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Blood ketone body levels increase during starvation and untreated diabetes. Here we tested the hypothesis that ketone bodies directly inhibit insulin action in skeletal muscle. We investigated the effect of d,l-β-hydroxybutyrate (BOH; the major ketone body in vivo) on insulin-mediated glucose uptake (2-deoxyglucose) in isolated mouse soleus (oxidative) and extensor digitorum longus (EDL; glycolytic) muscle. BOH inhibited insulin-mediated glucose uptake in soleus (but not in EDL) muscle in a time- and concentration-dependent manner. Following 19.5 h of exposure to 5 mM BOH, insulin-mediated (20 mU/ml) glucose uptake was inhibited by ∼90% (substantial inhibition was also observed in 3-O-methylglucose transport). The inhibitory effect of BOH was reproduced with d- but not l-BOH. BOH did not significantly affect hypoxia- or AICAR-mediated (activates AMP-dependent protein kinase) glucose uptake. The BOH effect did not require the presence/utilization of glucose since it was also seen when glucose in the medium was substituted with pyruvate. To determine whether the BOH effect was mediated by oxidative stress, an exogenous antioxidant (1 mM tempol) was used; however, tempol did not reverse the BOH effect on insulin action. BOH did not alter the levels of total tissue GLUT4 protein or insulin-mediated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 but blocked insulin-mediated phosphorylation of protein kinase B by ∼50%. These data demonstrate that BOH inhibits insulin-mediated glucose transport in oxidative muscle by inhibiting insulin signaling. Thus ketone bodies may be potent diabetogenic agents in vivo.
- ketone bodies
- soleus
- extensor digitorum longus
- glucose transporter 4
uncontrolled diabetes is associated with increased oxidation of free fatty acids (FFA), which results in accelerated ketone body [acetoaceate (AcAc), β-hydroxybutyrate (BOH), and acetone] production by the liver (17). On the one hand, ketone bodies can lead to acidosis (ketoacidosis) if excessive levels are reached in blood (18). On the other hand, they can be beneficial by serving as alternative energy substrates for key extrahepatic oxidative tissues (e.g., heart and brain) (17, 24, 34). Short-term starvation is another condition associated with elevated rates of FFA oxidation and marked elevations in blood ketone body levels (8). A common denominator between uncontrolled diabetes and starvation is insulin resistance (6, 9, 10), defined as diminished glucose transport by skeletal muscle in response to insulin. The elevated levels of FFA during uncontrolled diabetes and starvation can contribute to the insulin resistance (27). Indeed, it is well documented that FFA inhibit insulin-mediated glucose transport in skeletal muscle (1, 27, 32, 39). However, whether ketone bodies can cause insulin resistance in skeletal muscle is not clear.
Generally, early studies showed that acute exposure of rodent skeletal muscle preparations to AcAc or BOH did not alter insulin-mediated glucose uptake in a noteworthy fashion (4, 27). Similarly, short-term AcAc or BOH infusion did not alter whole body glucose disposal during hyperinsulinemia in pigs or humans (5, 21), where skeletal muscle accounts for ∼90% of insulin-mediated glucose disposal (10). Interestingly, subsequent studies demonstrated that, whereas acute exposure (4 h) to BOH did not alter insulin-mediated glucose uptake in cardiomyocytes, prolonged exposure (16 h) resulted in marked inhibition (31). These findings suggest that earlier studies with skeletal muscle reported a lack of effect of ketone bodies, owing to an insufficient exposure period. Indeed, starvation and untreated diabetes are associated with prolonged exposure to ketone bodies.
The purpose of the present investigation was to study the effect of BOH on glucose transport in isolated mouse muscle preparations. We demonstrate that prolonged exposure of mouse oxidative muscle to physiological concentrations of BOH diminishes insulin-mediated glucose uptake. Furthermore, the effect of BOH is mediated by interference with insulin signaling and not by altering the amount of GLUT4 protein levels.
Materials and animals.
