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Bone-targeting drug delivery system of biomineral-binding liposomes loaded with icariin enhances the treatment for osteoporosis
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Osteoporosis is a bone-incapacitating malady and it is characterized by obvious bone mass loss and bone microarchitecture deterioration. Current treatments for osteoporosis have many limitations, including the non-obvious therapeutic effect and long-term safety issues. Icariin is a pharmacologically active flavonoid glycoside, which shows potential application in treatment of osteoporosis. But its clinical application is limited by the inherent disadvantages such as poor water solubility, first pass effect after oral administration, and low bioavailability. Moreover, due to lack of targeting ability, icariin cannot accumulate at the local diseased region to provide early protection from fractures. To solve the application problems of icariin and enhance its therapeutic effects on osteoporosis, this work aimed to design a targeting drug delivery system of biomineral-binding liposomes (BBL) mediated by pyrophosphate ions.
Biomineral-binding liposomes enhanced the binding ability of liposomes with hydroxyapatite particles. It increased the serum level of alkaline phosphatase and reduced that of tartrate-resistant acid phosphatase 5b. Meanwhile, BBL increased the mechanical strength of femoral midshaft, preserving the trabecular bone microarchitecture. Moreover, BBL could initiate bone turnover/remodeling of rats with osteoporosis.
This drug targeting delivery system of BBL loading with icariin showed more therapeutic advantages than the free icariin for the treatment of osteoporosis, which may be a kind of valid candidate in future osteoporosis therapy.
KeywordsLiposomes Osteoporosis Icariin Hydroxyapatite Pyrophosphate
- ALN-TEG-Chol
alkaline phosphatase
biomineral-binding liposomes
bone mineral density
bone morphogenic protein-2
bone surface per bone volume
bone volume per tissue volume
central composite design
dynamic light scattering
empty biomineral-binding liposomes
enzyme-linked immunosorbent assay
free drug
Generally Regarded As Safe
hematoxylin and eosin
horseradish peroxidase
- Micro-CT
micro-computerized tomography
non-binding liposome
phosphate-buffered saline
polydispersity index
- PPi
pyrophosphate ions
- PPi-TEG-Chol
sham-control surgery
small intestinal submucosa
trabecular bone
- Tb.N
trabecular number
- Tb.Sp
trabecular separation
- Tb.Th
trabecular thickness
tris (tetra-n-butylammonium) hydrogen pyrophosphate
transmission electron microscopy
- TRACP 5b
tartrate-resistant acid phosphatase 5b
Osteoporosis is a typical age-related disease and it is more common in female than in male. Osteoporosis affects about half of the over-75-year-old female [1]. Osteoporosis is characterized by fragile bones and microarchitectural deterioration, which causes approximately 9 million cases of the bone fractures every year [2].
Current clinical treatments on osteoporosis mainly include estrogen therapy, bisphosphonates, and selective estrogen receptor modulators [3]. But these treatments showed obvious restrictions, including non-obvious therapeutic effect and long-term safety issues. For example, bisphosphonates were widely used for osteoporosis therapeutics, which avoided further bone deterioration in osteoporosis. But, it can't replenish the already lost bone [3, 4]. What's more, oral bisphosphonates may cause esophageal irritation and the intravenous injection of bisphosphonates with rapid speed may cause renal toxicity [3]. Estrogen therapy showed some non-skeletal adverse consequences such as breast carcinoma and vascular events [3]. Some other pharmacological treatments for osteoporosis include growth factors, calcium and vitamin D supplementation, calcitonin, and parathyroid hormone. Among them, treatment with calcium plus vitamin D supplementation for osteoporosis is controversial [5, 6]. It was reported that calcitonin can induce vascular symptoms and gastrointestinal symptoms [7, 8], and parathyroid hormone may cause life-threatening hypercalcemia [9]. Therefore, more candidates for osteoporosis need to be investigated in the basic research.
Icariin (C33H40O15, MW 676.65) is a kind of flavonoid glycoside extracted from the Chinese traditional medicine of Herba Epimedii. It has been reported that icariin could help with the treatment of osteoporosis [10]. Compared with the drugs mentioned above, icariin focuses on the maturation of osteoblasts [11]. It improves the activity of alkaline phosphatase (ALP) and increases the expression of receptor activator of nuclear factor κ-B ligand to promote the bone formation [11]. It also affects the bone morphogenic protein-2 (BMP-2)/Smad4 pathway thus up regulates the expression of BMP-2 and Smad4, resulting in the formation of calcified nodules in bone [11]. Icariin also leads to G2/M block,which decreases the bone resorption and attenuates the expression of tartrate-resistant acid phosphatase (TRACP) by osteoclasts thereby accelerating the accumulation of trace elements such as calcium and phosphorus in bones and improving osteoporosis [11]. Icariin has been widely used in orthopedic practice, and many of its therapeutic effects on bone problem and fractures have been reported [12, 13]. Moreover, icariin is more effective in promoting osteogenic differentiation than other natural flavonoids like genistein [11]. Meanwhile, icariin is a botanical compound that can stimulate increased sex hormone levels and interact with the estrogen receptor to produce hormone-like action [14]. But the inherent disadvantages of icariin such as poor water-solubility, first pass effect after oral administration, and low bioavailability limited the clinical applications. Moreover, due to lack of targeting ability, icariin cannot accumulate at the local diseased region to provide early protection from fractures.
Among the nano-sized drug delivery carriers, liposomes were widely used, having good biocompatibility and controlled release ability [15, 16]. Currently, liposomes, such as paclitaxel liposomes and doxorubicin liposomes, have been used in clinical therapy [17]. Liposome composed of phospholipid is a kind of spherical vesicle with lipid bilayer. The phospholipid is composed of hydrophilic heads and hydrophobic tails which formed a self-assembled nanostructure through hydrophobic interactions [18]. The hydrophilic cargos can be wrapped in the aqueous core while the hydrophobic drugs were kept in the lipid bilayer of liposomes [19]. On the other hand, it was reported that an alendronate-tri(ethyleneglycol)-cholesterol (ALN-TEG-Chol) conjugate showed rapid and strong binding ability to hydroxyapatite (HA) [20]. With other excipients, ALN-TEG-Chol was used to prepare biomineral-binding liposomes (BBL) showing rapid and strong binding ability with HA. The same concept can be extrapolated easily to other targeting moieties, e.g. tris (tetra-n-butylammonium) hydrogen pyrophosphate as a specific binding moiety to the same surface has been developed.
Since HA is a main mineral constituent of bone, we investigated the in vitro targeting ability of BBL via the binding experiment of BBL with HA. The in vivo therapeutic effect of BBL taking non-binding liposome (NBL) as control was evaluated on the osteoporosis animal model constructed by ovariectomy (OVX) plus glucocorticoid (GLU) injection. We detected the bone formation marker of ALP and bone resorption marker of TRACP 5b by ELISA. Meanwhile, the mechanical strength and bone microstructure were evaluated respectively by a three-point bending test and a micro-computerized tomography (Micro-CT) analysis. We also carried out histological studies including TRACP staining, Alizarin red staining, and hematoxylin and eosin (H&E) staining.
Characterization of BBL preparations
Composition and characterization of liposomes
Molar ratios (A/B/C)
Particle size (nm)
Zeta potential (mV)
Drug loading (%)
Encapsulation efficiency (%)
152.3 ± 0.7
0.24 ± 0.01
− 1.3 ± 0.2
3.8 ± 0.83
78.6 ± 4.9
193.1 ± 0.8
0.19 ± 0.01
− 5.53 ± 0.1
4.3 ± 0.67
87.4 ± 3.7
BBL enhancing the binding potential and kinetics with HA particles
In the binding kinetics study (Fig. 3C, D) measured by HPLC method, most of BBL loaded with icariin could swiftly bind to the biotechnical HA particles within 5 min and reached a binding plateau after 10 min with a binding rate of 75%. In the absence of PPi-TEG-Chol, NBL demonstrated a very limited non-specific binding to HA particles (< 15%). As for the commercial synthetic HA, the result of binding kinetics is similar except that the binding plateau of BBL and NBL is respectively about 50% and 15%, which indicated that for the same kind of liposomes, the biotechnical HA particles showed stronger affinity than the synthetic HA did. Meanwhile, PPi-TEG-Chol enhanced the binding ability of liposomes with HA particles.
BBL showing a sustained-release profile
Detection of ALP and TRACP 5b in serum of rats
BBL enhancing the bone mechanical strength of rats subjected to OVX plus GLU
The peak load values of femur in the groups of NBL, FD, and BBL were 182.50 ± 12.70 N, 206.00 ± 8.20 N, and 262.10 ± 26.80 N, respectively, which were significantly higher than that in the PBS group with a value of 129.60 ± 13.90 N (P < 0.01, P < 0.01 and P < 0.05).
As for the ultimate stiffness of femur, the value resulted from PBS group was 348.30 ± 30.20 N/mm; but in the groups of NBL, FD, and BBL, it remarkably increased to 430.20 ± 29.90 N/mm, 506.90 ± 22.10 N/mm, and 623.80 ± 25.60 N/mm, respectively.
A similar increasing trend was observed in the ultimate strength of femur. The values from PBS, NBL, FD, and BBL was 34.40 ± 3.20 MPa, 43.70 ± 1.40 MPa, 44.20 ± 3.50 MPa and 60.70 ± 0.60 MPa, respectively.
The Young's modulus values of femur in NBL (754.80 ± 96.10 MPa), FD (777.30 ± 17.30 MPa) and BBL (935.90 ± 26.20 MPa) were also significantly higher than that in the PBS group (505.20 ± 60.20 MPa).
Moreover, among all the strength parameters of peak load, ultimate stiffness, ultimate strength and Young's modulus, there were no differences between the treatments of PBS vs. EBBL and SHAM vs. BBL; the values in FD group were significantly lower than that in BBL group. These results suggested that BBL loaded with icariin could significantly enhance the bone mechanical strength of rats subjected to the operation of OVX plus GLU.
