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Alterations in glucose metabolism have been demonstrated for diverse disorders ranging from heart disease to cancer. The first step in glucose metabolism is carried out by the hexokinase (HK) family of enzymes. HKI and II can bind to mitochondria through their N-terminal hydrophobic regions, and their overexpression in tissue culture protects against cell death. In order to determine the relative contributions of mitochondrial binding and glucose-phosphorylating activities of HKs to their overall protective effects, we expressed full-length HKI and HKII, their truncated proteins lacking the mitochondrial binding domains, and catalytically inactive proteins in tissue culture. The overexpression of full-length proteins resulted in protection against cell death, decreased levels of reactive oxygen species, and possibly inhibited mitochondrial permeability transition in response to H2O2. However, the truncated and mutant proteins exerted only partial effects. Similar results were obtained with primary neonatal rat cardiomyocytes. The HK proteins also resulted in an increase in the phosphorylation of voltage-dependent anion channel (VDAC) through a protein kinase Cε (PKCε)-dependent pathway. These results suggest that both glucose phosphorylation and mitochondrial binding contribute to the protective effects of HKI and HKII, possibly through VDAC phosphorylation by PKCε.
Mammalian hexokinases (HKs) convert glucose to glucose-6-phosphate (G6P), thus maintaining the downhill concentration gradient necessary to move glucose into the cell through glucose transporters (13, 24, 33, 42). Four isozymes of HKs are present in mammals: HKI, II, III, and IV (32, 50). HKIV is also known as glucokinase. The molecular masses of HKI, II, and III are about 100 kDa, whereas glucokinase has a molecular mass of 50 kDa. The protein and gene structures of the 100-kDa enzymes suggest that they evolved from gene duplication and fusion of an ancestral 50-kDa enzyme. In HKI and HKIII, only their C-terminal halves retained catalytic activity (6, 7, 10, 27, 35, 45, 54, 56), while both halves of HKII are catalytically active and sensitive to G6P (5). There is also functional interaction between the N- and C-terminal halves of HKII, as glucose binding by the N-terminal half causes the activity of the C-terminal half to be regulated at significantly lower concentrations of G6P (4).
In addition to their role in glucose metabolism, HKI and HKII are also believed to play a role in regulating cell death (37). The levels of HKI and HKII are markedly elevated in many cancer cells (41), suggesting that their overexpression may play a role in dysregulated growth. The overexpression of HKI and HKII also leads to protection against oxidant-induced death in tissue culture. Bryson et al. showed that HKI overexpression in an established epithelial cell line leads to protection against oxidant-induced cell death (17). Furthermore, the induction of endogenous HK expression had similar effects. This protection was glucose dependent, suggesting that the increase in glucose phosphorylation may be the main mechanism for cellular protection by HKI. Ahmad et al. expressed HKII in lung epithelial cells and showed that the expression of this protein also protects against oxidant-induced cell death (2). Thus, the overexpression of both HKI and HKII protects cells against damage from oxidative stress.
The mechanisms by which HKI and HKII protect against cell death are not clear, and two hypotheses have been proposed to explain the mechanism for this phenomenon: increase in glucose phosphorylation due to elevated HK activity and HK binding to mitochondria. HKI and HKII contain highly conserved 21-amino-acid sequences at their N termini that are predicted to form a hydrophobic α helix (49, 58). This structure is essential and sufficient for the binding of HKI and HKII to mitochondria. The mitochondrially bound HKs preferentially use mitochondrially generated ATP as a substrate (8, 14-16). The specificity of HKI and HKII binding to the mitochondria is believed to be due to its interaction with voltage-dependent anion channel (VDAC) (1, 9, 22, 26). VDAC is a 30-kDa protein in the outer membrane of the mitochondria that allows the transport of many solutes and metabolites in and out of the intermembrane space (19, 20, 29, 30). Although VDAC plays a major role in the physiological process of solute and metabolite transport, it is also believed to form part of a pathological channel known as the mitochondrial permeability transition pore (mPTP). The opening of mPTP allows an influx of solutes with molecular masses of <1,500 Da into the matrix and an abrupt dissipation of the mitochondrial membrane potential (ΔΨm) (25, 52). The exact molecular structure of mPTP has not been characterized, but it is thought to be a macromolecular protein complex (25, 52) consisting of cyclophilin D (CypD) in the matrix, adenine nucleotide translocator (ANT) in the inner membrane, and VDAC in the outer membrane.
Whether HK binding to VDAC causes the closure of mPTP and the inhibition of the mitochondrial permeability transition (MPT) is not clear, and several studies have suggested both mPTP-dependent and -independent pathways for the protective effects of HK binding to mitochondria. Pastorino et al. showed that the displacement of HKII from the mitochondria promotes Bax translocation and cytochrome c (cyto c) release in the setting of a prodeath stimulus, while the overexpression of HKII had opposite effects (39). Since the opening of mPTP is believed to be independent of Bax (11, 34), these results suggest an mPTP-independent pathway. Majewski et al. recently showed that HK binding to the mitochondria inhibits apoptosis and that these protective effects are independent of Bax and Bak (28). Finally, Azoulay-Zohar et al. studied the effects of purified HKI protein on mitochondrial swelling in isolated mitochondria (9). They showed that HKI interacts with and closes VDAC and possibly mPTP in isolated mitochondria. However, they noted that in tissue culture the protective effects of HKI were reversed by staurosporine. Since mPTP opening is insensitive to staurosporine (11, 34, 44), these latter results suggest that HKI binding to the mitochondria may not influence mPTP opening. Thus, there is no clear evidence that HK binding to mitochondria inhibits MPT and the closure of mPTP.
The binding of HKs to the mitochondria may be dependent on the phosphorylation state of VDAC. Recently, Pastorino et al. demonstrated that glycogen synthase kinase 3β (GSK-3β) can phosphorylate VDAC and that this phosphorylation affects HK binding to the mitochondria (38). The phosphorylation of VDAC in turn appears to regulate cell survival, as an increase in phosphorylation led to an increase in cell death. Baines et al. showed that protein kinase Cε (PKCε) interacts with and phosphorylates VDAC and that incubation of recombinant PKCε with isolated mitochondria results in a significant decrease in mPTP opening (11). Thus, VDAC is phosphorylated by GSK-3β and possibly PKCε, and its phosphorylation state may regulate HK binding to mitochondria, mPTP opening, and cell death.
In this paper, we studied the relative contributions of glucose phosphorylation activity and mitochondrial binding of HKI and HKII to their overall protective effects and showed that both of these activities contribute to and are needed for this process. We also demonstrate that HKI and HKII reduce the intracellular levels of reactive oxygen species (ROS) and inhibit MPT. Furthermore, our results suggest that HK overexpression leads to VDAC phosphorylation through a PKCε-dependent pathway.
Construction of full-length, truncated, and mutant HKI and HKII.Plasmids containing the HKI and HKII cDNAs were kindly provided by Daryl Granner (Vanderbilt University, Nashville, TN). The constructs for this study are shown in Fig. 1A, and the details are available in the supplemental material.
Transfection of the constructs into HEK293 cells.The constructs were transfected into the HEK293 cells by the Invitrogen Lipofectamine Plus kit. About 3 h after transfection, medium plus serum was added and the cells were incubated for 2 days before cell viability was measured. The medium was changed to serum-free medium 24 h prior to the viability studies. The overexpression of HK proteins was confirmed by Western blotting. Since the exogenous HKs are fused to green fluorescent protein (GFP), they are larger than the native HKs and can be distinguished. To establish stable transfectants, cells were treated with 2 mg/ml of G418 on the first day followed by 500 μg/ml.
Viability studies.Viability studies are described in the supplemental material.
Measurement of the MPT in live cells.To measure MPT, we used 10 μM of CellTrace calcein blue acetoxymethyl ester (AM), which is the blue version of calcein AM. This form of calcein was used in place of green calcein to avoid interference with GFP fluorescence. Tetramethylrhodamine ethyl ester (TMRE) at 100 nM was also added to delineate the mitochondria. Cells were monitored at baseline and 15- and 30-min intervals after the addition of H2O2 by use of confocal microscopy.
IP of VDAC and its phosphorylated form.For PKCε, we used PKCε inhibitor peptide (Santa Cruz Biotechnology) at a final concentration of 750 nM (46). To isolate mitochondria, cells were washed in phosphate-buffered saline and incubated for 30 min on ice in lysis buffer (68 mmol/liter sucrose, 200 mmol/liter mannitol, 50 mmol/liter KCl, 1 mmol/liter EGTA, 1 mmol/liter EDTA, 1 mmol/liter dithiothreitol, and one Complete Mini protease inhibitor tablet [Roche]). Cells were then homogenized twice with an ultrasound sonicator and centrifuged at 4°C (500 × g) to remove nuclei, unbroken cells, and debris. The supernatant was centrifuged at 14,000 × g for 15 min. Immunoprecipitation (IP) studies were performed using a Protein G IP kit (Sigma). For phospho-VDAC, VDAC antibody was used as the IP antibody and phosphothreonine antibody was used to probe the membranes.
Preparation of neonatal rat cardiomyocytes (NRCM) and adenoviruses.NRCM preparation and adenoviral construction were performed as described previously (3) and in the supplemental material.
Overexpression of HK constructs in HEK293 cells.In order to characterize the relative contributions of glucose phosphorylation and mitochondrial binding of HKs to their overall protective effects, we cloned full-length, truncated (lacking the N-terminal mitochondrial binding domain), and mutant HKI and HKII cDNAs into a GFP-containing plasmid (Fig. 1A) and transfected them into HEK293 cells. The full-length enzymes can bind to mitochondria and can phosphorylate glucose. Although the truncated HKI and HKII proteins cannot bind to mitochondria, they contain the catalytic domains and maintain their glucose-phosphorylating activity. The catalytically inactive enzymes contain the mitochondrial binding sequence but do not phosphorylate glucose. Western blot analysis of extracts from transfected cells demonstrated the expression of GFP fusion proteins of full-length, truncated, and mutant HKs in these cells (120-kDa band in Fig. 1B). Furthermore, our results demonstrate the expression of endogenous HKI and HKII proteins in HEK293 cells (100-kDa band in Fig. 1B). Confocal analysis of transfected cells demonstrated that the majority of the overexpressed full-length and mutant proteins localize to the mitochondria, while the truncated protein is mostly cytoplasmic (Fig. 1C). It should be noted that a portion of cells transfected with the full-length and mutant proteins also displayed green fluorescence throughout the cell (data not shown). Transfection efficiency in our experiments is shown in Fig. S1 in the supplemental material.
Full-length HKs result in full protection, while truncated and mutant proteins exert partial protection.Hydrogen peroxide was used to induce cell death. Concentration curve and time course studies demonstrated that a 60-min treatment of HEK293 cells with 1 mM H2O2 resulted in an ∼35 to 40% reduction in TMRE uptake (see Fig. S2A and B in the supplemental material). This H2O2 concentration and treatment time course were used for subsequent viability studies.
Forty-eight hours after transfection, cells were treated with the mitochondrial marker TMRE and were analyzed under confocal microscopy at baseline and 15 min after treatment with H2O2. While the full-length proteins led to the retention of TMRE in response to H2O2, the overexpression of the truncated or mutant proteins resulted in only partial protection (Fig. 2A). Cells treated with TMRE were also subjected to flow cytometry, and the data show that full-length proteins exert complete protection, while the mutant and truncated proteins partially protect against H2O2-induced cell death (Fig. 2B). Similar results were obtained when trypan blue exclusion was used as an additional measure of cell viability (Fig. 2C). Constructs lacking mitochondrial binding and glucose phosphorylation activity did not exert any protective effects. As shown in Fig. 2D and E, the protective effects of the HK constructs persisted for at least 6 h after the addition of H2O2. The HK constructs did not exert any protection in the absence of glucose in the medium (see Fig. S3 in the supplemental material).
In addition to performing the TMRE and trypan blue experiments, we also studied the effects of overexpression of HK proteins on cyto c release and Bax translocation into the mitochondria. The overexpression of full-length HKs led to a significant increase in the mitochondrial cyto c levels, suggesting a decrease in cyto c release into the cytoplasm. Similarly, full-length HKI and HKII decreased the mitochondrial Bax level, indicating a decrease in Bax translocation into the mitochondria. However, cells transfected with both truncated and mutant HKI and HKII displayed a lower degree of change in these parameters (Fig. 3A). Thus, in accordance with the TMRE and trypan blue studies, these results suggest that both glucose phosphorylation and mitochondrial binding contribute to the overall protective effects of HKs. We also assessed the effects of overexpression of HK constructs on cyto c distribution within the cells by confocal microscopy. HKI and II constructs prevented cyto c release into the cytoplasm in response to H2O2 (Fig. 3B).
Studies by da-Silva et al. suggested that mitochondrially bound HK plays a role in the rate of endogenous ROS generation, possibly through an ADP-recycling process (21). Thus, we assessed whether the overexpression of HKs changed the levels of cellular ROS in the presence of exogenously added H2O2. MitoSOX, a fluorescent marker of ROS, was added to transfected cells followed by the addition of H2O2. As shown in Fig. 3C, full-length proteins led to a significant reduction in the levels of ROS in cells treated with H2O2. The truncated and mutant proteins also resulted in a significant reduction in ROS levels but slightly less than that seen for the full-length protein (and did not reach statistical significance).
N- and C-terminal halves of HKI and HKII are partially protective against H2O2-induced cell death.HKI and HKII consist of two homologous 50-kDa halves. While the C-terminal half of HKI contains the only catalytically active site of the protein, both halves of HKII are fully capable of phosphorylating glucose. In order to better characterize the protective effects of HKI and HKII proteins, we overexpressed each half of these enzymes separately in HEK293 cells. Western blot analysis of transfected cellular extracts demonstrated the presence of 70-kDa proteins, representing each half of the proteins fused to GFP (Fig. 4A). The cells were then treated with TMRE in the presence and absence of H2O2 followed by flow cytometry. As shown in Fig. 4B, the overexpression of individual halves of the HKI and HKII proteins resulted in only partial protection against H2O2-induced cell death. Similar results were obtained when trypan blue exclusion was used to assess cell death (Fig. 4C). Although the N-terminal half of HKII can both bind to the mitochondria and phosphorylate glucose, its overexpression did not lead to full protection.
HKI and HKII are protective in primary cardiomyocyte cultures.The studies reported thus far were performed in HEK293 cells, which are an immortalized transformed cell line. Thus, it is essential to extend the studies to a primary cell line in order to better assess the physiological significance of these findings. Since both HKI and HKII are expressed in cardiac cells, we chose NRCM for our studies. NRCM do not take up DNA when transfected with routine techniques. Thus, full-length and truncated HKI and HKII adenoviruses were made to introduce these DNAs into the cell. Full-length HKI virus resulted in an increase in HK activity in cell extracts in a dose-dependent manner (see Fig. S4 in the supplemental material). As shown in Fig. 5A, the transfection of NRCM with different HK adenoviruses yielded green fluorescence in >90% of the cells. Since the HK and GFP cDNAs are under different promoters, the generated HKs are similar in size to the endogenous proteins. Western blot analysis showed significantly high levels of both HKI and HKII proteins in cells transfected with HK adenoviruses compared to GFP-transfected cells (Fig. 5B). In accordance with results obtained with HEK293 cells, the overexpression of full-length proteins resulted in significant protection, while truncated proteins exerted only partial protection (Fig. 5C).
Full-length HKI and HKII inhibit MPT.The mechanism for the protective effects of HK binding to mitochondria is not totally understood, and both mPTP-dependent and -independent pathways have been proposed. In the next series of experiments, we attempted to study whether HK binding to mitochondria can cause inhibition of MPT in intact cells and isolated mitochondria. Calcein AM can diffuse across the membrane and is trapped inside the cell after it is converted to a pentavalent acid form. Given the relatively impermeable nature of the mitochondrial membrane to this dye, it does not enter the mitochondria for hours. However, the induction of MPT in response to injurious insults allows the leakage of the dye into the mitochondria. In our experiments, we used the blue form of calcein, and the mitochondria were simultaneously stained with TMRE. This allowed us to delineate the mitochondria and cytoplasm in green fluorescence positive cells. As shown in Fig. 6, while the treatment of control GFP-positive cells with H2O2 resulted in a significant mitochondrial permeability after 15 min, full-length HKI and HKII reversed this effect. The overexpression of the truncated proteins also led to a partial reversal to a degree significantly less than that seen for the full-length proteins. Thus, the induction of MPT by oxidant injury may be reversed by HK overexpression, and this mechanism is dependent on mitochondrial binding of these proteins.
HK overexpression increases VDAC phosphorylation in a PKCε-dependent pathway.Since HK binding to mitochondria is dependent on the phosphorylation state of VDAC, we hypothesized that HKs regulate their mitochondrial binding by modulating VDAC phosphorylation. In order to test this hypothesis, we measured VDAC phosphorylation in response to the overexpression of HK proteins. Extracts of cells transfected with various HK constructs were run on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and their membranes were probed with VDAC antibody. We then measured phospho-VDAC by immunoprecipitating total VDAC and probing with a phosphothreonine-reactive antibody. As shown in Fig. 7A, full-length HKI and HKII resulted in about a 5-to 10-fold increase in VDAC phosphorylation without significant effects on the amount of total VDAC. The truncated and mutant proteins also increased VDAC phosphorylation, but to a lesser degree than the full-length proteins. These results suggest that the activation of the protein kinase that phosphorylates VDAC probably requires both the glucose phosphorylation and mitochondrial binding properties of HKs.
In order to characterize the protein kinases involved in HK-induced VDAC phosphorylation, we focused our studies on PKCε. This protein is shown to physically interact with VDAC in cardiomyocytes (12). The addition of a PKCε inhibitor peptide to HEK293 cells resulted in a significant decrease in VDAC phosphorylation at baseline and in the presence of HKI and HKII overexpression (Fig. 7B). These results suggest that PKCε is a mediator of VDAC phosphorylation in response to HKI and HKII overexpression.
HKs play a critical role in ATP production by catalyzing the first step in glucose metabolism and maintaining the gradient for glucose entry into the cell (13, 24, 33, 42). In the past several years, HKI and HKII have also been implicated as playing a role in cell death and survival. The overexpression of these enzymes in tissue culture protects cells from oxidant-induced cell death (2, 17). Some studies have implied that the increase in ATP production as a result of glucose metabolism may be the underlying mechanism for the protective effects of HKs (17). However, others have proposed that the binding of HKI and HKII to the mitochondria may lead to the closure of the proapoptotic channel mPTP, leading to cellular protection (9, 37). In this paper, we studied the mechanism for the protective effects of HKI and HKII. We overexpressed full-length HKI and HKII, truncated proteins (lacking the N-terminal mitochondrial binding domain), and catalytically inactive forms of HKI and HKII in HEK293 cells. The truncated proteins can phosphorylate glucose but cannot bind to mitochondria, while the mutant enzymes can bind to mitochondria but cannot phosphorylate glucose. We then exposed the cells to H2O2 and assessed cellular injury by several methods: TMRE uptake, trypan blue exclusion studies, Bax translocation into the mitochondria, and cyto c release into the cytoplasm. These studies demonstrated that full-length proteins can protect against H2O2-induced cell death, while the mutant and truncated proteins exert only partial protection. Similar results were obtained with primary cardiac cells. Thus, we conclude that both mitochondrial binding and glucose phosphorylation contribute to and are needed for the protective effects of HKs. The full-length proteins also decreased the levels of intracellular ROS, suggesting an antioxidant role for these proteins. We then determined that HKI and HKII overexpression lead to an increase in VDAC phosphorylation in a PKCε-dependent pathway.
The phosphorylation of glucose maintains the downhill gradient for glucose metabolism and extramitochondrial glucose flux through the pentose phosphate pathway. Induction of the pentose phosphate pathway and the generation of NADPH may also contribute to protection against cell death. In oocytes, maintenance of the pentose phosphate pathway through a continuous supply of G6P prolongs the survival of the germ cells, and this process was shown to be through calcium/calmodulin-dependent protein kinase II (36). Thus, the protective effects of glucose phosphorylation by HKs may be through both enhanced ATP production and induction of the pentose phosphate pathway.
The HK binding to the mitochondria and its glucose-phosphorylating activity may play an important role in the development of various disorders ranging from cancer to heart disease. The levels of HKI and HKII are markedly elevated in many cancer cells (37). For example, the levels of HKII are >100-fold higher than normal levels in some tumors (41). Although it is not expressed in normal liver tissue, HKII becomes the predominant HK isoform in liver cancer (18). The levels of HKI are also upregulated in some tumors but to a lesser degree relative to HKII (23, 47). In fact, this unique feature of cancer cells is used to detect rapidly growing cells by use of positron emission tomography (40, 51). In addition, evidence now suggests that a large pool of HKs is bound to the mitochondria in cancer cells (37, 41). For the heart, it has been shown that mitochondrial HK binding increases with insulin treatment and ischemia in an isoform-specific manner (48). Taken together, these data suggest a major role for mitochondrial binding and glucose-phosphorylating activities of HKI and HKII in the progression of a number of diseases and identify them as a target for therapy.
The ATP that is generated through the process of oxidative phosphorylation is transported out of the mitochondrial matrix by ANT. In the intermembrane space, ATP may get consumed by enzymes such as mitochondrial creatine kinase or adenylate kinase, or it may get shuttled into the cytoplasm through VDAC. It was originally believed that the mitochondrially bound HK would have preferential access to this highly localized concentration of ATP (31, 41, 56). Furthermore, the ADP that is produced by glucose phosphorylation can be effectively delivered to ANT for transport to the matrix and ATP synthase. This hypothesis has been challenged by observations that the ATP concentration in the cytoplasm is usually in the 3 to 5 mM range, which is well above the KmATP of HKs. Furthermore, through the actions of mitochondrial and cytosolic creatine kinases, ATP is effectively shuttled from the mitochondria to the cytoplasm. If HK binding to mitochondria does in fact increase their glucose phosphorylation activity, then the mitochondrial binding of HKs may reduce apoptosis by both inhibition of MPT and more-efficient glucose metabolism due to their better access to mitochondrially generated ATP.
While the C-terminal half of HKI contains the only active site of the enzyme (54), both halves of HKII are catalytically active. Thus, the N-terminal half of HKII can both bind to the mitochondria and phosphorylate glucose (5). Yet, it exerted only partial protection in our experiments. One implication of this observation is that both halves of HKs may be needed for the full protective effects of these enzymes. Several studies have demonstrated a functional interaction between the two halves of HKI and HKII. G6P regulation of the C-terminal half of HKI is believed to be through its binding to the N-terminal half (53, 55), and glucose binding by the N-terminal half of HKII causes the activity of the C-terminal half to be regulated by significantly lower concentrations of G6P (4). Thus, the physical and functional interaction between the two halves of HKI and HKII may also influence the antiapoptotic effects of these enzymes. Furthermore, it is believed that HKs may form multimers (56, 57), and their intermolecular interactions may have physiological implications both in terms of regulation of glucose phosphorylation and apoptotic activities of these proteins. Thus, it is also possible that some of our overexpressed HK proteins may interact with endogenous HKs and disrupt the multimer formation of these proteins. This phenomenon could potentially explain some of the effects we have observed in our overexpression experiments.
The phosphorylation of VDAC may play a role in regulating its ability to bind to HKII and the opening of the mPTP. Pastorino et al. showed that GSK-3β can phosphorylate VDAC and that this phosphorylation decreases the ability of HKII to bind to this protein (38). Another study has demonstrated that PKCε can interact with and phosphorylate VDAC and reduce Ca2+-induced mitochondrial swelling (12). Our results show that the overexpression of HKI and II increases VDAC phosphorylation in a PKCε-dependent pathway. It is unlikely that HKs directly activate PKCε, and other mediators probably play a role in this process. It remains unclear what signaling molecules lead to the activation of PKCε and its possible translocation into the mitochondria and to VDAC phosphorylation.
Another controversy in the HK field is related to the question of whether HK binding to VDAC leads to its closure or to its opening. Rostovtseva et al. have suggested that VDAC closure, not opening, results in mitochondrial swelling and cell death (43). This is probably due to a reduced mitochondrial metabolite exchange, which would lead to significant functional implications for a cell, especially in the brain and heart. This hypothesis was supported by Majewski et al., who showed that HK dislocation from mitochondria could lead to the closure of VDAC and subsequent mitochondrial swelling and cell death (28). However, Azoulay-Zohar et al. showed that HK binding to VDAC causes its closure rather than its opening (9). Although our data do not resolve this controversy, we favor the former model, which is suggested by Rostovtseva et al. (43).
In summary, our results indicate that both glucose phosphorylation and mitochondrial binding activities of HKI and HKII are required for their protective effects. Furthermore, HKI and HKII overexpression increases VDAC phosphorylation in a PKCε-dependent pathway. These studies suggest that targeting HK enzyme activity and its cellular distribution may provide potential therapeutic options in various disorders ranging from cancer to heart disease.
H.A. is supported by NIH grant K08 HL079387, R01 HL087149, the Schweppe Foundation, the American Heart Association, and a grant from the American Cancer Society, Illinois chapter.
We thank Daryl Granner for critical evaluation of the manuscript and providing the HKI and HKII cDNA plasmids.
- Received 6 February 2007.
- Returned for modification 5 April 2007.
- Accepted 5 November 2007.
↵▿ Published ahead of print on 26 November 2007.
↵† Supplemental material for this article may be found at http://mcb.asm.org/.
- American Society for Microbiology


