legacies, such as intellectual property regimes, and highlights the need for further analysis of pharmaceutical regulations to improve understanding of the barriers and political implications of generic drug policies. PMID:25915016

  16. [Investigation of variation of the production of biological and chemical compounds of Hyssopus officinalis L].

    PubMed

    Varga, E; Hajdú, Z; Veres, K; Máthé, I; Németh, E; Pluhár, Z; Bernáth, J

    1998-05-01

    Hyssopus officinalis L. (Lamiaceae family) has been cultivated in Central Europe for a long time. This essential oil containing species serves not only as spice but in many countries including Hungary, it is used as a folk medicine against certain respiratory diseases. Despite this fact, little is known about the variation of its productivity under Central European climatic conditions. The cultivated populations of hyssop can be characterised by a significant heterogenity. In the course of its breeding the uniformity of flower colour (e.g. blue form), and increase in the oil content are the main achievable purposes. The purpose of this work was to investigate both the variability of strains of different crigin and the time-dependent variations of its production parameters. The optimum of phytomass was obtained at the beginning of July. The essential oil content as well as compounds of the non volatile fractions were also investigated. The non volatile fractions for rosmarinic, caffeic acids were analysed mainly by TLC and densitometry. Both compounds were present in all samples and they are suitable for the characterisation of the plant. The essential oils were gained with Water Steam Distillation (WSD) and Supercritical Fluid Extraction (SFE) with CO2. The oils were analysed by GC, GC-MS techniques. In the essential oil composition of the populations studied significant heterogenity could be observed. In the case of applying SFE extraction the oil composition is more uniform, similarly to the obtained by WSD adding hexane. The heterogenity can be experienced in the offsprings, too. If only the main four components (beta-pinene, limonene, pinocamphone, isopinocamphone) are regarded, among the offsprings clear and mixed lines alike can be found. Results of these experiments justify the necessity and usefulness of selection which is going on. PMID:9703705

  17. Recent developments on new formulations based on nutrient-dense ingredients for the production of healthy-functional bread: a review.

    PubMed

    Rahaie, Somayeh; Gharibzahedi, Seyed Mohammad Taghi; Razavi, Seyed Hadi; Jafari, Seid Mahdi

    2014-11-01

    Bread is one of the oldest functional foods which its health effects have been investigated in many studies. The current communication presents a review of published studies in recent years on the topic and looks at possible future trends in the improved nutritional and health qualities which have been applied in the bakery industry, directing it further to the formulation design and production of functional breads. The results show that many beneficial ingredients such as dietary fibers, phenolic antioxidants, marine ingredients, and n-3 fatty acids can be used in the bread industry to increase its functionality and result in healthy products, low in calories, cholesterol and celiac disease. Moreover, the use of psyllium seed, amaranth seed, chestnut flour and prebiotics in gluten-free bread (GFB) baking may be the promising frontier to improve overall appearance, quality, sensory properties, and shelf-life of GFB. PMID:26396285

  18. Critical processing parameters of carbon dioxide spray drying for the production of dried protein formulations: A study with myoglobin.

    PubMed

    Nuchuchua, O; Every, H A; Jiskoot, W

    2016-06-01

    The aim of this study was to gain fundamental insight into protein destabilization induced by supercritical CO2 spray drying processing parameters. Myoglobin was used as a model protein (5mg/ml with 50mg/ml trehalose in 10mM phosphate buffer, pH 6.2). The solution was exposed to sub- and supercritical CO2 conditions (65-130bar and 25-50°C), and CO2 spray drying under those conditions. The heme binding of myoglobin was determined by UV/Vis, fluorescence, and circular dichroism spectroscopy, while myoglobin aggregation was studied by using size-exclusion chromatography and flow imaging microscopy. It was found that pressure and temperature alone did not influence myoglobin's integrity. However, when pressurized CO2 was introduced into myoglobin solutions at any condition, the pH of the myoglobin formulation shifted to about 5 (measured after depressurization), resulting in heme binding destabilization and aggregation of myoglobin. When exposed to CO2, these degradation processes were enhanced by increasing temperature. Heme binding destabilization and myoglobin aggregation were also seen after CO2 spray drying, and to a greater extent. Moreover, the CO2 spray drying induced the partial loss of heme. In conclusion, pressurized CO2 destabilizes the myoglobin, leading to heme loss and protein aggregation upon spray drying. PMID:27080205

  19. Selected physical and chemical properties of Feverfew (Tanacetum parthenium) extracts important for formulated product quality and performance.

    PubMed

    Jin, Ping; Madieh, Shadi; Augsburger, Larry L

    2008-01-01

    The objectives of this research are: (1) to assess selected formulation-relevant physical properties of several commercial Feverfew extracts, including flowability, hygroscopicity, compressibility and compactibility (2) to develop and validate a suitable extraction method and HPLC assay, and (3) to determine the parthenolide content of several commercial Feverfew extracts. Carr's index, minimum orifice diameter and particle-particle interaction were used to evaluate powder flowability. Hygroscopicity was evaluated by determining the equilibrium moisture content (EMC) after storage at various % relative humidities. Heckle analysis and compression pressure-radial tensile strength relationship were used to represent compression and compaction properties of feverfew extracts. An adapted analytical method was developed based on literature methods and then validated for the determination of parthenolide in feverfew. The commercial extracts tested exhibited poor to very poor flowability. The comparatively low mean yield pressure suggested that feverfew extracts deformed mainly plastically. Hygroscopicity and compactibility varied greatly with source. No commercial feverfew extracts tested contained the label claimed parthenolide. Even different batches from the same manufacturer showed significantly different parthenolide content. Therefore, extract manufactures should commit to proper quality control procedures that ensure accurate label claims, and supplement manufacturers should take into account possible differences in physico-chemical properties when using extracts from multiple suppliers. PMID:18446457

  20. Seasonal Variations in Alkenone Concentration and Production in the Oligotrophic North Pacific

    NASA Astrophysics Data System (ADS)

    Popp, B.; Prahl, F.; Sparrow, M.; Rust, T.

