THE VANISHING DISCOUNT APPROACH FOR THE AVERAGE CONTINUOUS CONTROL OF PIECEWISE DETERMINISTIC MARKOV PROCESSES

This work is concerned with the existence of an optimal control strategy for the long-run average continuous control problem of piecewise-deterministic Markov processes (PDMPs). In Costa and Dufour (2008), sufficient conditions were derived to ensure the existence of an optimal control by using the vanishing discount approach. These conditions were mainly expressed in terms of the relative difference of the alpha-discount value functions. The main goal of this paper is to derive tractable conditions directly related to the primitive data of the PDMP to ensure the existence of an optimal control. The present work can be seen as a continuation of the results derived in Costa and Dufour (2008). Our main assumptions are written in terms of some integro-differential inequalities related to the so-called expected growth condition, and geometric convergence of the post-jump location kernel associated to the PDMP. An example based on the capacity expansion problem is presented, illustrating the possible applications of the results developed in the paper.

Sugar and ethanol production as a rural development strategy in Brazil: Evidence from the state of Sao Paulo

Sugar and ethanol production are key components of Brazil`s rural development and energy strategies, yet in recent years sugar production has been widely criticized for its environmental and labor practices. This study examines the relationship between rural development and sugarcane, ethanol, and cattle production in the state of Sao Paulo. Our results suggest that the value added components of sugarcane production, which include sugar refining and ethanol production, may have a strong positive affect on local human development in comparison to primary agricultural production activities and other land uses. These results imply that sugar production, when accompanied by a local processing industry can stimulate rural development. However, this paper also highlights the significant environmental and social harms generated by the sugar industry at large, which may undermine its development benefits if not addressed. (C) 2011 Elsevier Ltd. All rights reserved.

Role of entomopathogenic fungi in the control of Tetranychus evansi and Tetranychus urticae (Acari: Tetranychidae), pests of horticultural crops

The spider mites Tetranychus urticae Koch and Tetranychus evansi Baker and Pritchard are important pests of horticultural crops. They are infected by entomopathogenic fungi naturally or experimentally. Fungal pathogens known to cause high infection in spider mite populations belong to the order Entomophthorales and include Neozygites spp. Studies are being carried out to develop some of these fungi as mycoacaricides, as standalone control measures in an inundative strategy to replace the synthetic acaricides currently in use or as a component of integrated mite management. Although emphasis has been put on inundative releases, entomopathogenic fungi can also be used in classical, conservation and augmentative biological control. Permanent establishment of an exotic agent in a new area of introduction may be possible in the case of spider mites. Conservation biological control can be achieved by identifying strategies to promote any natural enemies already present within crop ecosystems, based on a thorough understanding of their biology, ecology and behaviour. Further research should focus on development of efficient mass production systems, formulation, and delivery systems of fungal pathogens.

Economic feasibility of cowpea irrigation in Piaui State

The objective of this work was to evaluate the economic feasibility of cowpea irrigation in Piaui State Brazil. Water balances were carried out on a daily basis using the Thornthwaite and Mather (1955) method, for 165 sites, considering twelve sowings dates and available water capacity in the soil of 20, 40 and 60 mm. The net revenues were estimated with a probability of occurrence of 75%, later being spatialized to Piaui State. Cowpea irrigation was shown to economically viable for all sowing dates, irrespective of the available water capacity. Net revenues varied among several regions of the State, in function of the sowing date and available water capacity in the soil. Considering a planning strategy for Piaui State, sowing on February, I was shown to be most favorable, because it enabled higher net revenue values, covering larger areas of the State.

