Stability of dobutamine 500 mg in 50 ml syringes prepared using a Central Intravenous Additive Service

Objectives A pharmacy Central Intravenous Additives Service (CIVAS) provides ready to use injectable medicines. However, manipulation of a licensed injectable medicine may significantly alter the stability of drug(s) in the final product. The aim of this study was to develop a stability indicating assay for CIVAS produced dobutamine 500 mg in 50 ml dextrose 1% (w/v) prefilled syringes, and to allocate a suitable shelf life. Methods A stability indicating high performance liquid chromatography (HPLC) assay was established for dobutamine. The stability of dobutamine prefilled syringes was evaluated under storage conditions of 4°C (protected from light), room temperature (protected from light), room temperature (exposed to light) and 40°C (protected from light) at various time points (up to 42 days). Results An HPLC method employing a Hypersil column, mobile phase (pH=4.0) consisting of 82:12:6 (v/v/v) 0.05 M KH2PO4:acetonitrile:methanol plus 0.3% (v/v) triethylamine with UV detection at λ=280 nm was specific for dobutamine. Under different storage conditions only samples stored at 40°C showed greater than 5% degradation (5.08%) at 42 days and had the shortest T95% based on this criterion (44.6 days compared with 111.4 days for 4°C). Exposure to light also reduced dobutamine stability. Discolouration on storage was the limiting factor in shelf life allocation, even when dobutamine remained within 5% of the initial concentration. Conclusions A stability indicating HPLC assay for dobutamine was developed. The shelf life recommended for the CIVAS product was 42 days at 4°C and 35 days at room temperature when protected from light.

A Precise Formulation of the Third Law of Thermodynamics

The third law of thermodynamics is formulated precisely: all points of the state space of zero temperature I""(0) are physically adiabatically inaccessible from the state space of a simple system. In addition to implying the unattainability of absolute zero in finite time (or ""by a finite number of operations""), it admits as corollary, under a continuity assumption, that all points of I""(0) are adiabatically equivalent. We argue that the third law is universally valid for all macroscopic systems which obey the laws of quantum mechanics and/or quantum field theory. We also briefly discuss why a precise formulation of the third law for black holes remains an open problem.

Sparse partition universal graphs for graphs of bounded degree

In 1983, Chvatal, Trotter and the two senior authors proved that for any Delta there exists a constant B such that, for any n, any 2-colouring of the edges of the complete graph K(N) with N >= Bn vertices yields a monochromatic copy of any graph H that has n vertices and maximum degree Delta. We prove that the complete graph may be replaced by a sparser graph G that has N vertices and O(N(2-1/Delta)log(1/Delta)N) edges, with N = [B`n] for some constant B` that depends only on Delta. Consequently, the so-called size-Ramsey number of any H with n vertices and maximum degree Delta is O(n(2-1/Delta)log(1/Delta)n) Our approach is based on random graphs; in fact, we show that the classical Erdos-Renyi random graph with the numerical parameters above satisfies a stronger partition property with high probability, namely, that any 2-colouring of its edges contains a monochromatic universal graph for the class of graphs on n vertices and maximum degree Delta. The main tool in our proof is the regularity method, adapted to a suitable sparse setting. The novel ingredient developed here is an embedding strategy that allows one to embed bounded degree graphs of linear order in certain pseudorandom graphs. Crucial to our proof is the fact that regularity is typically inherited at a scale that is much finer than the scale at which it is assumed. (C) 2011 Elsevier Inc. All rights reserved.