    2003-04-01

    Since its introduction in 1986, the alkenone unsaturation index (UK37) has been used extensively by the paleoceanographic community to determine variations in past sea-surface temperature (SST). Despite this widespread use, however, surprisingly little is yet known about where and when the UK37 signal exported to sediments is produced in the euphotic zone. Independent lines of empirical evidence suggest subsurface production within the euphotic zone to be an important source of alkenone export in subtropical regions of the Pacific and perhaps other oligotrophic parts of the world ocean. In the present study, we examined evidence for subsurface alkenone production in the oligotrophic subtropical North Pacific gyre at the Hawaii Ocean Time-series station ALOHA (22o 45N, 158oW) in three different seasons. Highest alkenone production rates, as determined by uptake of 13C-labeled inorganic carbon into alkenones during 24-hour in situ incubations, and highest alkenone standing stocks were found within (Spring, Fall) or just below (Summer) the surface mixed layer. Lowest alkenone standing stocks and lowest production rates were found within the deep chlorophyll maximum (DCM). Measured UK37 values were converted into growth temperature (gT) estimates using a culture-based calibration equation (UK37 = 0.034 T + 0.039; Prahl et al., 1988) and compared with water temperatures actually measured by CTD at the depth of sample collection. In most cases, alkenone gT under-estimated actual water temperature by 2-3oC when alkenone production rates were high and over-estimated actual water temperature by 3-4oC when production rates were low. These results suggest a non-thermal, physiological control on alkenone unsaturation and indicate that light-limited alkenone production at the DCM in the oligotrophic North Pacific is quantitatively unimportant. The physiological mechanisms responsible for these observations and the implication of these results for improved confidence in UK37

  1. Pervasive multidecadal variations in productivity within the Peruvian Upwelling System over the last millennium

    NASA Astrophysics Data System (ADS)

    Fleury, S.; Martinez, P.; Crosta, X.; Charlier, K.; Billy, I.; Hanquiez, V.; Blanz, T.; Schneider, R. R.

    2015-10-01

    There is no agreement on the pluri-decadal expression of El Niño-Southern Oscillation (ENSO) in the Pacific over the last millennium. Marine records from the Peruvian margin indicate humid conditions (El Niño-like mean conditions) over the Little Ice Age, while precipitation records from the eastern equatorial Pacific infer arid conditions (La Niña-like mean conditions) for the same period. We here studied diatom assemblages, nitrogen isotopes, and major and minor elements at the lamination level in three laminated trigger cores located between 11°S and 15°S on the Peruvian shelf within the oxygen minimum zone (OMZ) to reconstruct precipitation and ocean productivity at the multiannual to multidecadal timescales over the last millennium. We respected the sediment structure, thus providing the first records of the mean climatic conditions at the origin of the lamination deposition, which ones represent several years. Light laminations were deposited under productive and dry conditions, indicative of La Niña-like mean conditions in the system, while dark laminations were deposited under non-productive and humid conditions, representative of El Niño-like mean conditions. La Niña-like mean conditions were predominant during the Medieval Warm Period (MWP; 1000-600 years BP) and Current Warm Period (CWP; 150 years BP to present), while El Niño-like mean conditions prevailed over the Little Ice Age (LIA; 600-150 years BP). We provide evidence for persistent multidecadal variations in productivity over the last millennium, which were disconnected from the mean climate state. Multidecadal variability has been stronger over the last 450 years concomitantly to increased variability in the NAO index. Two intervals of strong multidecadal variability were also observed over the MWP, congruent to decreased solar irradiance and increased volcanic activity.

  2. Variations of Carbon Isotopes during Shale Gas Production from the Horn River Basin, British Columbia, Canada

    NASA Astrophysics Data System (ADS)

    Norville, G.; Muehlenbachs, K.

    2014-12-01

    Chemical and stable isotope compositions of natural gases are key parameters for characterizing gas and hydrocarbon reservoirs. Produced gases were obtained from eight wells at multi-well pad sites located in the Horn River Basin (HRB), NE British Columbia. Shale gas wells were drilled and completed in the Devonian Muskwa, Otter Park and Evie Formations of the HRB, and gases collected as time series over short term (~50 days) and long term periods (~ 1250 days). δ13C of gases from HRB formations confirm high thermal maturity and the shale gases frequently showed partial or full isotope reversals among hydrocarbon components. A 10‰ variation in δ13C values of methane was observed during production. In general, during early phases of production shale gases appear enriched in 12C compared to gases sampled at later stages and δ13Cmethane values were approximately between -38‰ and -35‰ during times up to 50 days. The majority of cases of carbon isotope reversals between methane and ethane components of gases (δ13Cmethane > δ13Cethane) were observed at times greater than 100 days, while ethane and propane reversals were common throughout production. Gas production rates differed significantly among the sampled wells from ~ 50 to 400 e3m3/d. Higher rates were frequently associated with gases showing 12Cmethane enrichment. Subsequent to periods of well 'shut in' a change in the carbon isotope composition was detected with enrichment in 13Cmethane of gases. Carbon isotope signatures of produced gases likely reflect a combination of both the in-situ shale gas isotope signature as well as effects of isotope fractionation which may occur during transport through pores and fractures of the shale.

  3. Plutonium Immobilization Project Baseline Formulation

    SciTech Connect

    Ebbinghaus, B.

    1999-02-01

    A key milestone for the Immobilization Project (AOP Milestone 3.2a) in Fiscal Year 1998 (FY98) is the definition of the baseline composition or formulation for the plutonium ceramic form. The baseline formulation for the plutonium ceramic product must be finalized before the repository- and plant-related process specifications can be determined. The baseline formulation that is currently specified is given in Table 1.1. In addition to the baseline formulation specification, this report provides specifications for two alternative formulations, related compositional specifications (e.g., precursor compositions and mixing recipes), and other preliminary form and process specifications that are linked to the baseline formulation. The preliminary specifications, when finalized, are not expected to vary tremendously from the preliminary values given.

