Effect of water vapour stabilization of raw materials on the quality of the inhalation product

Generation of raw materials for dry powder inhalers by different size reduction methods can be expected to influence physical and chemical properties of the powders. This can cause differences in particle size, size distribution, shape, crystalline properties, surface texture and energy. These physical properties of powders influence the behaviour of particles before and after inhalation. Materials with an amorphous surface have different surface energy compared to materials with crystalline surface. This can affect the adhesion and cohesion of particles. Changes in the surface nature of the drug particles results in a change in product performance. By stabilization of the raw materials the amorphous surfaces are converted into crystalline surfaces. The primary aim of the study was to investigate the influence of the surface properties of the inhalation particles on the quality of the product. The quality of the inhalation product is evaluated by measuring the fine particle dose (FPD). FDP is the total dose of particles with aerodynamic diameters smaller than 5,0 μm. The secondary aim of this study was to achieve the target level of the FPD and the stability of the FPD. This study was also used to evaluate the importance of the stabilization of the inhalation powders. The study included manufacturing and analysing drug substance 200 μg/dose inhalation powder batches using non-stabilized or stabilized raw materials. The inhaler formulation consisted of micronized drug substance, lactose <100μm and micronized lactose <10μm. The inhaler device was Easyhaler®. Stabilization of the raw materials was done in different relative humidity, temperature and time. Surface properties of the raw materials were studied by dynamic vapour sorption, scanning electron microscopy and three-point nitrogen adsorption technique. Particle size was studied by laser diffraction particle size analyzer. Aerodynamic particle size distribution from inhalers was measured by new generation impactor. Stabilization of all three raw materials was successful. A clear difference between nonstabilized and stabilized raw materials was achieved for drug substance and lactose <10μm. However for lactose <100μm the difference wasn’t as clear as wanted. The surface of the non-stabilized drug substance was more irregular and the particles had more roughness on the surface compared to the stabilized drug substances particles surface. The surface of the stabilized drug particles was more regular and smoother than non-stabilized. Even though a good difference between stabilized and non-stabilized raw materials was achieved, a clear evidence of the effect of the surface properties of the inhalation particles on the quality of the product was not observed. Stabilization of the raw materials didn’t lead to a higher FPD. Possible explanations for the unexpected result might be too rough conditions in the stabilization of the drug substance or smaller than wanted difference in the degree of stabilization of the main component of the product <100μm. Despite positive effects on the quality of the product were not seen there appears to be some evidence that stabilized drug substance results in smaller particle size of dry powder inhalers.

Automated design of self-stabilization

Self-stabilization is a property of a distributed system such that, regardless of the legitimacy of its current state, the system behavior shall eventually reach a legitimate state and shall remain legitimate thereafter. The elegance of self-stabilization stems from the fact that it distinguishes distributed systems by a strong fault tolerance property against arbitrary state perturbations. The difficulty of designing and reasoning about self-stabilization has been witnessed by many researchers; most of the existing techniques for the verification and design of self-stabilization are either brute-force, or adopt manual approaches non-amenable to automation. In this dissertation, we first investigate the possibility of automatically designing self-stabilization through global state space exploration. In particular, we develop a set of heuristics for automating the addition of recovery actions to distributed protocols on various network topologies. Our heuristics equally exploit the computational power of a single workstation and the available parallelism on computer clusters. We obtain existing and new stabilizing solutions for classical protocols like maximal matching, ring coloring, mutual exclusion, leader election and agreement. Second, we consider a foundation for local reasoning about self-stabilization; i.e., study the global behavior of the distributed system by exploring the state space of just one of its components. It turns out that local reasoning about deadlocks and livelocks is possible for an interesting class of protocols whose proof of stabilization is otherwise complex. In particular, we provide necessary and sufficient conditions – verifiable in the local state space of every process – for global deadlock- and livelock-freedom of protocols on ring topologies. Local reasoning potentially circumvents two fundamental problems that complicate the automated design and verification of distributed protocols: (1) state explosion and (2) partial state information. Moreover, local proofs of convergence are independent of the number of processes in the network, thereby enabling our assertions about deadlocks and livelocks to apply on rings of arbitrary sizes without worrying about state explosion.

