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1 Introduction
Curcumin is a polyphenol derived from the rhizome of the herb Curcuma longa. Traditionally, it has been used for many conditions, particularly as an anti-inflammatory agent (Gupta et al., 2012). Curcumin also possesses antioxidant, antiviral, antibacterial, antifungal, antiparasitic, antitumoral, and anticarcinogenic activities. Additionally, it is considered a hepato-, nephro-, and myocardial infarction- protector (Gupta et al., 2013). It has also been established that curcumin displays immunomodulatory and antirheumatic activities. These effects are mediated through the regulation of various transcription and growth factors, inflammatory cytokines, protein kinases, and other enzymes (Aggarwal et al., 2007).
The pharmacological safety and efficacy of curcumin makes it a potential compound for treatment and prevention of a wide variety of chronic illnesses, diabetes, allergies, arthritis, and Alzheimer's disease (Aggarwal and Sung, 2009). Similarly, the efficacy of curcumin in various malignant diseases including cancer has been established (Shanmugam et al., 2015). Nevertheless, the poor bioavailability of curcumin has been underlined as a major drawback. The first reported study that examined the uptake of curcumin using Sprague-Dawley rats showed negligible amounts of curcumin in the rat's blood plasma after oral administration of 1 g/kg of curcumin, suggesting that curcumin was poorly absorbed from the gut (Prasad et al., 2014). Recently, nanotechnological delivery systems for drugs and nutraceuticals have emerged as promising solutions to improve the bioavailability of therapeutic agents and bioactive compounds (Wang et al., 2014).
Nanoemulsions, fine oil-in-water dispersions stabilized with small amounts of emulsifiers, are small enough not to scatter light in the visible region of the spectra; thus, they appear clear instead of being optically opaque. Compared to micron-sized emulsions, nanoemulsions provide a greater surface area and have the potential to increase solubility due to a combination of large interfacial adsorption of the core compound, enhance the bioavailability by ensuring rapid delivery of active ingredients to cell membranes, and improve the controlled release, all of which enable better precision targeting of the encapsulated materials (Lovelyn and Attama, 2011). Furthermore, because of their small size, nanoemulsions do not cream after relatively long periods of storage (Hernández-Jaimes et al., 2013).
Different processes have been used to obtain nanoemulsions although, the most widely used for the preparation of oil-in-water nanoemulsions comprise high-energy emulsification methods such as high-pressure homogenization, microfluidization, and ultrasonication, all of which can reduce the globule size to nano-scale (Monroy-Villagrana et al., 2014; Silva et al., 2012). Compared with the traditional mechanical methods, ultrasound is a superior tool to prepare nanoemulsions with smaller and homogeneous globule size and physical stability; and the energy consumption is considerably lower than other classical devices (Tang et al., 2013).
The purpose of the present work was to evaluate the effect of varying the composition and preparation method on the entrapment efficiency, curcumin concentration, droplet size, and polydispersity index of curcumin nanoemulsions prepared by ultrasonication and stabilized by soybean lecithin.
2 Materials and methods
2.1 Chemicals and reagents
Curcumin (C, purity ≥ 98 %) was purchased from LKT Laboratories (St. Paul, MN) and soybean lecithin (SL, 95 % phosphatidylcholine) from Avanti Polar Lipids (Alabaster, AL). Medium chain oil (MCO) composed of caproic acid-C6:0 (1.65 mol %), caprylic acid-C8:0 (67.14 mol %), C10:0-capric acid (30.57 mol %), and lauric acid-C12:0 (0.64 mol %) was used as oil phase solvent (Original Thin Oil®, Sound Nutrition, Dover, ID) and glycerol (Gly; 99.5 % USP grade, vegetable-based, KIC Chemicals, Inc., New Paltz, NY) as aqueous phase co-solvent. HPLC grade solvents were purchased from Tecsiquim (Mexico City) and all other reagents were purchased from SIGMA (Mexico City). Deionized distilled water (DW) was used in all the experiments.yellow, red, purple and black colors grown in Querétaro, México.
2.2 Preparation of nanoemulsions by ultrasonication
Emulsions with MCO as the dispersed phase (5 %) and DW as continuous phase (85 %), with SL as emulsifier (10 %), were prepared to evaluate the effect of the ultrasonic operating parameters as features of the device, ultrasonic amplitude, and irradiation time, used in its preparation. The emulsions were prepared adding the dispersed phase to the continuous phase and this mixture was pre-emulsified for 3 min at 20,000 rpm using a T25 digital ULTRA-TURRAX homogenizer (IKA Works, Inc., Wilmington, NC). The formed coarse emulsion was passed through the sonication devices: Branson Digital Sonifier S-450D (Emerson Electric Co., St. Louis, MO) or an Ultrasonic Processor VCX 130 PB (Sonics & Materials, Inc., Newtown, CT.) at determined ultrasonic amplitude (10-80) and irradiation time (1-15 min) in order to evaluate the effects on droplet size (DS) and polydispersity index (PDI) of the obtained nanoemulsions.
2.3 Preparation of curcumin nanoemulsions
Initially eight curcumin nanoemulsion (CN) formulations were produced by combined 14 evaporation-emulsification and ultrasonication 15 methods (EES) described by Ganta and Amiji (2009) with slight modifications, varying ingredients composition as indicated in Table 1. Briefly, the continuous phase was prepared by adding SL to pure DW, or a mixture (1:1) of DW and Gly (45, 42.5, 40, or 37.5 % w/w NE), and stirred for 15 min. The oil phase was prepared adding C previously solubilized in absolute ethanol to MCO, and the solvent was evaporated using a nitrogen stream. Both the aqueous and the oil phases were heated by separate at 75 °C for 4 min. The oil phase was dispersed drop-wise into the continuous aqueous phase with stirring. After the last oil phase drop was added, the mixture was homogenized for 3 min at 20,000 rpm using a T25 digital ULTRA-TURRAX homogenizer to produce a coarse curcumin-in-water emulsion. The coarse emulsion was then ultrasonicated at 20 % amplitude using a Branson Digital Sonifier S-450D for 12 min to obtain the nano-sized droplets; the probe diameter used was 13 mm.
Then, the formulation that displayed the smallest mean droplet size and had a translucent appearance was selected, and used as the starting point to prepare ten more CN varying the curcumin load as indicated in Table 2, by thin-film hydration emulsification and ultrasonication methods (TFHES) as reported by Anuchapreeda et al. (2012) with slight modifications. Briefly, the SL was dissolved in 5 mL of absolute ethanol by stirring for 5 min and then added to MCO, with further stirring for 3 min. C was added to the mixture, dispersed by vigorous mixing and sonicated for 15 min in a Barnstead Aquawave 9376 ultrasonic bath (1.75 L, 115 V, 50/60 HZ, 500 W). The mixture was rotary evaporated to generate the dried thin film, which was hydrated with pure DW (85 % w/w NE), or a mixture of DW + Gly (42.5 + 42.5 % w/w NE), warmed at 45°C and stirred for 15 min. The mixture was homogenized as describe2d above to produce the coarse curcumin-in-water emulsion, which was subsequently ultrasonicated under the same conditions described above in order to obtain the nano-sized droplets.
All nanoemulsions were prepared in duplicate, and evaluated for droplet size (DS), polydispersity index (PDI), zeta potential (ζ), curcumin concentration (CC), and entrapment efficiency (EE).
2.4 Characterization of CN
The DS and PDI of CN were measured with a Nano-ZS90 dynamic light scattering device (Malvern Instruments Inc., Worcestershire, UK) at 90° fixed angle at 25 °C. DS were reported as "Z-average" diameters (the scattering intensity-weighted mean diameter), which were calculated from the signal intensity versus DS data. Samples were diluted with DW prior to making the DS measurements to avoid multiple scattering effects, using a 1:200 sample-to- water dilution factor. For the ζ, CN samples were diluted with DW using a dilution factor of 1:100 sample-to-water, placed in the electrophoretic cell of the Zetasizer, and the average surface charge was determined.
2.5 Determination of CC and EE
CC in CN was determined by HPLC according to the method reported by Shaikh et al. (2009). A standard curve was prepared from known concentrations of C in ethanol. The CN was centrifuged at 4,000 rpm (2,057g) at 5 °C for 10 min using a centrifuge (Eppendorf 5810R, rotor radius: 11.5 cm). The supernatant was filtered through a membrane filter to remove the remaining insoluble curcumin; 5 mL of ethanol were added to 5 μL of the filtering supernatant CN and 10 μL were injected into a Waters HPLC System fitted with a Waters Econosphere C18 (5 μm, 250 X 4.6 mm) column. C was detected at 428 nm with a Waters UV-visible detector model 2487. The mobile phase consisted of acetonitrile, 2.8% acetic acid and methanol, at a flow rate of 1 mL/min. Retention time for C was 4.6 min.
The amount of C in the CN was calculated from the final concentration of C after preparation and centrifugation. Curcumin EE in the nano-emulsion was calculated with the following equation:
Where: %EE is the entrapment efficiency of curcumin in the CN, in percent; MAC is the measured amount of curcumin in CN, in mg/g NE; and TAC is the total amount of curcumin used to prepare CN, in mg/g NE.
3 Results and discussion
3.1 Impact of ultrasonic operating parameters on nanoemulsions
Nanoemulsions can be prepared by using the chemical potential of the components (low-energy emulsification), or by means of a mechanical device (high-energy emulsification); high-energy methods used for preparation of nanoemulsions include ultrasonication, which can reduce the globule size at nanometric scale (McClements, 2010; Solans et al., 2005). However, it is necessary to evaluate the possible operating and compositional variables during the formation of nanoemulsions by ultrasonication. In this study, nanoemulsions prepared with MCO as the dispersed phase, DW as continuous phase, SL as emulsifier, and previously pre-emulsified in the homogenizer, were passed through the sonication devices (Branson Digital Sonifier S-450D or Ultrasonic Processor VCX 130 PB) to an irradiation time of 1 min, to different ultrasonic amplitude (10-80 %), to examine the dependence of emulsion droplet size and polydispersity index on this operating variable. The results are presented in Figure 1. Irrespective of the device used, the ultrasonic amplitude had a significant effect on the droplet size (ANOVA F = 59.92; p < 0.001) and polydispersity index (ANOVA F = 71.20; p < 0.001) of the nanoemulsions produced. When the ultrasonic amplitude increased from 10 to 30 % no significant differences (p < 0.05) in the mean droplet size of the nanoemulsions were found. However, at greater ultrasonic amplitude (40-80 %) the mean droplet size increased (p < 0.05). The polydispersity index was found significantly higher for the ultrasonic amplitudes of 70 and 80 %.
According to Leong et al. (2009), the intense shear force applied during the formation of an emulsion depends on the energy input, which is the product of power delivered and the residence time. The variation in ultrasonic amplitude from 10 to 80 % represented an increase in the energy delivered to the emulsion. But nevertheless, an excess energy supply causes an intense turbulence promoting a higher rate of collision between droplets, their coalescence and larger droplet sizes (Jafari et al., 2006). This phenomenon, where the particle size increased with increased input energy, referred as "over-processing", could be attributed to poorer function of the emulsifiers, and an increase in the Brownian motion; hence, to higher probability of collision and coalescence at higher energy input. In these conditions, the droplet size distribution of the emulsion is a result of the competition between two opposite processes, drop breakage and drop-drop coalescence (Tang et al., 2012).
Fresh interface is created whenever a droplet is formed from breakage of an original droplet. Between its formation and its subsequent encounter with the other droplets, some surfactant will adsorb onto this fresh interface. If the timescale of collision is shorter than the timescale of adsorption, the fresh interface of the newly formed droplets will not be fully covered with surfactant and leads to coalescence. So, drop coalescence will depend on the relative rates of surfactant adsorption and drop collision. In our case, at higher ultrasonic amplitudes, the rate of drop collision is greater than drop breakage. It represents a greater coalescence rate, leading to an increase in the droplet size.
Also, similar nanoemulsions prepared with MCO, DW, and SL were passed through the sonication devices, to an ultrasonic amplitude of 20 %, to different irradiation times from 1 to 15 min; At this ultrasonic amplitude, the irradiation time had a significant effect on the size (ANOVA F = 63.41; p < 0.001) of the droplets produced, and on the polydispersity index (ANOVA F = 6.41; p < 0.01) of the nanoemulsions. Increasing irradiation time from 1 to 10 min the mean globule size was significantly reduced (p < 0.05); however, after 10 min, no significant decrease in mean globule size was observed (Figure 2). In this sense, Cavazos-Garduño et al. (2014) studied the effects of ultrasonic amplitude, irradiation time, and emulsifier concentration in the characteristics of betulinic acid nanoemulsions. They found that the globule size was affected by ultrasonication conditions, mainly by the irradiation time; from 20 to 40 % of ultrasonic amplitude. When the irradiation time increased the mean globule size was reduced. However, after 250 s no further decrease in mean globule size was observed.
According to Leong et al. (2009), the minimum droplet size and the time required to achieve the minimum droplet size is clearly affected by the equipment configuration used. In this work, the equipment used had significant effect on the droplet size (ANOVA F = 14.09; p < 0.001) and the polydispersity index (ANOVA F = 11.52; p < 0.01) of the nanoemulsions produced. The effect of the sonication device used on the preparation of nanoemulsions on droplet size and polydispersity index can be examined in Figures 1 and 2; in these, (a) corresponds to the Branson Digital Sonifier S- 450D and (b) to the Ultrasonic Processor VCX 130 PB, at a determined ultrasonic amplitude (Figure 1) and a determined irradiation time (Figure 2). At the same conditions of ultrasonic amplitude (Figure 1), the effect of the sonication device on globule size showed, in applying sonication amplitudes of 10, 20 and 30, a smaller globule size (p < 0.05) for the sonication device (a), which could be expected because of their greater power of sonication; however, at higher sonication amplitudes (40-80), the globule size was much higher (p < 0.05) for this sonication device than for sonication device (b). This can be explained, as previously mentioned for over processing, which is expressed more on the sonication device with a higher power. Similarly the polydispersity index was found to be much higher (p < 0.05) for the device of sonication power of 450 W (up to 0.94) than for the device of sonication power of 130 W (0.14-0.29). In all cases, smaller globule sizes (p < 0.05) can be noted for the device (a) at the same conditions of irradiation time, compared with the device (b) (Figure 2). Although the polydispersity index was found to be higher (0.21 - 0.16) than for the sonication device of 130 W of power sonication (0.16 - 0.13).
3.2 Impact of SL concentration on CN
The mean droplet size of nanoemulsions are a function of the formulation composition and preparation conditions (Hernández-Jaimes et al., 2013; Chaparro- Mercado et al., 2012), so that droplet size may be tailored by formulation design in order to attain the desired stability, physicochemical properties and functional performance (McClements, 2010). Nanoemulsion characteristics were affected by composition, independently of the preparation method employed. Increasing SL for a constant C loading (2.5 mg/g NE), Formulations in Table 1, had a significant effect (ANOVA F = 7,485; P < 0.001) on the size of the droplets produced (Figure 3a). At 10 % w/w of SL on NE, which corresponds to a 1:2 ratio of oil-to- emulsifier, the mean droplet diameter produced was 113 nm, while the mean droplet diameter produced with less emulsifier (5 % w/w on CN) was greater (P < 0.05) than this value (ca. 140 nm), which suggested that there was insufficient emulsifier to cover all the droplets formed by ultrasonication. For these SL concentrations there was a decrease in mean droplet diameter with increasing emulsifier concentration. This trend was expected because there should be more emulsifier present to cover any new droplet surfaces formed during ultrasonication, and because the droplet surface is more rapidly covered by a layer of emulsifier molecules. Nevertheless, higher increases of SL concentration (15 and 20 % w/w on CN) caused an increase (P < 0.05) in globule size (142 and 164 nm, respectively). This could occur through a number of mechanisms: (a) multilayers may have formed around each droplet; (b) droplet flocculation may have been promoted; or (c) LS aggregates may have been formed in the continuous phase that contributed to the light scattering signal (Qian and McClements, 2011).
PDI values are related to the quality of the dispersion and represent the width of the size distribution. PDI values smaller than 0.1 or 0.2 indicate suitable measurements and overall good quality of the colloid suspension. Values close to 1 are found for poor quality emulsions, which either do not represent droplet sizes in the colloidal range or exhibit a very high polydispersity (Klang and Valenta, 2011). In this work, the SL also had significant effect on the polydispersity index (ANOVA F = 85.81; p < 0.001) of the CN. The PDI of the CN produced (0.13, 0.14, 0.18 and 0.22 to 5, 10,15 and 20% w/w of SL, respectively) also caused that elevated concentrations of LS increase (P < 0.05) the dispersion and the width of the size distribution.
When CN were examined for entrapment efficiency (% EE), after centrifugation at 2,057g for 10 min, we found that % EE changed significantly (ANOVA F = 108.59; p < 0.001) depending on the amount of emulsifier used (Figure 3b). At 0.5 g of SL on NE (5 % w/w of emulsifier), the % EE was only 19; this value increased significantly (P < 0.05) to 100 when 2 g of emulsifier were employed (20 % w/w), which suggests a high affinity of curcumin for LS. Nonetheless, higher increases on LS concentration caused an increase in mean droplet size and PDI. Moreover, in practice it is often desirable to minimize the total amount of emulsifier employed to prepare an emulsion due to economic, sensory, or regulatory reasons.
3.3 Impact of Gly on CN
The addition of Gly in the aqueous phase of CN prepared by the EES (see Formulations in Table 1) showed a significant effect on the droplet size (ANOVA F = 2,872; p < 0.001) and the polydispersity index (ANOVA F = 21.68; p < 0.001) of the nanoemulsions. Its addition resulted in all cases in significant changes in mean droplet size (see solid bars in Figure 3a). But, while the mean droplet sizes were significantly smaller (98 and 90 nm) at the lower concentrations of SL as emulsifier (5 and 10 % w/w on CN) than the same formulations prepared without Gly (open bars in Figure 3a); mean droplet diameters prepared with more LS added (15 or 20 % w/w) produced significantly higher mean droplet diameters (199 and 323 nm, respectively) than the same formulations without Gly. A possible explanation of the droplet size reduction by addition of Gly at low LS concentrations is that Gly in the continuous aqueous phase reduced water's surface tension. LS moved freely and was able to absorb around the MCO droplet, thereby resulting in an increased surface to volume ratio of the droplet (Zhou et al., 2010). Increased SL concentrations resulted in a sharp increase in the viscosity of the continuous aqueous phase. This higher viscosity generated difficulty in SL movement and a slower diffusion and further adsorption at the oil droplet during the preparation procedure. According to McClements (2012), changes in viscosity of the continuous phase may influence droplet size through a number of different mechanisms: (a) increased droplet fragmentation produced by increased disruptive shear stresses; (b) decreased droplet re-coalescence due to decreased droplet collision frequency; or (c) increased droplet re-coalescence caused by a reduction in emulsifier adsorption rate. However, the relative importance of these factors is highly system-dependent, and varies with the type of mechanical device employed and the operating conditions (Hakansson et al., 2009).
Irrespective from the mean droplet size, an effect of Gly on the NE appearance was also observed. When the formulation was composed of 5 and 10 % w/w of SL, the NE appeared as an opaque solution. However, when the formulation was prepared with Gly as co-solvent, the NE appeared as a semi-transparent solution; as it was previously reported by Zhou et al. (2010).
In contrast to the concentration of emulsifier present on CN preparation, addition of Gly, at all SL concentrations tested, did not affect the % EE. NE prepared with or without Gly achieved similar % EE (Figure 3b).
3.4 Impact of the Method of Preparation on CN
CN prepared at 10 % w/w SL (1:2 ratio of oil to SL), 42.5 % Gly, and 2.5 mg of curcumin loading per g NE by the EES method (Formulation FEES4, in Table 1), was considered according to the impact of SL concentration and addition of Gly on CN, as the best formulation with the smallest droplet size (DS) and polydispersity index (PDI); it showed a pellet of curcumin at the bottom after been centrifuged in order to separate the excess curcumin.
The EES method produced CN with only 56 % EE (Table 3). In this sense, many hydrophobic bioactive compounds like curcumin are crystalline at ambient temperature and are often difficult to incorporate into fluid products because of their tendency to aggregate and sediment (Porter and Wasan, 2008). These crystalline hydrophobic bioactive components may be dispersed within a carrier lipid prior to emulsion formation, but it is important to ensure that the entire lipid phase remains liquid throughout the process, which can be accomplished using two different approaches: melting and dissolution. In practice, the first approach is unsuitable for many hydrophobic bioactive components because they may be chemically unstable at elevated temperatures, so they are often dissolved in a solvent. This solvent may be a carrier lipid (such as a triacylglycerol oil) or an organic solvent (such as an alcohol) but, from a thermodynamic point of view, a crystalline material has a finite solubility in a given solvent that depends on the nature of the bioactive component, the nature of the solvent, and environmental conditions. It is also possible to use a combination of dissolution and melting steps to produce emulsions containing encapsulated hydrophobic components. In this case the crystalline material is dispersed in the carrier oil, which is then heated to dissolve the crystals. An oil- in-water emulsion is then formed by homogenization of the liquid oil and water phases together in the presence of a water-soluble emulsifier. The advantage of this method is that considerably lower temperatures can be used to melt all of the crystalline material. Nevertheless, according to Li et al. (2012) crystals may form in the emulsion when the system is cooled and then they may aggregate and sediment.
EES = evaporation-emulsification and ultrasonication methods; TFHES = thin-film hydration-emulsification 22 methods DS = droplet size; PDI = polydispersity index; ζ = zeta potential; EE = entrapment efficiency; CC = curcumin concentration. Values reported are mean ± SD. n=2. Means with different letters are significantly different (P < 0.05) by one-way ANOVA.
* Corresponding to formulations FEES4 in Table 1 and FTFHES4 in Table 2.
In order to achieve greater % EE, CN with the same formulation (10 % w/w SL, 1:2 ratio of oil to SL, 42.5 % Gly, and 25 mg of curcumin loading) were also prepared by the TFHES (Formulation FTFHES 4, in Table 2). The method of preparation of CN showed a significant effect on the entrapment efficiency (ANOVA F = 14.09; p < 0.001) of the nanoemulsions. This method of preparation of CN showed significantly better results of entrapment efficiency (100%), in contrast with the EES method (56%), which corresponds to 2.5 and 1.4 mg of curcumin entrapped/g NE, respectively. Other variables as mean droplet size and distribution, and surface charge had no significant effects (Table 3). According to McClements (2012), a variety of substances have shown to inhibit nucleation and thereby promote supersaturation. Incorporation of these substances into a system may be useful for preventing undesirable nucleation and crystal growth of a bioactive component. These substances include additives capable of forming micelles or vesicles such as phospholipids that may be able to incorporate hydrophobic solutes within the non-polar regions of their internal structures. Consequently, the maximum concentration of solute that can be solubilized in the system would be increased, leading to a reduction in the driving force for nucleation. Whether the CN is prepared by TFHES the SL form part of the lipid phase, this is dissolved in ethanol together with MCO and then C is added and dissolved in the mixture. The lipid phase is dried to evaporate the solvent and then the aqueous phase (DW or DW and Gly) is added to generate an emulsion. In this way the presence of SL in the lipid phase increases or promotes the solubility of curcumin and allows greater entrapment efficiency.
3.5 Impact of C loading on CN
Because the main goal of this study was to develop a formulation of a CN with the highest C loading, CN with were prepared by the TFHES. The 10 formulations (at 10 % of SL) are listed in Table 2. The C loading on CN showed a significant effect on the droplet size (ANOVA F = 150.54; p < 0.001), polydispersity index (ANOVA F = 101.09; p < 0.001), zeta potential (ANOVA F = 183.85; p < 0.001), and entrapment efficiency (ANOVA F = 10,205; p < 0.001) of the nanoemulsions prepared. The effects of the C loading on CN on the mean droplet diameters produced are shown in Figure 4a. As the amount of C applied increased from 0 mg/g NE (F TFHEs 2) to 2.5 mg (FTFHEs4), 5.0 mg (F TFHEs 6), 7.5 mg (F TFHEs 8), and 10.0 mg (F TFHEs 10), the mean diameter of the NE increased significantly (p < 0.05) from 77 to 108, 156, 186, and 243 nm, respectively. The PDI varied from 0.12 to 0.11, 0.48, 0.51, and 0.59.
CN were examined for entrapment efficiency (% EE). When CN were centrifuged to separate the non- emulsified C after sonication, pellets of excess C could be observed when more than 2.5 mg of C were added. We found that the % EE decreased significantly (p < 0.05) by increasing the total amount of C applied (Figure 4b), thereby implying that there were excess amounts of free C after the emulsification process. From 25 to 50, 75, and 100 mg of C, the % EE in the NE were: 100, 46, 29, and 17, respectively. These results are consistent with those reported by Anuchepreeda et al. (2012). Amounts of C entrapped in the CN were 2.5, 2.3, 2.1 and 1.7 mg per g of NE, to 2.5, 5.0, 7.5 and 10 mg of C applied per g of NE. These results indicate that for this CN formulation (10 % w/w SL, 5 % w/w MCO, 42.5 % w/w Gly, and 42.5 % DW), its maximum ability to incorporate C was 2.5 mg per g NE. Compared to the loading amount of C in NE in a previous report (Anuchapreeda et al., 2012), our formulation exhibited a 3-fold greater loading of C, while other reports indicate amounts of C entrapped from 0.25 to 2 mg per g (Ahmed et al., 2012; Chen et al., 2011; Ganta and Amiji, 2009; Li et al., 2014; Sari et al., 2015).
3.6 Stability of CN
The time course-dependent change in the dispersion and mean droplet diameter of the CN, prepared with 2.5 mg of C/g NE and 42.5 % w/w of Gly, were evaluated during storage at 4°C for 180 days are presented in Table 4. The mean droplet diameter changed from 108 to 169 nm at day 120, while no significant changes (p < 0.05) on polydispersion (PDI) were observed. The zeta potential of CN ranged from -7.9 to -12.3. Based on the zeta potential data, it is likely than an electrostatic repulsion between the nanoemulsion droplets played a role in slowing down droplet flocculation, and contributed to their long-term stability. Although only particles with zeta potential values higher than +30 mV or lower than - 30 mV are generally considered to be stable due to the strong repulsion forces (Liu et al., 2012), apart from charge-induced stabilization, phospholipids also lead to improve molecular packing at the interface, and nanoemulsion stability. Phospholipids with short and saturated acyl hydrocarbon chains decrease the molecular packing and promote the formation of stable nanoemulsions (Klang and Valenta, 2011).
DS = droplet size; PDI = polydispersity index; ζ= zeta potential; EE = entrapment efficiency; CC = curcumin 32 concentration. Values reported are mean ± SD. n=2. Means with different letters are significantly different (P < 33 0.05) by one-way ANOVA. 3345
*Corresponding to formulation FTFHES4 in Table 2.
On the entrapment efficiency (% EE), we found that % EE decreased during storage from 100 to 95 after 180 days (Table 4). This represents a reduction of only 5 % EE. Nevertheless, when Gly was not used as co-solvent, the CN showed a significantly (p < 0.05) higher mean droplet diameter during storage (see Figure 5a) and a significantly higher reduction on % EE (30 % after 180 days) than when Gly was used as co-solvent (Figure 5b). This is because even though the emulsions are thermodynamically unstable, and the presence of crystalline material or impurities could promote nucleation and instability during storage, substances including co-solvents as
Gly, are able to inhibit nucleation and may be useful for preventing undesirable nucleation, crystal growth, and precipitation of a bioactive component (Warren et al., 2010). Gly increased the micro- viscosity of the continuous phase, slowed down the diffusion of solute molecules through the solution, thereby delaying their incorporation into the solid- liquid interface, and thus promoted physical stability.
This study showed that as composition (emulsifier concentration, co-solvent addition, and bioactive component loading) as preparation method (EES or TFHES) employed to form CN had effects on entrapment efficiency, mean droplet size, polydispersity index, and stability. The entrapment efficiency of C into CN was favored by Gly addition in the aqueous phase of NE and its preparation by TFHES. The CN prepared by this method, using 5 % w/w of MCO, 10 % w/w of SL, and 42.5 % of Gly showed an entrapment efficiency of 100 % and were stable for 120 days at 4°C. When increasing amounts of C beyond 2.5 mg per g were used, the bioactive incorporated in the emulsion became saturated.