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Royals' First-Ever Education Day Game January 7 at 10:30 a.m.
May 20, 2019 - ECHL (ECHL) - Reading Royals News Release
Reading, PA - The Reading Royals, proud ECHL affiliate of the Philadelphia Flyers and Lehigh Valley Phantoms, announced Monday the team will host its first-ever Education Day Game Jan. 7, 2020 at 10:30 a.m. The day will promote educational lessons at a hockey game, including science experiments, health tips and history.
Perks Include:
Discounted $10 tickets for K-12 Students
Students will receive a ticket, hot dog, fountain drink and Royals hat
An educational learning packet provided by the Royals
In-game entertainment tailored to students
Bus Parking is available
To learn more, sign your school up, sponsor a school or the game please contact:
Dakota Procyk (firstname.lastname@example.com | 610-898-7352) - Royals Senior Ticketing Manager
Chris Hazel (firstname.lastname@example.com | 610-898-7293) - Royals Group Sales Manager
"We are looking forward to having students from the area here to cheer on the Royals." said General Manager David Farrar. "This will be a fun and educational day that will enhance school curriculums. We are hoping this will become an annual event at Santander Arena."
Royals season memberships are available for 2019-20 by visiting the Royals Box Office at Santander Arena (700 Penn Street) and by calling 610-898-7825. For the latest team news, visit royalshockey.com/news, and follow the team on Facebook (Facebook.com/ReadingRoyals), Twitter (Twitter.com/ReadingRoyals) and Instagram (Instagram.com/ReaadingRoyals). Use #RestoreTheRoar to join the conversation.
• Discuss this story on the ECHL message board...
ECHL Stories from May 20, 2019
- Oilers Win in Toledo to Force Game 7 - Tulsa Oilers
- Manchester Membership Terminated - ECHL
- Royals' First-Ever Education Day Game January 7 at 10:30 a.m. - Reading Royals
- Weekly Sports League and Franchise Report - OSC Original by Dan Krieger
The opinions expressed in this release are those of the organization issuing it, and do not necessarily reflect the thoughts or opinions of OurSports Central or its staff.


