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The Scientific World Journal
Volume 2012 (2012), Article ID 605610, 15 pages
Robust Optimization of Alginate-Carbopol 940 Bead Formulations
1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, C/ Professor García González 2, 41012 Seville, Spain
2Department of Industrial Management, School of Engineering, University of Seville, C/ Camino de los Descubrimientos s/n, 41092 Seville, Spain
Received 31 October 2011; Accepted 8 December 2011
Academic Editor: Ali Nokhodchi
Copyright © 2012 J. M. López-Cacho et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Formulation process is a very complex activity which sometimes implicates taking decisions about parameters or variables to obtain the best results in a high variability or uncertainty context. Therefore, robust optimization tools can be very useful for obtaining high quality formulations. This paper proposes the optimization of different responses through the robust Taguchi method. Each response was evaluated like a noise variable, allowing the application of Taguchi techniques to obtain a response under the point of view of the signal to noise ratio. A Taguchi orthogonal array design was employed to investigate the effect of eight independent variables involved in the formulation of alginate-Carbopol beads. Responses evaluated were related to drug release profile from beads ( and AUC), swelling performance, encapsulation efficiency, shape and size parameters. Confirmation tests to verify the prediction model were carried out and the obtained results were very similar to those predicted in every profile. Results reveal that the robust optimization is a very useful approach that allows greater precision and accuracy to the desired value.
1. Introduction
The use of natural polymers for the design of drug delivery systems has long been the subject of great interest during the past decades. Sodium alginate is a sodium salt of alginic acid, a naturally occurring nontoxic polysaccharide found in marine brown algae. Alginate has been widely used as food and pharmaceutical additives, such as tablet disintegrant, thickening, and suspending agent. It contains two uronic acids, α-L-guluronic (G) and β-D-mannuronic acids (M), and is composed of homopolymeric blocks and blocks with an alternating sequence [1]. This polymer can form a reticulated structure when it contacts with Ca2+ and thus it has been used to produce sustained release particulate systems for various drugs, proteins, and even cells [2–4]. Gelation occurs by an ionic interaction between the calcium ions and the carboxylate anions of G-G blocks as calcium ions diffuse from the external source into the droplet forming a polyanionic microcapsule.
The addition of a polycation (poly-L-lysine or chitosan) to the gelation medium induces the formation of polyanionic-polycationic complexes, which stabilizes the ionic gel network and reduces the alginate permeability [5, 6].
The main advantage of using alginate to encapsulate drugs is that the alginate gelation process occurs under very mild conditions without using high temperatures or chemical crosslinking agents. Another advantage of using alginate is that the alginate gel can also be converted to sol by adding chelating agents, such as Na+ and EDTA. However, the drug releasing properties of Ca-sodium alginate matrices suffer from some serious problems. Firstly, the drugs could be leaked during the gel formation due to the long immersion time, which decreased the encapsulation efficiency. Secondly, the burst release of the drugs from pure Ca-sodium alginate beads is severe due to the quick breakdown of beads in the in vitro release process. Currently, much effort has been made for improving the performance of Ca-sodium alginate beads as drug delivery carriers.
Therefore, many factors are involved in the formulation of alginate microspheres. Some of them are summarized in Table 1.
Drug release from calcium-alginate beads depends on the swelling of the beads and the diffusion of the drug in the gel matrix [17]. Although alginate beads do not swell appreciably in acidic fluid [18], the beads swell and erode/disintegrate rapidly in the intestinal fluid, leading to a quick release of the loaded drug within a few minutes [6, 19] and hence calcium alginate matrix alone does not seem suitable as an oral controlled release system [20].
Polymeric materials have been widely used in order to conveniently modify and modulate the drug release from controlled-release microparticles. However, a large number of factors, including the chemical-physical properties of the raw materials (both drug and excipients), the composition and the relative amounts of the components in the formulations, as well as the manufacturing process parameters, can influence the drug release behavior from the final products [6, 7, 21, 22].
In the present study, we attempted to reinforce calcium-alginate beads containing methylene blue as a model drug by incorporating Carbopol 940 as hydrophilic polymer. This is a poly acrylic acid in anionic form that contains many free hydroxyl groups. Since it can form a gel, it has been used in combination with other polymers to control the drug release.
There are previous reports about the effect of carbomers on characteristics of calcium-alginate beads [23, 24] but not for Carbopol 940. Therefore, we intended to investigate the effect of this hydrophilic and swelling polymer on release behavior of calcium-alginate beads.
The preparation of calcium-alginate beads for drug entrapment is a stepwise procedure. The industrial experimentation includes a great number of parameters and a full factorial design that yield large number of experiments. Conventional optimization procedures involve altering one independent factor at a time keeping all others remain constant, which enables to assess the impact of those particular parameters on the process performance. These procedures are time consuming and cumbersome because require more experiments and cannot provide information about the mutual interactions of the parameters [25]. To reduce these numbers of experiments, a small set of trials with all possible combinations is selected by using various statistical tools [26].
Statistical experimental design methods, such as the fractional factorial design [8], the Plackett-Burman method [27], response surface methodology [28], the Box-Behnken design [29, 30], and the Taguchi method [31], provide a systematic and efficient plan for experimentation to achieve certain goals so that many control factors can be simultaneously studied. In contrast to the traditional "one-factor at a time" approach, these methods can be used to examine and optimize the operational variables while considering the interactive effects among the control factors.
The Taguchi method focuses on product robustness against uncontrollable influences, or noise. The method is designed to reduce variability, and optimize function or performance with the lowest cost components. Taguchi method of orthogonal array design of experiment (DOE) involves the study of any given system by a set of independent variables (factors) over a specific region of interest (levels). This approach also facilitates to identify the influence of individual factors, and establish the relationship between variables and operational conditions. In this methodology, the desired design is sought by selecting the best performance under conditions that produce consistent performance [32] and the results from small-scale experiments are valid over the scale up schedule [33].
Robustness is essential in the production of nearly all products. The variation in the quality of the product may follow from environmental factors and/or manufacturing variables that cannot be easily controlled (noise factors). In addition to emphasizing that the variability in the quality of the product and factors interactions should be reduced [34], the Taguchi method uses the signal-to-noise ratio (), which is directly transformed from the quadratic quality loss function, as a measure to determine the robustness of a process. Thus, optimizing process parameters by the Taguchi method is an attempt not only to bring the average quality near to the target value, but also to simultaneously minimize the variation in quality [35]. Therefore, this method has been extensively applied in industry and its application caused significant changes in several industries, in manufacturing processes and total quality control [36–38].
This technique is somehow not very well known for optimization of pharmaceutical processes. This paper offers a rapid and efficient methodology to study and optimize pharmaceutical formulations, based on the Taguchi orthogonal array design. To do this, as an example, we used alginate-Carbopol beads formulated by ionotropic gelation with methylene blue (MB) as hydrophilic drug model.
After the selection of noise and control factors, we selected the profiles (responses) to optimize with the aim to demonstrate the applicability of this methodology in the optimization of different profiles such as drug release, swelling rate, or the morphology of the beads. Afterward, the experimental design and data analysis procedure, we selected the best profiles for Taguchi optimization and then we compared the results with predicted ones by lineal regression. Finally we compared the accuracy of the optimization.
2. Materials and Methods
2.1. Materials
Sodium alginate (viscosity 2% w/v: 250 cP) and triethanolamine (TEA) were purchased from Sigma Aldrich. Calcium chloride (Panreac, Spain) was selected as cation donor salt. MB was used as hydrophilic drug model. Carbopol 940 (Acofarma, Spain) was added to control the drug release from the alginate beads. Sodium tripolyphosphate and Tris(hydroxymethyl) aminomethane (TRIS) were obtained from Sigma (Spain).
2.2. Preparation of Beads
The beads were prepared by following the extrusion/precipitation method [39, 40]. Briefly, a sodium alginate aqueous solution containing 0.01% (w/v) MB and 2% (w/v) of sodium alginate was prepared by a simple mixing step. Carbopol 940 was dispersed in purified water and then was added to the above solution. As a function of the experiment, TEA was added to this solution. The beads were prepared by dropping the alginate-Carbopol solution (50 mL) containing MB from a syringe using a perfusion pump (Perfusor fm, Braun), through a 0.9 mm diameter needle into a gently stirred 0.25 M calcium chloride aqueous solution (IKA Eurostar). Different concentrations of Carbopol, at different dropping rate and stirring rates were used, as was reported in Table 2. The obtained hydrogels were maintained into the calcium chloride solution for different time periods to complete the chemical reaction. The beads were collected by decanting the calcium chloride solution, washed with deionized water and dried to a constant weight. At this stage, different drying methods were used: room temperature (20°C), rotary evaporator (reduced pressure, vacuum and 80°C), or oven (100°C).
2.3. Characterization of Beads
2.3.1. Entrapment Efficiency
The MB content in the dry samples was determined by dissolving the beads, previously weighed, in a tripolyphosphate solution (0.03 M; 100 mL). The resulting solution was filtered and the drug concentration was analyzed by UV spectrophotometry, at 664 nm, using a UV-visible spectrophotometer (Hitachi U-2000). Entrapment efficiency was calculated as the percentage (w/w) of the theoretical drug content. Results were based on triplicate determinations.
2.3.2. In Vitro Drug Release Studies
The drug release profiles of beads were determined using the USP 28 paddle method. The dissolution medium was 900 mL (sink conditions) of Tris-buffer solution adjusted at different pH and NaCl concentration values as a function of the experiment. The stirring speed was 50 rpm and the temperature was maintained at °C. Accurately weighed samples of 700 mg beads were used for the test. At selected time intervals for a period of 420 min, aliquots each of 3 mL were withdrawn from de dissolution medium through a 0.45 μm membrane filter and replaced with an equivalent amount of the fresh dissolution medium. Concentrations of MB were then spectrophotometrically determined at 664 nm. Each experiment was carried out in triplicate and the results were averaged.
Tris-buffer solution was selected as the dissolution medium because in the formation of alginate gel, alginate reaction with calcium ions turns reversible with sodium ions, and a disaggregation of the beads occurs [6]. We selected this buffer to control swelling process by modifying NaCl concentration.
2.3.3. Swelling Process