BBL contributing to restore the bone microarchitecture of rats with osteoporosis symptoms
BBL promoting the bone remodeling process in osteoporosis rats according to histological results
Osteoporosis is one of the most common diseases of the elderly characterized by imbalance of bone formation and bone resorption, resulting in the deterioration of bone microarchitecture, low bone density, and poor bone strength [22]. In consideration of the limitation of systemic therapies, this study constructed a targeting drug delivery system for osteoporosis as the following steps. We synthesized the key component of BBL, pyrophosphate-tri(ethyleneglycol)-cholesterol (PPi-TEG-Chol), by chemical process for preparing BBL. Because of the high affinity of PPi with HA [20, 21, 23] crystals which is the major inorganic components in bones [24, 25], we chose it as the targeting moiety and conjugate it with cholesterol to form PPi-TEG-Chol, in which cholesterol was chosen as the molecule to introduce the bone-binding moiety due to its major role in the liposome lipid bilayer and a single secondary hydroxyl group in its structure facilitates chemical modification [26]. Moreover, both PPi and its major predictable metabolic product (i.e. phosphate) are considered as Generally Regarded As Safe (GRAS) by the FDA [27]. Liposomal formulation was chosen as our working platform owing to its long proven biocompatibility, versatility and the great potential of clinical translation [28, 29]. From the data generated by DLS analysis, BBL was found to be bigger than NBL in particle size and size distribution (193.1 nm and 152.3 nm), pointing out the addition of PPi-TEG-Chol did enlarge the particle size of the liposome formulation which may be due to the longer chain of PPi-TEG-Chol than that of single molecular of cholesterol.
We prepared the biotechnical HA under the conditions that are consistent with the bone biomineralization, taking the SIS membrane as the biomineralization template. In the biomineralization process of SIS, it is very important to ensure that the upper liquid would not leak from the edges and the SIS membrane would remain immersed into the liquid during the experimental period. The ions, Ca2+ and (HPO4)2−, diffused from the separate sides of SIS membrane and combined together to form the precipitate on some localized zones of SIS where there is a enough excessive saturation of Ca2+, (HPO4)2− and OH−. As a result of the particular lower nucleation activation energy of SIS membrane towards the inorganic species, inorganic phases were prior to nucleation and emerged. After that, inorganic phase became larger along vertical direction of SIS film and it was oriented by the aligned collagen fibers of SIS. Above all, the procedure was growth of crystal cell of single-crystal flower-like HA, then growth plate-like HA rods. The size and structure of HA was regulated by SIS biotemplate. Growth direction of HA was perpendicular to SIS membrane. Because the manufacturing process and mechanism of HA resembled to that of the natural bones, the biotechnical HA is important in the long-term bone regeneration [30, 31]. It was reported that HA crystal belonged to the hexagonal system and classified into a(b)-plane HA and c-plane HA, in which the a(b)-plane HA is mainly positively charged calcium ions, and the c-plane HA is mainly negatively charged phosphate ions and hydroxyl groups. On the surface of long bone of amniotes, HA crystals possess a c-axis direction, which cause the growth of the a(b)-plane [32]. We synthesized the c-axis orientation HA according to our previous report [33], which caused the growth of the a(b)-plane and thus provided plenty of positive binding site for the negatively-charged PPi-TEG-Chol, showing a strong binding affinity. Meanwhile, although there is no PPi-TEG-Chol in the component of NBL, on the surface of NBL there is a very small amount of negative charges. Therefore, fluor-NBL groups could also show slight fluorescencein in the binding-ability detection.
We took the combination injection of OVX and GLU to establish osteopenia model in rats [34, 35], which showed evident decrease of bone formation, as proved by the reduced concentrations of serum ALP and BMD. These outcomes were accordance with some former findings by Jing et al. [36]. Treating the osteoporosis rats with the novel liposomal formulation provided a local drug (bone anabolic/anti-catabolic reagents) releasing to increase the bone formation and decrease the bone resorption. Serum ALP, an index of bone formation, was significantly lower in PBS group than that in SHAM group. BBL group was statistically superior to both FD and NBL groups in increasing the serum ALP of the OVX + GLU rats. OVX combined with GLU injection increased the serum concentration of TRACP 5b, which was a sensitive marker of bone resorption. Treatment with BBL was statistically superior to other therapeutic interventions in inhibiting the raise of serum TRACP 5b. Cortical bone played a key role in bone strength and the bone density and mechanical properties were linearly correlated [37]. In this research, the mechanical characteristics of rat femora declined in PBS group when compared to SHAM group, pointing out the raise in the brittleness of the cortical bone of the OVX + GLU rats. Treatment with BBL was statistically superior to FD and NBL treatment in increasing femoral midshaft peak load, stiffness, ultimate strength, and Young's modulus. These perceptions provide evidence for the increase in measured mechanical characters including both the outside (cortical bone size and shape) and the inside bone characters (nature of the material properties of bone tissue). This can put down to the decreased bone resorption and/or the increased bone formation or both. Measuring the microarchitectural parameters, such as Tb.Sp, BS/BV, BMD, Tb.N, Tb.Th and BV/TV, may help us estimate the bone strength [38]. The OVX + GLU rats demonstrated a decrease in BMD, Tb.N, Tb.Th and BV/TV when compared with SHAM group. In addition, significantly higher levels of Tb.Sp and BS/BV were seen in PBS group when compared with SHAM group. It was discovered that treatment with BBL medicine prescription was statistically superior to other treatments in inhibiting the decrease of BV/TV and suppressing the increase of Tb.Sp. These parameters showed that BBL improved the trabecular organization and bone quality in the OVX + GLU rats. In histological analysis, we discovered that BBL strengthened the osteoblast activity and depressed the osteoclast function by up-regulating TB volume, as well as increasing cancellous bone mineralization rate and decreasing TRACP positive cells.
We have successfully developed the novel biomineral-binding liposome formulation for the treatment of osteoporosis in the OVX + GLU rats. As the major formulation excipient, the pyrophosphate was conjugated to cholesterol and acted as the bone-binding moiety. The drug-containing liposome formulated with modified cholesterol demonstrated strong and fast binding capability to HA. When challenged with a disease model in rats of osteoporosis, the biomineral-binding liposome formulation of icariin demonstrated significantly better therapeutic efficacy than all the controls. Therefore, the application of BBL loaded with icariin can be a novel and effective candidate in future therapy of osteoporosis.
Icariin was purchased from Zelang (Nanjing, China; purity, 98%). Standard icariin was offered by Must BioTechnology Company (Chengdu, China; purity, ≥ 98%). Tris (tetra-n-butylammonium) hydrogen pyrophosphate (TBAP) was bought from Sigma-Aldrich Co. (St. Louis, MO). Soybean lecithin was got from A.V.T. Pharmaceutical Co. Ltd. (Shanghai, China). Cholesterol was got from solarbio Co. (Beijing, China). HA particles (DNA grade, Bio-Gel HTP gel) named as 'synthetic HA' in present study were got from Bio-Rad (Hercules, CA). The other reagents and solvents, if not appointed, were supplied by Kelong Chemical Reagent Factory (Chengdu, China).
Preparation and characterization of liposomes
Liposomes were prepared by a combined method of a thin-film dispersion and a mechanical extrusion, including a main component of soybean lecithin (A), cholesterol (B), and PPi-TEG-Chol (C). The component ratio of BBL and NBL was optimized according to our previous report by central composite design that is widely used in designation of pharmaceutical dosage forms [39]. As shown in Table 1, to prepare BBL [A/B/C: 70/20/10 (molar ratios)] and NBL [A/B/C: 70/30/0 (molar ratios)], mixture of lipids and icariin was dissolved in 10 mL solvent of chloroform/methanol (1:1, v/v) and placed into a round bottom flask. The solvent was then removed under moderate vacuum until a thin film formed on the flask wall. The thin-film was further dried under vacuum condition for 24 h to confirm no chloroform left. Then the dried thin film was hydrated with phosphate-buffered solution (PBS, pH 7.4). Finally, the liposome suspensions were extruded through the 200-nm polycarbonate membrane in an Avanti® Mini-Extruder to obtain the desirable size-dispersion liposomes. The empty biomineral-binding liposomes (EBBL) without icariin were prepared similarly except addition of icariin. Meanwhile, we prepared the fluore-labeled BBL (fluore-BBL) and fluore-labeled NBL (fluore-NBL) using sodium fluorescein to replace the aforementioned icariin in the preparation process.
Morphology of liposomes was observed under TEM on a JEM-100SX electron microscope (Japan). Particle size and the zeta potential of liposomes were characterized by DLS (Zetasizer Nano ZS90, Malvern Instruments, Malvern, UK).
Detections about encapsulation efficiency and drug-loading efficiency were conducted using an ultrafiltration tube with a molecular weight cut-off of 5 kDa (Solarbio Science and Technology Co., Ltd., Beijing, China). The un-encapsulated icariin (Wfree) was quantified using an Agilent 1260 HPLC system (Infinity, USA). Measurement was conducted on a reverse-phase C18 column (Agilent, 4.6 × 250 mm, 5 μm). The flow phase was a kind of mixture of acetonitrile and water (30:70, v/v) with a flow rate of 1.0 mL/min and an injection volume of 10 μL. Samples were diluted with methanol and filtered through a 0.22-μm membrane before injection. The detection wavelength was 270 nm. The selectivity, linearity, precision, and recovery of methods were fully validated. The encapsulation efficiency and the drug-loading efficiency were calculated using the following formula as: Encapsulation efficiency (%) = (Wtotal − Wfree)/Wtotal × 100%; Drug loading (%) = (Wtotal − Wfree)/Wliposomes× 100%.