On the thermal stabilization of carbon-supported SiO2 catalysts by phosphorus:evaluation in the oxidative dehydrogenation of ethylbenzene to styrene and a comparison with relevant catalysts

A strategy to enhance the thermal stability of C/SiO2 hybrids for the O2-based oxidative dehydrogenation of ethylbenzene to styrene (ST) by P addition is proposed. The preparation consists of the polymerization of furfuryl alcohol (FA) on a mesoporous precipitated SiO2. The polymerization is catalyzed by oxalic acid (OA) at 160 °C (FA:OA = 250). Phosphorous was added as H3PO4 after the polymerization and before the pyrolysis that was carried out at 700 °C and will extend the overall activation procedure. Estimation of the apparent activation energies reveals that P enhances the thermal stability under air oxidation, which is a good indication for the ODH tests. Catalytic tests show that the P/C/SiO2 hybrids are readily active, selective and indeed stable in the applied reactions conditions for 60 h time on stream. Coke build-up during the reaction attributed to the P-based acidity is substantial, leading to a reduction of the surface area and pore volume. The comparison with a conventional MWCNT evidences that the P/C/SiO2 hybrids are more active and selective at high temperatures (450–475 °C) while the difference becomes negligible at lower temperature. However, the comparison with reference P/SiO2 counterparts shows a very similar yield than the hybrids but more selective to ST. The benefit of the P/C/SiO2 hybrid is the lack of stabilization period, which is observed for the P/SiO2 to create an active coke overlayer. For long term operation, P/SiO2 appears to be a better choice in terms of selectivity, which is crucial for commercialization.

Dynamics of nitrogen and suspended solids removal in experimental stormwater biofilters under intermittent wetting and drying

This research study comprehensively analyses the dynamics of nitrogen and suspended solids removal in stormwater biofilters. The study focuses on pollutant removal during an event with time, rather than the conventional event-mean analysis. Antecedent dry days (number of days in between rainfall) during which biofilters remain dry and the inflow concentration of pollutants were two other important variables analysed in this study. The research outcome highlights the significance of dry-phase processes and the process of stabilization on filter performance and sets a paradigm shift from the current approach towards an innovative way of performance analysis of biofilters.

Effects of the sensorimotor training volume on sensorimotor function in patients following lower limb arthroplasty

Background Sensorimotor function is degraded in patients after lower limb arthroplasty. Sensorimotor training is thought to improve sensorimotor skills, however, the optimal training stimulus with regard to volume, frequency, duration, and intensity is still unknown. The aim of this study, therefore, was to firstly quantify the progression of sensorimotor function after total hip (THA) or knee (TKA) arthroplasty and, as second step, to evaluate effects of different sensorimotor training volumes. Methods 58 in-patients during their rehabilitation after THA or TKA participated in this prospective cohort study. Sensorimotor function was assessed using a test battery including measures of stabilization capacity, static balance, proprioception, and gait, along with a self-reported pain and function. All participants were randomly assigned to one of three intervention groups performing sensorimotor training two, four, or six times per week. Outcome measures were taken at three instances, at baseline (pre), after 1.5 weeks (mid) and at the conclusion of the 3 week program (post). Results All measurements showed significant improvements over time, with the exception of proprioception and static balance during quiet bipedal stance which showed no significant main effects for time or intervention. There was no significant effect of sensorimotor training volume on any of the outcome measures. Conclusion We were able to quantify improvements in measures of dynamic, but not static, sensorimotor function during the initial three weeks of rehabilitation following TKA/THA. Although sensorimotor improvements were independent of the training volume applied in the current study, long-term effects of sensorimotor training volume need to be investigated to optimize training stimulus recommendations.

Algebraic design techniques for reliable stabilization

In this paper we study two problems in feedback stabilization. The first is the simultaneous stabilization problem, which can be stated as follows. Given plantsG_{0}, G_{1},..., G_{l}, does there exist a single compensatorCthat stabilizes all of them? The second is that of stabilization by a stable compensator, or more generally, a "least unstable" compensator. Given a plantG, we would like to know whether or not there exists a stable compensatorCthat stabilizesG; if not, what is the smallest number of right half-place poles (counted according to their McMillan degree) that any stabilizing compensator must have? We show that the two problems are equivalent in the following sense. The problem of simultaneously stabilizingl + 1plants can be reduced to the problem of simultaneously stabilizinglplants using a stable compensator, which in turn can be stated as the following purely algebraic problem. Given2lmatricesA_{1}, ..., A_{l}, B_{1}, ..., B_{l}, whereA_{i}, B_{i}are right-coprime for alli, does there exist a matrixMsuch thatA_{i} + MB_{i}, is unimodular for alli?Conversely, the problem of simultaneously stabilizinglplants using a stable compensator can be formulated as one of simultaneously stabilizingl + 1plants. The problem of determining whether or not there exists anMsuch thatA + BMis unimodular, given a right-coprime pair (A, B), turns out to be a special case of a question concerning a matrix division algorithm in a proper Euclidean domain. We give an answer to this question, and we believe this result might be of some independent interest. We show that, given twon times mplantsG_{0} and G_{1}we can generically stabilize them simultaneously provided eithernormis greater than one. In contrast, simultaneous stabilizability, of two single-input-single-output plants, g0and g1, is not generic.