2-Deoxy-d-[1,2-3H]glucose (2-DG), 3-O-[3H]methylglucose (3-OMG), and [carboxy-14C]inulin were from Amersham Biosciences. d,l-BOH, sodium salt, sodium (S)-3-hydroxybutyrate (l-BOH), (R)-(−)-3-hydroxybutyric acid (d-BOH), 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol), and 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) were from Sigma. Human insulin (Actrapid) was from Novo Nordisk. Antibodies against GLUT4 and GLUT1 were from Chemicon, and antibody against dihydropyridine receptor (DHPR) was from Abcam. Antibodies against the β-subunit of the insulin receptor (IR) were from Millipore, against tyrosine-phosphorylated IR (p-IR)(pY972) from Invitrogen, against insulin receptor substrate-1 (IRS-1) from Chemicon, and against tyrosine-phosphorylated IRS-1(p-IRS-1; pY612) from Invitrogen. Antibodies against malondialdehyde (MDA), nitrotyrosine, and phosphorylated protein kinase Cδ (p-PKCδ) were from Academy Bio-Medical, Upstate Biotechnology, and Cell Signaling Technology, respectively.
Male NMRI mice weighing 25–30 g were housed at room temperature with a 12:12-h light-dark cycle. Food and water were provided ad libitum. The mice were purchased from B & K Universal (Sollentuna, Sweden). Animals were euthanized by rapid cervical dislocation, and the soleus and extensor digitorum longus (EDL) muscles were isolated and incubated in Tyrode solution with the following composition (in mM): 121 NaCl, 5 KCl, 1.8 CaCl2, 0.4 NaH2PO4, 0.5 MgCl2, 24 NaHCO3, 5 glucose, and 1% bovine serum albumin (fatty acid free), unless indicated otherwise. The air phase in the vial containing the Tyrode solution was continuously gassed with 95% O2-5% CO2, resulting in a pH of 7.4 in the solution. EDL and soleus muscle weights ranged from 11 to 19 mg wet wt. All procedures were approved by the Stockholm North Ethics Committee.
Glucose uptake/transport.
Muscles were transferred to vials containing 1.5 ml of Tyrode solution with or without additions, incubated in a shaking water bath (110 oscillations/min, 25°C) for a total of 19.5 h (unless stated otherwise), and frozen in liquid nitrogen. The pH of the medium averaged 7.48 (7.42, 7.54; n = 2) at the beginning of the incubation and 8.12 (8.09, 8.15) at the end of the 19.5-h incubation period; BOH did not affect the pH at either the beginning (mean = 7.45, 7.44, and 7.46) or the end (mean = 8.12, 8.12, and 8.13). No medium changes occurred during the incubations. [It should be noted that glucose transport in isolated rodent muscles is constant at medium pH, ranging from 6.8 to 8.3 (28).] To control for the osmotic effect of BOH, 5 mM NaCl was always added to the Tyrode solution bathing the contralateral muscle. The low temperature was used to enhance viability of the muscle. We have shown previously that muscle viability is well maintained under such conditions, as judged by the ability to generate tetanic force (29). Furthermore, the extracellular space in muscles incubated for 19.5 h was virtually identical to those incubated for only 2 h (all muscles had values of 0.2–0.3 ml/g wet wt; BOH did not affect extracellular space under any condition studied). In all glucose uptake experiments, radiolabeled 2-DG (1 mCi/mmol 2-DG, 1 mM 2-DG; or 0.2 mCi/mmol glucose, 5 mM glucose) and inulin (1 μCi/ml medium) were present during the last 30 min of incubation, as described elsewhere (30). For measurement of glucose transport, radiolabeled 3-OMG (1 mCi/mmol 3-OMG, 1 mM 3-OMG) was present during the last 15 min of incubation (30). To assess the effects of BOH on insulin-mediated glucose uptake/transport, insulin (20 mU/ml) was added 90 min before freezing. Other modes of glucose uptake activation were also studied to assess specificity of BOH action. To examine the effects of BOH on hypoxia-induced glucose uptake, muscles were continuously gassed with 95% N2-5% CO2 during the last 90 min of incubation. AICAR is converted in the cell to AICAR monophosphate, which is an AMP mimetic that activates AMP-activated protein kinase (AMPK) and AMPK kinase (16). To examine the effects of BOH on AICAR-induced glucose uptake, 2 mM AICAR was added 110 min before freezing. To examine the role of reactive oxygen species in BOH effects on glucose uptake, muscle was incubated with 1 mM tempol, a stable, membrane-permeable nitroxide that acts as a scavenger of superoxide (15).