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In brief
Greeley " The Greeley Central High School thespian troupe and art magnet program is presenting "Anything Goes" Wednesday-Saturday.
All shows start at 7:30 p.m.
The 1934 musical comedy known for songs such as "I Get a Kick Out of You," "It's De-lovely" and the title song follows passengers aboard a transatlantic ship, including a gangster, a businessman, an English aristocrat, a wealthy debutante and her mother, a nightclub singer. The show's music and lyrics are by Cole Porter.
Advance-purchase tickets are $6 for adults and $5 for students. Tickets sold at the door, 1515 14th Ave., are $1 more. The cast has more than 55 students, with an additional 20 students working behind the scenes and 20 musicians made up of students and professionals from around Greeley.
Proceeds from the play help the thespians attend the Colorado State Thespian Convention. Water and desserts will be sold at intermission to help support the GCHS arts magnet student scholarships.


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Our 2019 accommodation listings offer a large selection of 2,885 holiday rentals near Silver Sands Beach. From 162 Houses to 2,582 Condos/Apartments, find the best place to stay with your family and friends to discover Silver Sands Beach area.
Whether you are travelling solo or with family and friends, here are the areas with the largest selection of holiday rentals for a long holiday or just a weekend break in Silver Sands Beach:
For other neighbourhoods, please use our search bar to access the selection of holiday homes available.
HomeAway offers a large selection of holiday homes near great places in Silver Sands Beach. From HomeAway travellers, the most popular points of interest to stay near are:
But there are many other points of interest around Silver Sands Beach listed on HomeAway where you can find your place to stay. Please use our search bar to access the selection of holiday rentals available near the point of interest of your choice.
Yes, of course. HomeAway offers 162 Houses in Silver Sands Beach. Our other popular types of Silver Sands Beach holiday rentals include:
But you can also enjoy a great stay in one of our other holiday rentals including Cottages and more.
Yes, you can select your preferred holiday accommodation with pool among our 2,671 holiday homes with pool available in Silver Sands Beach. Please use our search bar to access the selection of holiday rentals available.