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Apr 23, 2018
One month ago today, my father passed away unexpectedly. As this podcast is something I do in my spare time, there are more important things going to eat up that time. For now, it's time to take a step back from the podcast.
Based on a True Story will be back at some point. I don't know when. If you stay subscribed, you'll be the first to get new episodes when they're available.
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Sharpe ratio
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AYON ORION II gets rave review from TAS - Connoisseur-Level Audio for Those on a Budget
There are so many reasons to recommend this amplifier: fabulous sonics, world-class build-quality, a manufacturer that seems to really care about what it is doing, how it is doing it, and has its customers' best interests at heart, and yes, overall coolness. More?
Ayon electronics are manufactured to EU standards, in the EU—Austria, in fact— so you can be pretty sure that the workers earn a living wage and the environment gets a break. Given a suitable pair of loudspeakers, decent upstream electronics, and, of course, good recorded material, the Orion II is a reminder that vacuumtube amplification is an excellent way to do the job. Ignoring other factors such as cost, weight, size, flexibility, efficiency, maintenance requirements, and durability, tubes may even be the best way.
My friend Carl was smitten by the Orion II after hearing it at my home after a dinner party. "How can I convince my wife that it is worth the price?" he asked, hoping that I could feed him some good ammunition for the argument soon to take place. To his dismay, knowing he had two kids in college, I told him that he most likely could not convince her but that, yes, the Orion II was definitely worth it. Absolutely worth it.
Start saving,….. Carl.