HA rods' synthesis and characterization
Because HA crystals are typically c-axis orientation on the surface of vertebrate long bone [33], to mimic the binding process of BBL with natural bone in vivo, we used a small intestinal submucosa (SIS) as the bio-template and prepared the plate-like single crystal HA with c-axis direction which was referred as 'biotechnical HA'.
In the reaction system, the important key was the SIS, which acted as the bio-mineralization template. SIS was obtained according to the standard procedures [40]. Firstly, the tunica serosa and tunica muscularis of the fresh porcine small intestine should be removed, and SIS was washed with a saline solution. Secondly, SIS was immersed in solvent of methanol/chloroform (1:1, v/v) overnight in a fume hood, and the organic solvents were washed away with deionized water. Thirdly, SIS was kept in a mixed solvent of trypsin (0.05%) and ethylenediamine tetraacetic acid (0.05%) for overnight at 37 °C. Then saline solution was used to wash SIS to remove the trypsin and ethylenediamine tetraacetic acid. SIS was further treated with sodium dodecyl sulfate (0.5%) NaCl solution (0.9%). After shaking for 4 h, SIS was washed again with NaCl solution (0.9%). At last, SIS was immersed into a mixture of peroxyacetic acid (0.1%) and ethanol (20%) for 30 min, and further washed with NaCl solution (0.9%). The final product was freeze-dried and stored at 4 °C.
Binding ability and kinetics of BBL on the synthetic and biotechnical HA particles
The fluorescein sodium-loaded liposomes including fluore-BBL and fluore-NBL were prepared using the method described above. For the binding ability experiment, both the commercial synthetic HA and the biotechnical HA produced by bio-template SIS were added into the fluorescein sodium-loaded liposomal solutions. The mixtures were agitated for half an hour at room temperature. Further, it was filtered, washed with water, and lyophilized. Finally, HA particles were observed under a fluorescence microscope. For the binding kinetics experiment, these two types of HA (100 mg) were added into 1.0 mL of icariin-loaded liposomal solutions. HA was eliminated by centrifugation (10,000×g, 5 min) after incubation for 1, 3, 5, 10, 30 min respectively at room temperature. The supernatant was collected and the content of icariin left in liposomal supernatant (Wleft) after binding was analyzed by HPLC method mentioned above. Binding rate (%) was calculated according to the following formula as: Binding rate (%) = (Wtotal − Wleft)/Wtotal× 100%. NBL without PPi-TEG-Chol were used as control in the experiment.
In vitro icariin release study of BBL
The in vitro release analysis of icariin from liposomes was conducted in PBS medium (10 mM, pH 7.4). Liposomal formulations and free icariin were put into a dialysis bag (MWCO, 3 kDa) placed in 30 mL of release medium with gentle stirring at 37 °C. At pre-designed time intervals, 1.0 mL of samples were taken out from the release medium and replaced with fresh medium. Every group of sample was diluted to 2.0 mL and filtered through a 0.22-μm membrane (Millipore). Amount of icariin in all samples was determined using HPLC method as mentioned above.
Ovariectoporosis model
All Sprague–Dawley (SD) rats obtained from the Laboratory Animal Center of Southwest Medical University were maintained at 20–25 °C under a 12-h light/dark cycle and allowed for food and water. All animal experiments were approved by the Animal Ethics Committee of Southwest Medical University (Permit No. 20160126). The animal handling and surgical procedures were carried out in accordance with the guidelines of the Local Animal Use and Care Committees of Lu Zhou.
For establishing the osteoporosis model, 3-month-old mature female SD rats were subjected to bilateral OVX or sham-control surgery (SHAM) according to the Ref. [25]. Briefly, rats were anesthetized by intraperitoneal injection of sodium pentobarbital (1%, 8 mL/kg). The back fur of rats was shaved, cleaned with iodophor solution, and then covered with a sterile cloth. A single longitudinal lumbar lateral skin incision was made near the midpoint of lower edge of free ribs and iliac crest, where the ovary was located. Before removing the ovary, a suture was put in around the ovarian artery and vein to ligate the ovary. The muscles were repositioned in layers and sutured with re-absorbable sutures. The skin incision was closed using nylon 4-0 sutures. OVX rats were injected intraperitoneally with dexamethasone (a synthetic GLU, 0.5 mg/kg) twice a week for 4 weeks. The rats in SHAM group were subjected to SHAM surgery, in which the ovaries were exposed but kept intact. The bone mineral density (BMD) of bilateral femur was measured using micro-CT (SIMENS healthcare, Berlin and Munich, Germany) at 7 weeks post surgery, respectively. The rats were divided into six groups (n = 8) following as: SHAM, PBS as control, NBL, free drug (FD) and BBL. The animals were treated with or without icariin as mentioned above on every day by intraperitoneal injection, in which the formulations were normalized to the amount of icariin (90 mg/kg), and FD was prepared by dissolving icariin into PEG 400 (0.2%) and further being diluted with saline for injection. Seven weeks post-treatment, animals were anesthetized and blood was collected and subjected to detection for the bone formation marker of ALP and bone resorption marker of TRACP 5b. The bilateral femoral bones were extracted for bone biomechanical examination, Micro-CT scanning, and histology analysis.
Serum biochemical analysis
The bone formation was assessed by measuring serum level of ALP and the bone resorption was evaluated by measuring serum level of TRACP 5b. Measurements of serum ALP and TRACP 5b were performed by a sandwich enzyme-linked immunosorbent assay (ELISA, Qiao Du Biotechnology Co., Ltd. Shanghai, China) according to the protocols offered by provider. Briefly, the standards and samples were added into the standard wells and the sample wells, respectively. Then horseradish peroxidase (HRP) were added to each well, and the mixture were incubated for 60 min at 37 °C. After rinse with washing solution for 5 times, a chromogen solution were added to each well and mixed gently. The mixture was incubated for another 15 min in the dark at 37 °C. At last, a stopping solution was added to each well to end the reaction, and then optical density was measured at 450 nm using a microplate reader within 15 min.
Bone biomechanical examination
Mechanical characteristics of femur from the treated rats were evaluated by a three-point bending test using a universal testing machine (Jinan Huaxing Test Equipment Co., Ltd. ShanDong, China). Prior to test, the bones were balanced to room temperature and kept moist until the test was finished. The length of bone was obtained using a caliper. The femur was placed on the holding device with supports located apart 12 mm from each other. A bending force was applied to the cross head at a speed of 0.033 mm/s until the femur fractured. According to the experimental data, the load–displacement curve can be plotted for each sample. Some mechanical characteristics were obtained from these curves, including peak load (the maximum force that the bone withstood before fracture), ultimate stiffness (the extrinsic rigidity of femur before fracture), ultimate strength (the maximum stress of femur before fracture) and the Young's modulus representing the intrinsic stiffness of an intact bone.
Micro-CT analysis
To evaluate skeletal microarchitecture, the right femora (n = 6) were subjected to a high-resolution Micro-CT analysis using a Micro-CT imaging system (Siemens, Inveon), according to the method described in a publication [41].
The quantitative parameters of the bone microstructure were measured, including BV/TV, BS/BV, Tb.Th, Tb.N, Tb.Sp and BMD. All the digitalized data and 3-dimensional images were supplied by the built-in software of Micro-CT (Siemens, Inveon).
Histological analysis
In order to assess the bone mineral areas, femora were fixed in 4% paraformaldehyde, decalcified with EDTA (10%, pH 7.4), and embedded using paraffin. Longitudinal serial sections (6 μm) were mounted on polylysine-coated microscope slides. For general histological studies, H&E staining, TRACP staining, and Alizarin Red staining were performed according to manufacturer's protocol. The stained areas were quantified by ImageJ software.
Statistical analysis
All data are expressed as mean ± SD after at least three separate tests. The differences among the treatment groups were analyzed for significance using the Student t-test. A P value less than 0.05 was regarded as statistical significance and a higher significance level was set at P < 0.01.
Authors' contributions
The study was designed by JYL and ZRZ, with XDS and ZBL performing the majority of experimental work. JH, JW and FJP performed all HPLC spectroscopy experiments and assisted with the statistical analysis. ZRZ, TRB and CHL supervised the project and wrote the manuscript, with contributions from all authors. All authors read and approved the final manuscript.
All authors are grateful for support from the following research platforms of the Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, the Drug Discovery Research Center, the Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
Competing interests
The authors declare that they have no competing interests.
Availability of data and materials
All data generated or analyzed during this study are included in this published article and its additional information files.
Consent for publication
All authors agreed to submit this manuscript.
Ethics approval and consent to participate
All animal experiments were approved by the Animal Ethics Committee of Southwest Medical University (Permit No. 20160126). The animal handling and surgical procedures were carried out in accordance with the guidelines of the Local Animal Use and Care Committees of Lu Zhou.
This work was supported by the Collaborative Fund of Luzhou Government and Southwest Medical University (2016LZXNYD-J06, 2017LZXNYD-T07), General Program of Science and Technology Agency of Sichuan Province (2017JY0160, 2018RZ0120), Science and Technology Project of the Health Planning Committee of Sichuan (18PJ547, RZ20170048), Key Fund and the Youth Fund and the Transformation Project of Science and Technology Achievements of Southwest Medical University (2018-ZRZD-018, 2017-ZRQN-073, 2018002), Key Science and Technology Project of Luzhou Government (2018-SYF-19), Base Project of Luzhou TCM Hospital and Southwest Medical University (2017-LH004).
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Supplementary material
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Copyright information
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


text:
The court closed the case of the protest of 94 workers of uranium mine "Ingulska" without considering Featured
On 9 February, the Court hearings in the case of the protest of 94 workers of uranium mine "Ingulska" was held in Kropyvnytskyi. As it was informed before, 94 miners from uranium mine "Ingulska" of the State Enterprise "Eastern Mining and Processing Plant"" (Kirovohrad region), who were fighting for salary raise, got sued by administration of enterprise. In this way, the administration of the company reacted to the protest action that was recently held in the mine, when miners decided to stay underground after work. The management considered this as a strike.