The Relationship Between Liquidity, Trading Activity and Return - Studies of the Finnish and Swedish Stock Markets

Liquidity, or how easy an investment is to buy or sell, is becoming increasingly important for financial market participants. The objective of this dissertation is to contribute to the understanding of how liquidity affects financial markets. The first essays analyze the actions taken by underwriters immediately after listing to improve liquidity of IPO stock. To estimate the impact of underwriter activity on the pricing of the IPOs, the order book during the first weeks of trading in the IPO stock is studied. Evidence of stabilization and liquidity enhancing activities by underwriters is found. The second half of the dissertation is concerned with the daily trading of stocks where liquidity may be impacted by policy issues such as changes in taxes or exchange fees and by opening the access to the markets for foreign investors. The desirability of a transaction tax on securities trading is addressed. An increase in transaction tax is found to cause lower prices and higher volatility. In the last essay the objective is to determine if the liquidity of a security has an impact on the return investors require. The results support the notion that returns are negatively correlated to liquidity.

Small-scale commercial production of tilapia fry and fingerlings in concrete raceways

This paper discusses the investment prospects in Tilapia fry and fingerling production in raceways created from the concrete drainage channel of a reservoir or pond of an existing fish farm in Nigeria. With an initial capital of 1,300 and an annual operating cost of 310 spent on procurement of fish feed and brood stock for a 10 m super(2) raceway per se, a net profit of 4,100 and 5,090 would be realized from Sarotherodon galilaeus in the first year and subsequent years of production respectively, assuming that the fingerling production rate has been maintained through the production period. It is concluded that the application of this approach of optimizing the use of available resources in the fish farm for the productive breeding of Tilapia fry and fingerlings will apart from alleviating the problem of scarcity of stocking materials in the country, increase the profit margin accruing to the fish farmer

The phytoplankton species composition and abundance of Ogun River, Abeokuta, southwestern Nigeria

The phytoplankton species composition and abundance in Ogun River, Ogun state, Southwest Nigeria was studied for a period of seven months (December, 2011 - June, 2012), a total of forty-one genera belonging to five taxonomic groups were recorded from Ogun River. The phytoplankton species composition was surpassed by Chrysophyta with 15 species consisting of 36.6% followed by Chlorophyta with 14 consisting of 34.1%. This was followed by Cyanophyta (7 species) consisting of 17.1%, Euglenophyta with 3 species consisting of 7.3% and Pyrrophyta with 2 species consisting 4.92%. Cyanophyta was the highest in abundance consisting of 41% while the lowest in abundance was Pyrrophyta consisting of 1.5%. The low nature of phytoplankton abundance and diversity observed in this study must have been caused by the polluted nature of the water due to the anthropogenic activities carried out around its shores The dominance of Cyanophyta in this river is similar to findings from Lake Victoria, Lake Bishoftu, Lake Chaohu and the temple pond of Thirupour.

Seed production and culture techniques of Genetically Improved Farmed Tilapia (GIFT) in brackishwater environment

Effects of different levels of salinity on survival, growth and gonadal development of Genetically Improved Farmed Tilapia (GIFT) were studied under laboratory conditions in glass aquarium, for a period of ten weeks. The initial individual size of the GIFT was 20.23±4.45 and the salinity levels tested were 0, 5, 10, 15 and 20 ppt. The highest survival of 87.5% was found in 0 ppt and the lowest 60.5% in 20 ppt. Though the survival decreased progressively with increased salinity, there were no significant differences (P>0.05) among 0, 5, and 10 ppt. Similar to what has been observed in survival, the specific growth rate (SGR %/day) also decreased as of 1.30, 1.24, 1.08, 0.90 and 0.71, respectively, with the increased salinity of 0, 5, 10, 15 and 20 ppt. The gonadal development was highest in 0 ppt with a GSI value of 3.75 and lowest of 2.01 in 20 ppt. In the second experiment, gonadal development and seed production performance of GIFT in brackishwater condition were investigated for a period of three months. Each of the three fine meshed hapas of 20 square meters made from nylon net was placed in a freshwater (0 ppt) and in a brackish water (10-15 ppt) pond of the Brackishwater Station (BS). GIFT of 65 g average weight from a single cohort were stocked into three hapas at a rate of 2 per m. The male vs female ratio was 1:3. The development of gonad was faster with the higher gonadosomatic index (GSI %) of 3.85 % in freshwater condition than that of 2.73 % in brackish water. Within three months of the study period, a total of 70,510 and 44,250 GIFT fry were produced respectively, in freshwater and brackishwater conditions. Finally under third experiment, a participatory on-farm trial was carried out to evaluate the production performance of GIFT in monoculture and in polyculture with silver barb in coastal freshwater pond conditions. Nine ponds were selected for three treatment combinations of GIFT monoculture (T1), GIFT and silver barb polyculture (T2), and silver barb monoculture (T3). The ponds have been stocked in April, 05 at a density of 25,000 fry per ha. Fishes were fed with rice bran at the rate of 6% bw per day. In one month culture period, GIFT attained an average weight of 16.27 g in monoculture and 17.23 g in polyculture, against an average stocking weight of 0.37 g. Silver barb reached an average weight of 16.62 g in polyculture with GIFT and 10.01 g in monoculture, against an average stocking weight of 3.79 g.