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Jul 24 - Gibraltar Welcomes the Launch of its First MAC Counter
Gibraltar today welcomed the opening of its first MAC counter. The world-renowned high-end make-up brand can be found at S.M Seruya's central store at 139 Main Street.
MAC has fact become one of the most popular make-up brands, with its fair prices and long lasting properties. It was once marketed for use by make-up artists but has taken over as one of the leading brands for consumers.
Gibraltar's first Mac counter opened up today under the watchful eye of Deepak Ramchandani who is no stranger to make-up. The response proved extremely positive, with prices almost levelling those of MAC products sold in the US.
The girls manning the already popular counter have undergone specific MAC training. Girls across Gibraltar can now breath a sigh of relief knowing that they no longer have to pay extortionate packaging fees when buying MAC products online. This will also save fans of the brand from taking a trip up to the nearest MAC counter in Puerto Banus where prices skyrocketed due to tax.


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[Notice] 5/29 PT Maintenance Notice
Hello players.
There will be a scheduled maintenance on 5/29 18:00 PT.
Please check below for more information and
please remember that you cannot login during the maintenance.
[5/29 18:00 PT Maintenance Notice]
#Period: 5/29 18:00 ~ 19:00 PT
1. New Hero Added
- 1 new hero will be added.
- One-Armed Taejin Jin
- More info about this hero can be checked at the Hero Deck.
2.Summon Chance Hero / Rune will Change
- The heroes and runes that get a boost can be seen at Notice >> Chance Up.
3. One-Armed Taejin Jin Growth Mission
- There will be hero growth missions for Byron that will give you diverse rewards.
- More info about the growth missions can be found within the game at Event > Growth Missions.
4. Challenge Tower Extension
- The Challenge Tower will be extended to 100th floor.
- Defeat each floor's boss to get diverse rewards.
- More info about rewards can be checked within the game.
5. Double Ruby and Gold Event
- All players who purchase gold or rubies between 5/29 PT maintenance ~ 6/5 07:59 PT will get the same amount as a bonus!
- Please check the Attention screen for more information about the Double Ruby and Gold event.
- There is no purchase limit.
6.One-time Pack Renewal
- Package content adjustment
- More information can be found at Shop >> Items
※ The period for special missions will increases depending on the time of the maintenance.
※ The maintenance may end early or be delayed.
※ Please end the game before maintenance and we cannot help you if there is any errors by not doing so.
We are sorry to cause inconvenience due to the maintenance and
promise to finish it as fast as possible.
Thank you.


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The individual species' use of technology started with the transformation of natural sources into easy assets. Fact be advised, any community targeted initiative is an effective cause to consider the adoption of SD-WAN expertise, as a result of it is changing into increasingly clear that the traditional legacy network has turn into a barrier for enterprise agility. Know-how administration is the set of policies and practices that leverage technologies to construct, preserve, and enhance the competitive advantage of the agency on the idea of proprietary knowledge and know-how.
Bigwood, Michael P. "Managing the New Expertise Exploitation Process." Research-Expertise Administration, November-December 2004, 38. The representatives of this perspective have been, overwhelmingly, schooled within the humanities or the social sciences and had just about no first-hand data of engineering follow.
This exclusive image-processing technology will be integrated into future fashions of Sony's WEGA TELEVISION sequence, making it attainable for users to view and experience the vast potential of the excessive-definition period. As humans, we use both technology and science together, that is why we confuse these two to be the same.
OPEN LEARNING – tutorial methods by which many aspects of the learning process are beneath the management of the learner. Entertainment Expertise: This is a means of using various technological parts to create an entertainment experience. In the case of SaaS corporations, they're building merchandise, not networks.
One other expertise management process, Strategic Know-how Roadmapping (TRM) was mentioned by Rachel Wells et al in Research Technology Management. At the moment's technology has been within the technique of growth for hundreds of years. This has spurred huge demand for technology that is geared for the cloud – whether or not it's software program, networking providers, or enterprise providers.


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CCLI Song #7083344 © XI Worship Music (BMI). All rights reserved. Used by Permission.
Written by: Makayla McKibben, Shane Selby
Verse 1
God we give you
Permission to have your way
Come invade this place
Let the glory of heaven reign
Let us be consumed
Move your sons and daughters
Move with signs and wonders
Move, O King of heaven, move
Move shake prison walls and
Move let shackles fall
Come move, O King of heaven, move
Verse 2
We abandon the religion
That binds us down
Break down every wall
Let us see you for who you are
Let us be consumed
We have one desire, to draw closer to you
Set our hearts ablaze with passion
Let us be consumed


text: Tyler and Eric get back into the swing of things after an extended but much needed absence from The Bitcave. They discuss Suicide Squad, No Man's Sky, Battlefield 1, and their mutual excitement for the upcoming Nosulus Rift. Eric also rants about his dislike for Activision and their business strategy of charging full price for ten year old titles. This episode is best enjoyed with a glass of grapefruit juice and a piece of buttered toast.


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The Futuregasm Podcast #2 - Talking to Heather Morrison about sex toys for disabled people
Recently I had the pleasure of speaking to Heather Morrison about how her and her brother at Deliciously Disabled are creating sex toys for people with physical disabilities. It's an inclusive and exciting project that you should have a listen to.
You can do that here. Or you can go to the Soundcloud link here (I'd recommend the latter if you're on a mobile).
Show notes
Deliciously Disabled's page on the project
Their GoFundMe (go help out if you can!)
And you can reach out to Heather at firstname.lastname@example.com


text: I want to fuck Someone give me a hot bitchs number The naked girls trib, rubbing their pussies together in explosive squirting orgasms, they are not letting any of that precious squirt juice go to waste and they are not stopping until they are dry and full at the same time, till they collapse in a slippery heap, spent from cumming so much pussy juice! The lesbians Priest fucks altar boy into a 69 so they can lick and finger bang each other. Great seeing everyone get a turn to squirt-blast all over each Sexy girls naked kissing having lesbian sex until the wells ran dry, and they STILL found the reservoir. Her stepmom teaches her how to trib, rubbing their pussies against each other and experiencing explosive orgasms.


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contact us
Tel: +44 (0)1865 818030
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professional development
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Forthcoming events
Past events
15th August 2019
MPKH QUBE Event: Work the language of communication
Online Knowledge Hub Event
QUBE Online
The Language of Project Working
One of the most significant yet hidden influences on project communication is status. Have you noticed how:
• people will hang on every word of someone senior in your organization's hierarchy (even if they are talking rubbish, or contradicting last week's message)?
• some people always struggle to get heard - even if you want to hear what they have to say?
• you feel powerful in some situations and powerless in others?
• in meetings, some people know how to encourage or close down discussion and debate, and others don't?
Consultant, change agent and author of Project Delivery, Uncertainty and Neuroscience, Carole Osterweil, will co-facilitate our QUBE@Work Session on Thursday 15th August (17.30-19.00 BST) and explore how status creeps into communication - like a hidden language. Join us at this workshop to share your observations and experience of status - both good and bad. Discover how perceptions of status drive our behaviours and colour our language. Learn how recognising the hidden power of status can help you manage the involvement of 'senior' and 'junior' stakeholders in your projects - making it easier to share truth to power, influence 'resistors' and present to high status groups or individuals.
The language of project working is the fourth of a new Series of bi-monthly facilitated evening workshops on QUBE for the major projects community.
The sessions are designed to encourage you to take away some insight you can use – a technique, an example, a sense of how others do things or simply a confirmation of your own intuitive approach. The sessions will also help you build and extend your professional network as well as develop your skills on collaborating and co-working in a virtual environment.
For more information and to register:
Click here to view full flyer
This event is not bookable online
Click here to email us for more information regarding this event or phone: +44 (0)1865 818030
about us
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my profile
hints for main reps
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website: The Manvers Group © 2019


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If your looking for a great SUV look no further. The Audi Q5 is known for its quality ride and superior looks. With tons of options you couldn't go wrong choosing this as your next SUV. AWD, leather, sunroof, bluetooth, power seats, alloy wheels, ABS, and tons more options.
At Napleton Autowerks Indiana we have a large selection of new and pre-owned vehicles ready for delivery. Please contact us for more information or to schedule a test drive.
Your buying risks are reduced thanks to a CARFAX BuyBack Guarantee. Off-road or on the street, this Audi Q5 quattro 4dr 2.0T Premium Plus handles with ease.
Is it possible to fall in love with a vehicle? It is when your vehicle is as prestige as the Audi Q5. No matter the varying terrain or weather conditions, this all-wheel drive vehicle will help you reach your destination safely and securely in a well-appointed cabin with many features found on cars twice the price.
It's not a misprint. And the odometer isn't broken. This is a very low mileage Audi Q5. A rare find these days.
More information about the 2016 Audi Q5:
With the 2.0 TFSI engine and 8-speed automatic, the 2016 Audi Q5 performs similarly to its V6-equipped big brother while being much more fuel-efficient. The standard Q5 has an EPA highway rating of 27 mpg. The Q5 has the longest wheelbase in its class and that gives it an especially smooth, settled ride. With either 3.0L V6, the Q5 has an excellent towing capacity as well. The Q5's rear-biased quattro all-wheel drive system brings more driving enjoyment than is typical in an SUV this size, while the interior has just as much versatility and flexibility as other utility vehicles in this class. Add to the mix a 2.0L hybrid -- or even the potent SQ5 -- and the appeal of the Audi Q5 is hard to ignore.
This model sets itself apart with excellent towing capability, available Audi Drive Select customization, excellent ride quality, strong safety feature content, hybrid fuel economy, and Strong performance