For analysis of 2-DG uptake or 3-OMG transport, frozen muscles were added to preweighed Eppendorf tubes containing 0.5 ml of 1 N NaOH. The muscle was weighed and then digested at 70°C for 15 min. The tubes were cooled on ice and centrifuged at 23,000 g for 5 min. Aliquots of the supernatant were added to scintillation cocktail and counted for 14C and 3H, as described earlier (30).
d-BOH dehydrogenase.
For analysis of d-BOH dehydrogenase activity (which converts d-BOH to AcAc), muscles were isolated and frozen in liquid N2. Muscles were homogenized with a motor-driven ground glass homogenizer in ice-cold buffer (20 μl/mg wet weight) consisting of (in mM) 50 TEA, 1 EDTA, 2 MgCl2, 2 dithiothreitol, and 0.05% Triton X (vol/vol), pH 7.5. The homogenate was centrifuged for 30 s at 1,400 g. The supernatant (50 μl) was assayed by following the d,l-3-BOH-dependent (20 mM) formation of NADH on a spectrophotometer at 340 nm at room temperature (3). Two types of blanks were used: 1) homogenization buffer and 2) reaction mixture lacking substrate. Both blanks changed insignificantly during incubation (60 min). Reaction rates were linear with respect to extract volume and assay duration (data not shown).
Western blots.
For Western blot analyses, muscles were incubated in Tyrode solution with or without BOH for 19.5 h and then frozen in liquid nitrogen. Insulin was present during the last 90 min in half of the samples. Blots were performed for GLUT4, GLUT1, IR, p-IR, IRS-1, p-IRS-1, DHPR, MDA, nitrotyrosine, and p-PKCδ. Briefly, frozen muscles were homogenized in ice-cold lysis buffer (40 μl/mg wet wt) consisting of (in mM) 20 HEPES (pH 7.6), 150 NaCl, 5 EDTA, 25 KF, 1 Na3VO4, 20% glycerol (vol/vol), 0.5% Triton X-100 (vol/vol), and 1 tablet protease inhibitor cocktail (Roche) per 50 ml. Lysates were cleaned by centrifugation for 10 min at 1,000 g. The protein content was determined using the Bradford assay (Bio-Rad). Aliquots of the lysate (20 μg) were then subjected to SDS-PAGE (12% Bis-Tris gels; Invitrogen). Proteins were transferred onto polyvinylidine fluoride membranes. Membranes were blocked in 5% (wt/vol) nonfat milk and Tris-buffered saline containing 0.05% Tween-20 followed by incubation with primary antibody and made up in 5% (wt/vol) nonfat milk (GLUT4, 1:5,000; IR, 1:200; p-IR, 1:1,000; IRS-1, 1:200; p-IRS-1, 1:1,000; MDA and nitrotyrosine, 1:1,000; p-PKCδ and DHPR, 1:500) overnight at 4°C. Membranes were then washed and incubated for 1 h at room temperature with secondary antibody (donkey anti-rabbit or donkey anti-mouse, 1:5,000). Immunoreactive bands were visualized using enhanced chemiluminescence (Super Signal; Pierce). Band densities were analyzed with Image J (http//rsb.info.nih.gov/).
Phosphorylation of protein kinase B.
Aliquots of supernatant protein (prepared as for Western blots; see above) were used for analysis of phosphorylated protein kinase B (p-PKB) and total PKB using the PathScan ELISA Kit (7160 and 7170, respectively; Cell Signaling Technology), following the supplier's test procedures.