The judge, who was responsible for carrying out the civil case in the lawsuit of the State Enterprise ''Eastern Oriental ore mining and processing enterprise'' to 94 employees of the mine '' Ingulska'", closed the case without considering it.
The Chairman of the Confederation of Free Trade Unions of Ukraine and the Independent Trade Union of Miners of Ukraine Mykhaylo Volynets made a comment:
"During the negotiations, reached the agreement and managed to find the consensus. As a result, the company withdrew the lawsuit, the court closed it without consideration. We do appreciate the solidarity and support that we received from our trade union brothers and sisters and partners during this struggle".
Related items
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- Donetsk region: Four female employees still on hunger strike against wage arrears
- Despite of rockslide and dangerous conditions miners protesting for 11 days underground
- Miners holding underground protest for 10 days

subset: commoncrawl


text:
Overly excited to have an upstairs, feels like a home 🥰 Most relaxing place 🌲🍂✨
Quickest swim of my life to get back home to football and beer #priorities 🏊🏼♀🍺
Wedding season across the pond 🇬🇧🎉
Beach walks with the dogs 🏖🚶🏻♂
Sunburnt and dodgy driving ⛳
Pleased to have signed my one year contract extension with Tydd St Mary Football Club in what will be my 5th season with the club. #tfl ⚽⚽⚽
Last night.... same setup, different location 📍 . Time to grow a new community in #cambridgeshire 💚 . Tomorrow in #paris 🇫🇷 . .
Today I found out that I play my best golf when I can't feel my hands #golf
Had so much fun putting this together for @hattie1xx, how I'm going to cope without you for the next 9 months I don't know, I can't wait to meet your perfect little girl 💗💗
So I'm very fortunate to work at some amazing gyms and this is one of them @tyddstgilescountryclub The facilities are amazing, the pool is like a bath and the food is incredible. I was joined today by @lifestyle_services_by_tina as she loved my LBT class so much yesterday! I'm keeping her focused on exercise and she's keeping focused on nutrition put together we would be perfect 😂😂 #ifyoudidntknowilovemyjob 💪😍💚
Lets see if this still works 🙈👍 #dayoff #golfday
Big sky reflected
She can twat it ! Wants to come with me every time now 👍⛳ #daddydaughtertime #daughtergoals
Great day for golf... not so great for @harrygriffinn #golf #willheeverbeatme
My first round @tyddstgilescountryclub lush course! and managed to shoot 84, really strong round for me! @large_phil doing bits too! Let's keep improving! ⛳🏌🏻♂
Work views 🌅 #sunrise #work
Whoop whoop the day is here 🎉🎈🎊🎁 #happybirthday #happyfriday
#amateurs_bnw #amateurphotography
What a perfect way to spend my weekend
Lovely little swim date this afternoon @staceyclayton1990 #swimming #waterbabies
Ball was a little below feet,difficult shot but managed to get it out #golf #golfaddict
A big well done to our winner of the Men's Autumn Open 2017 - Andrew Hicks ⛳🏆 #golf #tyddgolfandcountryclub
Love this!!!!! #wedding #mr @lilyjayneflorist @letterhiredotcom
Today has been mega busy at work, and I still have another shift to go! Quick half an hour at the gym to keep me awake, looking forward to my Sunday swim tomorrow 👌
Lovely afternoon tea spent with cousins and mums 💕
Good morning from @tyddstgilescountryclub ☀ #golf #sunrise
Today's dog walk with the mutts. #olly #mutt
My mate @adamgarford chipping onto the green ⛳🏌🏼 #chippychippy #illpickuponthishole @oasiswez @markogreen87
Decent round of golf. Cracking course! #tyddstgiles #golf
Afternoon walks 🌳 #giantdaisy #walks
Private plates slowing moving throughout the house! #mrcaf #cafex
Nice place to live lovely Sunday
💪🏃☀ . . . . . . . #gym #fitness
Day 4. Gym Class, Swim, Steam Room & Lunch w/ my challenger and team member @sashlll at @tyddstgilescountryclub I want to live here 😍 #28daychallenge #fitter
Walking to the Christmas Eve dinner... through the foggy countryside
Taking in this gorgeous view thus morning. I love being on golf courses so much. There's this feeling of calm. Always takes me back to working on the women's Tour. Doubt I'll get out to play this week with the kids hanging off me but nice to enjoy #halfterm #golfgirl . . . .
rosé squad
Winding up to smoke one down par5 13th hole. Was on the green in two 🏌🏾♂. Also love adding the titleist Ap2's to the bag 🙌🏾. #golf #poorgolfer mensfashion
; Day 7: Last day of chill, next up- Euro tour! Paris & Switzerland here I come ❤


text:
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text: IT Auditor SAP Job ID REF42077K Job posted 18.01.2019 Location Stuttgart , Germany Fields of work Information Technology Join as Associate Job type Full-time Start Date According to arrangement Apply now Welcome to Bosch Do you want beneficial technologies being shaped by your ideas? Whether in the areas of mobility solutions, consumer goods, industrial technology or energy and building technology - with us, you will have the chance to improve quality of life all across the globe. Welcome to Bosch. The Robert Bosch GmbH is looking forward to your application! Your tasks Take responsibility: You will plan and perform IT security audits on all SAP systems within the Bosch group. Conscientious coordination: You will align audit results with the audited entity. Reliable implementation: You will monitor measure implementations. Help shape the future: You will ensure the secure operation of existing audit tool as well as further development of new functions. Your profile Personality: responsible and team player Working Practice: independence, able to convince and willing to innovate Experience: several years of relevant professional experience in audit methods and experience in the field of SAP security Knowledge: Knowhow in Database Technology (MS SQL Server, ODBC) and Programming (MS Access, T-SQL Programming, VBA Scripting) Languages: very good German and English skills both written and spoken Education: completed degree with a focus in information technology (Computer Science etc.) or similar qualification Contact & Additional information Need support during your application? Lindsay Rauch (Human Resources) +49 711 811 32097 Need further information about the job? Stefan Lindner (Functional Department) +49 711 811 18910 This location offers Health & Sport We offer a wide range of corporate sports activities and health provision. Childcare Take advantage of our intermediary service for childcare offerings. In-house social counseling and care services Take advantage of our in-house social counseling service, including online counseling options and our intermediary service for care services. Flexible and mobile work We offer you flexible work(time) models. Employee discounts Bosch employees profit from various discounts. Room for creativity Our working environment offers room for creativity. Please speak to your superiors or recruitment contact for your individual benefit plan. Apply now Share it


text:
The laughter and screams emanating from the Berto Center practice floor Monday sounded strange for a Bulls team that has lost four straight.
"(Jerome) James did like a baseline dunk," guard Derrick Rose later explained. "It was just fun today, I will tell you the truth. I didn't get dunked on. I move out of the way if I can't (block) it. But James is a big guy, so everybody just let him dunk."
Word on the street: Ever wonder about a day in the life of longtime Cubs radio broadcaster Pat Hughes? That is one of the features in the new Cubs annual edited by Al Yellon that is available at local bookstores and at maplestreetpress.com.
Local attractions: Northwestern football coach Pat Fitzgerald will lead 14 staff members and 13 players to have their heads shaved at 6 p.m. Wednesday in Evanston (Jay's Barbershop, 1579 Maple Ave). Each participant shaves his head for financial pledges to support St. Baldrick's, which raises money for childhood cancer research. … Former Buffalo Grove resident and current Ravens safety Tom Zbikowski will help St. Matthias Parish kick off fundraising to refurbish the school gym (4910 N. Claremont, Chicago). He will make a donation and address students at a 10 a.m. Tuesday pep rally.


text:
Information Technology Jobs in Lawton, IA 51030
(18 Jobs)
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2 weeks ago
Contractor | Pay: $100 - $130/hour
A large end user is searching for a high level technical architect to over see the immplementation of D365 for Finance and Operations. Key Skills and Responsibilities: Oversee the development and technical design of D365 D365 experience required At least 8...
Sioux City, IA, USA
6 days ago
Full Time | Pay: $60,000 - $80,000/year
Network and Systems Administrator (Direct Hire) This is a Permanent *Direct Hire position with one of our client companies in the Sioux City, IA area. This company is growing and has a great new opportunity for Network and Systems Administrator with a grea...
Sioux City, IA 51102, USA
Full Time | Pay: $13 - $15/hour
Our Technical Support Advisors provide support to resolve customer technology problems through a series of trouble shooting activities in a virtual call center environment. Common solutions include resolving username and password problems, data sharing &am...
North Sioux City, SD 57049, USA
Full Time | Pay: $80,000 - $100,000/year
Information Technology Manager (Direct Hire) This is a *Direct hire position with one of our client companies in the Sioux City, Iowa Area. The client company is a mid-sized organization (under 1,000 employees) is seeking an I.T. Manager with leadership in...
South Sioux City, NE, USA
4 weeks ago
Full Time
The Management Information System Specialist is chartered with managing enterprise IT assets across hardware, software, peripherals, printers, mobility, and IT infrastructure assets for the facilities. The Specialist will lead a team of 20-30 resources thr...
Sioux City, IA, USA
Full Time
We are quickly transforming the company from a traditional production line based screening firm to a technology based leader in the industry. One of our main goals is to utilize technology to its fullest extent in all aspects of our business to provide the...
CareerBuilder LLC
Norcross, GA, USA
Full Time
CareerBuilder Employment Screening has created the need to quickly build out our software engineering teams with talented, driven individuals to take our company and technology to the next level. Our systems interact with many different client and vendor s...
CareerBuilder, LLC
Norcross, GA, USA
Full Time
As a Hands-On Software Development Manager at CareerBuilder Employment Screening (CBES), you'll have the opportunity to build something extraordinary and lead awesome people. We are seeking a strong candidate to guide our development, overseeing up to thre...