The effect of sucrose on protein stability and fibrillation of prion and S6 protein

Aggregation and fibrillation of proteins have a great importance in medicine and industry. Misfolding and aggregation are the basis of many neurodegenerative diseases like Alzheimer and Parkinson. Osmolytes are molecules that can accumulate within cells and act as protective agents and they can inclusively act as protein stabilizers when cells are exposed to stress conditions. Osmolytes can also act as protein stabilizers in vitro. In this work, two different proteins were studied, the ribosomal protein from Thermus thermophilus and the mouse prion protein. The existence of an unstructured N-terminal on the prion protein does not affect its stability. The effect of the osmolyte sucrose on the fibrillation and stabilization of these two proteins was studied through kinectic and equilibrium measurements. It was shown that sucrose is able to compact the native structure of S6 protein in fibrillization conditions. Sucrose affects also folding and unfolding kinetic of S6 protein, delaying unfolding and increasing folding rate constants. The mechanism of stabilization by sucrose is non-specific because it is distributed for all protein structure, as it was demonstrated by a protein engineering approach. Sucrose delays the process of formation and elongation of S6 and prion protein from mouse. This delay is the result of the compaction of the native structure refered above. However, cellular toxicity studies have shown that fibrils formed in the presence of sucrose are more toxic to neuronal cells.

Histological Outcomes on the Development of New Space-making Devices for Maxillary Sinus Floor Augmentation

Background: Previous studies have pointed out that the mere elevation of the maxillary sinus membrane promotes bone formation without the use of augmentation materials. Purpose: This experimental study aimed at evaluating if the two-stage procedure for sinus floor augmentation could benefit from the use of a space-making device in order to increase the bone volume to enable later implant installation with good primary stability. Materials and Methods: Six male tufted capuchin primates (Cebus apella) were subjected to extraction of the three premolars and the first molar on both sides of the maxilla to create an edentulous area. The sinuses were opened using the lateral bone-wall window technique, and the membrane was elevated. One resorbable space-making device was inserted in each maxillary sinus, and the bone window was returned in place. The animals were euthanatized after 6 months, and biopsy blocks containing the whole maxillary sinus and surrounding soft tissues were prepared for ground sections. Results: The histological examination of the specimens showed bone formation in contact with both the schneiderian membrane and the device in most cases even when the device was displaced. The process of bone formation indicates that this technique is potentially useful for two-stage sinus floor augmentation. The lack of stabilization of the device within the sinus demands further improvement of space-makers for predictable bone augmentation. Conclusions: It is concluded that (1) the device used in this study did not trigger any important inflammatory reaction; (2) when the sinus membrane was elevated, bone formation was a constant finding; and (3) an ideal space-making device should be stable and elevate the membrane to ensure a maintained connection between the membrane and the secluded space.

Brazil and Turkey, a comparative analysis of both countries' economic development and institutional design from the Great Depression to the early 21st century