The amount of absorbed water was determined following described methods by many authors [7, 41, 42]. In a first stage, a certain number of beads, accurately weighed (), were placed in glass beakers containing 80 mL of tris-buffer and NaCl concentration set by DOE. Next, the glass beakers were placed in a thermostatic bath at 25°C and 150 rpm. At time intervals of 1 h, beads were filtered and weighed ().
Swelling percentage () was calculated using the following expression [43]: where is the wet weight of beads and is the initial weight of beads.
2.3.4. Morphological Properties of Beads
Morphological characteristics of beads were observed by Scanning Electron Microscopy, SEM (Philips XL30). The samples were sputter-coated with Au/Pd using a vacuum evaporator (Edwards) and examined at 20 kV accelerating voltage.
The size and shape of the beads were determined using image analyzer software (Image Pro Plus). The length and breadth were measured from the digital images of each bead and its size calculated from the average of these two dimensions [44].
For each formulation, 30 beads were randomly selected for measurement; the results were then averaged.
2.4. Optimization Methodology
Optimization methodology adopted in this study was divided into four phases (with various steps): planning, performance, analysis, and validation. The schematic representation of the designed methodology was depicted in Figure 1 (modified from [34]).
2.4.1. Phase I. Planning
Defining the Problem and the Goal
First step in Phase I is to determine the factors to be optimized in the production and characterization of alginate-Carbopol beads that have critical effect on the drug release, encapsulation efficiency, and in the morphological properties of the beads. The goal is to evaluate the effect of different factors on the elaboration of the beads and to obtain the perfect combination between the levels of the factors to optimize theirs properties.
Identifying the Factors to Be Optimized
Six process parameters (flux rate, stirring rate, incubation time, drying mechanism, NaCl concentration, and pH of the dissolution medium) and two formulation parameters (presence of TEA and Carbopol concentration) were evaluated. The normal practice is to experiment with the feasible range, so that the variation inherent in the process does not mask the factors effects. The controls factor and theirs levels are exposed in Table 2.
Identifying the Test Conditions to Optimize
The responses to be optimized from the characterization of alginate-Carbopol beads are those that have critical effect on the drug release, encapsulation efficiency, and morphological properties of the beads. Selected responses are exposed in Table 3.
Experimental Design and Data Analysis Procedure
The fundamental principle of the Taguchi method is to improve the quality of a product by minimizing the effect of the causes of variation without eliminating the causes [45]. Three major tools used in the Taguchi method are the orthogonal arrays, analysis of variance (ANOVA), and the signal to noise ratio ().
The Taguchi approach provides an opportunity to select a suitable orthogonal array depending on the number of control factors and theirs levels [46]. The orthogonal arrays give equal credence to all the parameters being investigated while ANOVA determines the contribution of each parameter in the design of the experiment. This is a fractional factorial approach and reduces the number of experiments.
Orthogonal array is a matrix of numbers arranged in rows and columns. Each row represents the level of factors in each run and each column represents a specific level for a factor that can be changed for each run.
ratio is an indicative of quality, and the purpose of the Taguchi experiment is to find the best level for each operating parameter to maximize the ratio [47]. Analysis of the experimental data using the ANOVA and effects of the factors gives the output that is statistically significant for finding the optimum levels.
In the Taguchi method, quality is measured by the deviation of a characteristic from its target value, and a loss function is estimated for the deviation as , where denotes the proportionality constant, represents the target value and is the experimental value obtained for each trail. In case of bigger and better quality characteristics, the loss function can be written as and the expected loss function can be represented by: where ) can be estimated from number of samples as:
In order to measure the quadratic loss function, the Taguchi introduces the signal-to-noise () ratio for measuring the quality through orthogonal array based experiments. ratios take into account both the variability in the response data and the closeness of the average response to a target value. The ratio characteristics can be divided into three categories when the variable is continuous [48]:nominal the best:smaller the better:bigger the better:
where is the average of observed data, is the number of observations, and the observed data for the th run. In the nominal best study, and are nominal values those are to be achieved.
For each type of characteristics, with the above ratio transformation, the higher the ratio, the better is the result. The uncontrollable factors which cause the functional characteristics of a product to deviate from their target values are called noise factors. The overall aim of quality is to make products that are robust with respect to all noise factors [49].
The design was performed by an array. In the present study, three levels of seven factors and two levels of one factor (Table 2) were considered and the size of experimentation was represented by symbolic array of (which indicated 18 experimental trials) (Table 2). The three levels of all the factors have been assigned (except TEA (21)), with a layout of .
2.4.2. Phase II. Performance of Experiments
After phase I, in which the factors to be optimized, theirs levels and the experimental matrix were selected, the experiments were carried out by triplicate (Table 4) and the selected variables were determined.
2.4.3. Phase III. Analysis of the Data and Optimization
Analysis of Data
At this stage, a statistical analysis of variance was performed to determine which test parameters were statistically significant for every variable. Moreover, the influence of each factor on the different response variables selected was determined.
After the analysis of the data, we proceeded to determine the optimal set parameter configuration. Optimization process was made applying the marginal means methodology (also called average rate or main effects analysis).
In order to do that, we obtained the average value of ratio of every variable in every level of response and then the results were plotted in a graphic of marginal means. In the Taguchi method, we always tried to maximize the ratio, so we select the levels with the higher values of ratio in every factor that give us the maximum final ratio. The difference in every response is the method followed for the consecution of the ratio, as it was explained before. ratios for every variable were obtained as Table 3 exposes.
2.4.4. Phase IV. Validation Experiments
With ratio and ANOVA analysis, the optimal combination of the testing parameters could be predicted for a 95% confidence level. Also we can predict the future results that every combination is going to obtain by regression of the main influencing factors according to the ANOVA.
In order to validate this methodology, validation experiments were further performed using the optimized conditions obtained for each response and then the results will be compared to the predicted by regression. If final results are similar to the predicted, we could validate the proposed methodology.
3. Results and Discussion
The application of the experimental design methodology has the objective of identifying the most significant factors influencing the formulation of alginate-Carbopol beads containing a water-soluble drug, and establishing the best levels for optimizing different response variables.
Results obtained for these parameters, expressed as mean values, are presented in Table 4. ANOVA could be used as a tool for the detection of main effects. Data reported in Table 5 revealed that the release parameters (i.e., and AUC of release profiles) were significantly affected by Carbopol concentration and addition of TEA into the polymeric solution. Also, the presence of TEA significantly influenced on the entrapment efficiency and the particle size, whereas the swelling percentage was also affected by the NaCl concentration into the dissolution medium. Finally, the morphological parameters, expressed as shape factor, were mainly affected by the drying procedure and the stirring rate applied from the stirrer apparatus.
Contribution degrees of each factor to every response have been graphically showed in Figure 2. These findings will be discussed in next sections.
3.1.1. Release Profiles: Time to Release 50% of Entrapment Drug () and Area under the Curve (AUC)
As shown in Table 5, all factors except the NaCl concentration exert significant influence on . In the case of AUC, NaCl concentration neither pH had influence on this response. From Figures 2(a) and 2(b), we can conclude that the Carbopol concentration (factor B) had the most significant effect on release characteristics. However, this effect is positive in case of (97.11) and negative in case of AUC (−6316).
The influence of the Carbopol percentage on drug release profile is due to the effect of this polymer on the structure of the beads, as was discussed by other authors [50]. The density of the beads increases as the concentration of this polymer increases, suggesting that the beads formed at higher concentrations are more compact and less porous than those prepared at low polymer concentration [7]. The presence of a higher network density in the structure has been demonstrated by other authors in the preparation of Carbopol and PVP microspheres [16, 50]. Moreover, taking into account the swelling properties of this hydrophilic polymer, it is confirmed that the presence of the gel layer thickness acts as a barrier for the penetration medium thereby retarding the diffusion of MB [7, 11].
All these contribute to produce a slowing in MB release rate (increasing the ), making difficult the output of the drug to the dissolution medium (diminishing the AUC).
3.1.2. Entrapment Efficiency
According to ANOVA analysis, the factor with higher contribution and statistical significance on the entrapment capacity of the drug was the incorporation of TEA into formulations.
TEA is a weak base that ionizes carboxylic groups in the chains of carbomers. As a result, the structure of the gel changes its conformation, going from a relaxed state in spiral form to a rigid form, which provides viscosity and consistency to the beads. This structural conformation increases the entrapment efficiency. The same results have been obtained by other authors when they added chitosan to the alginate matrix to prepare beads [5].
Once the base was added, the increase of entrapment efficiency is as consequence of the creation of a higher network density and the electrostatic interaction between the drug and the polymers [16]. At the end of the process, the resulting beads become harder and thicker, favoring entrapment efficiency inside the beads but making difficult its later release.
3.1.3. Swelling Percentage
After the ANOVA analysis, we can determine that practically all factors have statistical influence on this dependent variable. The factor presenting the higher influence was NaCl concentration in the dissolution medium followed by TEA addition and Carbopol concentration.
According to ANOM test for the factor NaCl concentration (data not showed), the presence of sodium ions acts hindering the swelling process. Swelling percentage will increase as NaCl concentration decreases ().
This result can be explained on the basis of the swelling mechanism of these polymeric structures alginate-Carbopol. It is well accepted that the alginate beads in an aqueous medium without sodium ions do not swell well, but when these ions are present in the medium, the preformed complex between the alginate and calcium turns unstable [51, 52]. This could be explained by the ionotropic phenomenon that occurs between the Ca2+ ions of the alginate beads and the Na+ ions present in release medium that finally produces a capture of the Ca2+ by the chlorine ions. This fact produces a disaggregation of the bead structure leading to erosion and dissolution of the swollen beads and increasing the drug release rate [5, 9, 51]. This can be appreciated in Figure 3, where beads corresponding to batch 11 with higher NaCl concentration have lower swelling percentage at the same time than others.