CareerBuilder LLC
Norcross, GA, USA
4 weeks ago
Full Time
This role will be part of the Dealer Services business team providing business application solutions to enhance dealers' experience while doing business with GM Financial. Day to day activities will involve developing on the Salesforce.com platform, creati...
GM Financial
Norcross, GA, USA
Part Time Retail Inventory Associate - Dist058 - Sioux City, IA
Part Time Retail Inventory Associate - Dist058 - Sioux City, IA
2 weeks ago
Part Time
Efficiency is everything! I know, I know...we just said accuracy is everything but speed and accuracy go hand in hand when you're a Retail Inventory Associate. Location, location, location. You will never get bored with going to the same location over and ...
Sioux City, IA, USA
Full Time
ATS has improved the performance for the world's most sophisticated companies, and we owe our success to our employees. Your time and your knowledge are important - make the most of both. At ATS, we've continually empowered our employees to develop their s...
Sioux City, IA, USA
Full Time | Pay: $18 - $25/hour
Woodhouse Chrysler Dodge Jeep Ram of Sioux City is looking for all levels of technicians and a Transmission Technician to join our team!! Be a part of one of the most important teams in the dealership - The service department!...
Woodhouse Chrysler Dodge Jeep Ram
2101 6th St, Sioux City, IA 51101, USA
Part Time
Realistic Job Preview: The Realistic Job Preview gives you an honest, objective and vivid portrait of what it means to work as a Transportation Security Officer (TSO) and provides employee testimonies about both the good and the challenging aspects of bein...
Sioux City, IA, USA
Full-Time / Part-Time | Pay: $19 - $22/hour
Openings for Customer Service Representatives! Sharpen your skills as a Customer Representative in the growing Security industry through this opportunity at OfficeTeam. Do you want to apply your outgoing personality to further the benefit of a valuable bus...
Sioux City, IA 51104, USA
Full Time
Ensure conformance to environmental regulations and company environmental policies and guidelines. Responsible for Environmental Management System, Risk Management Program, wastewater treatment plant operation, air permitting and reporting, EPCRA reporting...
1000 Cunningham Dr, Sioux City, IA 51106, USA
Part Time
Jobs in this category are responsible for: selling and servicing customers in one or more departments, including Home Appliances and Footwear; maintaining knowledge of products and using this knowledge to assist and educate customers on options available; ...
United States
4 days ago
Full Time
As the primary point of contact for WORKTERRA clients, the Client Executive will consistently deliver accurate, timely and succinct responses for all of their service needs. The Client Executive (CE) is responsible for the day-to-day interaction and manage...
Pleasanton, CA, USA
Full Time | Pay: $13 - $15/hour
Our Technical Support Advisors provide support to resolve customer technology problems through a series of trouble shooting activities in a virtual call center environment. Common solutions include resolving username and password problems, data sharing &am...
Elk Point, SD 57025, USA
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text:
What Is Contract Manufacturing?
Basically, there are different elements to contract manufacturing; for example a customer may already have an idea of what they require and may come to us with a specification or formulation of what they want. They may have specific requirements for manufacture to be carried out to very fine tolerances on some of the components… Continue reading »


text:
ajarora's Ratings
1. The Favourite (2018)
R | 1 hr 59 min | Biography, Comedy, Drama
Rated on 06 Jan 2019
In early 18th century England, a frail Queen Anne occupies the throne and her close friend, Lady Sarah, governs the country in her stead. When a new servant, Abigail, arrives, her charm endears her to Sarah.
Director: Yorgos Lanthimos | Stars: Olivia Colman, Emma Stone, Rachel Weisz, Nicholas Hoult
Votes: 55,520
2. The Expanse (2015– )
TV-14 | 1 hr | Drama, Mystery, Sci-Fi
Rated on 02 Jan 2019
A police detective in the asteroid belt, the first officer of an interplanetary ice freighter and an earth-bound United Nations executive slowly discover a vast conspiracy that threatens the Earth's rebellious colony on the asteroid belt.
Stars: Steven Strait, Cas Anvar, Dominique Tipper, Wes Chatham
Votes: 64,607
3. Maniac (2018)
TV-MA | 40 min | Comedy, Drama, Sci-Fi
Rated on 02 Jan 2019
Two strangers are drawn to a mysterious pharmaceutical trial that will, they're assured, with no complications or side-effects whatsoever, solve all of their problems, permanently. Things do not go as planned.
Stars: Jonah Hill, Emma Stone, Sonoya Mizuno, Justin Theroux
Votes: 45,205
4. The Man in the High Castle (2015– )
TV-MA | 1 hr | Drama, Sci-Fi, Thriller
Rated on 02 Jan 2019
In a dystopian America dominated by Nazi Germany and Imperial Japan, a young woman discovers a mysterious film that may hold the key to toppling the totalitarian regimes.
Stars: Alexa Davalos, Luke Kleintank, Rufus Sewell, Rupert Evans
Votes: 64,412
5. Counterpart (2017– )
TV-MA | 1 hr | Drama, Sci-Fi, Thriller
Rated on 02 Jan 2019
A hapless UN employee discovers the agency he works for is hiding a gateway to a parallel dimension that's in Cold War with our own, and where his other self is a top spy. The war slowly heats up thanks to spies from both sides.
Stars: J.K. Simmons, Harry Lloyd, Olivia Williams, Nazanin Boniadi
Votes: 14,705
6. A Wednesday (2008)
Not Rated | 1 hr 44 min | Crime, Drama, Mystery
Rated on 29 Dec 2018
A retiring police officer reminisces about the most astounding day of his career. About a case that was never filed but continues to haunt him in his memories - the case of a man and a Wednesday.
Director: Neeraj Pandey | Stars: Anupam Kher, Naseeruddin Shah, Jimmy Sheirgill, Deepal Shaw
Votes: 66,868
7. Quarry (2016– )
TV-MA | 1 hr | Crime, Drama, Thriller
Rated on 29 Dec 2018
Quarry, a disillusioned Vietnam War vet, returns home to Memphis in 1972 only to find rejection and scrutiny at every step. A mysterious man known only as The Broker gives him an offer he can't refuse - to work for him as a hitman.
Stars: Logan Marshall-Green, Jodi Balfour, Damon Herriman, Edoardo Ballerini
Votes: 9,774
8. Persepolis (2007)
PG-13 | 1 hr 36 min | Animation, Biography, Drama
Rated on 10 Dec 2018
A precocious and outspoken Iranian girl grows up during the Islamic Revolution.
Directors: Vincent Paronnaud, Marjane Satrapi | Stars: Chiara Mastroianni, Catherine Deneuve, Gena Rowlands, Danielle Darrieux
Votes: 80,968
9. Sigeuneol (2016– )
1 hr 20 min | Crime, Drama, Fantasy
Rated on 10 Dec 2018
Detectives from the present and a detective from the past communicate via walkie-talkie to solve a long-time unsolved case.
Stars: Je-hoon Lee, Hye-su Kim, Jin-Woong Cho, Hyun-Sung Jang
Votes: 1,465
10. Patriot (II) (2015– )
TV-MA | 58 min | Comedy, Drama, Thriller
Rated on 16 Nov 2018
Follows the complicated life of intelligence officer John Tavner, whose latest assignment - to prevent Iran from going nuclear - requires him to forgo all safety nets and assume a perilous non-official cover.
Stars: Michael Dorman, Kurtwood Smith, Michael Chernus, Kathleen Munroe
Votes: 7,596
11. Homecoming (2018– )
TV-MA | 30 min | Drama, Thriller
Rated on 13 Nov 2018
Good intentions. Erratic bosses. Mounting paranoia. Unforeseen consequences spiraling out of control. Heidi (Julia Roberts) works at Homecoming, a facility helping soldiers transition to ... See full summary »
Stars: Julia Roberts, Bobby Cannavale, Stephan James, Shea Whigham
Votes: 10,171
12. Bodyguard (2018– )
TV-MA | 1 hr | Crime, Drama, Thriller
Rated on 11 Nov 2018
A contemporary thriller featuring the Royalty and Specialist Protection Branch of London's Metropolitan Police Service.
Stars: Richard Madden, Sophie Rundle, Vincent Franklin, Ash Tandon
Votes: 54,910
13. Blade Runner (1982)
R | 1 hr 57 min | Sci-Fi, Thriller
Rated on 05 Aug 2018
A blade runner must pursue and terminate four replicants who stole a ship in space, and have returned to Earth to find their creator.
Director: Ridley Scott | Stars: Harrison Ford, Rutger Hauer, Sean Young, Edward James Olmos
Votes: 616,391
14. The Boondocks (2005–2014)
TV-MA | 22 min | Animation, Action, Comedy
Rated on 05 Aug 2018
Based on the comic strip, Huey and Riley move away from the city and out to the suburbs with their irascible grandfather. Biting socio-political commentary ensues.
Stars: Regina King, John Witherspoon, Gary Anthony Williams, Cedric Yarbrough
Votes: 24,117
15. Trailer Park Boys (2001–2018)
TV-MA | 30 min | Comedy, Crime
Rated on 05 Aug 2018
Three petty felons have a documentary made about their life in a trailer park.
Stars: John Paul Tremblay, Robb Wells, Mike Smith, John Dunsworth
Votes: 32,188
16. Hilleo (2014–2015)
TV-14 | 1 hr | Action, Comedy, Crime
Rated on 05 Aug 2018
An old murder incident involving a group who ran an illegal broadcasting station brings together different people - a mysterious errand guy "Healer" who possesses disguise and fighting ... See full summary »
Stars: Chang-Wook Ji, Min-Young Park, Tae-mi, Ji-won Do
Votes: 3,239
17. O Mecanismo (2018– )
TV-MA | 41 min | Crime, Drama, Thriller
Rated on 05 Aug 2018
Dramatic fiction series loosely inspired by an investigation of corruption in Brazil's private and state oil companies and construction companies.