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NEWARK, N.J. — Call it pay for praise, greenbacks for good news, bucks for beneficial publicity. The Newark City Council has awarded the Newark Weekly News a $100,000 no-bid contract to publish positive news about the city.
Howard Scott, who owns Newark Weekly News, pitched the idea to the city council, which unanimously approved the idea earlier this month.
"Do we have critical reporters on staff? No. Do we have investigative reporters? No," Scott said. "Our niche is the good stuff. People have come to know it, and they love it."
Under the contract, the paper will work with the city's public information office to spread positive aspects of the city.
The paper can only generate stories based on leads from the council and the mayor's office.
John O'Brien, executive director of the New Jersey Press Association, said it was bad public policy to use tax dollars this way.
"The press role is supposed to be that of a watchdog," O'Brien said.
Copyright 2005 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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Las Vegas hotels slash rates during the summer, when fewer conferences are scheduled and temperatures hover around 100 degrees. This year looks particularly promising for bargains, as Vegas is reeling from a combination of fewer visitors and a recent increase in the volume of hotel rooms.
We highlight some hotel discounts below. For more options, consider blind-booking Web sites like Hotwire and Priceline; hotels can sell rooms through these sites and fill their beds without publicizing their discounts (keep in mind that reservations booked through these sites are typically not changeable or refundable).
Circus Circus, from $42 per room per night
Vegas.com is featuring a series of discounted hotel packages for weekend, midweek, and weeklong getaways to Las Vegas this summer—starting at $125 per room for a three-night midweek stay at Circus Circus. Accommodations are in a 375-square-foot standard manor room, furnished with two double beds and game tables with chairs in the seating area. Add $27 to stay three nights in a standard room at the Sahara or $203 for three nights in a luxury room at Paris Las Vegas. Weekend getaways start at $194 for two nights in a standard room at the Plaza; add $76 for two nights at the Stratosphere, also in a standard room, and $168 for two nights in a pyramid room at the Luxor. Weeklong vacations start from $627 for seven nights in a standard room at the Imperial Palace; add $69 for seven nights in a standard room at the Rivera and $405 for seven nights in a deluxe room at the Flamingo.
When: June 20-22 for weekend getaways; July 22-25 for midweek trips; and Aug. 8-15, 2008, for weeklong vacations.
Details: Taxes and fees of about $25 are included. Breakfast is not included. Based on single or double occupancy. Note that if you find a lower price for a Vegas hotel online, the company's Best Vegas Rate Guarantee promises to give you back double the difference.
Contact: 800/851-1703, Vegas.com.
Mandalay Bay, from $110 per room per night
The Summer on the Vegas Shore package includes one night at Mandalay Bay Resort and Casino, $20 in credit to be used at the beach (Sand Dollars), $10 in 'freeplay' or 'blackjack bet' to play in the Beachside Casino, a two-for-one House of Blues breakfast, and $300 in savings certificates for Mandalay Place. Perhaps the best perk is the included "fly back free" certificate good for a round-trip flight between Las Vegas and any major airport in the continental U.S. Upgrades to packages with additional perks start at $20 per room per night and include a $500 travel gift card redeemable towards both airfare and hotel costs (in place of the "fly back free" certificate); free access to Mix lounge at the top of THEhotel; a $50 discount off a cabana rental; complimentary access to Moorea Beach from Monday to Thursday; and VIP (meaning early) pool access from Sunday to Thursday. Add $50 per room per night and you'll also get two free spa and fitness passes and $100 off cabana rental Monday-Thursday. The starting rate of $100 is good for accommodations in a 550-square-foot deluxe room at the newly remodeled Mandalay Bay.
When: June 12-Sept. 4, 2008.
Details: Taxes are an additional 9 percent. Breakfast is not included. Based on single or double occupancy. The free travel certificates are received upon check-in and are valid only if the subsequent trip to Vegas is booked through Archer Travel Group for a minimum of three nights at Mandalay Bay or THEhotel at Mandalay Bay. You must redeem the certificates within three months of original stay in order to get the full value. (If redeemed within five months, travel credit will be $400; within seven months, $300; and within nine months, $200. After nine months, offer ends.)
Contact: 877/632-7800, mandalaybay.com.
The Signature at MGM Grand, from $149 per room per night
The Summer Splash package, which is geared towards families, includes one night at The Signature at MGM Grand, continental breakfast for two at Delights Gourmet Delicatessen in Tower Two, a $25 entertainment credit valid at KA by Cirque du Soleil and Crazy Horse Paris, a 20 percent discount at the Signature Poolside Grill—where kids under 10 eat free with the purchase of an adult meal—and a 20 percent discount on a spa treatment. While the all-suite resort is a nonsmoking and no-gambling property, it's only steps away from MGM Grand. The starting rate features accommodations in a junior suite that sleeps four people. It has a deluxe king-size bed (with a pillow-top mattress and 300-thread-count Egyptian cotton sheets) and a separate sitting area with a pullout couch. Each suite also has a fully equipped kitchen or kitchenette and an oversize marble bathroom with a Jacuzzi tub. Most suites have a private balcony with views of the Las Vegas Strip and the mountains. Other amenities include a flat-screen TV in the living room and bathroom, high-speed Internet access, and plush bathrobes. The hotel boasts a private heated pool complex complete with poolside cabanas and cocktail service, two state-of-the-art fitness centers, a lounge, and a Starbucks coffee shop. Rates start from $149 per room per night.
Don't miss these Travel stories
Lords of the gourd compete for Punkin Chunkin honors
With teams using more than 100 unique apparatuses to launch globular projectiles a half-mile or more, the 27th annual World Championship Punkin Chunkin event is our pick as November's Weird Festival of the Month.
- Airports, airlines work hard to return your lost items
- Expert: Tourist hordes threaten Sistine Chapel's art
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- Lords of the gourd compete for Punkin Chunkin honors
When: Through Aug. 31, 2008.
Details: Additional taxes are 7 percent and the resort fee is $15. Based on single or double occupancy with children (no age limit). To book, refer to code SUM011.
Contact 877/727-0007, signaturemgmgrand.com.
Wynn Las Vegas Resort and Country Club, from $199 per room per night
The discount Web site TravelWorm recently partnered with the upscale Wynn Las Vegas Resort and Country Club to offer a one-night stay from $199 per room per night—savings of as much as 50 percent compared to regular room rates, which can be as high as $400 per night in the same room category. You'll stay in a 640-square-foot suite, with floor-to-ceiling windows, a bathroom with a separate tub and shower, flat-screen TVs in both the living room and bathroom quarters, and European linens. Centrally located on the Las Vegas Strip, the resort features four heated pools with private cabanas, an 18-hole golf course designed by architect Tom Fazio, and a salon and spa. Dining and nightlife options include nine upscale and six casual restaurants, six lounge bars, and a 12,000-square-foot nightclub, Tryst. For live entertainment, check out aerial acrobatic performances at Le Reve or "Monty Python's Spamelot" performed in the Grail Theater.
When: Through Sept. 5, 2008.
Details: Additional taxes are 9 percent. Breakfast is not included. Based on single or double occupancy.
Contact: 888/321-9676, travelworm.com.
Getting there: According to a recent search on Kayak, the lowest round-trip fares to Las Vegas, departing in mid-July, start at $155 from L.A. (U.S. Airways), $159 from Denver (Frontier), $264 from Seattle (Alaska Airlines), $355 from New York City (Spirit), $384 from Houston (multiple carriers), and $424 from Miami (American).
New airfare option: Virgin America, which has been making inroads in the U.S. market, just announced that it will begin nonstop service between New York City (JFK) and Vegas (McCarren International) on September 4. Advertised fares start at $159 each way, but we searched their Web site and actually found fares as low as $148 each way for mid-September travel.
Air/hotel package alternative: Southwest Vacations frequently has Vegas specials and currently touts a summer sale that includes airfare and a three-night stay at any of seven Harrah's Entertainment Group Las Vegas properties from $259 per person (starting rate based on flights out of Denver and a stay at the Imperial Palace). Note that you must book by June 19 for travel through October 28, and you'll save about $90.
For tips on what to do in the area, visit the official site of the Nevada Commission on Tourism. Read these guidelines before you book any Real Deal.
Copyright © 2012 Newsweek Budget Travel, Inc.