In addition, TEA incorporation produces a rigid structure inside the beads and increase carboxylic groups with negative charge. These groups have a high affinity for water molecules so more quantity of water can get inside the bead, increasing the swelling of the beads in time and intensity. These results were visualized by photographing the samples during the swelling process tests. We can notice a higher swelling in batches with TEA addition (Figure 4) than in other lots without TEA at the same time.
3.1.4. Shape Factor
According to ANOVA analysis, the stirring rate and the drying method of beads are the factors that have the higher influence on this morphological parameter.
Stirring rate has an important statistical significance concerning the shape and size parameters [7]. When alginate-Carbopol drops fall into CaCl2 solution, stirring rate produce a force that molds the final morphological aspect of the beads, in relation to their shape and surface. As the stirring rate increases, beads will be less spherical and more irregular in its surface, which produces an increase of shape factor and a decrease in its circularity (inverse of SF), as we can demonstrate in Figure 5.
From the evaluation of the drying process, we must keep in mind the characteristics of every treatment, because they can affect many properties of the beads [40]. Drying technique could influence several bead characteristics such as size [53–55], shape, mechanical properties [54], swelling properties [54, 55], drug release kinetics [56] and even drug migration to periphery of the beads along with water during drying [53, 57].
When the beads were dried at environmental conditions, the water evaporation is slow and progressive. This slow loss of water allow the colloidal structure to settle slowly without getting to fracture point, obtaining at the end more spherical and smooth beads (Figure 6(a)).
During the oven process, the drying temperature was about 100°C and hence, heat energy was supplied to the system, producing a strong and quick loss of water from the beads. As a consequence, the shape was altered producing roughs on the surface of the beads (Figure 6(b)).
When the gelled structures were yielded in a rotary evaporator, the process was submitted to 80°C into a thermostatic bath and applying vacuum. In this case, the evaporation process is quicker than oven process even when we are applying less temperature. With the quicker loss of water, we obtain more irregular beads than oven process but with lesser imperfections on the surface of the beads (see Figure 6).
Analyzing the effect produced by the different characteristics of each drying method, we can conclude that the irregular surface of the beads may be resulted mainly from the heat energy and the alteration on the shape of the beads is determined by the water loss rate.
All these characteristics not only are going to influence on shape and size parameters, but also they are going to affect the release process [40]. As higher are size parameters we are going to obtain a quick release rate. In other words, the use of rotary evaporator as drying method will give rise to a quicker but less controlled drug release (low with high AUC).
3.1.5. Diameter Medium
According to ANOVA test, TEA addition was the most significant contributor factor on particle size of the beads. As was explained above, the solutions containing TEA were more viscous. Then, when this polymer solution was dripped into CaCl2 solution, the gelled beads presented higher sizes and higher entrapment efficiencies [7].
3.2. Determination of Optimal Conditions Using Taguchi Robust Methodology
The appropriate selection of the parameters can improve the quality of the product, especially when at least two quality characteristics are to be simultaneously considered. The selection of the response parameters should account for the objectives of the study and the feasibility and ease of handling the optimization process [33].
The previous experiments revealed that the selected factors affected the release profile, the entrapment efficiency, the swelling process, and the morphological and dimensional properties of the beads depending to the analyzed variable. In the beginning of the optimization process, the marginal means graph for every response variable at each level of factors has been determined (Figure 7). Following these directives, we could select the best combination of factors and their levels that will give us the best results for each profile (Table 6).
In order to validate this methodology, the confirmation tests were performed using their optimal combination of parameters levels. By using the predicted optimal combinations (Table 7) and a forecasting procedure (using linear regression) we can evaluate the adequacy of the optimizations if theirs results are closer to the predicted values.
For every evaluated response and following the combinations obtained by the Taguchi optimization and after confirmation tests by triplicate, we could see that predicted results are inside the confidence intervals obtained by practically all the optimal batches.
The Taguchi optimization selects the best combination under conditions that produce consistent performance to obtain as possible an optimal value. In the Taguchi method, the robustness of a process is taken into more consideration than the final value of the optimized response.
The success of the results by applying the Taguchi method is partly due to the ability to get good results in formulations or contexts with high variability. As argued in earlier sections, this variability is not always controllable by the researcher, so efficient methods to work in uncertain environments are always interesting to apply.
Applying the Taguchi method to our results, we demonstrated that Taguchi method makes the final product less sensitive to variations than classical optimizations and that this methodology can be used as a tool for the optimization of other pharmaceutical forms.
4. Conclusions
In the present work, we have focused on the applicability of the Taguchi robust methodology in the pharmaceutical field to optimize pharmaceutical processes. A technological process based on the production of alginate-Carbopol beads has been selected as an example, taking into account our experience in that field.
Various formulation variables such stirring rate, flux rate, reaction time, drying method, and polymer concentration, and other variables such as NaCl concentration and pH were selected in the study. The influence of these parameters on drug entrapment efficiency, particle size, surface morphology, swelling behavior, and in vitro drug release has been analyzed.
From the ANOVA tests, it may be concluded that the drug release rate from the beads was mainly affected by the Carbopol concentration and the stirring rate of the stirred during the bead formation process. The alginate-Carbopol MB-loaded beads had higher swelling percentages in absence of NaCl in the dissolution medium, and using higher polymer concentrations and with TEA into the polymeric solution. Beads dried at ambient conditions showed more satisfactory sustained release profile.
The Taguchi design method was used to optimize the parameter values for obtaining the desired characteristics. Finally, the confirmation tests to verify the model prediction were carried out and the obtained values were very similar to the predicted ones. This result reveals the feasibility of robust optimization. Therefore, this methodology was then validated, being a perfect complement to the classical DOE methodology in environments with high variability and noise conditions.
The authors declare no financial relationships related to any products involved in this study that might lead to a conflict of interest.
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Call for crossings to be closed after man dies in collision with King's Lynn to London train at Ten Mile Bank, near Downham Market
PUBLISHED: 00:02 13 July 2012 | UPDATED: 10:26 13 July 2012
© Archant Norfolk 2012
An investigation was under way last night after a man died when a train was in collision with a car on a remote level crossing in the Fens.
Call to close level crossings with a history of crashes in the Fens
Yesterday's crash is the latest in a string of collisions to have occurred on crossings in the Fens between King's Lynn and Ely.
Some have automatic barriers. But others, like the crossing where yesterday's fatal collision occurred, have manually-operated gates and depend on flashing lights to warn drivers of an approaching train, which could be travelling at 70mph or more on open stretches of the line.
Manuel Cortes, leader of the Transport Salaried Staffs' Association union, said: "Level crossing fatalities are the biggest killer on our rail network. Road and rail just do not mix in a fast-moving transport system with trains moving at up to 90mph.
"The sooner Network Rail starts to close these potential dangerous crossings, the better it will be for both rail passengers and road users."
The crash happened after the London-bound First Capital Connect service from King's Lynn collided with a silver Kia Sportage, on a farm crossing without barriers between Ten Mile Bank and Welney, at around 1.15pm.
Its warning lights were still flashing yesterday afternoon, along with those on a nearby road crossing, as crash investigators worked to piece together how the 4x4 had ended up in the path of the train.
Last night Manuel Cortes, leader of rail union the Transport Salaried Staffs' Association, said: "The sooner Network Rail starts to close these potential dangerous crossings, the better it will be for both rail passengers and road users."
Police said the driver was pronounced dead at the scene, while all 65 people on board the 1.56pm service from Lynn to King's Cross escaped unhurt. Passengers were taken off the train to continue their journey by coaches at around 4pm.
Many were visibly shaken as they were led away up the line towards the buses, before being driven from the crash scene.
What remained of the car was crumpled beneath the front carriage of the train. The dead man's name was not being released last night, but officers said his family had been informed.
A spokesman for Magpas Helimedix, which flew doctors to the crash scene by helicopter from its base near Huntingdon, said: "The Magpas doctor pronounced the death of a male driver of the car on the scene, our thoughts are with his family and his friends at this time.
"The Helimedix team also checked the welfare of the passengers on the train and found no one to be injured."
The car was pushed 500m down the line by the train, which was believed to have been travelling at 70mph when the impact occurred on a straight section of single track.
All four coaches remained on the rails, as they came to a halt beyond a second crossing where the line crosses the Ten Mile Bank to Welney road.
A British Transport Police (BTP) spokesman said: "BTP officers were called to Pleasant level crossing, near Downham Market, following a report of a car being struck by a train.
"Norfolk and Cambridgeshire officers also attended the incident, which was reported to BTP at 1.15pm, along with local fire and ambulance services. The driver of the vehicle was pronounced dead at the scene.
"Police are currently working to establish the full circumstances including how the car came to be on the tracks."
Train passenger Ashley Tuttle, who was travelling from King's Lynn to Cambridge on a shopping trip with her boyfriend Alex Nevozajs, said: "Suddenly we felt this massive bang and there was loads of smoke and debris flying past the window."
Student Miss Tuttle, 17, said windows on the train were scratched by flying debris, before it came to a halt.
"It was quite scary," she said. "There was quite a lot of smoke and they didn't really tell us what was going on for about 10 minutes."
Joshua Palmer, who lives next to the crossing where the crash happened, told reporters he was at home listening to music when he heard a loud crash. He said he saw a cloud of smoke as he looked outside.
Insp Bob Munn, heading the British Transport Police investigation at the scene, said there were no suspicious circumstances and the crash was being treated as an accident.
Parts of the car and pieces of ballast were strewn along the line, which runs through open farmland as it approaches Littleport.
Last night Station Road, between Ten Mile Bank and Welney, remained closed in both directions near the Cross Drove junction.
Trains between Downham and Ely were replaced with shuttle buses, while services to and from London started and terminated at Ely. Services are expected to return to normal later today.