Density-Profile Processes Describing Biological Signaling Networks: Almost Sure Convergence to Deterministic Trajectories

We introduce jump processes in R(k), called density-profile processes, to model biological signaling networks. Our modeling setup describes the macroscopic evolution of a finite-size spin-flip model with k types of spins with arbitrary number of internal states interacting through a non-reversible stochastic dynamics. We are mostly interested on the multi-dimensional empirical-magnetization vector in the thermodynamic limit, and prove that, within arbitrary finite time-intervals, its path converges almost surely to a deterministic trajectory determined by a first-order (non-linear) differential equation with explicit bounds on the distance between the stochastic and deterministic trajectories. As parameters of the spin-flip dynamics change, the associated dynamical system may go through bifurcations, associated to phase transitions in the statistical mechanical setting. We present a simple example of spin-flip stochastic model, associated to a synthetic biology model known as repressilator, which leads to a dynamical system with Hopf and pitchfork bifurcations. Depending on the parameter values, the magnetization random path can either converge to a unique stable fixed point, converge to one of a pair of stable fixed points, or asymptotically evolve close to a deterministic orbit in Rk. We also discuss a simple signaling pathway related to cancer research, called p53 module.

Metastable Periodic Patterns in Singularly Perturbed Delayed Equations

We consider the scalar delayed differential equation epsilon(x) over dot(t) = -x(t) + f(x(t-1)), where epsilon > 0 and f verifies either df/dx > 0 or df/dx < 0 and some other conditions. We present theorems indicating that a generic initial condition with sign changes generates a solution with a transient time of order exp(c/epsilon), for some c > 0. We call it a metastable solution. During this transient a finite time span of the solution looks like that of a periodic function. It is remarkable that if df/dx > 0 then f must be odd or present some other very special symmetry in order to support metastable solutions, while this condition is absent in the case df/dx < 0. Explicit epsilon-asymptotics for the motion of zeroes of a solution and for the transient time regime are presented.

Desingularization of singular Riemannian foliation

Let F be a singular Riemannian foliation on a compact Riemannian manifold M. By successive blow-ups along the strata of F we construct a regular Riemannian foliation (F) over cap on a compact Riemannian manifold (M) over cap and a desingularization map (rho) over cap : (M) over cap -> M that projects leaves of (F) over cap into leaves of F. This result generalizes a previous result due to Molino for the particular case of a singular Riemannian foliation whose leaves were the closure of leaves of a regular Riemannian foliation. We also prove that, if the leaves of F are compact, then, for each small epsilon > 0, we can find (M) over cap and (F) over cap so that the desingularization map induces an epsilon-isometry between M/F and (M) over cap/(F) over cap. This implies in particular that the space of leaves M/F is a Gromov-Hausdorff limit of a sequence of Riemannian orbifolds {((M) over cap (n)/(F) over cap (n))}.

Stability of periodic travelling shallow-water waves determined by Newton`s equation

We study the existence and stability of periodic travelling-wave solutions for generalized Benjamin-Bona-Mahony and Camassa-Holm equations. To prove orbital stability, we use the abstract results of Grillakis-Shatah-Strauss and the Floquet theory for periodic eigenvalue problems.

A new perspective on the PPP hypothesis

This paper the stastistical properties of the real exchange rates of G-5 countries for the Bretton-Woods peiod, and draw implications on the purchasing power parity (PPP) hypothesis. In contrast to most previous studies that consider only unit root and stationary process to describe the real exchange tae, this paper also considers two in-between processes, the locally persistent process ans the fractionally integrated process, to complement past studies. Seeking to be consistent with tha ample evidence of near unit in the real exchange rate movements very well. This finding implies that: 1) the real exchange movement is more persistent than the stationary case but less persistent than the unit root case; 2) the real exchange rate is non-stationary but the PPP reversion occurs and the PPP holds in the long run; 3) the real exchange rate does not exhibit the secular dependence of the fractional integration; 4) the real exchange rate evolves over time in a way that there is persistence over a range of time, but the effect of shocks will eventually disappear over time horizon longer than order O (nd), that is, at finite time horizon; 5) shocks dissipation is fasters than predicted by the fractional integracion, and the total sum of the effects of a unit innovation is finite, implying that a full PPP reversion occurs at finite horizons. These results may explain why pasrt empirical estudies could not provide a clear- conclusion on the real exchange rate processes and the PPP hypothesis.