Apos uma década de rápido crescimento econômico na primeira década do século 21, Brasil e Turquia foram considerados duas das economias emergentes mais dinâmicas e promissoras. No entanto, vários sinais de dificuldades econômicas e tensões políticas reapareceram recentemente e simultaneamente nos dois países. Acreditamos que esses sinais e a sua simultaneidade podem ser entendidos melhor com um olhar retrospectivo sobre a história econômica dos dois países, que revela ser surpreendentemente paralela. Numa primeira parte, empreendemos uma comparação abrangente da história econômica brasileira e turca para mostrar as numerosas similaridades entre os desafios de política econômica que os dois países enfrentaram, assim como entre as respostas que eles lhes deram desde a virada da Grande Depressão até a primeira década do século 21. Essas escolhas de política econômica comuns dão forma a uma trajetória de desenvolvimento notavelmente análoga, caracterizada primeiro pela adoção do modelo de industrialização por substituição das importações (ISI) no contexto da recessão mundial dos anos 1930; depois pela intensificação e crise final desse modelo nos anos 1980; e finalmente por duas décadas de estabilização e transição para um modelo econômico mais liberal. Numa segunda parte, o desenvolvimento das instituições econômicas e políticas, assim como da economia política subjacente nos dois países, são analisados comparativamente a fim de prover alguns elementos de explicação do paralelo observado na primeira parte. Sustentamos que o marco institucional estabelecido nos dois países durante esse período também têm varias características fundamentais em comum e contribui a explicar as escolhas de política econômica e as performances econômicas comparáveis, detalhadas na primeira parte. Este estudo aborda elementos do contexto histórico úteis para compreender a situação econômica e política atual nos dois países. Potencialmente também constitui uma tentativa de considerar as economias emergentes numa perspectiva histórica e comparativa mais ampla para entender melhor as suas fraquezas institucionais e adotar um olhar mais equilibrado sobre seu potencial econômico.

Remoção de matéria orgânica em sistemas de lagoas de estabilização no Nordeste brasileiro

Stabilization pond is the main technology used for treatment wastewater, in northeast Brazil, due to lower cost of deployment, operation and maintenance compared to other technologies. Most systems of stabilization ponds has been in operation for some time, on average 10 years of operation, receiving high organic loads and do not have good removal efficiencies of the main parameters for which have been designed. Therefore it is necessary to work to quantify the efficiency of current systems. This study evaluated the biodegradability of organic matter in raw sewage, the removal of organic matter in reactors and determination of the kinetic constant removal of organic matter (k), both in reactors and in raw sewage, based on the analysis made in the laboratory and through mathematical methods proposed in the literature, in nine systems stabilization ponds, located in Rio Grande do Norte. In relation the degradation kinetics in stabilization ponds, it was observed that many papers published in the literature were obtained in pilot-scale systems, which often, due to the action of external factors such as wind and temperature, these can t be considered as a reference in the analysis of the kinetic constant K, so the need for more research into systems of scale. This study had three distinct phases and simultaneous, routine monitoring, study of the daily cycle and the determination of kinetic constant of degradation of organic matter (K). The monitoring showed that the removal efficiencies of organic matter on most systems were lower than suggested by the literature, the best efficiencies of around 76% (BOD) and 72% (COD) and the worst of the order of 48% (BOD) and 55% (COD). The calculation of K in raw sewage (Ke) was within the range of variation expected in the literature (0.35 to 0.60 days-1). Already for the results obtained for K in the reactors (Kr), there were well below the values recommended in the literature (0.25 to 0.40 d-1 for complete mix and from 0.13 to 0.17 d-1 for flow dispersed), in line with the overloads that organic systems are subject

Avaliação da flotação por ar dissolvido no polimento de efluentes de lagoa de estabilização

Experience in the use of stabilization ponds shows that this is a system with low cost, easy operation and maintenance and suitable for tropical countries. One of its disadvantages is due to high concentrations of suspended solids, mainly due to algal biomass in the effluents. Accordingly, the dissolved air flotation has been shown to be an efficient post-treatment technology. However, the efficiency of this process is related to coagulation and flocculation steps, as well as the adjustment of the involved variables in the process. The objective of this work was to evaluate the algae removal efficiency from wastewater stabilization ponds and the influence of the factors involved in the process using dissolved air flotation. For this, we used primary facultative and maturation effluents of ETE Ponta Negra in Natal. We did tests of coagulation, flocculation and flotation with the samples, using the equipment flotatest. In this process were tested coagulants aluminum sulfate and ferric chloride, and varied the factors pH, coagulant concentration, polymer concentration and rate of recirculation. At the end of the experiments were analyzed turbidity, suspended solids, color, COD and chlorophyll "a". These results were submitted to descriptive statistics to verify the efficiency of the process in general, and regression analysis to identify models that describe the process and demonstrate the factors that have greater influence on flotation. After step methodology, high values were found removal efficiency of suspended solids, reaching values greater than 90% in the best cases. It was concluded that flotation is more efficient in the facultative pond effluent using ferric chloride, and the variability of algae may negatively influence the process. Regression analyzes showed that pH is the most influential variable in the coagulation-flocculation-flotation, and its optimal value among the tested is 5.5 for both coagulants