subset: commoncrawl


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The Airbnb debate rumbles on – the brand strategists hit back!
Two weeks ago we featured DesignStudio's Airbnb logo. One week ago copywriter Rob Mitchell of We All Need Words wrote an Opinion piece calling for an end to convoluted brand stories. His article was cheered by some people and incensed others; Sam Peskin and Liam Hamill of VentureThree want to have their say and defend brand strategy. Again you can add your views using the comment thread below…
To say that the Airbnb rebrand has polarised opinion is to put it lightly. But in evaluating all of the contributions so far, perhaps the most curious thing is the apparent disconnect in critical response between the design and strategy disciplines. For a piece of work that is so clearly defined by a sense of 'joined-up' thinking, there have been very few responses that have considered the project as it was executed and intended – holistically.
It begs the question of what we really mean when we talk about a rebrand. Is it just a fancy way of justifying the redesign of a logo? Or is it something bigger?
In this column last week, Rob Mitchell of We All Need Words criticised the "puffed-up nonsense" that went into "justifying the logo" as an "over-cooked brand story masquerading as strategy".
We sympathise with Rob in that we're painfully familiar with agency processes that sound exactly like this. Strategy has gotten a bad reputation from valueless navel-gazing like "If your brand was an animal, what would it be?" Not to mention the constant agonising over "pyramids" and "playbooks" when what really matters is the power of the thinking that goes into them.
In a world where it is possible to analyse the 50 most successful businesses of the past century, and prove "a cause-and-effect relationship between financial performance and their ability to connect with fundamental human emotions, hopes, values, and greater purposes" (Jim Stengel, Grow), an approach to brand as logo and words, as Rob appears to champion, simply doesn't cut the mustard. Such a definition massively underplays the value of brand as a force for business and the world.
We all pride ourselves on having sensitive bullshit detectors. And yes, there's a lot of it around. But here's the simple truth: businesses that stand for something bigger than their product, and seek to have a meaningful impact on the world, enjoy more success and more longevity than those that don't.
They connect with consumers on a different level. They give their employees a clear and inspiring reason to get out of bed in the morning. They set the direction for how they want to develop and grow.
They do this through understanding that brand goes beyond a logo, an identity and even marketing. It defines your purpose and reason for being. It represents what you stand for and believe in. It drives culture and performance, product innovation, the customer experience and more. It gives people belief, pride and motivation. Businesses that embrace brand in this way do better. Simple.
"Here's the simple truth: businesses that stand for something bigger than their product, and seek to have a meaningful impact on the world, enjoy more success and more longevity than those that don't."
Sam Peskin and Liam Hamill
IBM's "smarter planet" brand idea had nothing to do with clever words and logos. It was all about the power of an idea to drive business change and action. Persil's "dirt is good" whilst a clever and unexpected turn of language came from forensic strategic insight into the attitudes of parents towards play and cleanliness. Sky's "believe in better" isn't just a tagline, it's a philosophy that drives the entire culture of the business.
John Mackey, the founder of Whole Foods who is not a planner, strategist or brand manager puts the power of brand for business better than we ever could: "Every business has the potential for some other higher purpose besides just making money. Of course, it has to make money just like my body has to make red blood cells if I'm going to live. But the purpose of my life is not to produce red blood cells. My purpose is more transcendent than that. Similarly, business has that purpose for some type of larger contribution to society. So business people need to begin thinking in those terms… What is the value that it's creating for other people? What is its contribution to the larger society?"
This is what the Airbnb brand aspires to; brand as purpose and idea, not product, logo and words. "Belong anywhere" isn't about justifying a design solution, it's about unifying the company's efforts behind a meaningful and valuable strategic direction.
When all's said and done, perhaps giving a logo a name like a character from the Jungle Book strays a little into the land of brand bollocks. But the overall thinking and ambition behind Airbnb's rebrand is to be admired.
- Standards Manual return with catalogue of 400 objects relating to New York City Transit
- Emma King's publication rewrites Orwell's "1984" using Donald Trump's tweets
- It's a new dawn, it's a new day – it's Best of the Web!
- Bolade Banjo photographs the perseverance of Detroit's student athletes
- Alex Grigg animates Steve Stoute's homage to Biggie Smalls
- Billy Clark applies his graphic sensibilities to his minimal yet textured illustrations
- Polaroid's creative director Danny Pemberton introduces new brand Polaroid Originals
- Artist Dominique Pétrin on creating her very own domestic product
- Universal Everything animate emotive wallpapers for new iPhone devices
- Herburg Weiland's meticulous editorial designs are typographically-driven
- The Visual History of Type author Paul McNeil selects and dissects his six favourite faces
- Breakdown Press' Joe Kessler picks out his most-treasured books