A comment on "Rational learning lead to nash equilibrium" by professors Ehud Kalai and Ehud Lehrer

Kalai and Lebrer (93a, b) have recently show that for the case of infinitely repeated games, a coordination assumption on beliefs and optimal strategies ensures convergence to Nash equilibrium. In this paper, we show that for the case of repeated games with long (but finite) horizon, their condition does not imply approximate Nash equilibrium play. Recently Kalai and Lehrer (93a, b) proved that a coordination assumption on beliefs and optimal strategies, ensures that pIayers of an infinitely repeated game eventually pIay 'E-close" to an E-Nash equilibrium. Their coordination assumption requires that if players believes that certain set of outcomes have positive probability then it must be the case that this set of outcomes have, in fact, positive probability. This coordination assumption is called absolute continuity. For the case of finitely repeated games, the absolute continuity assumption is a quite innocuous assumption that just ensures that pIayers' can revise their priors by Bayes' Law. However, for the case of infinitely repeated games, the absolute continuity assumption is a stronger requirement because it also refers to events that can never be observed in finite time.

Teoria de carteiras e a alocação de parques eólicos offshore

The consumption of energy on the planet is currently based on fossil fuels. They are responsible for adverse effects on the environment. Renewables propose solutions for this scenario, but must face issues related to the capacity of the power supply. Wind energy offshore emerging as a promising alternative. The speed and stability are greater winds over oceans, but the variability of these may cause inconvenience to the generation of electric power fluctuations. To reduce this, a combination of wind farms geographically distributed was proposed. The greater the distance between them, the lower the correlation between the wind velocity, increasing the likelihood that together achieve more stable power system with less fluctuations in power generation. The efficient use of production capacity of the wind park however, depends on their distribution in marine environments. The objective of this research was to analyze the optimal allocation of wind farms offshore on the east coast of the U.S. by Modern Portfolio Theory. The Modern Portfolio Theory was used so that the process of building portfolios of wind energy offshore contemplate the particularity of intermittency of wind, through calculations of return and risk of the production of wind farms. The research was conducted with 25.934 observations of energy produced by wind farms 11 hypothetical offshore, from the installation of 01 simulated ocean turbine with a capacity of 5 MW. The data show hourly time resolution and covers the period between January 1, 1998 until December 31, 2002. Through the Matlab R software, six were calculated minimum variance portfolios, each for a period of time distinct. Given the inequality of the variability of wind over time, set up four strategies rebalancing to evaluate the performance of the related portfolios, which enabled us to identify the most beneficial to the stability of the wind energy production offshore. The results showed that the production of wind energy for 1998, 1999, 2000 and 2001 should be considered by the portfolio weights calculated for the same periods, respectively. Energy data for 2002 should use the weights derived from the portfolio calculated in the previous time period. Finally, the production of wind energy in the period 1998-2002 should also be weighted by 1/11. It follows therefore that the portfolios found failed to show reduced levels of variability when compared to the individual production of wind farms hypothetical offshore

Control of Brachiaria decumbens and Panicum maximum by S-metolachlor as influenced by the occurrence of rain and amount of sugarcane straw on the soil

Com o objetivo de estudar o controle em pré-emergência de Brachiaria decumbens e Panicum maximum pelo herbicida S-metolachlor em função do intervalo de tempo entre a aplicação e a ocorrência de chuva e da quantidade de palha de cana-de-açúcar na superfície do solo, dois experimentos foram desenvolvidos em vasos mantidos em casa de vegetação. No primeiro, foram estudadas cinco quantidades de palha sobre o solo (0, 3, 6, 10 e 15 t ha-1) e cinco dosagens de S-metolachlor (0; 0,96; 1,44; 1,92 e 2,40 kg ha-1). No outro, foram avaliadas duas quantidades de palha sobre o solo (0 e 10 t ha-1) e sete intervalos de tempo entre a aplicação de S-metolachlor e a simulação de chuva (1 dia antes; logo após; 4, 8, 12, 16 e 20 dias após a aplicação). As dosagens de S-metolachlor não foram afetadas pelos níveis de palha na superfície do solo. Além disso, sem a manutenção de palha sobre o solo, o controle das plantas daninhas pelo herbicida S-metolachlor não foi influenciado pelos intervalos de tempo entre a aplicação e a simulação de chuva, até 20 dias. Com 10 t ha-1 de palha, o controle de B. decumbens e P. maximum pelo S-metolachlor não foi prejudicado quando choveu até 12 dias da sua aplicação ou um dia antes, mas, nesse caso apenas para P. maximum.