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Create an Account - Increase your productivity, customize your experience, and engage in information you care about.
October 16, 2019
120 Old Hampton Lane
October 19, 2019
First Street
October 19, 2019 - October 20, 2019
60 Pine Chapel Road
October 19, 2019
3165 N. Armistead Ave.
October 20, 2019
10 Ruckman Road
July 29, 2019, 7:00 AM - 6:00 PM
Campers will enjoy weekly themed activities, local field trips, enrichments, games, swimming and more. Two parent paid fieldtrips include Busch Gardens and Ocean Breeze.
Activities include: swimming, STEM, golf, sailing, ceramics, talent show, and more. Two parent paid fieldtrips include Busch Gardens and Ocean Breeze.
July 29, 2019, 9:00 AM - 2:00 PM
Campers will enjoy weekly themed fun, swimming, outdoor play, enrichments, and much more.
July 29, 2019, 10:00 AM - 2:00 PM @ Little England Cultural Center
Tactful strategies and concentration are part of learning the fundamentals of this challenging board game. Participants who already know how to play will have the opportunity to match their skills against other players. Ages: 18-70. Register one week prior.
July 29, 2019, 9:00 AM - 2:00 PM @ Hampton Senior Center
The Hand and Foot card game is a game, which is often compared to Canasta. The objective of the game is to get rid of the two sets of cards in your hand, known as the hand and the foot. Each player is dealt a hand of cards. In the center of the table is a face-down pile of cards called the stock and a face-up pile called the discard pile. Come learn to play if you don't know how.
July 29, 2019, 5:00 PM - 6:00 PM @ Hampton Senior Center
Get fit fast in this complete total body walking program that gives you serious fat burning, muscle conditioning and stretching. This is a video-instructed program offered to the community at NO cost. We ask you to wear proper exercise attire and athletic shoes.
June 29, 2019, 10:00 AM - December 31, 2020, 5:00 PM @ Hampton History Museum
This dynamic photo and artifact-rich experience explores Hampton's integral ties to, and love of, the water that surrounds the city, its seafood and maritime heritage, and passion for sailing as embodied in the locally developed Hampton One sailboat, and the competitive sailing culture that grew out of it.
July 29, 2019, 9:30 AM - 11:30 AM
Designed for children age 1 to 4 years old
An energetic playgroup focused on social skills and school readiness.
Offers free play, circle time, snacks, and an art project
July 29, 2019, 7:00 PM - 8:00 PM @ Willow Oaks Branch Library
For Ages 12 - 17. Need volunteer hours for school? Love reading or just being in the library? Join us for Teen Volunteer Hour. REGISTRATION IS REQUIRED. See the front desk for details.
View all calendars is the default. Choose Select a Calendar to view a specific calendar.


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Selling a home can be a stressful process. It takes time, effort to receive the price you want without waiting for an incredibly long time. This article provides tips and tricks that you can implement immediately to get the results you are hoping for.
Improving the lighting in your home will increase its appeal. Take down any dark curtains you might have up, replace light bulbs with higher wattage bulbs and clean all of the windows until they shine. A bright, well-lit home, is at the top of the buyers wish list, right behind a good location, so be sure to do all that you can to illuminate your home.
If you want to sell your home but the time is not right, take the time to improve your home. The time you spend waiting to sell can be used to make any improvements or repairs to your home that not only increase your comfort but will also increase the sale value when the time is right.
When you are getting ready to sell your home and your agent is coming over to take pictures think of what potential buyers will see. Some people will be turned off by pictures if you have a lot of clutter or mess. Clean the house really well and make sure things are put away.
Sellers are more motivated and inclined to negotiate during the fall months. They may have rejected offers during the spring and summer months that they would be more than happy to accept this late in the year. If a home that you looked at earlier in the season is still on the market, go back with a low offer and it may be accepted.
Have your real estate agent do a rough estimate of everything that would have to be paid for by you at the time of closing. This is important, because it will show you how low you can drop your price without having to bring your own money to the table. Sometimes, there are costs that a first time seller is not aware of.
Don't miss out on potential buyers by listing your home for sale during the fall and winter months, especially if the house is located near schools or has kid-friendly features. Parents and families are very reluctant to buy a new home and move during the school year, which generally runs from August to May. Use that extra time to make small improvements and increase curb appeal.
To improve your home's value for less than $20, replace all of your light switches. Light switches are surprisingly eye catching to buyers. A stylish and new looking light switch can raise their opinion of the entire room. On the other side, a worn and dirty light switch can make your entire look less clean.
In your home, upgrade your old kitchen and bathrooms. Bathrooms and kitchens are often the major selling points of a home. Generally, a bathroom that has been modernized can provide over a 100% return, where a kitchen that has been modernized can provide a 90% return on your home.
If you have potential buyers coming to look at your home, avoid having noisy items, such as TV and radio, playing. Buyers are coming to look at your home, not watch TV or listen to music with you. You should be courteous to the potential buyers and let them concentrate on your home. Always remember to turn down your volume.
One of the keys to selling a home is to take the initiative to make your property as appealing to a buyer as possible. This article is one resource that you can use to make the process a little less frustrating and a little more profitable. Remember that you have the ability to change the circumstances surrounding the sale of your home.


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Chris Camp & His Blues Ambassadors
Formed as an outlet for the musical talents of a guy you may know better as The Whip Guy, this group can play those swinging sounds to bridge any diplomatic impasse on the dance floor or barroom. When Chris Camp lays down his bullwhips and pulls out the harmonica and takes to the stage to sing the blues and more, fellow friends and musicians Mark Sanders (drums), Bill McKenzie (bass, vocals), Jeff Helton (guitar, vocals) and Roger Wainwright (keyboard, vocals) don't miss a beat or a note in bringing the songs to a peaceful and desirable resolution. After years of talking about starting a band, Chris gathered a corps of experienced players, all contributing decades of gig knowledge to broker a good deal of fun with music. Expect to hear standards like "Mojo Working" right alongside a Clapton or Elvis number, bringing it all back home to blues-based, American music built for comfort and designed in good faith to negotiate a fine time for all.
Chris Camp & His Blues Ambassadors
Friday, Dec. 14, 8pm
Saturday, Dec. 15, 8:30pm
Lime Street Cafe


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How to ask for a return
If you want or need to ask for a return you always have to contact Teamecommerce via email. To make the procedure faster we invite you to use the RETURN FORM and to print the PRECOMPILED LABEL. In alternative you can also contect us at email@example.com, use the online chat or call us at (+39) 0354491296.
Once we received your return request we will assess it and we'll accept it or not based on each case, attaching the complete instructions of how to make the return. NO RETURN will be accepted if not preventively accepted in written form.
Requirements needed to achieve an exchange or a refund
Every return products will have to be in the condition state as they were at the moment of the order, as brand new to be re-selled again. All the labels, seals, boxes and original cases has to be intact and rendered. If these conditions will not be observed the product will be considered as "USED" and it will be shipped again to the sender in charge with all the shipping costs OR will be withheld with a penalty from 60% to 80% of the purchase value, based on the conditions of the return product.
Shipping costs for returns
In the following table you can see the average charge for shipping costs of returns. If you have questions about it please contact the Customer Service sending an email at email@example.com.
|Reason for return
|Costs and Transport borne by
|Non-compliant product
|Product arrived damaged
|Product change (within 15 days)
(example for model change)
|Right to Withdraw


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The development of equilibrium existence theory
Posada, German
Pomery, John G.
Master of Arts
This paper presents a review of the literature on existence of competitive equilibrium, starting with Walras. Special attention is given to determination of the sources of notions employed in Debreu's Theory of Value a sketch of whose existence proof is included. Posterior generalizations and variations are briefly described; the outline is not intended to be exhaustive, but representative of the research trend. A chapter is devoted to the measure theoretic approach to equilibrium and core theory, in the belief that it has been enlightening for mathematical economics. In this chapter a generalization of the concept of a private ownership economy is proposed by introducing a measure space for the production sector; this type of economy appears as a natural extension of the Debreu notion.


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Business calendar
Pioneer Oil Producers Society.Luncheon. 11:30 a.m.-1:30 p.m., Houston Engineering and Scientific Society Club, 5430 Westheimer.Speaker:Wayne Kelly, managing director, RSK (UK) Ltd.Topic:Oil imports. Cost: $22.Information:www.pioneeroilproducers.com.
The After Hours Network: Meeting. 6-8 p.m., Little Napoli Italian Cuisine, 6445 Westheimer. Speaker: Steve Davis, radio host. Topic: Setting your goals in life and business for 2011. Cost: $15. Information:www.afterhoursnetwork.com.
BNI Greenway: Breakfast. 7-8:30 a.m., Briar Club, 2603 Timmons. Cost:$30.Information: Brian McElroy, 713-789-5293.
Institute of Real Estate Management: LEED Green Associates Study Group. First of two parts, continuing Jan. 25, 4-6 p.m., Kirksey Campus, 6909 Portwest Drive.Cost: Free. Information: 713-783-9225. Registration:www./leedap.kirksey.com.
Transportation Club of Houston.Luncheon. 11: 15 a.m.-1 p.m. , Houston Club, 811 Rusk. Speaker:County Judge Ed Emmett.Cost:$15-$45.Information:www.transclubhou.org.
Services Cooperative Association: Networking breakfast. 7:15-8:30 a.m., H.E.S.S. Club, 5430 Westheimer. Speaker: Elaine Latham, Rovai Dreams. Topic: Balance of home and work life. Cost: $22-$30. Information: 713-932-7495, ext. 48, or www.servicesca.org/crossroads.htm.
Hotel and Lodging Association of Greater Houston:Luncheon. 11:30 a.m.,Café on the Park, 1 Reliant Park.Speaker:Greg Shaheen, senior vice president-basketball and business strategies, NCAA.Cost:$35-$50.Information:713-437-5250.
Small Business Social Media Summit: First of three-part workshop, continuing Feb. 3 and Feb. 17. 8:30 a.m.-noon, J.W. Marriott, 5150 Westheimer. Part I: The power of e-mail marketing and Facebook. Information: Shelley Roth with Springboard, firstname.lastname@example.com, or 713-937-1006.
American Woman's Society of Certified Public Accountants:Dinner meeting. 5:30-8 p.m., Sheraton Brookhollow, 3000 North Loop West.Speakers:Deloitte tax team.Topic:Annual tax update.Cost:$20-$40.Information:www.awscpahouston.org.
Tech Connection:Networking. 5:30-7:30 p.m., Hyatt Regency Houston, 1200 Louisiana.Participants:BioHouston, Greater Houston Partnership, Houston Angel Network, Houston Technology Center, MIT Enterprise Forum of Texas, Rice Alliance for Technology & Entrepreneurship, TiE Houston, and University of Houston Small Business Development Center.Information:713-658-1750; www.houstontech.org/events/856.
Energy Prospectus Group:Luncheon. 11 a.m.-1:30 p.m., H.E.S.S. Club, 5430 Westheimer. Speaker: Chris Bloomer, geologist.Topic: Bakken Shale update. Cost: $30-$40.
American Industrial Hygiene Association Gulf Coast Section: Meeting. 5:30-8 p.m.,Brady's Landing,8505 Cypress.Speaker:Philip Hilder, former attorney-in-charge of the U.S. Justice Department's Organized Crime Strike Force in Houston.Topic:Criminal Prosecution for a Safety Violation Is No Accident.Cost:$10-$25.Information:Gerry Luther, 281-356-6038, ext. 238.
Galleria Estates:Homebuyers class. 9 a.m.-5 p.m., Power Center 12401 S. Post Oak.Topic:The homebuying process, who qualifies for down payment assistance.Information:713-721-5555.
The Chronicle lists business events on a space-available basis. Send a description of the event, date, time, address, cost and phone number to: Katherine Feser, Business Calendar Editor, email@example.com, two weeks before publication.