Transmission of Methylobacterium mesophilicum by Bucephalogonia xanthophis for Paratransgenic Control Strategy of Citrus Variegated Chlorosis

Methylobacterium mesophilicum, originally isolated as an endophytic bacterium from citrus plants, was genetically transformed to express green fluorescent protein (GFP). The GFP-labeled strain of M. mesophilicum was inoculated into Catharanthus roseus (model plant) seedlings and further observed colonizing its xylem vessels. The transmission of this endophyte by Bucephalogonia xanthophis, one of the insect vectors that transmit Xylella fastidiosa subsp. pauca, was verified by insects feeding from fluids containing the GFP bacterium followed by transmission to plants and isolating the endophyte from C. roseus plants. Forty-five days after inoculation, the plants exhibited endophytic colonization by M. mesophilicum, confirming this bacterium as a nonpathogenic, xylem-associated endophyte. Our data demonstrate that M. mesophilicum not only occupy the same niche of X. fastidiosa subsp. pauca inside plants but also may be transmitted by B. xanthophis. The transmission, colonization, and genetic manipulation of M. mesophilicum is a prerequisite to examining the potential use of symbiotic control to interrupt the transmission of X. fastidiosa subsp. pauca, the bacterial pathogen causing Citrus variegated chlorosis by insect vectors.

An integrated molecular map of yellow passion fruit based on simultaneous maximum-likelihood estimation of linkage and linkage phases

The development of genetic maps for auto-incompatible species, such as the yellow passion fruit (Passiflora edulis Sims f.flavicarpa Deg.) is restricted due to the unfeasibility of obtaining traditional mapping populations based on inbred lines. For this reason, yellow passion fruit linkage maps were generally constructed using a strategy known as two-way pseudo-testeross, based on monoparental dominant markers segregating in a 1:1 fashion. Due to the lack of information from these markers in one of the parents, two individual (parental) maps were obtained. However, integration of these maps is essential, and biparental markers can be used for such an operation. The objective of our study was to construct an integrated molecular map for a full-sib population of yellow passion fruit combining different loci configuration generated from amplified fragment length polymorphisms (AFLPs) and microsatellite markers and using a novel approach based on simultaneous maximum-likelihood estimation of linkage and linkage phases, specially designed for outcrossing species. Of the total number of loci, approximate to 76%, 21%, 0.7%, and 2.3% did segregate in 1:1, 3:1, 1:2:1, and 1:1:1:1 ratios, respectively. Ten linkage groups (LGs) were established with a logarithm of the odds (LOD) score >= 5.0 assuming a recombination fraction : <= 0.35. On average, 24 markers were assigned per LG, representing a total map length of 1687 cM, with a marker density of 6.9 cM. No markers were placed as accessories on the map as was done with previously constructed individual maps.

Meat Quality of Lambs Fed on Palm Kernel Meal, a By-product of Biodiesel Production

This study aimed to establish the optimum level of palm kernel meal in the diet of Santa Ines lambs based on the sensorial characteristics and fatty acid profile of the meat. We used 32 lambs with a starting age of 4 to 6 months and mean weight of 22 2.75 kg, kept in individual stalls. The animals were fed with Tifton-85 hay and a concentrate mixed with 0.0, 6.5, 13.0 or 19.5% of palm kernel meal based on the dry mass of the complete diet. These levels formed the treatments. Confinement lasted 80 days and on the last day the animals were fasted and slaughtered. After slaughter, carcasses were weighed and sectioned longitudinally, along the median line, into two antimeres. Half-carcasses were then sliced between the 12th and 13th ribs to collect the loin (longissimus dorsi), which was used to determine the sensorial characteristics and fatty acid profile of the meat. For sensorial evaluation, samples of meat were given to 54 judges who evaluated the tenderness, juiciness, appearance, aroma and flavor of the meat using a hedonic scale. Fatty acids were determined by gas chromatography. The addition of palm kernel meal to the diet had no effect on the sensorial characteristics of meat juiciness, appearance, aroma or flavor. However, tenderness showed a quadratic relationship with the addition of the meal to the diet. The concentration of fatty acids C12:0, C14:0 and C16:0 increased with the addition of palm kernel meal, as did the sum of medium-chain fatty acids and the atherogenicity index. Up to of 19.5% of the diet of Santa Ines lambs can be made up of palm kernel meal without causing significant changes in sensorial characteristics. However, the fatty acid profile of the meat was altered.