Significant differences between means were determined with Student's t-test for paired samples. P < 0.05 was regarded as statistically significant. Values are presented as means ± SE.
Effect of BOH on basal and insulin-stimulated glucose uptake.
Exposure of soleus muscle to 5 mM BOH for 2 h did not affect glucose uptake in the absence (basal) or presence of insulin (Fig. 1A). However, following 9.5 h of exposure to BOH, the response to insulin was decreased by ∼50% and almost completely abolished after 19.5 h. The insulin effect on 2-DG uptake in the absence of BOH appeared to decrease as a function of time. Whether this is a real phenomenon or attributable to experimental variability is unclear. Noteworthy is that following 19.5 h of incubation in pyruvate in the absence of BOH, the insulin effect on 2-DG uptake was, in fact, relatively greater (see Fig. 5A) than after 2 h of incubation (Fig. 1A).
The effect on insulin action was concentration dependent, with half-maximal inhibition occurring at a BOH concentration of ∼2 mM (Fig. 1E). On the other hand, in EDL muscle, BOH did not affect glucose uptake after 2 or 9.5 h and only slightly decreased uptake in the presence of insulin after 19.5 h (Fig. 1B). Thus BOH has negative effects on glucose uptake primarily in oxidative muscle. In all subsequent experiments, muscles were incubated for 19.5 h in the absence or presence of 5 mM BOH.
BOH exists as d- and l-stereoisomers.
To determine whether differences between the two ligands exist, muscles were incubated in 5 mM d- or l-BOH. Only d-BOH showed a negative effect on insulin-mediated glucose uptake, and this was observed only in soleus (Fig. 1C) and not in EDL muscle (Fig. 1D). Thus, d-BOH, which is the primary stereoisomer in vivo (33), is the inhibitory moiety.
d-BOH is the substrate that is recognized by d-BOH dehydrogenase.
To determine whether the differential effects of BOH on EDL and soleus muscles could derive from differences in the capacity to utilize BOH, we measured the activity of d-BOH dehydrogenase. Activity in the EDL was detectable but low (0.03 ± 0.001 μmol·min−1·g wet wt−1; n = 3), whereas a robust activity was measured in the soleus (0.44 ± 0.07; n = 3). Heart, which is very oxidative and is known to have a high capacity to utilize BOH, had an activity of 2.5 μmol·min−1·g wet wt−1 (n = 1).
Effect of BOH on hypoxia- and AICAR-mediated glucose transport.
To study the specificity of the BOH effect, other modes of glucose uptake were also studied. Hypoxia and AICAR increase glucose uptake in skeletal muscle via insulin-independent pathways (12). Neither hypoxia- nor AICAR-mediated glucose uptake was significantly affected by BOH (Fig. 2, A and B).
Effect of BOH on total GLUT4 expression, insulin signaling, and glucose transport.
Since the effects of BOH on insulin-mediated glucose uptake were most marked at 19.5 h, the latter incubation duration was used in subsequent experiments to investigate how BOH exerts its effects. The reduction in insulin-stimulated glucose uptake by BOH could result from decreases in the expression of GLUT4 transporters or decreases in activity of the signaling molecules that recruit GLUT4 transporters to surface membranes; the latter case would indicate that BOH was specifically inhibiting the transport of glucose as opposed to its metabolism, i.e., phosphorylation. To address these possibilities, we first determined the total GLUT4 protein levels in control and BOH-treated muscles. Figure 3, A and B, shows representative Western blots of GLUT4 content in soleus and EDL muscles. The densitometric evaluation of the blot revealed that the total GLUT4 expression was not affected by BOH under any condition studied (Fig. 3). GLUT1 expression was also not affected by BOH (control soleus plus insulin = 4,129 ± 584 arbitrary units, BOH soleus plus insulin = 4,142 ± 405; n = 4 for each group).