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Clarksville Pool and Leisure
Our Story
Clarksville Pool & Leisure was born out of the growing need for a quality, committed, and reputable pool company in Clarksville that brings service to your home. If you are a pool owner, there should be no reason for you to have to make the trip to a pool store for the items needed to maintain your pool. At Clarksville Pool & Leisure we bring everything to you. This will enable you to relax and enjoy your pool…not spend countless hours cleaning and maintaining it.
At Clarksville Pool & Leisure we believe in "Going the Extra Mile." What exactly does that mean for you, the client? In Biblical times, the law allowed a Roman soldier to make a Jewish man carry his backpack for exactly one Roman mile, or a thousand paces. At that time, no one liked being forced to carry anything any distance for a Roman soldier. Jesus said if they were required to carry it a mile…then go with him two miles – Matthew 5:41. At Clarksville Pool & Leisure we have adopted this philosophy. It will show in the quality of our work and the commitment to our clients.
A Committed Pool Company
We are passionate about our customers. We are dedicated to making our customers feel important.
Weekly Maintenance
At Clarksville Pool and Leisure we bring everything to you. This enables you as a pool owner to relax and enjoy your pool.
Pool Problem Solvers
Contact Our Staff Today
Clarksville Pool and Leisure guarantees clear communication on every estimate and services provided. Contact us today with your pool needs!
What Our Customers Are Saying
Don't just take it from us, let our customers do the talking!
"Recently worked with CPL for an opening, inspection and cleaning. They were very professional and prompt. Priced great and honestly, they were the only ones in town that I could find that offer all of those services! Some of the other pool companies offered some but not all, but this place was a one stop shop. "
"Only place in Clarksville I could find that didn't rip you off and did weekly maintenance that went above and beyond to help my renters out. "
"We have had our pool for 8 years. During that time we have worked with four different pool companies. Randy and the team from Clarksville Pool and Leisure have consistently delivered knowledge, expertise, and service that is unsurpassed by any other company in the area. Our pool has never looked nor functioned better. Highly recommend!!!!. "