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Time Warner Cable Delivers TV Service in Waxhaw, NC
If you live in Waxhaw, NC, by now you've heard the great news. Time Warner Cable is your cable television and telecommunications provider! Are you part of the 94% of Waxhaw residents who still watch TV on a traditional screen? That's 4,449 North Carolinians. No matter your preferred method of watching TV, there is a programming package to suit your viewing preferences.
Everyone appreciates the programming Time Warner Cable offers in Waxhaw. If you like state-of-the art features, look no further than Time Warner Cable. You'll get TWC TV™, which gives you the ability to program your DVR and record or delete shows, or even watch TV from any of your wireless devices. This feature and more are only available from Time Warner Cable.


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Baxley digs Romney, Keller digs McCain
Because he's a Mormon and because he once sounded like a moderate on issues on like abortion and gay rights, a lot of folks have been doubting Mitt Romney's ability to win over devoted social conservatives. Well, it seems one of Florida's leading voices for values voters, state Rep. Dennis Baxley, is more than comfortable with the former Massachusetts governor.
"I'm a big Romney fan,'' the Ocala Republican told Buzz. "He is the one candidate that I see in the winnable tier that has stepped up to address values issues in a very challenging climate (MA). He's the kinda fresh-faced leader that is in a winnable posture that value conservatives need to run to."
Like Romney backer Tom Feeney, Baxley is persuaded the Romney has matured an evolved sincerely on some of the social issues on which he's now being cast as a flip-flopper. And because he sees a commitment on issues that matter profoundly to to him, Baxley is comfortable supporting someone with some religious beliefs is disagrees with. Like what? "Basically everything Joseph Smith had to say in new revelations."
In other Florida presidential news, look for U.S. Rep. Ric Keller of Orlando to jump aboard the McCain train soon.


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The console was launched on March 23rd and has sailed past the one million milestone in Europe and other PAL territories in under ten weeks.
David Reeves, SCEE president, chose MCV to stress that the figure is for sell-through rather than sell-in and hugely impressive in a historical context. "Early last week we went through the one million mark on PS3. And we did that in nine and a half weeks," he confirmed.
"That was faster than both PS2 and PSOne. And I think that the analysts out there will also realise that it's faster than our brothers and sisters in the competitive world."
In terms of software sales, Reeves claimed that around two million units of first party software have been sold into the channel, with Resistance: Fall of Man notching up around 600,000 units and Motorstorm edging past the 500,000 mark.
He also admitted that there has been something of a lull in releases since launch, but promised that "our big bangs will be arriving around September and October; Phil [Harrison] will be announcing these at a later date, but they will probably be in the arena of social gaming as well as more traditional games".
Reeves was also bullish about take-up of the online service, revealing that around 460,000 gamers have already registered to the PlayStation Network.
But he refused to be drawn on any comparisons with Microsoft's rival service.
"I don't feel we're competing with Xbox Live in any way. We're in a different stadium. And with the introduction of Home at Christmas, we're going in a completely different direction with something very entertaining.
"We don't have our eyes on the competition in any way."


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Manto's Vai Finaliza balances class and flash, using red trim and embroideries to accent the clean white fabrics. Constructed from 100% cotton materials: 550 GSM Pearl weave and lightweight ripstop pants. All artwork and patch placements meet IBJJF requirements so you can sport your new Manto Gi during your next Worlds or Pan Ams outing. As always, Manto uses multiple drawstring loops and a round cord drawstring for easier untying and a steadier hold. A highlight of the Vai Finaliza is the jacket's interior panel... which adds something unique to the Gi. It's something we've never seen from Manto before, a fully sublimated yoke panel, featuring detailed artwork and crystal clear text.
Other specs include reinforced knees, contrast stitching, and interior taping.
Size GuideA0: < 5'5" < 130 lbsA1: 5'5" - 5'8" 130-160 lbsA1L: 5'7"-5'10"130-160 lbsA2: 5'9" - 6'1" 160-195 lbsA2L: 5'11"- 6'2" 160-195 lbsA3: 6'1" - 6'3" 195-230 lbsA4: 6'3" - 6'6" 230-250 lbsA5: 6'3" - 6'6" 240-285 lbs


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In the media's ongoing crusade to get Barack Obama re-elected by any means necessary, no news outlet stands out quite like NBC.
Yes, CNN, ABC, and any outlet using the profane term "white Hispanic" are as guilty as Al Sharpton of selling their editorial souls to gin up racial division for Obama in the crucial swing state of Florida, but under the appalling, un-American leadership of Steve Capus (pictured), NBC News has won the Gold for creating phony racial firestorms for three years running.
The fallout from NBC's latest and greatest act of racial fraud is still happening:
Lilia Luciano, a Miami-based NBC News correspondent, is no longer working for the network, TVNewser has learned.
Luciano last reported for NBC News March 31. Until that point, she had been reporting mainly on the Trayvon Martin story. Sources tell TVNewser Luciano's dismissal came after an investigation which also led to the firing of a seasoned NBC News producer over a similar, misleading edit. In a story for the "Today" show on March 20, Luciano used part of the George Zimmerman 911 call in which an entire phrase (italicized below) was taken from a later part of the conversation:
Zimmerman: This guy looks like he's up to no good or on drugs or something. He's got his hand in his waistband. And he's a black male.
Dispatcher: Are you following him?
Zimmerman: Yeah.
Dispatcher: Okay, we don't need you to do that.
In my opinion, Ms. Luciano and the other two terminated producers should file a wrongful termination lawsuit. Why are they being singled out for termination when the perpetrators of the last two NBC racial frauds still have their jobs? It's also not fair. After all, when you consider the tone and history of NBC News under Capus's leadership, any employee would be under the impression that this kind of fraud is encouraged.
Also, Capus has already made clear that what happened to the Zimmerman 911 audio was nothing more than a big oops:
NBC News' decision to air an edited call from George Zimmerman to police in the moments before he shot Trayvon Martin was "a mistake and not a deliberate act to misrepresent the phone call," according to the president of the network's news division.
So he's firing people for making an honest mistake?
That's just wrong.


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NetWellness is a global, community service providing quality, unbiased health information from our partner university faculty. NetWellness is commercial-free and does not accept advertising.
Monday, September 25, 2017
Is it stress?
i`m a 31 yr old male who recently has noticed that i`ve been wetting the bed lately. I have never done this before even as a child. could this be because of stress? should i be concerned? it has happened about four times in the past two weeks.
Bedwetting can be secondary to a variety of diorders one of which can be stress related. Urinary tract infection and problems with bladder-nervous system interaction can be a factor also. I suggest you contact your physician to be properly evaluated.
Martin I Resnick, MD
Formerly, Professor of Urology
School of Medicine
Case Western Reserve University