Influence of a probiotic soy product on fecal microbiota and its association with cardiovascular risk factors in an animal model

Background: Previous work showed that daily ingestion of an aqueous soy extract fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416, supplemented or not with isoflavones, reduced the total cholesterol and non-HDL-cholesterol levels, increased the high-density lipoprotein (HDL) concentration and inhibited the raising of autoantibody against oxidized low-density lipoprotein (ox-LDL Ab) and the development of atherosclerotic lesions. Objective: The aim of this study was to characterize the fecal microbiota in order to investigate the possible correlation between fecal microbiota, serum lipid parameters and atherosclerotic lesion development in rabbits with induced hypercholesterolemia, that ingested the aqueous soy extract fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416. Methods: The rabbits were randomly allocated to five experimental groups (n = 6): control (C), hypercholesterolemic (H), hypercholesterolemic plus unfermented soy product (HUF), hypercholesterolemic plus fermented soy product (HF) and hypercholesterolemic plus isoflavone-supplemented fermented soy product (HIF). Lipid parameters and microbiota composition were analyzed on days 0 and 60 of the treatment and the atherosclerotic lesions were quantified at the end of the experiment. The fecal microbiota was characterized by enumerating the Lactobacillus spp., Bifidobacterium spp., Enterococcus spp., Enterobacteria and Clostridium spp. populations. Results: After 60 days of the experiment, intake of the probiotic soy product was correlated with significant increases (P < 0.05) on Lactobacillus spp., Bifidobacterium spp. and Enterococcus spp. and a decrease in the Enterobacteria population. A strong correlation was observed between microbiota composition and lipid profile. Populations of Enterococcus spp., Lactobacillus spp. and Bifidobacterium spp. were negatively correlated with total cholesterol, non-HDL-cholesterol, autoantibodies against oxidized LDL (ox-LDL Ab) and lesion size. HDL-C levels were positively correlated with Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. populations. Conclusion: In conclusion, daily ingestion of the probiotic soy product, supplemented or not with isoflavones, may contribute to a beneficial balance of the fecal microbiota and this modulation is associated with an improved cholesterol profile and inhibition of atherosclerotic lesion development.

Delivery of daunorubicin to cancer cells with decreased toxicity by association with a lipidic nanoemulsion that binds to LDL receptors

A lipidic nanoemulsion termed LDE concentrates in neoplastic cells after injection into the bloodstream and thus can be used as a drug carrier to tumour sites. The chemotherapeutic agent daunorubicin associates poorly with LDE; the aim of this study was to clarify whether the derivatization of daunorubicin by the attachment of an oleyl group increases the association with LDE, and to test the cytotoxicity and animal toxicity of the new preparation. The association of oleyl-daunorubicin (oDNR) to LDE showed high yield (93 +/- 2% and 84 +/- 4% at 1:10 and 1:5 drug:lipid mass, respectively) and was stable for at least 20 days. Association with oDNR increased the LDE particle diameter from 42 +/- 4 nm to 75 +/- 6 nm. Cytotoxicity of LDE-oDNR was reduced two-fold in HL-60 and K-562 cell lines, fourteen-fold in B16 cells and nine-fold in L1210 cells when compared with commercial daunorubicin. When tested in mice, LDE-oDNR showed remarkable reduced toxicity (maximum tolerated dose > 253 mu mol kg(-1), compared with <3 mu mol kg(-1) for commercial daunorubicin). At high doses, the cardiac tissue of LDE-oDNR-treated animals had much smaller structural lesions than with commercial daunorubicin. LDE-oDNR is therefore a promising new preparation that may offer superior tolerability compared with commercial daunorubicin.