Levantamento e avaliação de critérios para a ampliação de escala da produção de biossurfactantes utilizando melaço como substrato

Biosurfactants are amphiphilic molecules synthesized by microorganisms such as bacteria, yeast or filamented fungi cultivated in various carbon sources among sucrose and hydrocarbons. These molecules are composed by a hydrophilic and hydrophobic part. They operate mostly at interfaces of fluids of different polarities. Because of this characteristic, they are potentially employed in numerous industries, such as the textile, medical, cosmetics, food and mainly in the petrochemical ones. Therefore industry has interest in developing new biosurfactant production processes in high scale, in order to become them economically competitive when compared to synthetic biosurfactants. This work aims to evaluate the biosurfactant production applying a non-conventional substrate sugar cane molasses proceeding from the sugar industry thus reducing the production costs. The strain identified as AP029/GLIIA, isolated from oil wells in Rio Grande do Norte state and used in these experiments belongs to the culture collection of Antibiotics Department of UFPE. The fermentation were carried out using different conditions according to a factorial planning 24 with duplicate at center point, in which the studied factors were molasse concentration, nitrate concentration, agitation and aeration ratio. The experiments were performed in a shaker at 38ºC of temperature. Samples were withdrawn in regular periods of time of up to 72 hours of fermentation in order to analyze substrate consumption, cellular concentration, superficial tension, critical micelle dilution (CMD-1 e CMD-2) as well as extracelullar protein production. The results showed a production of 3,480 g/L of biomass, a reduction of 41% on superficial tension, 67% of substrate consumption and 0,2805 g/L of extracellular protein

Effects of calcium gluconate and PMSF in the treatment of acute intoxication of chicken by TOCP

To examine the efficacy of calcium gluconate (two doses of Ca-Glu 5 mg/kg i.v.) to alleviate the injurious effects of organophosphorus induced delayed neuropathy (OPIDN) in the presence or absence of phenylmethanesulfonyl fluoride (PMSF go mg/kg i.m.), 14 groups of four isabrown hens were used. To measure the lymphocyte neuropathy target esterase (LNTE)activity, groups receiving just distilled water (control), groups receiving just Tri-orto-cresyl phosphate (TOCP; 500 mg/kg p.o.) (Positive control), and other groups receiving TOCP and Ca-Glu or PMSF simultaneously or 12 hours later following intoxication by TOCP were used. They were sacrificed 12 and 24 hours after the administration of TOCP. To observe a 28-day time course of neurotoxicity scores and calcium plasma concentration, five groups were used. Regarding free Ca(2+)in the plasma, the positive control produced a characteristic profile time course up and down (luring 28 days, and some hens with maximum score of neurotoxicity in 28 days. The treatment, which prevented greater oscillation in free Ca(2+) in the plasma, presented a decrease in OPIDN in relation to the positive control. Twelve hours after the administration of TOCP, LNTE was 70-80% inhibited when compared with control, whereas the first decrease in the free Ca(2+) in the plasma was significantly different from the control only 24 hours after the administration of TOCP. In summary, the sooner the Ca-Glu is started, the less severe the neuropathy effects.

Generic Bifurcations of Planar Filippov Systems via Geometric Singular Perturbations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A teoria da ruína aplicada em um modelo de empresa financeira com risco de crédito

In this work we study a new risk model for a firm which is sensitive to its credit quality, proposed by Yang(2003): Are obtained recursive equations for finite time ruin probability and distribution of ruin time and Volterra type integral equation systems for ultimate ruin probability, severity of ruin and distribution of surplus before and after ruin