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Let me start off by saying HAPPY 2013 everyone!!!!!
Yeah yeah yeah I know, we vanished over the holiday season & kind of forgot to give a heads up to anyone who follows along. It wasn't intentional I assure you, it's just, we kind of got swept up in it all. I'm sorry, it wont happen again.
What I mean to say is, it's not uncommon for us to take a couple weeks off here & there, but we wont vanish without a heads up next time. Deal?
Good, lets move on.
Right, being as we've entered into a new year, I've decided it's about time to tackle some of the recipe ideas that I keep scribbling down at random intervals.
For example….. blueberry french toast. I have been wanting to make some of that since I spent a month in Boulder, Colorado last November. It's not that I had any whilst I was out there, but as soon as I left & got back to Athens, it was all I could think about at 03:00am when I was wide awake with jet-lag.
Can't make blueberry french toast without a decent blueberry bread though, so, I present to you my oat, buckwheat & blueberry loaf.
We may not actually make it as far as the blueberry french toast…. Mel & I have gotten through half of this gluten-free bread already & every time I look at it, it appears as if it's shrinking. Did I mention that it's also egg free, dairy free & vegan friendly?
Still, my craving for the delicious egg fried bread is what brought me to this beautiful, beautiful state of baking, & that, is never a bad thing.
Before I pass on the recipe, I just want to say that it's been snowing on our island! That may not sound like a big deal to you, but it's like being in the Twilight Zone.
I digress as always…. Happy 2013 xxx
– 3 tbs flaxseed meal
– 135ml (9tbs) boiling water
– 1.5 tbs instant yeast
– 2 tbs brown sugar
– 60ml (4 tbs) warm water
– 250ml (1 cup) rice milk, room temp
– 185g (1 cup) potato starch
– 75g (0.5 cup) tapioca flour
– 65g (0.5 cup) arrow root
– 90g (0.5 cup) buckwheat flour
– 60g (0.5 cup) oat flour
– 0.75 tsp salt
– 1 tsp guar gum
– 1.5 tsp xanthan gum
– 1 tsp baking powder
– 1 tsp bicarbonate of soda
– 70g (0.5 cups) frozen, organic blueberries
1. mix together the flaxseed meal & boiling water & let stand for 10 minutes. After the 10 minutes, you should notice that when you give it a stir, it has the same consistency as raw egg white.
2. mix together the brown sugar, yeast & warm water & allow to activate for 10 minutes.
3. in a large bowl, combine the dry ingredients & use a whisk to combine them thoroughly.
4. once the flaxseed has become thick & the yeast has risen, combine the two mixtures together along with the rice milk. Make a well in the center of the dry ingredients & pour in the wet mixture as well as the blueberries. Mix the ingredients together until all the dry ingredients have been incorporated & the dough holds its shape. Form a ball with the dough, place it back in the bowl & set it in a warm place to rise for 3 hours.
5. once the dough has risen, it is time to preheat your oven. Place your cloche inside the oven so it reaches the same temperature during the preheat & bring the temperature to 180C.
6. once the oven is hot, make sure your dough is formed into the shape you want, slice an X into the top of it, lightly dust it with oat flour & place it under the cloche to bake for an 1.25 hours. Remove the cloche & continue to bake for another 30 minutes uncovered. You'll know the bread is done because it will make a hollow sound when tapped.
7. transfer your bread to a wire cooling rack to cool.
If you liked the recipe, go check out our KICKSTARTER project for an upcoming Gluten-Free Cookbook!
**** I've used frozen blueberries because they hold their shape whilst kneading the dough, fresh will just get crushed.
**** if it's freezing where you are, set your oven temperature to 50C & place your dough in there to rise.
**** if you don't have a cloche, you can bake your bread inside a cast iron stew pot.
……..for a full history of our recipes, check out our archives. For the more sensitive tummies, check out our gluten-free archives….. and if you're just interested in something pretty, check out our designed page.


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Rockstar Games has revealed that Grand Theft Auto V's first story-centric add-on will arrive in 2014, and stars the original cast of Michael, Trevor, and Franklin.
On Rockstar's Newsire, the developer said, "we have big plans for substantial additions in 2014 continuing Michael, Franklin and Trevor's action, mayhem and unexpected adventures in Southern San Andreas."
Additionally, Rockstar detailed the future of its online multiplayer. A bigger update hits this week, with deathmatch and the race creator beta rolling out. Later in the month, we'll see four Capture mode variants -- Raid, Contend, Hold, and GTA -- which Rockstar will detail soon. Finally, on the subject of online heist missions, the developer wrote, "Heists are currently in development and we are working very hard to get them as polished and as fun as they can be. Stay tuned for much more detail in the New Year."
Rockstar has plenty more to announce for GTA 5 in the future, as well. For more on that, in addition to GTA Online's regular updates and the upcoming story expansion, stay tuned to IGN.