Influence of gamma radiation onto polymeric matrix with papain

Papain is a proteolytic enzyme that has been widely used as debridement agent for scars and wound healing treatment. However, papain presents low stability, which limits its use to extemporaneous or short shelf-life formulations. The purpose of this study was to entrap papain into a polymeric matrix in order to obtain a drug delivery system that could be used as medical device. Since these systems must be sterile, gamma radiation is an interesting option and presents advantages in relation to conventional agents: no radioactive residues are formed: the product can be sterilized inside the final packaging and has an excellent reliability. The normative reference for the establishment of the sterilizing dose determines 25 kGy as the inactivation dose for viable microorganisms. A silicone dispersion was selected to prepare membranes containing 2% (w/w) papain. Irradiated and non-irradiated membranes were simultaneously assessed in order to verify whether gamma radiation interferes with the drug-releasing profile. Results showed that irradiation does not affect significantly papain release and its activity. Therefore papain shows radioresistance in the irradiation conditions applied. In conclusion, gamma radiation can be easily used as sterilizing agent without affecting the papain release profile and its activity onto the biocompatible device is studied. (C) 2009 Elsevier Ltd. All rights reserved.

Development and Characterization of L-Alanyl-L-Glutamine Containing Pellets employing Extrusion-Spheronization Method and Drying Process in Fluidized Bad Equipment.

Development and Characterization of L-Alanyl-L-Glutamine Containing Pellets employing Extrusion-Spheronization Method and Drying Process in Fluidized Bad Equipment"". In this work, five formulations of L-alanyl-L-glutamine (glutamine dipeptide) containing pellets with different drug concentration were developed and evaluated: F1 (9.07%); F2 (17.70%); F3 (27.98%); F4 (37.74%) e F5 (47.53%). Pellets were prepared by extrusion-spheronization method and, further, dried in fluidized bad equipment. The following assays were carried out with the batches obtained: granulometry, friability, true density and morphologic analysis. Between the five formulations evaluated, pellets obtained from F3 present best yield (75.80%), most uniform particle size distribution (89.67% of pellets with size in the range of 0.80 to 1.18), most high true density (2.1634 g/ml) and best aspect (1.0795 +/- 0.0410). Due to these features, pellets obtained from F3 were considered adequate to further polymeric coating process in order to produce a multiparticulate system to prolong L-alanyl-L-glutamine release.

Molecular modeling as a promising tool to study dendrimer prodrugs delivery

Molecular modeling methodologies were applied to perform preliminary studies concerning the release of active agents from potentially antichagasic and antileishmanial dendrimer prodrugs. The dendrimer was designed having myo-inositol as a core, L-malic acid as a spacer group, and hydroxymethylnitrofurazone (NFOH), 3-hydroxyflavone or quercetin, as active compounds. Each dendrimer presented a particular behavior concerning to the following investigated properties: spatial hindrance, map of electrostatic potential (MEP), and the lowest unoccupied molecular orbital energy (E(LUMO)). Additionally, the findings suggested that the carbonyl group next to the active agent seems to be the most promising ester breaking point. (C) 2009 Elsevier B.V. All rights reserved.

Development and In Vitro Evaluation of Propranolol Hydrochloride Controlled Release Tablets Using HPMC as Matrix Former

The purpose of this paper was to produce controlled-release matrices with 120 mg of propranolol hydrochloride (PHCl) employing hydroxypropyl methylcellulose (HPMC, Methocel (R) K100) as the gel forming barrier. Although this class of polymers has been commonly used for direct compression, with the intent of use reduced polymer concentrations to achieve controlled drug release, in this study tablets were produced by the wet granulation process. HPMC percentages ranged from 15-34 % and both soluble and non soluble diluents were tested in the 10 proposed tablet compositions. Dissolution testing of matrices was performed over a 12 h period in 1.2 pH medium (the first 2 h) and in pH 6.8 (10 h). Dissolution kinetic analysis was performed by applying Zero-order, First-order and Higuchi models with the aim of elucidating the drug release mechanism. All physical-chemical characteristics such as average weight, friability, hardness, diameter, height, and drug content were in accordance to the pharmacopeial specifications. Taking into account that PHCl is a very soluble drug, low concentrations (15 %) of HPMC were sufficient to reduce the drug release and to promote controlled release of PHCl, presenting good dissolution efficiencies, between 50 % and 63 %. The Higuchi model has presented the best fit to the 15 % HPMC formulations, indicating that the main release mechanism was diffusion. It could be concluded that the application of the wet granulation method reduced matrices erosion and promoted controlled release of the drug at low HPMC percentages.