  4. Variation in the link between oxygen consumption and ATP production, and its relevance for animal performance.

    PubMed

    Salin, Karine; Auer, Sonya K; Rey, Benjamin; Selman, Colin; Metcalfe, Neil B

    2015-08-01

    It is often assumed that an animal's metabolic rate can be estimated through measuring the whole-organism oxygen consumption rate. However, oxygen consumption alone is unlikely to be a sufficient marker of energy metabolism in many situations. This is due to the inherent variability in the link between oxidation and phosphorylation; that is, the amount of adenosine triphosphate (ATP) generated per molecule of oxygen consumed by mitochondria (P/O ratio). In this article, we describe how the P/O ratio can vary within and among individuals, and in response to a number of environmental parameters, including diet and temperature. As the P/O ratio affects the efficiency of cellular energy production, its variability may have significant consequences for animal performance, such as growth rate and reproductive output. We explore the adaptive significance of such variability and hypothesize that while a reduction in the P/O ratio is energetically costly, it may be associated with advantages in terms of somatic maintenance through reduced production of reactive oxygen species. Finally, we discuss how considering variation in mitochondrial efficiency, together with whole-organism oxygen consumption, can permit a better understanding of the relationship between energy metabolism and life history for studies in evolutionary ecology. PMID:26203001

  5. Variation in the link between oxygen consumption and ATP production, and its relevance for animal performance

    PubMed Central

    Salin, Karine; Auer, Sonya K.; Rey, Benjamin; Selman, Colin; Metcalfe, Neil B.

    2015-01-01

    It is often assumed that an animal's metabolic rate can be estimated through measuring the whole-organism oxygen consumption rate. However, oxygen consumption alone is unlikely to be a sufficient marker of energy metabolism in many situations. This is due to the inherent variability in the link between oxidation and phosphorylation; that is, the amount of adenosine triphosphate (ATP) generated per molecule of oxygen consumed by mitochondria (P/O ratio). In this article, we describe how the P/O ratio can vary within and among individuals, and in response to a number of environmental parameters, including diet and temperature. As the P/O ratio affects the efficiency of cellular energy production, its variability may have significant consequences for animal performance, such as growth rate and reproductive output. We explore the adaptive significance of such variability and hypothesize that while a reduction in the P/O ratio is energetically costly, it may be associated with advantages in terms of somatic maintenance through reduced production of reactive oxygen species. Finally, we discuss how considering variation in mitochondrial efficiency, together with whole-organism oxygen consumption, can permit a better understanding of the relationship between energy metabolism and life history for studies in evolutionary ecology. PMID:26203001

  6. Genotypic variation and slime production among blood and catheter isolates of Candida parapsilosis.

    PubMed

    Branchini, M L; Pfaller, M A; Rhine-Chalberg, J; Frempong, T; Isenberg, H D

    1994-02-01

    Candida parapsilosis is an important nosocomial pathogen that can proliferate in high concentrations of glucose and form biofilms on prosthetic materials. We investigated the genotypic diversity and slime production among 31 isolates of C. parapsilosis from individual patients with bloodstream or catheter infections. DNA subtyping was performed by using electrophoretic karyotyping plus restriction endonuclease analysis with BssHII followed by pulsed-field gel electrophoresis. Slime production was evaluated by growing organisms in Sabouraud broth with 8% glucose and examining the walls of the tubes for the presence of an adherent slime layer. Overall there were 14 DNA subtypes among the 31 isolates. Eighty percent of the isolates produced slime; 67% of the isolates were moderately to strongly positive, 13% were weakly positive, and 20% were not slime producers. The ability of isolates of a given DNA type to produce slime under these conditions was variable. The results of these studies indicate moderate genotypic variation among clinical isolates of C. parapsilosis. The propensity of these isolates to form slime in glucose-containing solutions suggests that this phenotypic characteristic may contribute to the ability of C. parapsilosis to adhere to plastic catheters and cause infections. PMID:8150956

  7. DNA-based methodologies for the quantification of live and dead cells in formulated biocontrol products based on Pantoea agglomerans CPA-2.

    PubMed

    Soto-Muñoz, Lourdes; Torres, Rosario; Usall, Josep; Viñas, Inmaculada; Solsona, Cristina; Teixidó, Neus

    2015-10-01

    Pantoea agglomerans strain CPA-2 is an effective biocontrol agent (BCA) against the major postharvest pathogens present on pome and citrus fruits. Dehydration, such as freeze-drying, spray-drying and fluidized bed drying is one of the best ways to formulate BCAs. In this work, the survival of CPA-2 cells after formulation was determined by dilution plating and molecular methods as qPCR alone and combined with a sample pretreatment with a propidium monoazide dye (PMA-qPCR) and they were used to calculate treatment concentrations in efficacy trials on postharvest oranges. Furthermore, no significant differences in CPA-2 survival were observed as determined by dilution plating and PMA-qPCR after both the freeze drying and fluidized bed drying processes; however, an interesting significant difference was observed in the spray dried product comparing all quantitative methods. A difference of 0.48 and 2.17 log10 CFU or cells g/dw was observed among PMA-qPCR with qPCR and dilution plating, respectively. According to our study, dilution plating was shown to be an unreliable tool for monitoring the survival of CPA-2 after spray drying. In contrast, the combination of PMA and qPCR enabled a quick and unequivocal methodology to enumerate viable and VBNC CPA-2 cells under stress-dried conditions. Efficacy trials showed that, after 3 days, spray drying formulation rehydrated with 10% non-fat skimmed milk (NFSM) was as effective as fresh cells to control Penicillium digitatum in oranges. PMID:26114590

  8. Marginal Lands Gross Primary Production Dominate Atmospheric CO2 Interannual Variations

    NASA Astrophysics Data System (ADS)

    Ahlström, A.; Raupach, M. R.; Schurgers, G.; Arneth, A.; Jung, M.; Reichstein, M.; Smith, B.