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"We're hoping that biofuels made in such an efficient way can eventually replace current petroleum-based fuels"
A fungus and E. coli bacteria have joined forces to turn tough, waste plant material into isobutanol, a biofuel that matches gasoline's properties better than ethanol.
University of Michigan research team members said the principle also could be used to produce other valuable chemicals such as plastics.
"We're hoping that biofuels made in such an efficient way can eventually replace current petroleum-based fuels," said Xiaoxia "Nina" Lin, assistant professor of chemical engineering and leader of the research.
Gallon for gallon, isobutanol gives off 82 percent of the heat energy gasoline provides when burned, compared to ethanol's 67 percent. Ethanol also has a tendency to absorb water, corroding pipelines and damaging engines, but isobutanol doesn't mix easily with water. While ethanol serves as a mixer in the gasoline infrastructure today, many researchers argue that isobutanol could be a replacement.
Equally important, this system makes isobutanol from inedible plant materials, so fuel production won't drive up food costs. Lin's team used corn stalks and leaves, but their ecosystem should also be able to process other agricultural byproducts and forestry waste.
While much previous research has focused on trying to create a "superbug" that could tackle the whole job of processing waste plant materials into biofuels, Lin and her colleagues argue that a team of microbial specialists can do better.
The fungus Trichoderma reesei is already very good at breaking down tough plant material into sugars. Escherichia coli, meanwhile, is relatively easy for researchers to genetically modify. James Liao's lab at the University of California-Los Angeles provided E. coli bacteria that had been engineered to convert sugars into isobutanol.
The Lin group put both microbe species into a bioreactor and served up corn stalks and leaves. Colleagues at Michigan State University had pre-treated the roughage to make it easier to digest.
"If you've ever had puffed rice cereal, it's somewhat analogous," said Jeremy Minty, first author of the paper to be published in the Proceedings of the National Academy of Sciences and a recent doctoral graduate in Lin's lab.
The fungi turned the roughage into sugars that fed both microbe species with enough left over to produce isobutanol. The team managed to get 1.88 grams of isobutanol per liter of fluid in the ecosystem, the highest concentration reported to date for turning tough plant materials into biofuels. They also converted a large proportion of the energy locked in the corn stalks and leaves to isobutanol—62 percent of the theoretical maximum.
The harmonious coexistence of the fungi and bacteria, with stable populations, was a key success of the experiment.
"A lot of times, one species will dominate the culture and the other will die off," Minty said. "This is a common problem when you're trying to create these systems."
Convincing the microbes to play nicely pays off.
"You can put everything in one pot," Lin said. "The capital investment will be much lower, and also the operating cost will be much lower, so hopefully this will make the whole process much more likely to become economically viable."
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Transcribed by Judy Benson
While I have endeavored to be as correct as humanly possible, there could be some typographical errors
Newfoundland will books vol 1 pages 15 to 18 probate years 1827-1830
|Will of Richard Taylor
|In re
Richard Taylor deceased.
In the name of God. Amen. I Richard Taylor of Carbonear Conception Bay in the Island of Newfoundland. Planter, being thro the abundant goodness and mercy of God of the sound and perfect understanding and memory to constitute this my last will and testament and desire it may be received by all as such.
First. I most humbly bequeath my soul of God my Maker beseeching his most gracious acceptance of it, thro the all sufficient merits and mediation of my most compassionate Redeemer Jesus Christ who gave himself to be an atonement for my sins, in this hope & confidence I render up my soul with comfort humbly beseeching the most blessed and glorious Trinity one God most holy, most merciful and gracious, to prepare me for the Time of my Dissolution, and then to take me to Himself onto that Peace and Rest which he has prepar'd for all that love and fear his Holy Name, Amen. Blessed be God, I give my body to the earth from whence it was taken in full assurance of its Resurrection from thence at the last Day. As to my worldly estate I will give and bequeath them as follows.
First. I give my dear and loving wife Ann Taylor for the term of her life, this house in which I now dwell with all the furniture and likewise the land and tenements which lie about it with all and every thing appertaining thereto and at her death to be divided amongst her children as follows
Item, I give and bequeath to my eldest son William Taylor a Room which is situated as follows eastern part bounded on the east by Mr. Henry C. Watt's by the west from the Westward corner of the store now belonging to him up to the Westward side of the mare's house and from thence up to the bound Stone as far as the Public Path, southerly with this exception that if he should die without Issue and his widow in aftertime marry any one otherwise nam'd than Taylor by surname it shall devolve to the surviving brothers to be equally shar'd North & South by them or who they may appoint.
Second. Westerly from the Westward corner of William Taylor my son's store to the bounded stone farther Westward and as far back northerly as my bounds goe's the same breadth in back as front [excluding a cellar and Fish House now there which shall be the property of my son Jonathan] I bequeath to my son Richard Taylor.
Third. Westerly, from the bound stone of Richard's to the bound stone of Joseph's Westward [excluding the spot now in the possession of my son John say from the Back of his House to water side & from the path way to the fence parting Joseph's from Jonathan's] the Kitchen Gardens to stand & be kept fenced in the same place as they now are, the dwelling house with all the furniture the Cow house and the bounds as far northward as it extends the same breadth in back as front I bequeath to my son Jonathan the path way up and down to be kept the same breadth as it now is the ground to be the property of Jonathan this to be as free to one as the other for the use and benefit of the several son's viz Rich'd John Joseph and Jonathan.
Fourth. Westerly part from the path way Westward as far as my son Joseph's fence or bound stone and from the back of my son John's House to the Water's edge same in front as back, also Fifteen yards Westerly from the Eastward bound viz Mr. H. C. Watts's from the street northerly as far as my bounds extend's which is to my son Richard's garden the same in back as front I bequeath to my son John.
Fifth. Westerly from Robert Howell bounds Eastward as far as the bound stone in the little Garden put by me the same breadth in back as front [excepting the garden's which are to be left as they now are as mention'd before] I give & bequeath to my son Joseph Item the Eastward part allotted for my son William in case of his death without male issue, not liking it should go out of the family name I ordain to be separated equally between the surviving brothers North & South his Widow to be allow'd the use and privilege of it as long as she may live, each to have a regular Share of Flake Room from the Westward corner of William's store as far Westward as the extreme bounds to be divided as follows the Eastward for Richard next Westerly for Jonathan next Westerly for John and next Westerly for Joseph, the above to be wholely & soley there property there Heirs Executors, Administrators or Assigns for ever [excepting the case stated in William's] I do hereby constitute and appoint William Howell Junr son of William of Carbonear and Samuel Rumson of Carbonear my true and lawful Executors and doubting not but they will if God spares them see this my last will and testament fully executed according to my desire.
In witness whereof I have hereunto set my hand and seal in Carbonear this twenty third day of August in the year of our Lord One thousand Eight Hundred and Fifteen. Richard Taylor. [LS] Witness present Samuel Rumson. Wm. Howell of Wm. Wm. W. Bemister.
Codicil to the before Will and Testament. Whereas I the within mentioned Richard Taylor do think fit and proper to adjoin this codicil to my within mentioned will and testament. I do hereby wish all persons concerned to accept it as the same, viz I further give & bequeath to my son John the full & sole possession of the Pew now my property in the Methodist Chapel in this place whilst he lives & his heirs hereafter. Further to my daughter Ann who is now widow I give and bequeath the room I now occupy as a bed room &c to her to occuppy with free toleration to & from without molestation as long as she remains in a Widowhood state with all the furniture therein under the same restrictions. Richard Taylor [LS]. The 2nd day of Decr in the year of our Lord one Thousand eight hundred & twenty two. Witness S. C. Rumson. W. W. Bemister. Wm. Howell.
Codicil to the before codicil and will and testament. Whereas I the before mentioned Richard Taylor do hereby think fit and proper to adjoin this codicil to the one before mentioned in to my last will and testament adjoin'd hereunto I do hereby wish all persons concerned to accept it as the same viz I further give and bequeath out of the sum and sums of money now laying due to me and in my possession, that is to say in the hands of Messrs Gosse Pack & Fryer Merchants of Carbonear the sum of Three hundred Thirty six pounds two schillings & one penny due me pr a/c furnished since December the thirty first one thousand eight hundred and twenty six and One hundred and fifty pounds in Cash now in my possession in form and manner as follows,
First I desire my executors to take from the above sums the sum of Thirty six pounds two shillings and one penny to defray my funeral expenses or other charges necessary thereunto,
Second to my son Richard I bequeath the sum of Seventy pounds,
Thirdly to my son John Ninety pounds,
Fourthly to my daug'r Mary Noel the sum of Fifty pounds,
Fifthly to my daughter Ann Best the sum of Sixty pounds
Sixthly to my son Jonathan the sum of One hundred pounds,
Seventhly to my grand daughter Patience Rumson the sum of Twenty five pounds,
Eighthly to the widow of my son Joseph Mary Taylor the sum of twenty five pounds. Further to my son John I bequeath a black spfine(?) coat Waistcoat & trowsers, to my grandchild George Best a purple Coat, my watch I give to Benoni Taylor son of Mary Taylor, to my daughter Ann Best I give the cow now in my possession and sole property of myself, the rent of the part of the room held by lease now by Mr. Wm. Bennett Merch't I do hereby beg to be equally separated between my son William and my daughter Ann Best and after my son's William's death the whole of said rent as long as the lease holds to come to my daughter Ann Best, my bed which I now occupy I give to Joseph the son of my son Jonathan. Richard Taylor [LS]. Signed & sealed the nineteenth day of June in the year of our Lord one thousand eight hundred and twenty seven in presence of Samuel C. Rumson, W. W. Bemister, Wm. Howell.
Codicil to the before codicils and will. Whereas I the before mentioned Richard Taylor do hereby think fit and proper to adjoin this codicil to those before mention'd and to my last will & testament adjoining hereunto I do hereby wish all persons concerned to accept it as the same viz. I further give to my daughter Ann Best as long as she lives in a widowhood state a garden to the Westward of the dwelling house I now reside in and a small Bed Room she now occupys in the dwelling house to have free resource to & from said premises without any molestation also to my grand daughter Patience Rumson I give and bequeath the use of the dwelling house she now resides in as long as she lives with all appurtenances & paths thereto as it now stands, and I do hereby deny any buildings to be erected by Henry Rogers or his Heirs on any part of the land my property before the expiration of a lease now held by William Bennett. Richard Taylor [LS]. Signed & sealed the seventeenth day of November in the year of our Lord one thousand eight hundred and twenty seven in presence of Samuel Rumson. John Rork. Joseph Taylor.
Certified correct
D.M. Browning


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How long is a camel racing track compared to a regular horse racing track?
City: Dubai
Emerate: Dubayy
Country: United Arab Emirates
the lengths does not matters, its the race same as the horse races, minmum race is of 1000 meters and the longer races goes to kilometers, the race tracks in UAE are 5 to 6 KM mainly.
There is no standard sizes to say that camel track is longer or shorter yet in UAE the tracks are approx 5-6 km.
They are about 5 kms.
More Information
Get travel answers from locals in Dubai


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COTSWOLD Flyball Club enjoyed a storming weekend recently as both the Whirlwinds and Cyclones took victories at Barbury Castle.
The Cotswold club's teams were back in action at Barbury after a break and began their preparations for the upcoming National Championships in August with two magnificent wins.
The Whirlwinds, making their debut as a team based on new fast dogs blended with experienced dogs, went straight into Division Four and set the league on fire with four great match wins to take a competitive division in great style. The blend of Belle and Rosie with the experienced Poppi and Milo proved too much for several very experienced teams.
The Cyclones, in a good class Division Three, had a dramatic day which started with a final run from regular dog Flynn in the first match to signal his retirement due to a medical condition.
The newly reshaped team of Rocky, Dexter, Scrumpy and Tammi then got down to business, going into their last match needing a win to take what looked like second place. They were leading 2-1 when, in the fourth leg, Scrumpy and Dexter had a bone shuddering collision that left the latter dazed and unable to continue. This lead to a dash to the car park to bring Flynn from retirement for the last two legs, with the team only needing one. The rejigged line-up proved to be successful with Flynn, in the anchor role, running a perfect leg to take the match 3-1.
Then, in the very last match of the division, hosts and neighbours Bassett Dynamites turned over the so far undefeated Berkshire Bandits to set up a three-way tie. However, the Cyclones took the title on countback to fastest times.
The Zephyrs and Typhoons met in a very closely run Division Five where the head-to-head clash proved to be a highlight. The Typhoons, with Dylan, Reuben, Rhona and Cerys, went two legs up only to see the Zephyrs of Lexi, Mist, Boo, Woody and Mr Rocky switch their dogs around and take a titanic clash 3-2.
The Zephyrs, spurred on by this, completed the division in an excellent second place while the Typhoons, who lost the services of Reuben for the afternoon session and forfeited their last two matches, slippingto fifth with two wins.
The Sundowners took fourth in Division Seven with a spirited performance from Kelly, Moss, Fergus, Bailey and Mopp, who combined to produce several good runs.
Dexter has recovered from the effects of his collision and will be back in action at Mapledurham.