Stars: Caroline Abras, Enrique Diaz, Jonathan Haagensen, Sean Burgos
Votes: 33,261
18. Planet Earth II (2016)
TV-G | 6 hr | Documentary
Rated on 05 Aug 2018
David Attenborough returns in this breathtaking documentary showcasing life on Planet Earth.
Star: David Attenborough
Votes: 64,753
19. Black Panther (2018)
PG-13 | 2 hr 14 min | Action, Adventure, Sci-Fi
Rated on 05 Aug 2018
T'Challa, heir to the hidden but advanced kingdom of Wakanda, must step forward to lead his people into a new future and must confront a challenger from his country's past.
Director: Ryan Coogler | Stars: Chadwick Boseman, Michael B. Jordan, Lupita Nyong'o, Danai Gurira
Votes: 461,040
20. Ready Player One (2018)
PG-13 | 2 hr 20 min | Action, Adventure, Sci-Fi
Rated on 05 Aug 2018
When the creator of a virtual reality world called the OASIS dies, he releases a video in which he challenges all OASIS users to find his Easter Egg, which will give the finder his fortune.
Director: Steven Spielberg | Stars: Tye Sheridan, Olivia Cooke, Ben Mendelsohn, Lena Waithe
Votes: 278,169
21. Three Billboards Outside Ebbing, Missouri (2017)
R | 1 hr 55 min | Comedy, Crime, Drama
Rated on 05 Aug 2018
A mother personally challenges the local authorities to solve her daughter's murder when they fail to catch the culprit.
Director: Martin McDonagh | Stars: Frances McDormand, Woody Harrelson, Sam Rockwell, Caleb Landry Jones
Votes: 321,698
22. Death of a Nation (I) (2018)
PG-13 | 1 hr 48 min | Documentary, History
Rated on 03 Aug 2018
This docudrama draws parallels between the dramatic fracturing of the nation over Abraham Lincoln's presidency and the presidency of Donald Trump.
Directors: Dinesh D'Souza, Bruce Schooley | Stars: Dinesh D'Souza, Victoria Chilap, Pavel Kríz, Rafael Prazák
Votes: 5,607
23. Top Boy (2011– )
Not Rated | 1 hr | Crime, Drama, Thriller
Rated on 30 Jul 2018
A thriving but underground drugs business is being run by Dushane (Ashley Walters) and his friend Sully (Kane Robinson) to become the richest men on the block. To live rich Dushane and ... See full summary »
Stars: Ashley Walters, Kane Robinson, Shone Romulus, Malcolm Kamulete
Votes: 4,009
24. John Wick: Chapter 2 (2017)
R | 2 hr 2 min | Action, Crime, Thriller
Rated on 28 Jul 2018
After returning to the criminal underworld to repay a debt, John Wick discovers that a large bounty has been put on his life.
Director: Chad Stahelski | Stars: Keanu Reeves, Riccardo Scamarcio, Ian McShane, Ruby Rose
Votes: 261,045
25. Dunkirk (2017)
PG-13 | 1 hr 46 min | Action, Drama, History
Rated on 28 Jul 2018
Allied soldiers from Belgium, the British Empire, and France are surrounded by the German Army, and evacuated during a fierce battle in World War II.
Director: Christopher Nolan | Stars: Fionn Whitehead, Barry Keoghan, Mark Rylance, Tom Hardy
Votes: 448,074
26. Blade Runner 2049 (2017)
R | 2 hr 44 min | Drama, Mystery, Sci-Fi
Rated on 28 Jul 2018
A young blade runner's discovery of a long-buried secret leads him to track down former blade runner Rick Deckard, who's been missing for thirty years.
Director: Denis Villeneuve | Stars: Harrison Ford, Ryan Gosling, Ana de Armas, Dave Bautista
Votes: 361,857
27. Den 12. mann (2017)
Unrated | 2 hr 15 min | Drama, History, Thriller
Rated on 28 Jul 2018
They were 12 saboteurs. The Nazis killed 11 of them. This is the true story of the one who got away...
Director: Harald Zwart | Stars: Thomas Gullestad, Jonathan Rhys Meyers, Marie Blokhus, Mads Sjøgård Pettersen
Votes: 10,126
28. Bimilui Soop (2017– )
TV-14 | 1 hr | Crime, Drama, Mystery
Rated on 22 Jul 2018
A prosecutor without empathy and a bold female police are taking a murder case involving unrestrained political corruption.
Stars: Seung-woo Cho, Doona Bae, Jae-woong Choi, Joon-Hyuk Lee
Votes: 2,099
29. City of Men (2002–2018)
30 min | Comedy, Crime, Drama
Rated on 20 Jul 2018
In this original variation on the Latin American telenovela (slow, emotional soap), life in Rio de Janeiro, the Brazilian big city jungle, is told in short, fast alternating scenes from the... See full summary »
Stars: Darlan Cunha, Douglas Silva, Camila Monteiro, Roberta Rodrigues
Votes: 2,637
30. The Shadow Line (2011)
1 hr | Crime, Drama, Mystery
Rated on 16 Jul 2018
Detective Inspector Jonah Gabriel returns to work after a botched operation that resulted in him sustaining a near-fatal bullet wound. It may be his first day back on the job but he's soon ... See full summary »
Stars: Chiwetel Ejiofor, Christopher Eccleston, Kierston Wareing, Richard Lintern
Votes: 3,677
31. Happy Valley (2014– )
TV-MA | 58 min | Crime, Drama
Rated on 14 Jul 2018
Catherine Cawood is the sergeant on duty when flustered and nervous accountant Kevin Weatherill comes into her West Yorkshire station to report a crime.
Stars: Sarah Lancashire, Siobhan Finneran, Shane Zaza, Charlie Murphy
Votes: 26,411
32. Top of the Lake (2013– )
TV-MA | 1 hr | Crime, Drama, Mystery
Rated on 13 Jul 2018
Obsessed with the disappearance of a 12-year-old pregnant girl near a freezing lake in New Zealand, a brave detective will find herself up against small-town secrets and a side of herself that was meticulously kept at bay.
Stars: Elisabeth Moss, David Wenham, Peter Mullan, Thomas M. Wright
Votes: 28,906
33. The Honourable Woman (2014)
1 hr | Drama, Thriller
Rated on 13 Jul 2018
Centers on Nessa Stein, a woman who inherits her father's arms business and finds herself in a international maelstrom when as she continues to promote the reconciliation between Israelis and Palestinians.
Stars: Maggie Gyllenhaal, Stephen Rea, Lubna Azabal, Katherine Parkinson
Votes: 8,855
34. Smiley's People (1982)
6 hr | Drama, Mystery
Rated on 11 Jul 2018
The murder of a Soviet defector forces his old handler, British spymaster George Smiley, out of retirement. His investigation leads to an old nemesis, the Soviet spymaster known only as Karla. This will be their final dance.
Stars: Alec Guinness, Eileen Atkins, Bill Paterson, Vladek Sheybal
Votes: 3,173
35. Tinker Tailor Soldier Spy (1979)
TV-14 | 4 hr 50 min | Drama, Thriller
Rated on 11 Jul 2018
In the bleak days of the Cold War, espionage veteran George Smiley is forced out of semi-retirement to uncover a Soviet Agent within MI6's echelons.
Stars: Alec Guinness, Michael Jayston, Anthony Bate, George Sewell
Votes: 6,652
36. BoJack Horseman (2014– )
TV-MA | 25 min | Animation, Comedy, Drama
Rated on 11 Jul 2018
BoJack Horseman was the star of the hit TV show "Horsin' Around" in the '90s, now he's washed up, living in Hollywood, complaining about everything, and wearing colorful sweaters.
Stars: Will Arnett, Amy Sedaris, Alison Brie, Aaron Paul
Votes: 65,798
37. Parasyte: The Maxim (2014–2015)
TV-MA | 22 min | Animation, Action, Horror
Rated on 11 Jul 2018
17-year-old Shinichi Izumi is partially infected by a Parasyte; monsters that butcher and consume humans. He must learn to co-exist with the creature if he is to survive both the life of a Parasyte and human, as part monster, part person.
Stars: Adam Gibbs, Aya Hirano, Brittney Karbowski, Nobunaga Shimazaki
Votes: 16,040
38. House of Cards (1990)
TV-14 | 3 hr 46 min | Drama
Rated on 11 Jul 2018
The schemes of a ruthlessly ambitious British politician who will stop at nothing to get to the top.
Stars: Ian Richardson, Susannah Harker, Miles Anderson, Alphonsia Emmanuel
Votes: 11,672
39. Berserk (1997–1998)
Not Rated | 22 min | Animation, Action, Adventure
Rated on 11 Jul 2018
Guts is a skilled swordsman who joins forces with a mercenary group named 'The Band of the Hawk', lead by the charismatic Griffith, and fights with them as they battle their way into the royal court.
Stars: Nobutoshi Canna, Marc Diraison, Carrie Keranen, Kevin T. Collins
Votes: 23,071
40. Battlestar Galactica (2003)
TV-14 | 3 hr 3 min | Action, Adventure, Drama
Rated on 11 Jul 2018
Following the destruction of the Twelve Colonies of Kobol by the Cylons, a rag-tag fugitive fleet of the last remnants of mankind flees the pursuing Cylons while simultaneously searching for their true home: Earth.
Stars: Edward James Olmos, Mary McDonnell, Katee Sackhoff, Jamie Bamber
Votes: 59,828
41. The West Wing (1999–2006)
TV-14 | 44 min | Drama
Rated on 11 Jul 2018
Inside the lives of staffers in the West Wing of the White House.