    2014-12-01

    Since the 1960s terrestrial ecosystems have acted as a substantial sink for atmospheric CO2, sequestering about one quarter of anthropogenic emissions in an average year. Variations in this land carbon sink are also responsible for most of the large interannual variability in atmospheric CO2 concentrations. While most evidence places the majority of the sink in highly productive forests and at high latitudes experiencing warmer and longer growing seasons, the location and the processes governing the interannual variations are still not well characterised. Here we evaluate the hypothesis that the long-term trend and the variability in the land CO2 sink are respectively dominated by geographically distinct regions: the sink by highly productive lands, mainly forests, and the variability by semi-arid or "marginal" lands where vegetation activity is strongly limited by water and therefore responds strongly to climate variability. Using novel analysis methods and data from both upscaled flux-tower measurements and a dynamic global vegetation model, we show that (1) the interannual variability in the terrestrial CO2 sink arises mainly from variability in terrestrial gross primary production (GPP); (2) most of the interannual variability in GPP arises in tropical and subtropical marginal lands, where negative anomalies are driven mainly by warm, dry conditions and positive anomalies by cool, wet conditions; (3) the variability in the GPP of high-latitude marginal lands (tundra and shrublands) is instead controlled by temperature and light, with warm bright conditions resulting in positive anomalies. The influence of ENSO (El Niño-Southern Oscillation) on the growth rate of atmospheric CO2 concentrations is mediated primarily through climatic effects on GPP in marginal lands, with opposite signs in subtropical and higher-latitude regions. Our results show that the land sink of CO2 (dominated by forests) and its interannual variability (dominated by marginal lands) are

  9. An integrated process analytical technology (PAT) approach to monitoring the effect of supercooling on lyophilization product and process parameters of model monoclonal antibody formulations.

    PubMed

    Awotwe-Otoo, David; Agarabi, Cyrus; Khan, Mansoor A

    2014-07-01

    The aim of the present study was to apply an integrated process analytical technology (PAT) approach to control and monitor the effect of the degree of supercooling on critical process and product parameters of a lyophilization cycle. Two concentrations of a mAb formulation were used as models for lyophilization. ControLyo™ technology was applied to control the onset of ice nucleation, whereas tunable diode laser absorption spectroscopy (TDLAS) was utilized as a noninvasive tool for the inline monitoring of the water vapor concentration and vapor flow velocity in the spool during primary drying. The instantaneous measurements were then used to determine the effect of the degree of supercooling on critical process and product parameters. Controlled nucleation resulted in uniform nucleation at lower degrees of supercooling for both formulations, higher sublimation rates, lower mass transfer resistance, lower product temperatures at the sublimation interface, and shorter primary drying times compared with the conventional shelf-ramped freezing. Controlled nucleation also resulted in lyophilized cakes with more elegant and porous structure with no visible collapse or shrinkage, lower specific surface area, and shorter reconstitution times compared with the uncontrolled nucleation. Uncontrolled nucleation however resulted in lyophilized cakes with relatively lower residual moisture contents compared with controlled nucleation. TDLAS proved to be an efficient tool to determine the endpoint of primary drying. There was good agreement between data obtained from TDLAS-based measurements and SMART™ technology. ControLyo™ technology and TDLAS showed great potential as PAT tools to achieve enhanced process monitoring and control during lyophilization cycles. PMID:24840395

  10. Temporal variation of thoron decay product concentration in the atmosphere and comparison with radon decay product concentration.

    PubMed

    Winkler, R; Aehlig, K

    1998-04-01

    Seasonal and long-term variation of the airborne 212Pb concentration, representative of the equilibrium equivalent concentration of thoron decay products (EECRn220), was investigated from 1989 through 1996 at a semi-natural location in southern Germany. Continuous measurement yielded a long-term average concentration of 0.082 Bq m-3, while daily mean concentrations varied from < or = 0.01 to 0.34 Bq m-3. An average annual effective dose of 1.4 mSv due to outdoor thoron progeny concentration was estimated. This is about 2% of the dose due to the average short-lived radon progeny concentration (EECRn222) of 8.4 Bq m-3 measured for this location in the same period. In most years the seasonal pattern of 212Pb activity concentration in the atmosphere is characterized by two maxima: the first in May and the second one in September. Low concentrations are observed from November through February of each year. This is in contrast to the behaviour of the short-lived 222Rn progeny which exhibit enhanced concentrations exactly during these months. The most probable reason for the different temporal behaviour of 212Pb is the extremely reduced flux of thoron gas from the ground during the winter months. PMID:9615341

  11. Determination of Degradation Products of Cyclobenzaprine Hydrochloride, Lidocaine and Piroxicam in a Semi-Topical Formulation: MS-MS Confirmation of Unknown Impurities.

    PubMed

    Cioroiu, Bogdan Ionel; Grigoriu, Ioana Cezara; Cioroiu, Mona Elisabeta; Niculaua, Marius; Lupuleasa, Roxana; Lazar, Mihai Ioan

    2016-07-01

    Association of cyclobenzaprine hydrochloride, piroxicam and lidocaine in a topical formulation is one of the newest innovations in the pharmaceutical formulary field. In this study, a reversed-phase liquid chromatographic method was developed for the establishment of the impurities of cyclobenzaprine hydrochloride, lidocaine and piroxicam in the semisolid topical formulation. In this study, we not only determined 2,6-dimethylaniline, 2-pyrydilamine but also specified impurities of cyclobenzaprine hydrochloride (dibenzosuberenone, amitriptyline, carbinole, cyclobenzaprine N-oxide and anthrachinone). The target compounds were determined using a mobile phase that consisted of a mixture of phosphate buffer (0.025 M; pH 6.2)-acetonitrile-methanol (60 : 13 : 27, v/v/v). A minimum of three supplementary possible degradation products were determined. Using mass spectrometry, the unspecified impurities were identified and the use of correlation matrices permitted the association with the possible source compounds. The chromatographic conditions were qualified and validated according to ICH guideline requirements to confirm specificity, linearity, accuracy and precision. PMID:27056018

  12. Usnea barbata CO2-supercritical extract in alkyl polyglucoside-based emulsion system: contribution of Confocal Raman imaging to the formulation development of a natural product.