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Exercise your ears: the 112 podcasts shown below present the best ideas, information and stories from a larger group of 755 for the week, to hear while your hands and eyes are busy. Get all the files as a group … Continue reading →
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Indoor Cricket
World Masters/U-19's
|Sri Lanka
Lanka burst onto the international Indoor Cricket scene with a Test
victory over Australia in 2002.
now they're coming to Christchurch.
whole schedule and draw for the tournament has to be redone by Mark
and his team, and we will publish the amendments here as soon as we
receive them. We have also had to carry out significant renovations
to Indoor Cricket World to accommodate Sri Lanka's inclusion.
Sri Lanka were a sensation at the Indoor Cricket World Cup. Many considered them unlucky to lose one particular match against New Zealand, although we feel that their finishing in 3rd place was about right.
As for their Over 35 Men, well, going on what we saw in Wellington last year, we suspect they may once again be a pretty good chance for a top-three finish. However, with only one player with World Cup experience (Lyndon Hannibal), the remainder of their squad is an unknown quantity as far as their experinece of top-level competition. Lyndon was one of the stars of the World Cup, so he brings a wealth of recent experience, but at the moment we know nothing about the others in the squad.
Of course, similar sentiments were being expressed just before last year's World Cup . . . . we'll stick with our top-three prediction. Now, who are the two teams who are going to finish below Sri Lanka ? ?


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Jorge Grant is keen to make an impression during pre-season after putting pen to paper on a new three-year contract.
The midfielder signed a new contract to keep him at Nottingham Forest and he wants to impress Mark Warburton during the training camp in America and stake a claim for a starting spot.
He said: "I am absolutely buzzing; I just can't wait to get started now. It has been in the pipeline for a few weeks and I am delighted to get it over the line and I am ready for next season.
"The manager hasn't seen me play at all really so it will be nice for me to go into pre-season and impress in the first few weeks of training day in, day out so he can see what I'm like as a person and as a player.
"I am going to give it my all in pre-season and try and get in the starting eleven and impress the manager. Last season wasn't good enough from all of us and it needs to be a fresh start. The ambitions that the manager and the owners have going forward look really good so hopefully we can push on."