Stars: Martin Sheen, Rob Lowe, Allison Janney, John Spencer
Votes: 54,883
42. La casa de papel (2017– )
TV-MA | 1 hr 10 min | Action, Crime, Mystery
Rated on 11 Jul 2018
A group of very peculiar robbers assault the Factory of Moneda and Timbre to carry out the most perfect robbery in the history of Spain and take home 2.4 billion euros.
Stars: Úrsula Corberó, Itziar Ituño, Álvaro Morte, Alba Flores
Votes: 114,795
1 hr | Drama, Thriller
Rated on 11 Jul 2018
The missions of MI-5, the UK's domestic intelligence organization.
Stars: Peter Firth, Hugh Simon, Nicola Walker, Rupert Penry-Jones
Votes: 13,080
44. The Wonder Years (1988–1993)
TV-PG | 22 min | Comedy, Drama, Family
Rated on 11 Jul 2018
Kevin Arnold recalls growing up during the late 60s and early 70s; the turbulent social times make the transition from child to adult unusually interesting.
Stars: Fred Savage, Dan Lauria, Daniel Stern, Alley Mills
Votes: 31,484
45. Eastbound & Down (2009–2013)
TV-MA | 28 min | Comedy, Drama, Sport
Rated on 11 Jul 2018
Many years after he turned his back on his hometown, a burned-out major league ballplayer returns to teach Physical Education at his old middle school.
Stars: Danny McBride, Steve Little, Katy Mixon, Elizabeth De Razzo
Votes: 46,774
46. Hell on Wheels (2011–2016)
TV-14 | 42 min | Drama, Western
Rated on 11 Jul 2018
Cullen Bohannon, a former soldier and slaveholder, follows the track of a band of Union soldiers, the killers of his wife. This brings him to the middle of one of the biggest projects in US... See full summary »
Stars: Anson Mount, Colm Meaney, Robin McLeavy, Phil Burke
Votes: 43,901
47. The Hollow Crown (2012– )
2 hr 30 min | Drama, History
Rated on 11 Jul 2018
A mini-series of adaptations of Shakespeare's history plays: Richard II, Henry IV Parts 1 and 2, and Henry V.
Stars: Anton Lesser, Simon Russell Beale, Tom Georgeson, John Mackay
Votes: 4,799
48. Rectify (2013–2016)
TV-14 | 1 hr | Drama
Rated on 11 Jul 2018
Daniel Holden must put his life back together after serving 19 years on Georgia's Death Row before DNA evidence calls his conviction into question.
Stars: Aden Young, Abigail Spencer, J. Smith-Cameron, Adelaide Clemens
Votes: 21,595
49. The Young Pope (2016)
TV-MA | 9 hr 6 min | Drama
Rated on 11 Jul 2018
The beginning of the pontificate of Lenny Belardo, alias Pius XIII, the first American Pope in history.
Stars: Jude Law, Diane Keaton, Silvio Orlando, Javier Cámara
Votes: 26,748
50. Scrubs (2001–2010)
TV-14 | 22 min | Comedy, Drama
Rated on 11 Jul 2018
In the unreal world of Sacred Heart Hospital, intern John "J.D." Dorian learns the ways of medicine, friendship, and life.
Stars: Zach Braff, Donald Faison, Sarah Chalke, John C. McGinley
Votes: 221,269


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Top Garret Keizer Quotes
Browse top 8 most favorite famous quotes and sayings by Garret Keizer.
Favorite Garret Keizer Quotes
2. "If God came to India, he'd have to come as bread. If God came to Willoughby union he'd have to came as what?" ~ Garret Keizer
3. "Our advertising and even our arts convey the idea that we [Americans] as a society are brash, irreverent, and free of all constraint, when the best available evidence would suggest that we are in fact tame, spayed, and easily brought to heel." ~ Garret Keizer
4. "I'd probably put those salt and pepper shakers away now, David, because we're about to be visited by dribbling cannibal psychopath and we wouldn't want to tease these fellows. Of course, if they're very hungry, I do have this left arm that I don't use all that much." ~ Garret Keizer
7. "She doesn't hear the voice inside me that is shouting "A chocolate bar! Do you realize...I'm thirty-three years old with a wife as old and as educated as myself and the two of us need all the energy and know-how we've got to take proper care of our kid and you're three years past believing in the tooth fairy and your kid just got his first tooth? And you're celebrating with a chocolate bar! How could you let this happen to you? And where's the bum who's supposed to be this kid's father? What's he doing?" ~ Garret Keizer
8. "People in the city are poor because they are oppressed, discriminated against and alienated; people in the country are poor because they're too stupid to realize they ought to be living in the city." ~ Garret Keizer
Garret Keizer Quotes Pictures
Today's Quote
So when you get a chance to look at things and chill and relax, it makes you want it more, and that's why I'm so happy to be back!"
Author: Brandy Norwood
What Did Garret Keizer Talk About?
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Lindt Gold Milk Chocolate 300g
Product images are for illustrative purposes only and may differ from the actual product
At the airport it is €0.90 more expensive
€8.10* €9.00 -10%
Product Description
Where to pick-up
Lindt Gold Milk Chocolate is a real find for anyone who loves Swiss sweets. It is characterized by soft texture, pleasant smell of vanilla and cream, and an unusual taste. Gold Milk Chocolate is a classic example of premium chocolate from the "Gold" line.
Sugar, cocoa butter, whole milk powder, cocoa mass, lactose, skimmed milk powder, emulsifier (soya lecithin), barley malt extract, flavouring. Cocoa solids: 31% min.
Show description
Pick up the goods you pre-order at Baku airport "baku". You need to give order's number or your name to get the order.
€7.20 €8.00 -10%
After Eight Chocolates with peppermint cream centre 400g baku
€8.10 €9.00 -10%
Toblerone Crunchy Almonds 360g baku
€8.10 €9.00 -10%
Toblerone Fruit&Nut 360g baku
€8.10 €9.00 -10%
Lindt Gold Raisin Hazelnut 300g baku
€7.20 €8.00 -10%
Mars Bites 293g baku
€8.10 €9.00 -10%
Lindt Tablet Silver Dark Hazelnut 300g baku
€7.20 €8.00 -10%
Amari Gastone in clearbag 300g baku
€8.10 €9.00 -10%
Toblerone Gold 360g baku
€8.10 €9.00 -10%
Toblerone Dark 360g baku
€8.10 €9.00 -10%
Anthon Berg Marzipan Nougat Bars 280g baku
€6.30 €7.00 -10%
Chupa Chups Exotic Tropic Lollipops Bag 300g baku
€9.00 €10.00 -10%
Kinder Mini Country 420g baku
€7.20 €8.00 -10%
Fazer Geisha Travel Box 295 g baku
€9.00 €10.00 -10%
Godiva Dark Hazelnut 300g baku
€8.10 €9.00 -10%
Toblerone Crispy Coconut 360g. baku
€7.20 €8.00 -10%
Storck Toffifee 400g baku
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Tactical First Aid & "System Collapse" Medicine (Ellifritz)
February 23 @ 8:45 pm$250
Guest Instructor:
Greg Ellifritz (Active Response Training)
This hands-on class will develop proficiency in basic battlefield medical techniques utilizing the military's latest "Tactical Combat Casualty Care" protocols.
Students will learn to stop traumatic bleeding from gunshot and knife wounds using the latest pressure bandages, tourniquets, and hemostatic agents. Self care and care under fire will also be addressed.
Students will also learn simple patient assessment techniques, how to treat a sucking chest wound and tension pneumothorax as well as field fracture immobilization and expedient c-spine immobilization. Options for assuring clear airways (including improvised surgical airways) will be practiced.
In addition, students will learn how to treat themselves and families in the event of a long-term breakdown in our current medical system. Wound cleaning and disinfection under field conditions, injection of local anesthesia and wound closure (including minor suturing) will be practiced in our "trauma lab". If time permits, students will integrate all of these skills in several practical scenarios.
Information about what types of drugs to stockpile for natural disasters or a collapse in the health care system will be discussed, along with methods for legally acquiring those pharmaceuticals. The instructor will also discuss what items should be included in a comprehensive medical kit and how to improvise those items in an austere environment
Thanks for your interest in this class. If you have any trouble using the embedded registration form below, please try registering directly on our Eventbrite page (click here).


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According to a 2014 report[2] by the Texas Coalition for Affordable Power (TCAP), "deregulation cost Texans about $22 billion from 2002 to 2012. And residents in the deregulated market pay prices that are considerably higher than those who live in parts of the state that are still regulated. For example, TCAP found that the average consumer living in one of the areas that opted out of deregulation, such as Austin and San Antonio, paid $288 less in 2012 than consumers in the deregulated areas."
Maybe you're still stuck between 2 companies and you're looking for those tiny additional touches that make all the difference in the world. Only a small handful of Texas electricity companies offer a rewards program for their customers. Some of these rewards programs only offer one or two options, while there may be another company that offers you multiple options when it comes to your rewards.
When you're shopping for great Texas electricity providers, you want to be smart about it. Your choices go beyond Texas electricity rates. Bounce not only offers great deals, but you can sign up for rewards programs, refer your friends, track your usage by appliance, and more. Need more convincing? Bounce Energy gives back to the community and has great customer service by phone, Facebook, and Twitter. It was founded in Texas and serves Texans…and it's just the cool Texas brand.
There are many different options for term lengths in the Texas energy market. Different term lengths often have different price points, so if you're more flexible with the length of your contract, you could get a cheaper rate. Contracts with shorter term lengths are great if you prefer to avoid a long-term commitment while longer contracts usually provide the benefit of longer-term price stability.
Which ones the best? Like all things energy, it depends. Do you prefer predictability, or do you like the idea of potentially saving some cash by monitoring the market? Our (albeit conservative) recommendation: Fixed rate is probably best. Energy prices are on the rise — the U.S. Energy Information Administration predicts a 3 percent increase in residential electricity prices in 2018.