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Dharma Yoga is a beautiful devotional practice that emphasises good health, a clear mind and a kind heart. The method weaves together many teachings in order to bring all students closer to the goal of self realisation. This is an advanced class incorporating inversions, backbends and arm balancing postures.
Although Dharma is a very physical practice, it is also a deeply spiritual journey that will introduce you to the many facets of yoga, including pranayama (breathing techniques), kriyas (purification techniques), mudras (hand gestures) and meditation.


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Why Mug Shop for Promotional Mugs?
Here at Stupid Tuesday's Mug Shop we believe we offer a unique promotional mugs service that simply cannot be matched. Here are a few reasons, in no particular order, why we feel you should choose Mug Shop when ordering your promotional mugs.
In-house Artwork Service
For those times when you don't have print-ready artwork available. Here at Mug Shop we offer our own in-house artwork service FREE of charge*
Design Service
If you don't have your own artwork available, don't worry. We can design your mug artwork from scratch for a small additional charge.
We take the utmost care when producing our mugs. This means the end result is of the very highest quality.
Product sourcing
We have a wide range of promotional mugs already available via our website. However, we can source just about anything. So if you can't see what you're looking for, just ask!
Price Match Guarantee
We believe our prices are fiercely competitive. However, if you find a like-for-like quotation elsewhere we will endeavour to match or even beat it. (This is providing it is a verifiable competitive quotation.)
Customer service
We pride ourselves on our levels of customer service. From the initial point of contact through to delivery and after-sales.
Advice and guidance
Tell us what your mugs are for and we'll tell you the most appropriate mug. We'll also tell you how to get the best results from it.
Since 2007 we've regularly worked with large, multi-national companies. We also work with SMEs, health boards, universities, charities, local authorities and many other organisations.
All bases covered
Our in-house skills mean we've got all bases covered. From getting your artwork to look superb and impactful right through to sourcing the best possible mug. We're sure to find a promotional mug that suits you from our substantial range.
Don't just take our word for it. Take a look at what our customers say…
* Small, reasonable changes to artwork included free of charge. More details available upon sight of artwork.


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I cant log in
i left my MacBook with my son he did some experiment on it by creating a user account but unfortunatly he forget the password he used. what can i do because my Mac OS X installation DVD is bad what can i do?
Questa è una buona domanda?


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Tricycle operators beg Rivers govt for conducive environment
The Rivers State branch of the Keke Owners and Riders Association (KORAN) has urged the Rivers State government to create...Read more
The Rivers State branch of the Keke Owners and Riders Association (KORAN) has urged the Rivers State government to create...Read more
The Tombia community hall in Yenagoa Local Government Area, Bayelsa State was congested on Monday. Pregnant women and teenagers trooped...Read more
Youths from Ataba Community in Andoni Local Government Area of Rivers State have urged Governor Chibuike Amaechi and the Commissioner...Read more
He said: "Look at this place; we are no longer doing business here, because no customer will spend his money...Read more
A group, Cross River State Niger Delta Council (CRONDEC), has called on President Goodluck Jonathan not to bow to pressure...Read more
The new Provost of the College of Health Science and Technology, Port Harcourt, Dr. Charles Amadi has tasked lecturers on...Read more
Speaker of the Edo State House of Assembly, Hon Uyi Igbe, inaugurated a mobile clinic and free health care services...Read more
Amorighoye Sunny Mene (KSM), popularly called 'AS Mene', was the ACN flagbearer in the April 2011 general elections for the...Read more
For nearly two years, workers and managers of GMP, a metal company based in Port Harcourt, the Rivers State capital,...Read more
Benin City, the capital of the old Benin Kingdom and present day Edo State, is an ancient city struggling with...Read more
A proposed agriculture project of the Rivers State Sustainable Development Agency (RSSDA) in Etche Local Government Area of the state...Read more
Women in Rivers State are to benefit from the N96 million ($600,000) agricultural extension and curriculum development grant from the...Read more
The Ovie of Agbon Kingdom in Delta State, HRM Mike Omeru, Ogurimerime Ukori 1, was recently placed on the spot...Read more
An Ijaw rights and civil action group, the Ijaw People's Development Initiative (IPDI), has praised Niger Delta leader, Cheif Edwin...Read more
Lucky Felicia never dreamt of owning a car. In fact, as an inspector in the Nigerian Security and Civil Defence...Read more


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Strictly Come Dancing favourites Ian Waite and Vincent Simone are joining forces in 2019 with their brand new production - THE BALLROOM BOYS.
Argentine Tango legend Vincent and King of the Ballroom Ian, will be joined by two professional female dancers and a wonderful vocalist. The night will be packed with dances, songs and loads of banter!
Expect dances like the Waltz, Quickstep, Paso Doble, Foxtrot and of course, the Argentine Tango! Get ready for a high intensity evening of glitz and glamour with Ian & Vincent… THE BALLROOM BOYS!
Hit songs from the most sensational shows of our time. Join a host of West End stars for an evening of glitz and glamour!
Featuring highlights from The Phantom of the Opera, Les Misérables, The Lion King, Wicked, and many more!
The National Theatre takes Shelagh Delaney's career defining play on tour. Directed by Bijan Sheibani (Barber Shop Chronicles), this British classic is an exhilarating depiction of working-class life in post-war Salford.
When her mother Helen runs off with a car salesman, feisty teenager Jo takes up with Jimmy, a sailor who promises to marry her, before he heads for the seas leaving her pregnant and alone. Art student Geoff moves in and assumes the role of surrogate parent until, misguidedly, he sends for Helen and their unconventional setup unravels. Don't miss your chance to see one of the great taboo-breaking plays of the 1950s!
Escape to an enchanting winter wonderland with Northern Ballet's beautiful re-imagining of Cinderella. A glorious summer's day turns into tragedy. Devastated by the loss of her father, and excluded by her cruel stepmother and sisters, Cinderella finds solace on the frozen lake where she first sees her Prince Charming. As romance blossoms, a surprise encounter in a market place changes Cinderella's destiny.
Famous for their sparkling adaptations of fairytale classics, Northern Ballet's Cinderella is the most magical rags-to-riches story you will ever see.
JOHN RUTTER'S CHRISTMAS CELEBRATION. There's no better way to get into the Yuletide spirit than attending John Rutter's popular Christmas Celebration! Enjoy this unmissable festive favourite as celebrated composer John Rutter leads the Royal Philharmonic Orchestra in a magical evening of Christmas classics, including The First Nowell, Sleigh Ride and Frosty the Snowman. The nation's favourite orchestra will be joined by vocalists Elin Manahan Thomas and Louise Marshall, and a great choral force, as they perform a selection of John Rutter's own much-loved works, seasonal choral and orchestral favourites and sing-along carols. This magical, winter treat is full of sparkle and Christmas cheer and is not to be missed!


text: Cozy split entry home in Penn Hills featuring a large open kitchen with stainless steel appliances, granite countertops and tile backsplash. Off the kitchen is a large deck overlooking the beautiful fenced in yard. This home has freshly painted walls, hardwood floors throughout, skylights and split system air conditioning air on the main floor. Located just one block from the community park, close to shopping and PSU. Come see this move in ready home today! Sq. Ft. per tax record card. Buyer should verify. If applicable, commission is based on sales price after seller assist.


text: Good morning! I am brand new here and just looking for any advice. Over the summer, I began bleeding during sexual intercourse, and not just a little bit. It was almost like a second period and would last at least 24 hours. This has continued to happen. I went to my doctor shortly after it started and he said rough sex. It definitely wasnt that and continued happening. A new doctor ran a ton of tests, and I do not have any STDs and lubrication is not the problem. It seems we ruled out all of the minor things, and Im concerned I have cervical cancer due to this symptom. I have also been extremely tired and I know especially during my period I have a terrible pain shoot down my leg from my back. Can anyone tell me what they think this is and if they had any other similar symptoms? I know my doctor will want to run more tests. I feel like Im going crazy!!