Insulin induced marked increases in the levels of p-IR and p-IRS-1 in soleus muscle, and BOH did not alter the response (Fig. 4, A and B). In contrast, BOH inhibited insulin-mediated phosphorylation of PKB in soleus muscle by ∼50% (Fig. 4C). Again, BOH did not alter the insulin effect in EDL muscle (Fig. 4D). Insofar as insulin signaling was diminished by BOH in soleus muscle, one would expect a similar effect of BOH on glucose transport and GLUT4 translocation to surface membranes. Indeed, BOH also inhibited insulin-mediated glucose (3-OMG) transport in soleus but not in EDL muscle (Fig. 4, E and F). Moreover, 3-OMG transport in response to insulin also reflects the degree of insulin-mediated GLUT4 translocation to surface membranes in isolated rodent muscle preparations (19, 36). Thus the results indicate that BOH inhibits insulin-mediated glucose transport in soleus muscle by interfering with insulin signaling and not by altering the total availability of GLUT4 transporters.
Role of glucose metabolism, reactive oxygen species/reactive nitrogen species production, and p-PKCδ in BOH-induced insulin resistance.
To assess whether BOH-mediated inhibition of insulin action requires the presence or metabolism of glucose, muscles were incubated with 2 mM pyruvate instead of 5 mM glucose in the Tyrode solution. In soleus muscles, the inhibition of insulin-mediated sugar uptake also occurred when glucose was excluded from the medium (Fig. 5A). Again, no noteworthy effect was seen in EDL muscle (Fig. 5B). (Note that sugar uptake was measured with 1 mM 2-DG; hence, the lower rates of glucose uptake compared with 5 mM glucose elsewhere.)
BOH and AcAc induce reactive oxygen species (ROS) production in isolated cardiomyocytes and erythrocytes (14, 25), and excessive ROS production has been implicated in insulin resistance (7, 13). Therefore, we investigated whether ROS production plays a role in ketone body action by using the antioxidant tempol. Soleus muscles were coincubated with BOH and tempol for 19.5 h. If BOH decreases the effect of insulin on glucose uptake (see Fig. 1) via increased ROS production, then tempol would be expected to increase glucose uptake in the presence of insulin and BOH. However, incubation with tempol did not reverse the BOH-mediated inhibition of insulin-mediated glucose uptake in soleus muscle (Fig. 5C), nor did it affect transport in EDL muscle (Fig. 5D).
To more directly assess whether BOH induced ROS/reactive nitrogen species (RNS)-mediated alterations in protein structure, we used antibodies against MDA-protein adducts and nitrotyrosine. BOH did not affect MDA-protein adducts (Fig. 6A) or nitrotyrosine content in soleus (Fig. 6C) or EDL muscle (Fig. 6, B and D). These data do not support a role for excessive production of ROS/RNS in the inhibitory effect of BOH on insulin action.
Recently, activation (phosphorylation) of PKCδ was implicated in inhibition of insulin-mediated phosphorylation of PKB (35). Therefore, experiments were performed to investigate whether BOH altered the phosphorylation state of PKCδ. BOH did not alter p-PKCδ levels either in the absence of insulin (control = 0.88 ± 0.09, BOH = 0.87 ± 0.07; n = 5; units are density of p-PKCδ/DHPR) or in its presence (control = 1.05 ± 0.08, BOH = 0.97 ± 0.04; n = 3).
The major findings of the present study are that 1) prolonged exposure to physiological concentrations of BOH diminishes insulin- but not AICAR- or hypoxia-mediated glucose uptake in oxidative muscle, 2) the inhibitory effect of BOH is associated with diminished PKB phosphorylation, and 3) the development of insulin resistance by BOH is not associated with excessive ROS/RNS production.
Plasma ketone body concentrations vary greatly depending on the nutritional or pathological state. In healthy individuals, the BOH concentration is usually <0.2 mM, but during prolonged starvation and uncontrolled diabetes it can increase to 7–10 mM (11, 23). Thus the concentration of BOH used in the present study (5 mM) is clearly within the range observed in vivo.