Optimization of preservative system in ophthalmic suspension with dexamethasone and polymyxin B

A simplex-lattice statistical project was employed to study an optimization method for a preservative system in an ophthalmic suspension of dexametasone and polymyxin B. The assay matrix generated 17 formulas which were differentiated by the preservatives and EDTA (disodium ethylene diamine-tetraacetate), being the independent variable: X-1 = chlorhexidine digluconate (0.010 % w/v); X-2 = phenylethanol (0.500 % w/v); X-3 = EDTA (0.100 % w/v). The dependent variable was the Dvalue obtained from the microbial challenge of the formulas and calculated when the microbial killing process was modeled by an exponential function. The analysis of the dependent variable, performed using the software Design Expert/W, originated cubic equations with terms derived from stepwise adjustment method for the challenging microorganisms: Pseudomonas aeruginosa, Burkholderia cepacia, Staphylococcus aureus, Candida albicans and Aspergillus niger. Besides the mathematical expressions, the response surfaces and the contour graphics were obtained for each assay. The contour graphs obtained were overlaid in order to permit the identification of a region containing the most adequate formulas (graphic strategy), having as representatives: X-1 = 0.10 ( 0.001 % w/v); X-2 = 0.80 (0.400 % w/v); X-3 = 0.10 (0.010 % w/v). Additionally, in order to minimize responses (Dvalue), a numerical strategy corresponding to the use of the desirability function was used, which resulted in the following independent variables combinations: X-1 = 0.25 (0.0025 % w/v); X-2 = 0.75 (0.375 % w/v); X-3 = 0. These formulas, derived from the two strategies (graphic and numerical), were submitted to microbial challenge, and the experimental Dvalue obtained was compared to the theoretical Dvalue calculated from the cubic equation. Both Dvalues were similar to all the assays except that related to Staphylococcus aureus. This microorganism, as well as Pseudomonas aeruginosa, presented intense susceptibility to the formulas independently from the preservative and EDTA concentrations. Both formulas derived from graphic and numerical strategies attained the recommended criteria adopted by the official method. It was concluded that the model proposed allowed the optimization of the formulas in their preservation aspect.

Biochemical and biophysical characterization of lysozyme modified by PEGylation

PEGylation is a strategy that has been used to improve the biochemical properties of proteins and their physical and thermal stabilities. In this study, hen egg-white lysozyme (EC 3.2.1.17; LZ) was modified with methoxypolyethylene glycol-p-nitrophenyl carbonate (mPEG-pNP, MW 5000). This PEGylation of LZ produced conjugates that retained full enzyme activity with glycol chitosan, independent of degree of enzyme modification; its biological activity with the substrate Micrococcus lysodeikticus was altered according to its degree of modification. The conjugate obtained with a low degree of mPEG-pNP/NH(2) modification was studied by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), demonstrating a spectral peak at m/z 19,988 Da with 77% of its original enzymatic activity. Spectroscopic studies of Fourier transform infrared (FIR) and circular dichroism (CD) did not show any relevant differences in protein structure between the native and conjugate LZ. Studies of the effects of pH and temperature on PEGylated LZ indicated that the conjugate was active over a broad pH range, stable at 50 degrees C, and demonstrated resistance to proteolytic degradation. (C) 2010 Elsevier B.V. All rights reserved.