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Demystifying Nuclear Power: 70-Years After Nuclear Carnage/
Written by Caroline Phillips, Administrator
Seventy years ago the United States forced the world into the nuclear age by dropping the world's first atom bomb on Hiroshima, Japan, August 6, 1945. A second atomic bomb was dropped three days later on the city of Nagasaki, Japan, August 9, 1945. The bombing of these two residential cities resulted in the immediate death of at least 129,000 people.
On August 6, 2015, thousands of people gathered in Hiroshima to commemorate the loss of lives from the world's first atomic bombs and listen to Prime Minister Shinzo Abe and Hiroshima Mayor Kazumi Matsui speak about nonproliferation. Mayor Kazumi Matsui made an emphatic call for a world without nuclear weapons in a direct appeal to President Obama and other worldwide policy makers,
"Please come to the A-bombed cities, hear the survivors with your own ears, and encounter the reality of the atomic bombings. You will be impelled to start discussing a legal framework, including a nuclear weapons convention."
Mayor Matsui did not hesitate to point out Prime Minister Abe's ongoing campaign to reinterpret Japan's postwar "pacifist" constitution in order to allow Japanese troops to fight alongside allies overseas as an uneasy political backdrop to the ceremony.
Prime Minister Abe's push to restart nuclear reactors in the wake of the triple meltdown at Fukushima Daiichi, and the subsequent hasty cleanup of the heavily radioactively contaminated villages surrounding the decimated Fukushima Daiichi site is an ongoing human tragedy of epic proportions. It is also very concerning due to Japan's atomic history. Currently thousands of Japanese citizens are living in temporary housing, forced out of their cities and homes due to this ongoing nuclear disaster with 300 tons of radioactive water contaminating the Pacific Ocean every day. This ongoing human tragedy and nuclear power debacle makes it imperative that we reexamine humanity's relationship to nuclear power and its role in this nuclear age that has seen 5 major nuclear reactor meltdowns during 35-years.
Related Links:
We invite you to take a look at these related sites listed below for a deeper understanding of the atomic bombings of Hiroshima and Nagasaki.
The 'Nuclear Shadow' Over the Congo


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If you are looking for a hotel in Bologna near the airport, you couldn't find a better solution than that of staying at the Hotel Bologna Airport, with its restaurant and large car park.
Discover the convenience of a really good rest before a flight with the hotel near Bologna airport package.
By choosing from the hotel offers in Bologna near the airport, you will have the advantage of Airport parking with free connection by shuttle bus for the airport.
Discover the offer of a hotel with car parking near Marconi airport and choose the formula most suitable for your needs.
From € 42,00 per day
From € 63,00 per day


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- Telephone:
- 07574 178757
Key factsPrint summary
2012 FORD MONDEO 1.6 TITANIUM ECONETIC, ON 139k MILES FROM NEW, FULL SERVICE HISTORY (8 SERVICE STAMPS) - CAMBELT CHANGED ON 122k, **FULL MOT TILL 3rd APRIL 2020**, 1 FORMER KEEPER FROM NEW , FEW AGE RELATED MARKS AS EXPECTED , **HPI CLEAR**, DELIVERY OPTION AVAILABLE , Next MOT due 03/04/2020, Grey, 2 owners, AVAILABLE TO VIEW 7 DAYS A WEEK, AT DALE STREET MOTORS WE AIM TO PROVIDE QUALITY USED VEHICLES, £2,995
This car comes with
Metallic Paint, Tyre Pressure Monitoring System, Start/Stop System, 17in 5x2 - Spoke Alloys Wheels (215/50 Tyres) with Locking Wheel Nuts, 2 Cup Holders, Air Conditioning - CFC-Free with Dual-Zone Electronic Automatic Temperature Control (DEATC), Alloy Wheels - 17in, Anti-Lock Brakes (ABS), Emergency Brake Assist, Auto-Dimming Rear View Mirror, Bluetooth Hands Free, Body Coloured Bumpers, Centre Console - Storage Box, Cruise Control Includes Adjustable Speed Limiting Device (ASLD), Electrically - Operated Front and Rear Windows, with One - Shot Lowering/Closing and Global Opening/Closing, Electrically - Operated/Heated/Foldable Door Mirrors with Puddle Lights, Electronic Stability Programme (ESP), Ford Eco Mode - Driver Information System, Ford Convers+ Cluster Display - Premium Instrument Cluster with 256 Colour Screen Display, Front Fog Lights, Power Steering, Quickclear Heated Front Windscreen, Radio/CD, MP3 Compatible, Aux/USB Connection, Bluetooth Audio Streaming, Rain Sensing Front Windscreen Wipers, Remote Central/Double Locking, Sony DAB CD/MP3/USB Radio, Sony DAB Radio, Thatcham Category 1 Approved Alarm with Perimeter and Volume Sensing, Third Brake Light, Traction Assist, Upholstery Cloth, Voice Control System
- 201905127873307
- 2013
- 62
- £2,995
- 300
- 139,000
- Cars
- Md6fI70eNZw=
Vehicle summary
|Body style
|Engine size
|1560 cc
|Fuel type
|Number of doors
|Number of seats
|Gearbox type
|CO2 emissions
|112 g/km
|Insurance group
|Standard manufacturer's warranty (miles)
|60000 miles
|Standard manufacturer's warranty (years)
|3 years
|Standard paintwork guarantee
|No details available
Performance & economy
|Fuel consumption (urban)
|56.5 mpg
|Fuel consumption (extra urban)
|72.4 mpg
|Fuel consumption (combined)
|65.7 mpg
|0 - 60 mph
|11.9 seconds
|Top speed
|118 mph
|Engine power
|113 bhp
|Engine torque
|199.15 lbs/ft
|1500 mm
|Height inclusive of roof rails
|No details available
|4784 mm
|0 mm
|2092 mm
|Width including mirrors
|No details available
|Fuel tank capacity
|No details available
|Minimum kerb weight
|1496 kg
|Interior features
|Exterior features
|Sony DAB CD/MP3/USB Radio
|Alloy Wheels - 17in
|Sports Suspension
|No details available
Please note
This includes MPG figures which are calculated under European Standards, in test conditions, and will vary under normal driving conditions. The information displayed above describes the typical specification of the most recent model of this vehicle. It is not the exact specification for the actual vehicle being offered for sale which may vary. Specifications for older models may also vary. Please contact us prior to purchase to confirm the exact specification of this vehicle.
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The surface is treated with SelectGrip® which ensures an optimum retention capacity.
The base allows the contouring to fit the prosthetic solution.
The angles of 0º, 15° and 25° allow the adaptation of the majority of clinical cases.
Made of titanium grade 5 ELI maximum compatibility and long life is guaranteed.
The straight basis allows the reduction of the profile adapting to every clinical case.
Compatible with Straumann®, Synocta®, Soft Tissue Level®
Platform 4.8 (RN)
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Commentary pieces are made of pumpkin-spice and smiles and two heaping spoonfuls of snark and a bitter resentment of the passage of time. They can and will take many forms, are randomly organized, and are pretty much the only thing I write for this website anymore.
Apologies for the late box office report. It's hurricane season on the American East coast, and preparations have been underway for Hurricane Florence's arrival over the last few days. Sandbags have been piled around my back door to divert the inevitable torrent of water from collecting on my patio, dry food has been purchased and prematurely eaten, and every grocery store within one hundred miles has run out of bottled water. But, there's some good news to be had.
The Summer movie season is officially over and, according to box office stat-daddy Brad Brevet, shattered records every step of the way. August 2018 was up almost 30% from 2017, and the Summer as a whole was up 15% from last year. Leading the studio pack was, predictably, Disney and their ignominious brand of filmmaking by committee. They were the only studio to top $1 billion in domestic receipts during the three-month window – Incredibles II alone brought in over $600 million at the domestic box office to become the highest grossing animated feature in North America. It's an eye-rolling shame about Solo: A Star Wars Story.
[I'll address the diminishing returns of the Star Wars franchise in a future article, it's just really hard to do so considering the wacky climate surrounding The Last Jedi and the people fighting over it.]
Other hits that bolstered the Summer box office were Jurassic World: Fallen Kingdom (petergriffinvomiting.gif), a little movie called Crazy Rich Asians, Jason Statham's shark thriller The Meg, Ryan Reynolds' Deadpool 2, Tom Cruise's Mission: Impossible – Fallout, and carryover from numerous other early-year hits.
The year's current top domestic grossing studios as of the end of August:
- Disney: $2.74 Billion, 95.6% over this point last year.
- Warner Bros.: $1.1 billion, 19.4 below this point last year.
- Universal: $1.089 billion, 18.5% below this point last year.
- Sony: $801.5 million, 4% over this point last year.
- 20th Century Fox: $745.9 million, 24.5% below this point last year.
Brevet also mentions a stand-out year for Paramount Pictures, which is pulling in 43% more cash than last year thanks primarily to John Krasinski's thrilling A Quiet Place and Cruise-bruiser Mission: Impossible – Fallout.
A deluge of films left theaters at close of business August 31, chief among them was Black Panther, which ended its historic 175-day domestic run with $700.06 million. Now can we stop bothering Chadwick Boseman to do the Wakanda Forever pose?
Moving on.
This past weekend, September 7 – 9, saw The Nun and Peppermint – a pair of darker, more Autumn-appropriate films – wrestle the box office lead away from the Summery silliness of Crazy Rich Asians and The Meg. The Conjuring franchise is far from dead, it seems.
Before we get to the weekend's results, let's have Steve Harvey remind the audience of my predictions and put twenty-five seconds on the clock:
- The Nun will open to $20-25 million.
- Peppermint will open to $8-12 million.
- God Bless the Broken Road will open to $4 million.
- Crazy Rich Asians drops 15% for $16-18 million.
- The Meg earns another $8 million.
- Mission: Impossible – Fallout earns another $5 million.
- Searching and Operation Finale both earn around $4-5 million.
- Christopher Robin earns another $4 million.
- Alpha earns $3.2 million.
- The Happytime Murders was all a sick joke and never actually happened, we were dreaming.
- BlacKkKlansman earns another $3.5 million.
- Mile 22 earns $2 million.
- Incredibles II earns $1.5 million.
- Kin crashes down to $1.5 million.
Now, let's look at the latest numbers, courtesy of BoxOfficeMojo.com.
The Numbers
Overall the weekend of September 7 – 9 is up 21.9% over the previous weekend – though it does lag behind the four-day total with Labor Day totals added in. Total box office receipts on Monday showed, with The Nun leading the pack, that North Americans spent $120,615,604 at the box office Friday to Sunday, $8 million shy of Labor Day weekend. That's a healthy bump in numbers, one that major studios hope continues throughout the rest of the year.
Here's the top ten and some honorable mentions:
- The Nun debuts with $53.8 million, more than enough to recoup its $22 million budget. It had a $13,882 average across 3,876 theaters. Solid numbers showing that the Conjuring franchise is by no means dead. I haven't seen a single one of these movies and have no intention of doing so, but if the people are happy with their spooky movies, let them be spooked. As of Sep 12 it's earned $64.6 million domestic and $109.1 million international for a $173.7 million worldwide total.
- Jennifer Garner's revenge flick, Peppermint, debuted to $13.4 million over the weekend. It held a $4,504 average across 2,980 screens. That's barely over half the film's modest $25 million budget. Jennifer Garner deserves more than what looks like a clichéd, dog-whistle-racist, insipid excuse of a revenge flick. As of Sep 12 it's earned $17.3 million domestic and *cough* $1.4 million international for an $18.7 million worldwide total.
- The prodigal film has fallen two spots and 40% – proving that it is indeed fallible. Sort of. Crazy Rich Asians pulled in $13.1 million over the weekend across a still massive 3,865 theaters (expect that to drop). This is the first weekend it's dropped over 20%, but that may be due more to the aforementioned Autumn-esque competition. As of Sep 12 it's domestic sits at $139.7 million, international at $31 million, and worldwide at $170.7 million. $140 million over the film's initial operating budget.
- Another top-five mainstay has dropped over 40%. Though it lost 250 screens, The Meg held strong through its fifth weekend, though, adding another $6.09 million to its domestic earnings. As of Sep 12 it has a domestic of $133 million, foreign of $364 million, and worldwide at $497.2 million. It'll cross that half-billion mark soon enough – don't you worry Jon Turteltaub.
- In fifth is inventive social media thriller, Searching, which dropped only 24.7% after 802 theaters were added to its run. It earned $4.5 million in its second weekend of wide-release. With a $2,275 theater-average, that's not bad at all. It's domestic now sits at $16.01 million, international at $18.1 million, and worldwide at $34.1 million.
- Finally ejected from the top five is Tom Cruise's shattered ankle in IMAX, Mission: Impossible – Fallout. It lost 305 theaters and dropped 44.7% as a result, but still earned $3.8 million on the weekend. That's enough for a $213.5 million domestic, a China-boosted $522.2 million international, and a series-high $735.8 million worldwide. But none of that matters, because the film still hasn't passed Mission: Impossible II in North America. It's only two million away from passing it. Oh, but don't look at the franchise grosses adjusted for inflation – J.J. Abrams is the only loser on that list.
- Disney's Christopher Robin is still a thing. People just can't get enough of either Ewan McGregor or Winnie the Pooh. Or both. It earned another $3.4 million domestic after losing 407 theaters and dropping 35.5%. As of Sep 12 it has earned $92.8 million domestic, $51.4 million foreign, and $144.2 million worldwide. This is a solid performance, hampered only by the prevalence of Summer blockbusters on the roster.
- Operation Finale, the WWII movie, dropped 52.3% for $2.5 million dollars. So far its domestic total is $14.9 million, about ten million shy of its $25 million budget.
- Spike Lee's leggy BlacKkKlansman only dropped 37.9%, letting it haul in another $2.6 million. Sep 12 domestic total is $44.4 million, $22.2 millon international, and $66.6 million worldwide. John David Washington may not be a household name yet, but he will be.
- Rounding out the top ten is Alpha, the boy-meets-wolf doggy movie. It dropped 44.6%, losing 360 theaters, but managed to add another $2.5 million to the bank. As of Sep 12 it's earned $33.1 million domestic, $28.09 million international, and $61 million worldwide. Tack on marketing costs to its $51 million production budget and it looks shaky as to whether or not Alpha is breaking even or squeaking out a profit.
Some honorable mentions.
God Bless the Broken Road, of which I still know absolutely nothing, debuted to $1.3 million domestic. Which is . . . good?
Incredibles II, Mile 22, Hotel Adam Sandler 3, and The Happytime Murders all earned between $1-1.3 million. Incredibles II continues its historic run, Adam Sandler 3 is still there, and Happytime Puppet Fucking dropped 75.3% and won't come close to breaking even on its $40 million budget. Melissa McCarthy, please do better. You're better than this post – Hangover shock-comedy. Bridesmaids may have followed the Apatow formula a bit too religiously, and modern comedies may all be light action/dramas starring half the cast of SNL, and I know Paul Feig is directing thrillers now, but . . . fuck it. Movie comedies are in remission.
As far as my predictions go, I underestimated or overestimated everything. The Nun doubled my estimate; Peppermint came in a million over my high estimate; God Bless the Broken Road made $2.5 million less than my guess; the one time I figure Crazy Rich Asians drops 15% or less, I'm wrong; The Meg earned two million less; M:I – 6 didn't pass M:I-II; and everything else earned about a million less than my estimate – which would be fine if that didn't constitute a 25% margin of error with these low-earners.
Alright, enough of that. Let's speculate on this coming weekend's numbers – if it isn't too late to do so.
The Nun kicked off the Fall movie-season well enough, but we have a slate of anticipated movies dropping on Friday (today). Most notable among them are Shane Black's controversial The Predator, Anna Kendrick and Blake Lively picture A Simple Favor, Matthew McConaughey's latest White Boy Rick, and Unbroken: Path to Redemption – the sequel to director Angelina Jolie's 2014 film, Unbroken with added religious pandering.
So, some predictions.
- The Predator plays like Alien: Covenant and earns $30-35 million. A respectable R-rated opening.
- The Nun stays at number two and pulls in $20-25 million.
- I like Blake Lively and Anna Kendrick, so let's say A Simple Favor opens to a third-place $15-20 million?
- I don't expect Crazy Rich Asians to leave the top five. It will drop to fourth place and earn $10 million.
- Apparently Studio 8 expects McConaughey to draw in $8-10 million for White Boy Rick. I'm saying no. Give me "The Renaissance is Over" for $5-8 million, Alex.
- Christian movies may be infuriating, they may be propaganda made to proselytize rather than to tell a story, but they make money. I assume Unbroken: Path to Redemption to earn between $4-6 million.
- Peppermint has one or two more solid weekends ahead – probably earning $6-7 million.
- The Meg will drop further from all this new competition, probably earning only $3 million.
- Searching will hang tight with another $3 million.
- And closing out the top ten will be Mission: Impossible – Fallout. It will pass M:I-II, it doesn't have a choice. Physical ticket-sales and inflation don't matter to me, just the numbers. And here's hoping China keeps shoving it toward the big billion. Can't have this franchise losing steam. Expect a $1.5-2.5 million domestic weekend, though.
And that's all I care to talk about.
If you've stuck around this far, go ahead and share this or like it or something. It's called a "call-to-action," by the way – when YouTubers and magazines and all of those smiling faces and snarky beat-writers ask you to further engage with their material. No, dear reader, do not judge and disseminate our content because you find it of high merit or quality as a product – do it because we ask you to.
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Until next time!