The finding that the BOH effect on insulin-mediated glucose uptake was time dependent and expressed primarily in oxidative muscle may explain the general inability of earlier studies to document inhibitory effects of ketone bodies in skeletal muscle (see introduction), although one study did show that AcAc inhibited the insulin-mediated removal of glucose from the medium by isolating rat soleus muscle (20). The former studies either employed short-time exposure to ketones or measured whole body glucose disposal in response to insulin, which will reflect both oxidative and glycolytic muscles (4, 5, 21, 27). However, our findings are consistent with those observed in isolated rat cardiomyocytes (highly oxidative cells), where the decreased insulin effect on glucose uptake was also time dependent (31). Indeed, there are, despite the differences in preparations (cardiomyocytes vs. intact skeletal muscle preparations), several other similarities in the results. For example, BOH did not alter GLUT4 protein levels or insulin-mediated phosphorylation of the insulin receptor and did inhibit insulin-mediated PKB phosphorylation (26, 31). On the other hand, there were some differences as well. Thus, in cardiomyocytes, BOH inhibited insulin-mediated phosphorylation of IRS-1 and appeared to induce oxidative stress (25, 26), which differed from the current findings.
Although the time course of reversal of the BOH effect was not addressed in the current study, this was examined earlier in cardiomyocytes. There it was shown that ∼8 h were required to normalize insulin action following removal of BOH (31).
How prolonged exposure to BOH results in insulin resistance is not clear. In skeletal muscle, neither ROS/RNS nor phosphorylation of PKCδ appears to be involved. But it seems likely that the mitochondrial enzyme d-BOH dehydrogenase (which converts d-BOH to AcAc) is required to mediate the BOH effect. This is supported by the observation that l-BOH (which is not recognized by d-BOH dehydrogenase as a substrate) was ineffective in inducing insulin resistance, whereas d-BOH was effective. Moreover, BOH had no noteworthy effect on insulin action in EDL (glycolytic) muscle, which can be attributed to either the low amount or lack of detectable d-BOH dehydrogenase activity in glycolytic mammalian muscle (3, 37, 38). This was also the case in the present study, where activity was low in the EDL and about 15-fold higher in soleus. Thus mitochondrial metabolism of BOH is involved in transducing the inhibitory effect of BOH on insulin-mediated glucose transport in oxidative muscle.
2-DG glucose uptake technically reflects the sum of glucose transport and phosphorylation by hexokinase. In an earlier study, it was shown that exposure of isolated rat soleus muscle to AcAc decreased insulin-mediated glucose uptake, with no effect in EDL muscle (i.e., similar to the findings of the present study) (20). These investigators provided evidence supporting the idea that AcAc resulted in the inhibition of glucose phosphorylation (i.e., hexokinase) and that this contributed to the negative effect of BOH on insulin-mediated removal of glucose from the incubation medium. These authors demonstrated that AcAc significantly increased muscle citrate levels and that this was associated with large increases in glucose 6-phosphate levels, supporting the involvement of the Randle hypothesis (citrate inhibits phosphofructokinase, resulting in an accumulation of glucose 6-phosphate, which will inhibit hexokinase and, hence, glucose uptake). The latter hypothesis is often used to explain how FFA result in inhibition of glucose phosphorylation and glucose transport (23, 27). Noteworthy, however, is that Maizels et al. (20) also demonstrated that incubating soleus muscle in glucose-free medium containing AcAc and insulin did not result in an accumulation of citrate or glucose 6-phosphate. The current experiments demonstrate that, even when soleus muscle is incubated in glucose-free medium, insulin-mediated glucose (2-DG) uptake is still abolished by BOH (see Fig. 5), which indicates that BOH does not affect glucose uptake via the Randle hypothesis. Moreover, the experiments with 3-OMG demonstrate that BOH specifically interferes with the transport step, most likely by interfering with insulin signaling (as judged by diminished insulin-mediated PKB phosphorylation).