    PubMed

    Zugic, Ana; Lunter, Dominique Jasmin; Daniels, Rolf; Pantelic, Ivana; Tasic Kostov, Marija; Tadic, Vanja; Misic, Dusan; Arsic, Ivana; Savic, Snezana

    2016-08-01

    Topical treatment of skin infections is often limited by drawbacks related to both antimicrobial agents and their vehicles. In addition, considering the growing promotion of natural therapeutic products, our objective was to develop and evaluate naturally-based emulsion system, as prospective topical formulation for skin infections-treatment. Therefore, alkyl polyglucoside surfactants were used for stabilization of a vehicle serving as potential carrier for supercritical CO2-extract of Usnea barbata, lichen with well-documented antimicrobial activity, incorporated using two protocols and three concentrations. Comprehensive physicochemical characterization suggested possible involvement of extract's particles in stabilization of the investigated system. Raman spectral imaging served as the key method in disclosing extract's particles potential to participate in the microstructure of the tested emulsion system via three mechanisms: (1) particle-particle aggregation, (2) adsorption at the oil-water interface and (3) hydrophobic particle-surfactant interactions. Stated extract-vehicle interaction proved to be correlated to the preparation procedure and extract concentration on one hand and to affect the physicochemical and biopharmaceutical features of investigated system, on the other hand. Thereafter, formulation with the best preliminary stability and liberation profile was selected for further efficiency and in vivo skin irritation potential evaluation, implying pertinent in vitro antimicrobial activity against G+ bacteria and overall satisfying preliminary safety profile. PMID:26135231

  13. Analysis of cell line variation in biochemical production of protoporphyrin IX

    NASA Astrophysics Data System (ADS)

    Gibbs, Summer L.; Chen, Bin; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

    2006-02-01

    Protoporphyrin IX (PpIX) is produced via the heme synthesis pathway by the cell following administration of aminolevulinic acid (ALA). ALA synthase, the enzyme that produces ALA in the cell from glycine and succinyl-coenzyme A, is inhibited in a feedback mechanism by heme and thus is the rate limiting enzyme in the heme synthesis pathway. Since ALA is administered systemically, the rate limiting step that naturally exists in the cells is bypassed, however it is currently unclear why cells have different rate limiting steps in the ALA-PpIX synthesis pathway, and more specifically which types of cancer cells are most productive. It has been determined that when the same amount of ALA is administered to a wide panel of cancer cells in vitro that vastly differing amounts of PpIX are produced. The steps for the ALA-PpIX pathway occur in and around the mitochondria of the cell, but interestingly no correlation is seen between PpIX production and mitochondrial content of the cell, following ALA administration. However, total cell area shows positive correlation with PpIX production. Administration of the iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) in combination with ALA allows the final step in the heme synthesis pathway, conversion of PpIX to heme, to be delayed and thus increases the detectable amount of PpIX in each cell line. The cell lines that have the lowest PpIX production following administration of ALA alone show the largest increase in production following the combined administration of ALA and L1. PpIX fluorescence is thought to be a measure of cellular activity and the goal of the current study was to determine which cell lines would be the most promising targets for fluorescence detection or monitoring response to therapy. The results indicate that the cells with larger size and larger numbers of mitochondria may be good potential targets for this therapy. While this conclusion may appear obvious, it is not universally true, and cellular specific

  14. Late Pleistocene temperature and productivity variations in the Benguela Current System (ODP Leg 175, Site 1082)

    NASA Astrophysics Data System (ADS)

    Wenzel, C.; Rullkötter, J.

    2003-04-01

    Site 1082 (Walvis Basin) is located close to the major upwelling cells along the Southwest African coast with a year-round upwelling activity. Sediment samples spanning the last 770 kyr were investigated to reconstruct the paleoclimatic and paleoceanographic conditions in the Benguela upwelling system off Namibia. Alkenone-derived paleo-sea surface temperatures (calculated from the Uk'37index) roughly follow the 18O variations of planktonic foraminifera. The core shows warmer SST values (18-20°C) during interglacial stages and colder SST values (14-16°C) during glacial stages. Two long-term trends were observed: a decrease in SST values by 1°C from 770 kyr to 450 kyr and an increase in SST values by 2°C for the last 450 kyr. SST values in the northern Benguela System confirm the onset of the dominant 100 ka cycles associated with Northern Hemisphere glaciation over the past 650 kyr. One important result is the observed warming trend in the Benguela Current region over the last 450 kyr. In this period, the trend to warmer sea surface temperatures is more evident during glacials, suggesting a southward migration of the polar and subpolar frontal systems and an intensification of the influence of the warm Agulhas Current on the Benguela Current System during glacial stages 10, 8, 6 and 4. Another possible mechanism that could be responsible for such a warming trend of the eastern South Atlantic is a weakening of the cross-equatorial heat transport from the South to the North Atlantic as a result of a weakening of the thermohaline circulation. The accumulation profile of the alkenones indicates an elevated marine surface productivity may have fluctuated over time due to the upwelling activity in the southeastern Atlantic Ocean. The fluctuations in marine productivity are not related to the glacial-interglacial cycles which exhibit increased productivity during glacials at other locations. The marine biomarker distributions indicate that periods of higher

  15. Efficient lipase catalysed production of a lubricant and surfactant formulation using a continuous solvent-free process.

    PubMed

    Dossat, Valérie; Combes, Didier; Marty, Alain

    2002-08-01

    The transesterification of sunflower oil with a high oleic acid residue content (typically 83.5%) with butanol-1 by immobilised Lipozyme was carried out in a solvent free system and in a continuous way. During the first 6 h of reactor operation, a transition phase was observed, in which the main products were butyl ester and glycerol. This latter being insoluble in the reaction mixture, it is adsorbed onto the enzyme support thus leading to a decrease in enzyme performance. Step by step, less and less glycerol is produced and finally when glycerol is no longer produced a steady state is attained. The product composition is a mixture of butyl ester (65 molar%), monoglyceride (26 molar%), diglyceride (6 molar%) and residual triglyceride (3 molar%). This mixture has interesting lubricant and surfactant properties. The reactor was maintained without any loss in activity for a period of 3 months. This result is very different to that obtained using an organic solvent (n-hexane) which leads to a total loss of enzyme activity within a few hours. PMID:12067518

  16. Odour characteristics of seafood flavour formulations produced with fish by-products incorporating EPA, DHA and fish oil.