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VW Amarok LWB Canopy
Such is its comfort and quality that the VW Amarok bakkie is more popular as a lifestyle bakkie than a… read more
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Tough and Durable
You expect the workhorse Volkswagen Amarok single cab bakkie to be tough and durable and you would expect no less from the Amarok LWB canopy for sale from us. So it proves, because for every canopy for sale from Andy Cab, we use precision moulds, a UV-resistant gel coat to prevent peeling or discolouring. We guarantee the shell for 3 years and the mechanical parts for 1 year. The 6-week adjustment service is free too, as are six 6-monthly lubrication services.
Add Some Class
To add some class to your VW Amarok single cab canopy, you can have the windows treated with anti-smash-and-grab window tinting, or add a cab slider window or doggy/safety bars. A strengthened roof with a choice of roof racks and a polyurethane bin liner are available too, so your canopy can work just as hard as your Volkswagen.
Optional Features & Extras
- Curved rear glass door
- Fibreglass rear door with glazed rear window
- Dual side locking mechanism
- Spoiler with high level brake light
- Stylish roof side rails
- Integrated fresh air ducting
- Battery operated interior light
- Flush mounted side sliding windows
- Rubber glazed side mounted windows
- Safety glass (Smokey grey)
- UV resistant gel coat
- Colour matching with UV resistant paint
- Reinforcing of fibreglass roof for heavier loads
- Cabover Roof Racks
- Sporty Roof Racks
- Smash and Grab window tinting
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Before there were blogs there were these things called magazines, and the only metal magazine we still get excited about reading every month is Decibel. Here's managing editor Andrew Bonazelli…
If any band ever needed to run a "name our next album" contest, it's the Gates of Slumber. Indy's preeminent ripping doom trio are fixtures on not only Decibel's but plenty of metal mags/blogs' year-end best-of lists. Each successive record earns more acclaim as Karl Simon, Jason McCash and J. Clyde Paradis gradually fine-tune their righteous narco-trad metal assault. And yet, the titles of their last two records—2008's Conqueror and 2009's Hymns of Blood and Thunder—unintentionally evoke Jesu and Mastodon (they don't sound like either), and TGOS have done it again on new platter The Wretch (see: Kyuss), due out May 10 on Rise Above/Metal Blade. Hell, at least they're name-checking good bands.
Of course, that didn't stop us from commemorating Gates on the latest Decibel Flexi. The metallic silver-on-red slab is the most color that anything from Indiana has ever been afforded. As for the tune, it's the 2011 version of "The Jury," originally found on 2004 full-length debut …The Awakening. It's the longest dB Flexi to date at nearly seven minutes, meaning we had to press it at 33 1/3 rotation, as opposed to the conventional 45. (Brevity is the soul of shit, right?) Subscribers should have the issue within the next two weeks, but non-subscribers can order it here or simply try it on for size below.
The Gates of Slumber "The Jury" by Decibel Magazine
You can buy the June 2011 issue of Decibel here, or get a full subscription to ensure you never miss one of these awesome flexi discs!