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Hi everyone,
I have a couple more MFTeaser's to share with you all today in readiness of the MFT Stamps new release.
Today the MFT Design team are featuring the "Pure Innocence" range, and this month there will be three brand new Pure Innocence girls to be released … you are going to love them!!!!!! The PI's to be released include: PI – Bunch of Flowers; PI – Being Cute Is What I Do and PI – Little Angel.
For my first card I have used the PI – Being Cute is What I Do … of course the name says it all, how can a PI stamp not be cute hehe! I love them all!!!!!!!!!
I have used 3 Die-namic Dies on my card, the Rolled Flower which I cut from felt, the zigzag die and the Open Scallop Die. I also used the Grosgrain Texture board to add texture to my zigzag strip. For the layout I used one of the recent sketches from the Dare To Get Dirty Challenges.
Here is the inside of my card using one of the sentiments included in the set. I mirrored the layout from the outside.
|Stamps: PI – Being Cute Is What I Do – MFT Stamps
|Paper: White; Brown; Blue; DP – Crate Paper
|Other: Black Ink; Die-namics Zigzag Die; Die-namics Open Scallop Die; Die-namics Rolled Flower Die; Die-namics Grosgrain Texture Board; Circle Nestabilities; Glittered Garnishes; Foam Tape; Copics
For my second card today, I used PI – Bunch of Flowers … another cutie don't you think!!!!!!!!
I paper pieced the girls dress using the same designer paper I used for the background of my card. I also used the Ruffled Ribbon Collection - High Style to edge the two panels along the left side and bottom of my card.
Here is the inside of my card using one of the sentiments included in the set.
Ready for some TOP-SECRET news? Today, there is a prize hidden on one of the designer's blog posts. As you make your way through the Teaser Time posts, simply leave a comment on each blog, for your chance to win one of the Brand Spankin' New stamp sets being released on August 4th. A winner will be chosen from the comments on the pre-selected blog before tomorrow's teaser list goes live, and will be posted on Kim's blog HERE. Be sure to check tomorrow to see if YOU are the winner. You can play along each day for your chance to win. We will be giving away NINE new stamp sets this week! As always, you can find the master list of participating designers HERE Kim's blog.
Here are the Deets about the Release:
- Check out Kim's blog any time after 11AM EST each day to get the list of which Design Team members are also featuring these sets on their blogs today.
- The Guest Designer Contest will be posted on Saturday, July 31st. You'll have until Tuesday, August 3rd to enter for your chance to win OVER $125 worth of stamps from the upcoming release and play alongside the MFT Creative Team the following month.
- Join us for the release party on Wednesday, August 4th from 8-10 PM EST on the MFT Member Forum of SCS.
- All new products go live Wednesday at 10 PM EST in the MFT Boutique
- MFT Hop & Shop starts Wednesday at10 PM EST on Kim's blog
|Stamps: PI – Bunch of Flowers – MFT Stamps
|Paper: White; Pink; Purple; DP – Provocraft
|Other: Black Ink; Oval Nestabilities; Oval Punches; Ruffled Gingham Ribbon; Foam Tape; Copics


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To understand why you need VoIP, you need to get a better idea of why your business telephone system matters. If you believe that upgrading your communications system is trivial, then you're sorely mistaken. It can make or break your business and more importantly be the advantage that you need to beat your competitors. You'll Read more
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How Business VoIP Improves Operations
Business VoIP takes your company telephone system and gives it a massive upgrade. Unlike your past telephone system, you'll find that you can do things that you've never done before. VoiceNEXT is one of the leading providers of the technology. With our hosted PBX, our clients have experienced massive improvements to their business operations. Let's Read more
The Yealink VP-T49G Video Collaboration Phone
It's time to give another one of our amazing VoIP phones the spotlight. Today we're going to talk about the Yealink VP-T49G Video Collaboration Phone. This phone makes the perfect option for business professionals and higher-level executives. One of the reasons that we love this VoIP compatible phone is because it offers a robust set Read more
Why Choose VoiceNEXT as Your Next Phone Company
VoiceNEXT is one of the leading providers of VoIP technology, paving the way for advanced and affordable business telephony. We've successful serviced businesses from the real estate to medical industry – and more. It's the reason why Entrepreneur magazine ranked us as one of the "Best Entrepreneurial Companies in America." On our blog, we discuss Read more


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text: Virtual Sewing Quilting & Embroidery Expo Hi Sewing Friends! I'm "sew" excited to announce that my friend and mentor, Margaret Moorehead, will be hosting a Virtual Sewing Quilting and Embroidery Expo from September 12th through September 24th. This is a fantastic opportunity to watch some classes and demonstrations, and learn some techniques from the comfort of your own home 24/7!! And the best part, it's absolutely FREE!!! Margaret has collaborated with several top educators in the industry to present you with this online program. I prepared an actual video demonstrating how I combined my love of sewing with the adult coloring books, and I use the Sulky Iron-On Transfer Pens. Plus, I give you access to a free downloadable coloring book by Leonie Dawson. And, I'm adding more goodies to my website for expo attendees, including a short video with the best tips to successfully work with Sulky metallic threads and another video about my favorite notion, The Thread Director. Don't delay, sign up for this online event today! Sew Long for now! Posted by SewSimplifiedLLC Admin Monday, August 29, 2016 6:04:00 PM Comments(0)


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Sci-fi sequel Riddick took the top spot at the box office, bringing in $18.7 million in its opening weekend, Box Office Mojo reports.
Holding steady at No. 2 was Lee Daniels' biopic The Butler with $8.9 million. The Spanish comedy Instructions Not Included, which had a surprisingly strong debut last week, expanded nationwide this week and moved up a spot to third place with an $8.1 million haul.
Never miss an episode! Add new fall shows to your Watchlist
We're the Millers dropped a spot to No. 4 with $7.9 million, while Planes stayed at No. 5 with $4.3 million.
Last week's No. 1 film, One Direction: This Is Us, fell to sixth place with $4.1 million, while Elysium finished at No. 7 with $3.1 million.
Rounding out the Top 10 were Blue Jasmine (No. 8, $2.7 million), Percy Jackson: Sea of Monsters (No. 9, $2.5 million) and The World's End (No. 10, $2.3 million).