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Raleigh, N.C. — Drivers around Raleigh could see ramp meters controlling the flow of traffic onto highways if a bill that cleared the Senate Transportation Committee on Wednesday is signed into law.
House Bill 1025, which must clear the full Senate before returning the House, would make ignoring a ramp meter, which looks something like a traffic light, an infraction.
The state Department of Transportation is already eying several locations around Raleigh as places where they believe ramp meters could ease traffic flow at busy highway interchanges. But current law would treat ignoring a ramp meter the same as running a traffic light, a serious violation that brings with it insurance points and hefty fines.
"We do not believe the risk of running a ramp meter is anywhere near the risk of running an intersection," Kevin Lacy, an engineer with DOT, told the committee.
Changing the violation to an infraction would allow tests with the new systems, which are used in other states, to go forward.
Lacy said that four locations on the northern part of Interstate 540 in Wake County were the first places in line for ramp meters. The city of Raleigh has also asked the state to look at other interchanges on Interstate 440. Charlotte city officials have asked DOT to look at highway interchanges in Mecklenburg County.
Other portions of the measure, which binds together more than a dozen smaller transportation-related issues, would allow the department to advertise on the side of trucks that provide motorist assistance – a program that might net between $1 million and $2 million – and would repeal the legislative mandate for an annual report by DOT that details the number of crashes caused by drivers turning right on red. A DOT official said that the report details only one or two accidents every year, so is not very useful.
The measure passed on a voice vote and is headed to the Senate floor.


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We are delighted to have Something Collective in The Incubator Studio! Something Collective is is developing creative ways to meet and engage with you- The Sunset Community! Watch for upcoming events here and on the Moberly Web Page and at the Sunset Community Centre in the main lobby.
Thursday, September 15, 2011
Something Collective
Posted by Moberly Arts & Cultural Centre at 2:56 PM No comments:
Labels: artist residency, Something Collective
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Atlanta, GA
I have been teaching Mathematics for twenty-five years.30/hour
...teaching mathematics. I have worked on both the middle and high school levels. I have taught 6th, 7th and 8th grade mathematics on the middle school level and I have taught Algebra and Geometry on the high... read moreSee Tutors Like This


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United states of style Few designers can pull off American West-Coast style with the aplomb of Michael Kors. And his latest resort collection is a case in point, with the stunning monochrome checked outfit of long jacket (HK$22,680), top (HK$9,480) and trousers (all far left; HK$10,280). For those who want to get in on the spring trends early, there's the bright orange, marble-print top (left; HK$10,280). Unfortunately, the shorts are not available in Hong Kong. Michael Kors is in The Peninsula Arcade, Tsim Sha Tsui, tel: 2366 2301.
Cast in stones When it comes to shoes, Miuccia Prada nails it every season, whether at Prada or Miu Miu, where her resort collection has been turning many a well-coiffed head. The chunky, jewelled heels have already become the must-have item of early 2013. Expect style blogs to be gushing over these tall, gem-encrusted gold versions (above left; HK$18,900) very soon. For something a little less lavish, there's the navy suede sandal with a jewelled heel (above right; HK$10,650). Miu Miu is in The Landmark, Central, tel: 2523 7833.
Break the mould Treat yourself to an odd-shaped clutch from Jimmy Choo this year. Honestly, it will be quite the ice breaker at cocktail parties. The tangerine-anaconda rounded Calista clutch (above right; HK$19,600) is a bright little number, while the elongated Cosma in gold (above left; HK$15,400) is disco ball-inspired. Jimmy Choo is in The Landmark, tel: 2525 6068.
We are amused The 9th Muse store in Hong Kong is known for interesting jewellery, but the boutique carries a lovely range of other accessories, too. Take, for example, the sweet Hanbun scarf (right; HK$1,699), which mixes two off-beat prints, or the cosy and vibrantly coloured Kelia scarf (far right; HK$2,320) in baby alpaca wool, both by a label called A Peace Treaty. The 9th Muse is at 12/F, 1 Lyndhurst Tower, 1 Lyndhurst Terrace, Central, tel: 2537 7598.


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Election Officials are Prepared for Election Day – Are You? Wisconsin is prepared for record voter turnout on November 4th
MADISON, WI – The Government Accountability Board (GAB) today reminded voters to prepare for Election Day on Tuesday.
"The State of Wisconsin and its election officials are prepared for a record turnout of voters, but we want voters to know that there are easy ways for them to prepare as well," said Kevin Kennedy, Wisconsin's Chief Election Officer. "Preparing for Election Day helps make sure that every eligible Wisconsin voter is able to vote as easily as possible."
The Board suggests four things to voters to prepare for Election Day:
• Check voter registration status by using Voter Public Access at http://vpa.wi.gov, or call the municipal clerk's office.
• If a voter plans to register at the polling place, they should know their driver's license number or Social Security number, and bring proof of residence.
• Check polling place location using Voter Public Access, or call the municipal clerk's office.
• Remember what conduct and attire are permissible at polling places in Wisconsin, and know voters' rights and responsibilities.
"Voters should not wear political attire that brings undue attention to themselves or could cause a disturbance in the polling place," said Nat Robinson, Elections Division Administrator. "Election officials will not allow any advocacy or attire that creates a disturbance, or could constitute electioneering."
Voters with language and physical limitations that may make voting difficult may seek assistance from voting officials at the polling place, or may bring someone to assist them in the voting booth. People with physical disabilities that would impede their voting inside the polling place may also vote "curbside" at any polling location.
"Wisconsin has a long history of fair and open elections," said Kennedy. "But taking a few minutes to check over their materials and rights before leaving the house can save voters time and frustration at the polling place."
Voters are now required to use their Wisconsin driver's license number to register to vote, and to use the last four digits of their Social Security number if they do not have a state driver's license (or state ID card). In addition, Election Day registration requires voters to prove they have lived in Wisconsin for 10 days, so a current document – such as a lease, utility bill or other related documents which include current address – is needed to show proof of residence.
The state has at least 35,000 trained poll workers throughout the state prepared for a large turnout, and local election officials also have ordered extra ballots. Voters should anticipate a smooth process at polling places, open from 7:00 a.m. to 8:00 p.m.
To learn more about voting procedures, to find polling locations, and to check their registration status, voters should visit the G.A.B. web site: http://gab.wi.gov.


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Search Jim Cramer's "Mad Money" trading recommendations using our exclusive "Mad Money" Stock Screener.
NEW YORK (TheStreet) -- Investors need to expect the worst but prepare for the best, Jim Cramer said on "Mad Money" Friday from a safe place hiding under his desk. He said the markets panicked as expected today, but savvy investors should've been prepared for a selloff of this nature because they're a vital part of any long-term rally.
Cramer said he is taking problems in China and emerging-market slowdowns seriously, but also said the U.S. is in far better shape than when similar woes emerged in Europe a few years ago -- which means when the selling's over, it'll be a great time to buy.
That's why Cramer's game plan includes listening to Caterpillar (CAT) and Apple (AAPL), a stock Cramer owns for his charitable trust, Action Alerts PLUS, on Monday. Cramer said these companies will provide a reading on the global economy and the temperament of the markets.
On Tuesday, Cramer said, he'll be watching American Airlines (AAL), along with Ford (F) and DuPont (DD). American is just a buy, he said, but Ford's Latin American business may be at risk and he's curious to see if the new DuPont is less immune to the economic cycle.
Wednesday brings earnings from Biogen Idec (BIIB) and WellPoint (WLP), two stocks the market usually turns to when things head south.
Then, on Thursday, it's 3M (MMM), Under Armour (UA) and Colgate-Palmolive (CL) in the spotlight. Cramer said these three unconventional tech stocks should all do well as the market becomes less emotional by this point next week.
Finally, on Friday, it's Abbvie (ABBV), Weyerhaeuser (WY) and MasterCard (MA) reporting. Cramer said by Friday the markets will likely be oversold, making these stocks a bargain.
Off the Charts
In the "Off The Charts" segment, Cramer went head to head with colleague Bob Lang over the chart of Himax Technologies (HIMX), the chip maker powering many of today's LCD displays. Shares of Himax are up 350% since Cramer last mentioned the stock in October, but they were down 8.5% as the markets began to sell off this week.