    PubMed

    Peinado, I; Miles, W; Koutsidis, G

    2016-12-01

    Thermal degradation of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids was investigated. As a novelty, EPA, DHA or fish oil (FO) were incorporated as ω-fatty acid sources into model systems containing fish powder produced via Maillard reactions. Aroma composition of the resulting products was determined and complemented with sensory evaluation. Heating of the oils led to a fast decrease of both, EPA and DHA, and to the development of characteristic volatile compounds including hexanal, 2,4-heptadienal and 4-heptenal, the most abundant being (E,E)-2,4-heptadienal (132±44-329±122μmol/g). EPA and DHA addition to the model systems increased the concentration of these characteristic volatile compounds. However, it did not have a considerable impact on the development of characteristic Maillard reaction products, such as pyrazines and some aldehydes. Finally, the results of the sensory evaluation illustrated that panellists would chose samples fortified with FO as the ones with a more pleasant aroma. PMID:27374575

  17. Factors driving spatial and temporal variation in production and production/biomass ratio of stream-resident brown trout (Salmo trutta) in Cantabrian streams

    USGS Publications Warehouse

    Lobon-Cervia, J.; Gonzalez, G.; Budy, P.

    2011-01-01

    1.The objective was to identify the factors driving spatial and temporal variation in annual production (PA) and turnover (production/biomass) ratio (P/BA) of resident brown trout Salmo trutta in tributaries of the Rio Esva (Cantabrian Mountains, Asturias, north-western Spain). We examined annual production (total production of all age-classes over a year) (PA) and turnover (P/BA) ratios, in relation to year-class production (production over the entire life time of a year-class) (PT) and turnover (P/BT) ratio, over 14years at a total of 12 sites along the length of four contrasting tributaries. In addition, we explored whether the importance of recruitment and site depth for spatial and temporal variations in year-class production (PT), elucidated in previous studies, extends to annual production. 2.Large spatial (among sites) and temporal (among years) variation in annual production (range 1.9-40.3gm-2 per year) and P/BA ratio (range 0.76-2.4per year) typified these populations, values reported here including all the variation reported globally for salmonids streams inhabited by one or several species. 3.Despite substantial differences among streams and sites in all production attributes, when all data were pooled, annual (PA) and year-class production (PT) and annual (P/BA) and year-class P/BT ratios were tightly linked. Annual (PA) and year-class production (PT) were similar but not identical, i.e. PT=0.94 PA, whereas the P/BT ratios were 4+P/BA ratios. 4.Recruitment (Rc) and mean annual density (NA) were major density-dependent drivers of production and their relationships were described by simple mathematical models. While year-class production (PT) was determined (R2=70.1%) by recruitment (Rc), annual production (PA) was determined (R2=60.3%) by mean annual density (NA). In turn, variation in recruitment explained R2=55.2% of variation in year-class P/BT ratios, the latter attaining an asymptote at P/BT=6 at progressively higher levels of recruitment

  18. Phenotypic variation of Staphylococcus epidermidis slime production in vitro and in vivo.

    PubMed

    Christensen, G D; Baddour, L M; Simpson, W A

    1987-12-01

    Clinical studies performed by us and others have found an association between slime production and strains of coagulase-negative staphylococci that infect indwelling medical devices. By serial low-speed centrifugation of broth cultures we have isolated a stable, weakly adherent strain (RP62A-NA) from a strongly adherent, slime-producing, pathogenic strain of Staphylococcus epidermidis sensu stricto (RP62A, ATCC 35984). We obtained a second strain from RP62A-NA (RP62A-NAR) by serial subculture of glass-adherent cells of RP62A-NA. All three strains had the same pattern of biochemical reactions, antimicrobial susceptibilities, and plasmid analysis. Transmission electron micrograph sections stained with the mucopolysaccharide-specific stain alcian blue demonstrated that the adherent strains RP62A and RP62A-NAR were covered with an extracellular coat of polysaccharide-rich material. In contrast, the nonadherent RP62A-NA strain lacked this external coat. All three strains were used in a mouse model of foreign body infection and a rat model of catheter-induced infective endocarditis. The adherence characteristics of isolates of RP62A and RP62A-NA recovered from experimental animals were relatively stable, although we noted a slight but a significant increase in the adherence of RP62A-NA isolates recovered from the foreign body model. The adherence characteristics of RP62A-NAR isolates recovered from infected animals were variable; in general these isolates were less adherent than the laboratory strain of RP62A-NAR. In both models the 50% infective dose (calculated by the Reed and Muench method) was three times greater for the RP62A-NA strain than for the RP62A strain. The phenotypic expression of slime production is subject to both in vitro and in vivo variation and could play a role in the pathogenesis of foreign body infection. PMID:3679536

  19. Seasonal variation of endocrine disrupting compounds, pharmaceuticals and personal care products in wastewater treatment plants.

    PubMed

    Yu, Yong; Wu, Laosheng; Chang, Andrew C

    2013-01-01

    The occurrence of 14 endocrine disrupting compounds (EDCs), pharmaceuticals and personal care products (PPCPs) in influents, effluents and sludge from five wastewater treatment plants (WWTPs) in southern California was studied in winter and summer. All 14 compounds were detected in influent samples from the five WWTPs except for estrone. Paracetamol, naproxen and ibuprofen were the dominant compounds, with mean concentrations of 41.7, 35.7 and 22.3 μg/L, respectively. The treatment removal efficiency for most compounds was more than 90% and concentrations in the effluents were relatively low. Seasonal variation of the compounds' concentration in the wastewater was significant: the total concentration of each compound in the wastewater was higher in winter than in summer, which is attributed to more human consumption of pharmaceuticals during winter and faster degradation of the compounds in summer. The highest concentrations of triclosan and octylphenol were detected in sewage sludge, with mean concentrations of 1505 and 1179 ng/g, respectively. Risk quotients (RQs), expressed as the ratios of environmental concentrations and the predicted no-effect concentrations (PNEC), were less than unity for all the compounds except for estrone in the effluents, indicating no immediate ecological risk is expected. However, RQs were higher than unity for 2 EDCs (estrone and octylphenol) and carbamazepine in sludge samples, indicating a significant ecotoxicological risk to human health. Therefore, appropriate treatment of sewage sludge is required before its application. PMID:23178835

  20. Variations in productivity and eolian fluxes in the northeastern Arabian Sea during the past 110 ka

    NASA Astrophysics Data System (ADS)