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2:36 PM 1 Comment
10 Businesses We Admire for Brilliant Global Marketing
Just a few weeks ago, we looked at the ins-and-outs of Facebook's new Global Pages -- a platform for brands to easily share region-specific content with international markets. Dankeschön, Facebook. No longer is global reach reserved for deep-pocketed brands, nor is it an incredible hassle for already over-burdened social media and community managers.
In fact, a global presence is possible for any business with a creative strategy and an understanding of world markets. To give you an idea of what a great global marketing strategy looks like, we've compiled some brands that totally "get it." Take a look at ten companies which have traveled successfully across the globe with their marketing!
1) AirbnbAirbnb is the Craigslist of apartment rentals. The company, launched in 2008 out of San Francisco, has taken its national service to 192 countries for users to rent short-term apartments from other users. How did this start-up grow up so quickly? Unlike Craigslist, Airbnb has a fun, more user-friendly website that showcases the brand's transparent, trusting personality. The website is now available in 21 languages with consistent information, style, and personality to appeal to like-minded users across cultures. Notice the carryover between this page, for example:
And this page:
You're looking at Airbnb's mobile app page in both German and English. The brand tailored the headline to fit the language: in English, it reads '...at your fingertips' but in German it reads '...on your cellphone' using the less formal term for cellphone, 'Handy'. The brand tweaks its content to best suit the culture, but it's still obvious which brand you're interacting with regardless of language. And I think this global focus is working -- in 2011, Airbnb rentals in Italy saw a 946% increase and the UK at 748%. The company also opened 9 overseas offices in the past 4 years to accomodate its growing global presence. Having a strong, consistent voice across languages is a key factor when going global.
2) RezdySome companies may not be trying to attract global markets directly, but if their clients are, they better know how. Rezdy is an Australian-based reservation software designed to make online booking smoother for tourists and agents alike, a valuable tool when over 60% of travellers make reservations online. Though Rezdy's clients are Australian-based, they need to cater to their clients' international visitors. Click on the screen shot to check out this fun video on Rezdy's homepage:
The first feature the video spotlights is 'Internationalisation.' The video walks us through how easy the service is for users, but is sure to emphasize the language and currency customization tool upfront. Even if your company is marketing to other regional companies, consider their global customers as if they were your own.
3) World Wildlife FoundationWWF took its Earth Hour initiative, a voluntary worldwide event where participants turn off their lights for an hour to show how easy it can be to battle climate change, and brought it to Norway's mobile audience (1 in 4 Norwegians have 3G mobile access).
Scandanavian countries like Norway experience extreme daylight hours throughout seasons, making the country ready for WWF's Blackout campaign. Using digital agency Mobiento, the nonprofit placed the Blackout Banner across Norway's top media sites to promote Earth Hour. With one tap of the banner, the screen went black. Finger swiping the black screen slowly revealed the Earth Hour countdown. The banner attracted roughly 1,000,000 impressions and the campaign received three 2012 MMA Global Mobile Marketing Awards.
Case: Black out rich media banner for WWF Earth Hour from Mobiento.
Have a cool idea? Don't be afraid to try it out on one international market -- just make sure it's the appropriate audience. Also, don't be afraid of the dark.
4) DurexThe UK-based condom manufacturer is number one in the industry with 34% market share across 130 countries. Sure, sex sells, but how does Durex sell such a taboo product in foreign countries? All jokes aside, Durex is sure to play it safe. The company developed an internal platform for its marketers from different countries to connect and discuss the brand's presence overseas.
Anna Valle, head of global marketing for Durex, said of the online community, "It will help us to share the global vision, to engage, and be more consistent." Discussion among marketers fuels localized campaigns with an overarching brand personality -- risque. For example, check out this recent image Durex shared on Sina Weibo after President Obama had been re-elected. (Fair warning: if you don't like raunchy and/or political humor, don't click.) 12 hours after being posted, the image was forwarded 43,000 times with over 12,000 comments.
5) Pearse TrustWith offices in Dublin, London, Vancouver, and Atlanta, Pearse Trust has grown to be a global authority on corporate and trust structures. But it takes more than offices all over the map to reach an international audience. That's why Pearse Trust keeps content flowing on its Facebook page that engages its various markets. In this screenshot below, you can see Pearse Trust posts daily content featuring international affairs relating to the company's practice.
Within 3 days, Pearse Trust made daily Facebook posts, leveling out external articles with Pearse Trust content, featuring news from Germany, Ireland (where they have a Dublin office), and the UK (where they have a London office). This is a great example of focusing on common interests shared among your company's various markets while making the content relateable to customers by region.
6) McDonald'sWe all know it's a successul global brand, so unlike their menu, I'll keep it light. While keeping its overarching branding consistent, Mcdonald's practices 'glocal' marketing efforts. No, that's not a typo. McDonald's brings a local flavor, literally, to different countries with region-specific menu items. In 2003, McDonald's introduced the McArabia, a flatbread sandwich, to its restaurants in the Middle East.
You can also find the McVeggie in India or the EBI-Fillet-O shrimp burger in Japan. This glocal approach has helped put McDonald's at #7 on Interbrand's Best Global Brands 2012.
7) Innocent Drinks
Innocent Drinks is the leading smoothie company in the UK with 75% of the market share in 2011 -- additionally, Innocent products are now available in 13 countries across Europe. The company is known to have "chatty branding"; for instance, the website is very bubbly with contact information that reads "call the bananaphone" or "visit the Fruit Towers."
The brand won the #1 spot on Headstream's Social Brands 100 for its entertaining and playful online presence. Headstream attributes Innocent's online success to keeping the brand's personality in tact across 13 countries. "Key to Innocent's success," they said, "has been a consistent tone of voice -- one that's natural, honest, and engaging -- making social activity feel like a natural extension of the company's personality."
Global expansion and rapid growth can sometimes distract a company from consistent branding. As marketers, we need to be sure our brand's voice is interpreted the same way around the world.
8) Unger and KowittThe phrase 'glocal' can be defined as "Think Globally, Act Locally." But what happens when you switch the two around? Woah, fasten your seatbelts -- literally. Unger and Kowitt is a traffic ticket law firm based in Fort Lauderdale defending drivers in the state of Florida. Not very global, right? Well, Unger and Kowitt understands that America is a melting pot and that Florida is bursting at the seams with different cultures and languages.
Though a domestic service, the firm's website is available in English, Spanish, Portugese, and Creole. With these options, Unger and Kowitt can cater to Florida's nearly 3.5 million Floridians who speak Spanish, Portugese, or Creole. Don't miss out on expanding your client base -- sometimes you don't have to look far to attract international business.
9) Coca-ColaCoca-Cola is a great example of a brand using glocal marketing efforts. Though a large corporation, Coca-Cola focuses on small community programs and invests a lot of time and money in small-scale charity efforts. For example, in Egypt, Coca-Cola has built 650 clean water installations in the rural village of Beni Suef and sponsors Ramadan meals for children across the Middle East. In India, the brand sponsors the Support My School initiative to improve facilities at local schools. Not to mention, the brand sticks with selling an emotion that can't get lost in translation: happiness. Now, tell me this doesn't look like fun:
10) Results.comTen points at #10 for Results.com, a business execution firm with offices in New Zealand, Canada, and the United States. This global company knows the importance of delivering on your promise, no matter how far that delivery may take you. On the website, Results.com says "We have global influence" and can provide "face to face consulting to companies from around the world."
Results.com does, in fact, bring face to face consulting to its customers. The company is bringing John Spence, marketing consultant and guru, from Florida to New Zealand in March 2013 to share his ideas with CEOs and business managers in the region. Since November 2010, the company's website traffic has increased by 180%. I wouldn't be surprised if events like this are generating buzz down under!
What other brands out there do a great job with their global marketing?
Read more: http://blog.hubspot.com/blog/tabid/6307/bid/33857/10-Businesses-We-Admire-for-Brilliant-Global-Marketing.aspx#ixzz2DkR2uwgE


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Dennis Quaid week continues! Quaid's been shrunk to molecule-size and injected into Martin Short, who drinks Southern Comfort so that Quaid can catch some on the way down. And then they dance together: Short and his microscopic companion.
Innerspace is a strong contender for Dennis Quaid's most bizarre SF movie of all time, although it has plenty of competition. After Quaid is injected into Short, he manages to hook himself up to Short's optic nerve and his eardrum, so he can see and hear what Short sees and hears — and he can somehow talk to Short as well. This allows Quaid to give Short advice on how to "dominate" Meg Ryan — which apparently worked well enough that Quaid and Ryan were married soon afterwards.
The other greatest sequence involves Robert Picardo, the holographic doctor from Star Trek: Voyager, playing an immensely hairy Eastern European fence called The Cowboy, who disco dances in cowboy boots (and sometimes not much else.) Short gets the drop on Picardo and ties him up in the bathtub, then Quaid somehow uses his miniature gizmos to convert Short's face into Picardo's. You know it makes sense.
At least, it makes more sense than a guy who's one molecule thick being able to drink normal-sized liquor, as Roger Ebert gleefully points out.


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Learning from the Media
Information and media literacy is at the core of the media's social responsibility. Fostering literacy among the different age groups and including it in formal education has a direct impact on daily communication and interaction between the readers and the public and the media they chose every day to inform and entertain themselves. On the other hand, it also promotes a better understanding of and critical approach to the media that make up a country's communication offering, and enhances and elevates citizens' demand for communication.
Grupo Clarín was one of the pioneers in the promotion of media and information literacy through varied initiatives developed throughout its history since the inception of Diario Clarín and, later on, in the audiovisual contents produced by its signals. Today, those efforts are embodied in the prestigious workshops aimed at teachers and students developed by the Noble Foundation as part of the program "Los medios de Comunicación en la educación". The program workshops are free and they are attended every year by thousands of teachers and students.


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Comprehensive Rehabilitation Experts
ChildServe's Multi-trauma Rehab program helps children and young adults restore function following a traumatic accident. We provide expert care for wide range of complex needs in one location. We offer intensive medical and nursing services; care coordination by a whole team of pediatric experts; physical, occupational, and speech therapies; access to our adaptive equipment and orthotics program; and cutting-edge technology. As children and young adults reach their health and independence goals, our pediatric specialists support them by coordinating with schools and outpatient or community services for a smooth transition to home.
Why choose ChildServe?
ChildServe's Multi-trauma Rehab program has the only board-certified pediatric rehab doctor in Iowa, Fred Klingbeil"Dr. Fred," as many ChildServe kids call him, provides expert rehabilitation and medical management of children with special healthcare needs. As the only board-certified pediatric rehab doctor in Iowa, Dr. Fred's years of experience and knowledge in pediatric care are a valuable resource.
, MD, who treats children and young adults in the inpatient and outpatient programs.
, MD, who treats children and young adults in the inpatient and outpatient programs.
Pediatric Experts
Our pediatric experts have specialized training and additional knowledge to provide exceptional rehab to children and young adults.
We hold CARF accreditationsBeing CARF-accredited means that the Commission on Accreditation of Rehabilitation Facilities recognizes ChildServe as an organization that meets rigorous guidelines for service and quality and conforms to nationally and internationally recognized standards.
in pediatrics, brain injury, and inpatient and outpatient rehabilitation.
in pediatrics, brain injury, and inpatient and outpatient rehabilitation.
Specialized Technology
ChildServe offers cutting-edge facilities and specialized technology including our therapeutic pool, the Functional Electrical Stimulation bike (FES), body-weight supported treadmill, and whirlpool tubs for wound management.
Who We Serve
ChildServe offers Multi-trauma Rehab to children and young adults (birth through 21 years old) who may be experiencing multiple medical issues due to their accident or trauma including the following:
Traumatic brain injury
Respiratory conditions (tracheostomy, ventilator or oxygen support)
Feeding difficulties (tube or oral feeding)
Muscle weakness due to a long hospitalization
Our Approach
We Know Kids
Our entire organization is built around kids! ChildServe's pediatric specialists provide healthcare designed for the developmental needs of children and young adults. The pediatric experts in our Multi-trauma Rehab program, like our Therapists, Certified Wound Care Nurses, and Dietician, have specialized knowledge and skills to treat kids and young adults. Our facilities and equipment are designed to make children feel comfortable, safe, and inspired.
Expert Medical Care
ChildServe's pediatric specialists help children and young adults manage complex medical needs after being discharged from an acute care hospital. Our medical experts provide care to help kids heal from injuries; increase mobility, balance, and strength; develop independence and improve function; and emphasize nutrition to promote healing. We equip each child as needed with adaptive equipment like wheelchairs and walkers.
Pediatric Rehab
Our Pediatric Rehab Nurses and Therapists create customized rehab plans for each child. Plans may include physical, occupational, and speech therapy, along with therapeutic recreational activities, aquatic therapies, pet therapy, and music therapy. Our therapists help children and young adults learn or rebuild skills to help them transition to home.
We Care about Families
As part of ChildServe's continuum of care, our rehab specialists train parents regarding their child's condition and how to provide care at home. We offer a home and vehicle assessment to ensure safety upon discharge. Children and young adults may transition to outpatient therapy programs to continue receiving support from ChildServe's expert therapists. Our medical social workers offer care coordination for the transition to ChildServe's programs and other community resources as needed.
Our Team of Pediatric Specialists
ChildServe employs a variety of healthcare professionals, including but not limited to the following positions:
Pediatric Rehabilitation Medicine Physician
Pediatric Nurse Practitioner
Certified Wound Nurse
Certified Rehabilitation Nurse
Certified Brain Injury Specialist
Respiratory Therapist
Occupational Therapist
Physical Therapist
Speech Language Pathologist
Music Therapist
Aquatic Therapist
Medical Social Worker
Therapeutic Recreational Specialist
Assistive Technology Professional
Frequently Asked Questions
Who is eligible to receive services?
ChildServe's Multi-trauma Rehab program offers services to children and young adults (birth – 21 years) who have been discharged from an acute care hospital, but continue to require complex medical care.
How are referrals made?
To make a referral or request information, call our Access Specialist at 515-331-8106, or use the contact form below.
How are services authorized and funded?
Program costs are authorized and funded through commercial insurance and Medicaid. Specific fees will be discussed during the intake/admission process.
Where are services provided?
Multi-trauma Rehab services are offered at ChildServe in Johnston.
When are services provided?
Multi-trauma Rehab services are available 24 hours a day, seven days a week.
View our Annual Outcomes
ChildServe regularly gathers child and family satisfaction feedback, quality reports, and census data to monitor our services and continuously improve the care and services we provide.
Contact Us!
ChildServe – Johnston
5406 Merle Hay Road, Johnston, IA 50131
(515) 727-8750
If you would like to make a referral, or if you have additional questions, please use the contact form below.
ChildServe Center - Johnston
ChildServe improves the health and well-being of more than 4,600 children each year through specialized clinical, home, and community-based programs and services. We serve children with developmental delays, disabilities, acquired injuries, and other special healthcare needs.
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Johnston | 515-727-8750
Ames | 515-232-7220
Des Moines | 515-280-5332
Iowa City | 319-351-5437
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Join our mailing list to receive the latest news and updates from our team.