Some good news: According to J.D. Power's 2016 survey on retail electric providers (its most current survey of the space), Texas has the highest overall satisfaction with retail electric providers out of any state. And because rates, plans, and offers can be so similar from provider to provider, customer satisfaction scores are a great way to break a tie. Think of it like choosing who to hire when you have two candidates with similar resumes — you're going to pick the person with the glowing references.
In Texas, if you're renting an apartment, townhouse, or small home, you need affordable electricity that fits your lifestyle, budget, and lease term. That's why it's smart to shop for an electricity plan designed especially with renters in mind. Apartment electricity plans have better prices at lower electricity usage levels and shorter available contract lengths so that you can stay flexible and stay in budget.
To do so, we used five of the state's largest electricity companies to explore six things you'll have to evaluate when you're comparing plans and providers: We'll walk you through customer satisfaction scores, running the numbers on rates, and calculating the impact of different fees, discounts, and contract types. We'll weigh in on extra perks, like points, and green energy too.
Database of State Initiatives for Renewables & Efficiency (DSIRE) is a company and website that compiles a list of all the energy incentives available in the United States, by a particular state. The idea is to help inform the public about the latest and greatest energy programs and initiatives – all from one location. DSIRE receives funding from the United States Department of Energy and is run by the N.C. Clean Energy Technology Center and N.C State University. Browsing the site programs gives you access to viewing all Texas related initiatives.
If you think you have to pay the rates your current electricity provider charges, we have good news. The state of Texas allows you to choose which electricity provider you use. This means you can select a provider that has the cheapest Texas electric rates in your area and the best plan for your needs, whether you need a better deal for your residence, your business, or both. Thousands of consumers and businesses that have used our electricity rate comparison process agree that, when shopping for commercial electricity or residential electricity rates and plans, Vault Electricity is the one-stop source for the best options from top electric providers.
When you're ready to switch your service to a new electricity provider you'll find that the process is actually really easy and that the entire process will go quite smoothly for you. Simply call the provider of the plan you're choosing to make the switch to. Provide them with your full name, address and whether you need new service or are looking to switch provider. Note: Depending on the type of electricity plan you're switching to, you may also need to provide your social security number.
As a renter, it's important to know approximately how much electricity you will use each month in order to get the best deal on electricity. Some electricity plans are cheaper for lower energy usage customers, while other plans are designed with high usage customers in mind. If you're just moving into an apartment, ask your leasing agent to provide you with historic kWh usage information for your specific unit if possible.
This information is compiled by the Public Utility Commission of Texas from publicly available information from the Retail Electric Providers and PUC approved price to beat rates (through December 2006) using representative usage levels. Rates are calculated using the Commission Approved Residential Load Profile for each service area. The PUC makes no recommendation with respect to any REP. Although we believe these prices are accurate, the PUC makes no warranty that the prices in this table are currently being offered. Please contact the relevant REP for their current pricing offers and terms of service. Information on how to select a REP and contact information for REPs is located at www.powertochoose.com.
Intraday Data provided by SIX Financial Information and subject to terms of use. Historical and current end-of-day data provided by SIX Financial Information. All quotes are in local exchange time. Real-time last sale data for U.S. stock quotes reflect trades reported through Nasdaq only. Intraday data delayed at least 15 minutes or per exchange requirements.
One desired effect of the competition is lower electricity rates. In the first few years after the deregulation in 2002, the residential rate for electricity increased seven times, with the price to beat at around 15 cents per kilowatt hour (as of July 26, 2006, www.powertochoose.org) in 2006. However, while prices to customers increased 43% from 2002 to 2004, the costs of inputs rose faster, by 63%, showing that not all increases have been borne by consumers.[7] (See Competition and entry of new firms above for discussion on the relationship between retail prices, inputs, and investment.)
Prepaid electricity allows you to buy your electricity before consuming it. This is similar to a pre-paid cell phone in that you'll pay the Retail Electric Provider (REP) upfront. You can then manage how much electricity you use throughout the month. These prepaid energy plans are best for people who can pay their bills on time and can receive notices via text or email. They're also a good option for anyone who doesn't have money for a large deposit, people with bad credit, anyone who wants to cut down on their electric use, or who need to split the electric bill with their roommates.
Like most Texas residents, as a business owner you can shop around and choose the right electricity plan for your business. Thank you deregulation! Choices include basic business energy plans (typically 12 – 60 months), tiered rate plans where the energy rate decreases each year, plans with a cheaper energy rate at night, and even plans that contribute to veteran organizations. The options are growing as electricity companies get more creative and tailor their plans to different industries.
Looking for the cheapest energy rates from the best light companies in Texas? With Quick Electricity, you have the power to choose your home or business energy plan from the top rated electric companies in Texas. Whether you're looking for prepaid electricity companies for pay as you go electric, a 1-24 month fixed energy rate plan or solar panels, we will help you find the most affordable plan to suit your needs. Most energy companies in Texas have a free same day connection and some offer no deposit and no credit check electricity for those with credit problems. To make the switch easier for our customers, Quick Electricity has partnered with the #1 prepaid electricity provider in Texas, Payless Power. Prepaid energy is the best way to get your lights on today for a small fee of $30. For assistance, give us a call at (877) 509-8946.
To do so, we used five of the state's largest electricity companies to explore six things you'll have to evaluate when you're comparing plans and providers: We'll walk you through customer satisfaction scores, running the numbers on rates, and calculating the impact of different fees, discounts, and contract types. We'll weigh in on extra perks, like points, and green energy too.
Given the wide selection of electricity plans available, how do renters choose the best electricity plan? The key to finding the best plan is to have an idea about how much electricity you use and select the contract length that is close to your rental contract term. Typical apartment electricity plans are best for 500 – 1000 kWh usage per month and 1 – 12 month contract term lengths. Enter your zip code above to search and compare apartment electricity plans with this criteria.
When you use our rate comparison process, providers know that they are competing to win your business. Consequently, they offer cheap electric rates in hopes of becoming your new Texas electricity company. This benefits both you and the provider you select. You receive a cheap electric rate and the plan of your choice, and the provider adds another satisfied customer.
The price difference may be a few cents, but another Texas electricity company might offer better rewards, have better customer service, or may offer other plans you may be interested in the future. Some plans may draw you in with a low promotional rate, but once that promotional period is up you may be faced with a high rate. Be sure to read all the fine print when it comes to your electricity plan selection.
Compared to the rest of the nation, data from the U.S. Energy Information Administration which publishes annual state electric prices [8] shows that Texas' electric prices did rise above the national average immediately after deregulation from 2003 to 2009, but, from 2010 to 2015 have moved significantly below the national average price per kWh, with a total cost of $0.0863 per kWh in Texas in 2015 vs. $0.1042 nationally, or 17 percent lower in Texas. Between 2002-2014 the total cost to Texas consumers is estimated to be $24B, an average of $5,100 per household, more than comparable markets under state regulation.[9] [10]
For large businesses generally with monthly utility bills of more than $5,000, let ElectricityPlans do all of the legwork to get custom quotes from over 75 reputable electric companies. Many energy providers offer exclusive rates that cannot be found online. We have access to business electricity rates from dozens of Texas electricity providers and can walk you through the process of choosing the best electricity plan for your business.
Texas Electricity Rating advocates for consumers and evaluates providers in the Texas electricity market for features and characteristics that typical energy customers may miss, such as high deposits, variable rates, incentives, "free" plans, and minimum usage plans. Our mission is to help consumers find the best electricity providers to fit their individual needs, as well as educate customers about potential marketplace pitfalls.
Residential and business consumers in deregulated energy markets have the power to choose their energy supplier. SaveOnEnergy.com® gives consumers the opportunity to compare suppliers and find energy plans that satisfy their needs and budget. Whether in a deregulated city in Texas, New York, Ohio or another state, you can shop for electricity or natural gas and find the best plan for you!
Utility companies are responsible for transmission and delivery of electricity even in energy deregulated parts of Texas and should be contacted in the event of a power outage. Your retail energy supplier may provide you competitive electric rates or exceptional customer service, but they cannot repair power lines or restore your service. In the case of an emergency, contact:


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ChromaLuxe Photo Panels - Easels Flat Tops
ChromaLuxe® Photo Panels are an exciting new dimensional display/mounting option for images. Produced in a range of popular photo sizes, Chromaluxe panels feature an advanced, highly durable and extremely smooth UV resistant coating bonded to 16mm wood.
Expect brilliant colour reproduction and unsurpassed image clarity. They are also scratch and UV resistant with a long life span.
Designed to be digitally imaged using the sublimation printing process, ChromaLuxe® panels are fabricated into a range of display configurations that include easel back panels, hinged multiple panels, and wall mounted large-format panels.
Available in a range of traditional photo sizes as well as exciting new shapes – perfect for a fireplace mantle, library shelf, or the top of an armoire.
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Customer Testimonials
"Vicki Griffiths
Their Tech support is fantastic always willing to hep
"Korrine Miller
I really wanted to reply today to let you know just how I continue to be impressed with your service. I had ordered some keyrings from another company, I am fairly new to sublimation so of course wanted to test out what else was available to me. These keyrings were for a customer of mine. Well lets just say that there were issues with my order. So very late last night I decided I would order replacement keyrings from GJS Machinery, which I did. The order for my customer had to go out today and I was a little stressed last night as to how I was going to tell them that they now would have to wait another day. That was until this morning when my order from GJS arrived, my customer′s keyings have still been supplied today as they were meant to be. I will now be using GJS as my main supplier of sublimation blanks and will think twice about stocking anything in my business that you dont supply. Thank you again for a wonderful service that is so quick and reliable. It is rare these days to find companies that provide such excellent service.
Why Choose GJS
Maximum convenienceAt gjs.co, you can order our products 24/7 and we´ll deliver it to your door! Or simply call us. Our phones are open from 8am to 4:30pm Monday to Friday. We´ll make sure you get all the information you need to make informed decisions. It just doesn´t get any easier.
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