    Pourmand, Ali; Marcantonio, Franco; Schulz, Hartmut

    2004-04-01

    High-resolution (one to two samples/ka) radionuclide proxy records from core 93KL in the northeastern Arabian Sea provide evidence for millennial climate variability over the past 110 ka. We interpret 230Th-normalized 232Th fluxes as a proxy for eolian input, and authigenic uranium concentrations as a proxy for past productivity. We attribute orbital and suborbital variations in both proxies to changes in the intensity of the southwest Indian Ocean monsoon. The highest 230Th-normalized 232Th fluxes occur at times that are consistent with the timing of the Younger Dryas, Heinrich events 1-7 and cold Dansgaard-Oeschger stadial events recorded in the GISP2 ice core. Such high dust fluxes may be due to a weakened southwest monsoon in conjunction with strengthened northwesterlies from the Arabian Peninsula and Mesopotamia. Authigenic uranium concentrations, on the other hand, are highest during warm Dansgaard-Oeschger interstadials when the southwest monsoon is intensified relative to the northwesterly winds. Our results also indicate that on orbital timescales maximum average eolian fluxes coincide with the timing of marine isotopic stage (MIS) 2 and 4, while minimum fluxes occur during MIS 1, 3 and 5. Although the forcing mechanism(s) controlling suborbital variabilities in monsoonal intensity is still debated, our findings suggest an atmospheric teleconnection between the low-latitude southwest monsoon and North Atlantic climate.

  1. Approache Pluraliste du Developpement et Etude des Variations Procedurals en Production D'Orthographes Inventees. [A Pluralistic Approach to the Development and Study of Procedural Variations in the Production of Invented Spelling.

    ERIC Educational Resources Information Center

    Gelet, Isabelle Montesinos

    2002-01-01

    This study used a pluralistic model to examine the procedures used by two preschoolers to achieve written productions using invented orthographies. The model allows children's procedural variations to be taken into consideration by understanding the hierarchy of different processing modes available to children in completing the task and…

  2. [Product development on the basis of cereal and leguminous flours to coeliac disease in children between 6-24 months; I: formulation and acceptability].

    PubMed

    Cerezal Mezquita, P; Urtuvia Gatica, V; Ramírez Quintanilla, V; Romero Palacios, N; Arcos Zavala, R

    2011-01-01

    The revaluation of the Andean cultivations, quinua (Chenopodium quinua Willd) and lupin (Lupinus albus L.), to be used in nutritional mixtures, with traditional cereals like corn (Zea mays L.) and rice (Oryza sativa L.), originate mixtures without gluten which constitute a good alternative for the nutrition of children under 24 months that suffer from celiac disease, since they improve the quality of the protein, by essential amino acids compensation, and also impacts in the product's diversification strategy. In the present work, the percentage composition of each flour in the mixture was determined by means of Linear Programming by means of the Solver form from the Excel spreadsheet. Prolamines were determined in the quinua and lupin flours by the ELISA test and the HPLC technique was used in both products obtained called "sweet mix" and "dessert mix", to define the quantity of amino acids with the purpose of providing around the 15% of the proteins required in the day. The flour mixtures selected as optimum, sweet mix, suitable for the preparation of sweet pancakes, as well as for the dessert mix, that by addition of water or milk produce a semi solid dessert, were evaluated after three months of storage, being acceptable their microbiological, bromatological and sensorial requirements, corroborating the results with the good acceptance of the products, prepared from the formulated mixtures, by the children of two Day Care centers of the City of Antofagasta-Chile. PMID:21519742

  3. Isolation, Identification, and Characterisation of Degradation Products and the Development and Validation of a Stability-Indicating Method for the Estimation of Impurities in the Tolterodine Tartrate Formulation

    PubMed Central

    Prakash, Lakkireddy; Himaja, Malipeddi; Vasudev, Rudraraju

    2015-01-01

    A short and sensitive stability-indicating gradient RP-UPLC method was developed for the quantitative determination of process-related impurities and degradation products of tolterodine tartrate in pharmaceutical formulations. The method was developed by using the Waters ACQUITY UPLC™ BEH shield RP18 (2.1 × 100 mm, 1.7 μm) column with a mobile phase containing a gradient mixture of solvent A and B at a detection wavelength of 210 nm. During the stress study, the degradation products of tolterodine tartrate were well-resolved from tolterodine and its impurities and the mass balances were found to be satisfactory in all the stress conditions, thus proving the stability-indicating capability of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision, ruggedness, and robustness. During the stability (40°C/75% RH, 3 months) analysis of the drug product, one unknown impurity was detected by the above stability-indicating method. The unknown impurity was isolated by preparative HPLC and subjected to mass and NMR studies. Based on the spectral data, the unknown impurity was characterised as 2-(3-amino-1-phenylpropyl)-4-methylphenol (des-N,N-diisopropyl tolterodine). Structural elucidation of the impurity by spectral data is discussed in detail. PMID:26839802

  4. Validated chromatographic methods for determination of perindopril and amlodipine in pharmaceutical formulation in the presence of their degradation products.

    PubMed

    Zaazaa, Hala E; Abbas, Samah S; Essam, Hebat Allah M; El-Bardicy, Mohammed G

    2013-07-01

    Two specific, sensitive, and precise stability-indicating chromatographic methods have been developed, optimized and validated for determination of perindopril arginin (PER) and amlodipine besylate (AML) in their mixtures and in the presence of their degradation products. The first method was based on thin-layer chromatography (TLC) combined with densitometric determination of the separated bands. Adequate separation was achieved using silica gel 60 F254 TLC plates and ethyl acetate-methanol-toluene-ammonia solution, 33% (6.5:2:1:0.5 by volume), as a developing system. The second method was based on high-performance liquid chromatography, by which the proposed components were separated on a reversed-phase C18 analytical column using a mobile phase consisting of phosphate buffer (pH 2.5, 0.01 M)-acetonitrile-tetrahydrofuran (60:40:0.1% by volume) with ultraviolet detection at 218 nm. Different parameters affecting the suggested methods were optimized for maximum separation of the cited components. System suitability parameters of the two developed methods were also tested. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for the quantification of PER and AML in their commercial tablets. Both methods were also statistically compared to each other and to the reference methods with no significant differences in performance. PMID:23112269

  5. Study of non-thermal photon production under different scenarios in solar flares. 1: Scenarios and formulations

    NASA Technical Reports Server (NTRS)

    Perez-Peraza, J.; Alvarez, M.; Gallegos, A.