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GOLCAR Scouts have won an award for their camping skills.
The team of two girls and four boys from the 4th Golcar troop triumphed in the competition at Bradley Woods Scout Camp, near Brighouse, which featured teams from Huddersfield South West and Huddersfield East districts.
They were judged on everything they did on the weekend from setting up their tents through to cooking, making camping gadgets out of poles and pieces of string and clearing up at the end of the camp.
Scout leader Craig Ellis and assistant scout leader Suzanne Leach dropped them off at the camp. District leaders then took on the role of judges.
Suzanne said: "The team had to cook a three-course campfire meal using an oven they had made from clay.
"One of the dishes had to be made from pastry which is quite tricky on a campfire!
"They made camp gadgets from poles and string, including a flagpole, a gateway to their tents, a drying rack and a washing-up stand."
On the last day of camp they had a full kit inspection and had to dismantle their tents and clean up quickly and efficiently.


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Since that time, I have: ripped up all the carpet in my basement, carried it out to be thrown away, acquired a PODS storage unit, and packed up all my photos and decorative items throughout the house. For the weekend L and M came over and we: removed numerous shelving units into the pod, packed up two shelves of books, repaired the paint and plaster in both back rooms from the winter ice damn, prepped the back rooms, painted and put up new house numbers, purchased "banana cream pie" paint, purchased vinyl tiles, tiled the majority of the basement floor, repaired then painted both back ceilings white, painted both back rooms the bright creamy pie color, and (all by myself last night after work) prepped and taped the bathroom, painted the bathroom the same cream color, then (this morning in my supergirl underoos) peeled off all the tape and reattached all the hardware.
I've also hired my neighbors to take care of the exterior. D landscaped like crazy, trimming trees and overgrowth, then pruning the front. B edged the lawn, weeded the driveway, then painted the front of the house to make it look extra-clean. He did a bunch of other touch-up paint, and soon (hopefully tomorrow!) he'll paint the nasty peeling porch. I can't wait! Soon this house will look tremendous.
This evening M and I staged the back two bedrooms, moving minimal furniture into the freshly painted space, and making the bigger one "look like a bedroom". It's kind of funny. I mean, it's a Royal Oak bungalow. There are hundreds of them, exactly the same. You walk in the middle, living room and dining room /kitchen on either side, then a bath, then there are two bedrooms. Upstairs is generally a third bedroom. And yet, according to many professional house stagers, potential buyers could walk into mine and go, "Oh wait, why aren't there any bedrooms? There are just two offices in the back rooms.... where would the children sleep?"
It seems silly to me, but I have begrudgingly agreed to minimalize the "officeyness" of my office and add an air-mattress disguised as a bed. "Now the file cabinet is taking up a lot of room," M commented.
"It's supposed to look like a dresser. Anyway it's the bed that's taking up all the room," I grumped. "This office isn't made for a bed!" But nonetheless, I can understand the idea of staging each room to have a clear purpose. I'm going to have to look at pictures of bedrooms at Ikea and Pottery Barn, to make sure my room looks bedroomy enough.
I still have to make the bathroom look cutsier, and (although it breaks my heart again and again) I fear I have to paint my lovely lavender walls to be a less female color. M's having his cousin come give me an estimate on that. I'm not looking forward to it, even though I can see the practicality.
I also have to empty out the basement. And tidy the garage. And figure out where to put stuff that I will need soon, but shouldn't leave in the staged house. It's exhausting, just trying to think of everything, let alone do it!
My new mantra is: it's not my house, it's not my house. I'm not making it comfortable for me, I'm making it look appealing to the new owners. I hope they get here soon, fall in love with it, and offer me bundles of money for it. I'm eager for this whole thing to be through!


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Machine Learning / AI - Engineering & Research Internship
Job Code200169045
Posted: Oct 1, 2020
Weekly Hours: 40
Role Number:200169045
Apple is seeking highly qualified people for the position of AI/ML Engineer and AI/ML Researcher. The team pursu...Summary
Posted: Oct 1, 2020
Weekly Hours: 40
Role Number:200169045
Apple is seeking highly qualified people for the position of AI/ML Engineer and AI/ML Researcher. The team pursues research & development in the areas of machine learning (ML) with particular focus on deep learning (DL), computer vision (CV), natural language processing (NLP), information retrieval (IR), and reinforcement learning (RL). As a member of the team, you will work on some of the most challenging technical problems, develop new ML solutions that will impact future Apple products, and collaborate with the best product teams to integrate your ideas into products.
Key Qualifications
- In-depth expertise in deep learning (DL) and statistical machine learning (ML)
- Expertise in one or more of CV, NLP, RL, IR, search and speech, optimization, time series, generative models, signals, pattern recognition fields, and/or computer graphics fields
- Strong publication record demonstrating innovative research
- Good presentation skills
- Passionate about building extraordinary products
- Excellent programming skills in Java, Python, C/C++, CUDA or other GPGPU is a plus
- Knowledge of common ML frameworks
- Expected to perform well in a fast-paced environment, to execute on the tasks assigned, to meet the production deadlines and, at the same time, to explore independently new innovative ideas that can improve and transform the product experience of Apple customers
- Be able to deliver ML technologies aligned with the core values of Apple, ensuring the highest standards of quality, scientific rigor, innovation, and respect for user privacy
- Creative, collaborative, and product focused
You will research and develop innovative ML strategies for challenging problems that will affect future Apple products. You will collaborate with broader teams across Apple to transfer AI/ML solutions. You will have opportunities to provide technical mentorship and guidance and prepare technical reports for publication and conference talks. You are self-motivated, excellent problem solver, a go-getter. You are quick to build relationships and work well with change and ambiguity. You have strong programming skills with tried experience crafting, prototyping, and delivering advanced algorithmic solutions.
Internship opportunities are available in Cupertino, San Francisco, Seattle, Boston and Pittsburgh.
Education & Experience
Currently pursuing a PhD, Masters, or Bachelors degree in Machine Learning, Human Computer Interaction, Natural Language Processing, Robotics, Computer Science, Data Science, Statistics or related areas.
We are an equal opportunity employer and value diversity at our company. We do not discriminate on the basis of race, religion, color, national origin, gender, sexual orientation, age, marital status, veteran status, or disability status.
Additional Requirements
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