    1985-01-01

    In order to study the overall phenomenology involved in solar flares, it is necessary to understand their individual manifestation before building a corresponding description of the global phenomenon. Here the concern is with the production of X and gamma rays in solar flares. Flares are initiated very often within the closed magnetic field configurations of active centers. According (2) when beta = kinetic energy density/magnetic energy density approximately 0.2, the magnetic trap configuration is destructed within the time scale of the impulsive phase of flares ( 100 s). A first particle acceleration stage occurs during this phase as indicated by impulsive microwave and hard X-rays bursts. In some flare events, when the field strength beta is very high, the broken field lines may close again, such that later, in the course of the flash and main phases more hot plasma of very high conductivity is created, and so, the field and frozen plasma expand outward, as the kinetic pressure inside the closed loops increases. The magnetically trapped particles excite strong Alfven wave turbulence of small transverse scale.

  6. Production benefit of treatment with a dual active oral formulation of derquantel-abamectin in slaughter lambs.

    PubMed

    Geurden, T; Slootmans, N; Glover, M; Bartram, D J

    2014-09-15

    Gastrointestinal nematodes have a negative impact on the productivity of grazing sheep. Control of these infections has relied for decades on the use of anthelminics, leading to anthelmintic resistance (AR) worldwide, including the UK. The use of combination anthelmintics has been advocated as one of the tools in managing AR and decreasing the economic losses associated with AR. In this study, the benefit of a new combination (derquantel plus abamectin; DQL+ABA: Startect(®) Dual Active Oral Solution for Sheep, Zoetis, at 1 mL/5 kg bodyweight) was evaluated on a farm with suspected AR to benzimidazoles, by incorporating it into the existing treatment regime. In total 100 lambs were selected and allocated to one of two treatment groups, which were treated either with DQL+ABA or fenbendazole/levamisole at monthly intervals. All lambs were co-grazing the same pasture. Weight gain and carcass quality was evaluated, as well as treatment efficacy. The efficacy of DQL+ABA was high throughout the grazing season, whereas the efficacy of the fenbendazole/levamisole treatment regime was below the threshold for anthelmintic efficacy. The high efficacy of a monthly treatment with DQL+ABA resulted in a significantly higher average daily weight gain and shorter time to reach slaughter. PMID:24986436

  7. Naval fuel saltstone formulation change

    SciTech Connect

    Harley, J.P. Jr.; Langton, C.A.

    1987-10-19

    Laboratory results support a formulation change for Naval Fuels saltstone from a cement-only waste form to a cement and Class F fly ash waste form. The recommended base formulation is waste, concentrated to a SpG of 1.35, mixed with a 1:1 ratio of Type 1 Portland cement and class F fly ash to achieve a water to cementitious materials (includes fly ash) ratio of 0.4. Due to variations in waste water chemistry, permit modifications should specify formulation ranges such that saltstone physical and chemical properties are enhanced. Operations should be based on pretesting each waste batch and adjusting the base formulation within specified ranges (ie. Draft DPSOL 247 WW-0312, ``Saltcrete Formulation Testing for Rapid Set and Excess Water.``) EP toxicity and TCLP tests are included and show comparable results for both cement-only and cement/fly ash waste forms. Heat generation due to hydration, a current problem with the cementonly formulation, is significantly reduced in the cement/fly ash mixture. In addition to the improved physical characteristics of the cement/fly ash formulation, savings of approximately 33% in raw materials cost may be obtained due to the substitution of the lower cost fly ash for cement in the Naval Fuels waste solidification process.

  8. Naval fuel saltstone formulation change

    SciTech Connect

    Harley, J.P. Jr. and Co., Aiken, SC . Savannah River Plant); Langton, C.A. )

    1987-10-19

    Laboratory results support a formulation change for Naval Fuels saltstone from a cement-only waste form to a cement and Class F fly ash waste form. The recommended base formulation is waste, concentrated to a SpG of 1.35, mixed with a 1:1 ratio of Type 1 Portland cement and class F fly ash to achieve a water to cementitious materials (includes fly ash) ratio of 0.4. Due to variations in waste water chemistry, permit modifications should specify formulation ranges such that saltstone physical and chemical properties are enhanced. Operations should be based on pretesting each waste batch and adjusting the base formulation within specified ranges (ie. Draft DPSOL 247 WW-0312, Saltcrete Formulation Testing for Rapid Set and Excess Water.'') EP toxicity and TCLP tests are included and show comparable results for both cement-only and cement/fly ash waste forms. Heat generation due to hydration, a current problem with the cementonly formulation, is significantly reduced in the cement/fly ash mixture. In addition to the improved physical characteristics of the cement/fly ash formulation, savings of approximately 33% in raw materials cost may be obtained due to the substitution of the lower cost fly ash for cement in the Naval Fuels waste solidification process.

  9. Drivers of variation in aboveground net primary productivity and plant community composition differe across a broad precipitation gradient

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has long been a goal of ecology to determine what factors drive variation in aboveground net primary production (ANPP). Total annual precipitation has been shown to be a strong predictor of ANPP across broad spatial scales, but a poor predictor at local scales. Here we aim to determine the amount...

  10. Liposomal formulations for inhalation.

    PubMed

    Cipolla, David; Gonda, Igor; Chan, Hak-Kim

    2013-08-01

    No marketed inhaled products currently use sustained release formulations such as liposomes to enhance drug disposition in the lung, but that may soon change. This review focuses on the interaction between liposomal formulations and the inhalation technology used to deliver them as aerosols. There have been a number of dated reviews evaluating nebulization of liposomes. While the information they shared is still accurate, this paper incorporates data from more recent publications to review the factors that affect aerosol performance. Recent reviews have comprehensively covered the development of dry powder liposomes for aerosolization and only the key aspects of those technologies will be summarized. There are now at least two inhaled liposomal products in late-stage clinical development: ARIKACE(®) (Insmed, NJ, USA), a liposomal amikacin, and Pulmaquin™ (Aradigm Corp., CA, USA), a liposomal ciprofloxacin, both of which treat a variety of patient populations with lung infections. This review also highlights the safety of inhaled liposomes and summarizes the clinical experience with liposomal formulations for pulmonary application. PMID:23919478