In this context, it is of interest to compare the effects of FFA and BOH on insulin-mediated glucose transport. Although FFA can exert inhibitory effects on insulin-mediated glucose transport within 1 h (27), there is usually a time-dependent component that can continue for up to 18 h in isolated rat soleus muscle preparations (1, 32). Thus, in this respect, the effects of FFA and BOH are similar. Earlier, it was shown that FFA and ketone bodies inhibit glycolysis, and this was believed to be a consequence of elevated citrate levels (23, 27). However, it appears unlikely that the citrate mechanism applies to the BOH effect in the present study (see above).
The data in the present study suggest that BOH exerts its inhibitory effect on insulin action by altering mitochondrial metabolism that ultimately results in the inhibition of insulin signaling in oxidative muscle. The fact that the time dependency of the BOH effect is so prolonged leads us to speculate that the synthesis/degradation of a specific protein(s) is involved. However, it is unlikely that BOH has a generalized negative effect on protein synthesis/degradation, as evidenced by the finding that the expression of GLUT4 and insulin-signaling proteins was unaffected. Similarly, the expression of contractile proteins and ion channels (e.g., DHPR; see Fig. 3) appeared to be unaffected, as judged by lack of a BOH effect on muscle function. Thus 18-h exposure to 5 mM BOH did not negatively affect tetanic force in isolated muscles measured at 70 Hz (control = 152 ± 10 mN, BOH = 162 ± 34 mN; n = 3).
The findings of this study raise the question of why BOH can be simultaneously beneficial (as a substrate) and detrimental (causing insulin resistance) in the same tissue (skeletal muscle). The answer may be considered within the context of the thrifty gene hypothesis (22). The essential idea behind this hypothesis is that during the period of hunters and gatherers, humans who were exceptionally efficient in the intake or utilization of foods had a better chance of surviving periods of famine. During starvation or calorie restriction, muscle insulin resistance would be beneficial by channeling circulating glucose to critical tissues (e.g., brain). Ketones, together with FFA, would then supply the muscle with necessary substrate while at the same time inhibit glucose uptake. However, during the hunter/gatherer period there were larger fluctuations in nutrient availability, and people were more physically fit. Thus the potential negative effects of ketones were probably minimal. Nowadays nutrient availability is essentially unlimited, and people are generally less physically fit, especially in Western societies. Therefore, the danger of ketosis would be relegated mostly to uncontrolled diabetes, calorie restriction, or various ketogenic diet therapies. These events can last for weeks, months, or longer and therefore contribute to the symptoms seen in insulin-resistant states (e.g., the metabolic syndrome and related conditions). This would make ketone bodies bona fide physiological diabetogenic agents. Thus deciphering the mechanism behind ketone body-induced insulin resistance could prove useful in furthering our understanding of insulin resistance and associated diseases (e.g., type 2 diabetes).
In conclusion, our data demonstrated that prolonged exposure to BOH inhibits insulin-mediated glucose uptake in a concentration- and time-dependent manner in oxidative muscle. The BOH effect appears to require mitochondrial metabolism that ultimately results in the inhibition of insulin signaling. Thus ketone bodies may be potent diabetogenic agents in vivo.
The present study was supported by the Swedish Research Council, the Swedish Diabetes Foundation, the Swedish Center for Sports Research, and funds at Karolinska Institutet.
No conflicts of interest, financial or otherwise, are declared by the authors.
- Copyright © 2010 the American Physiological Society


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I was dragged screaming and kicking into reading PvP. Then again, I was dragged screaming and kicking into reading Sluggy Freelance (which I no longer read, due to an inane storyline followed by a complete change of venue that has lasted for months now). Basically, my roommate and I came to an agreement. He'd read several webcomics that I enjoy (such as College Roomies from Hell and occasionally Clan of the Cats) and I'd read PvP. Mostly, it was due to the fact he'd read the updates on my computer so PvP was there… and he'd find it funny and try to get me to read it.
Eventually it worked. And while I might disagree with Scott Kurtz's opinions on Keenspot and certain other things… well, the man knows how to draw an amusing and interesting comic strip. Which brings you to Thursday's PvP. The Miranda plot had seemingly been shelved for a while. Miranda was working in Max's shop (sort of the evil opposite to Jade, her sister) and had little opportunity to stress out Brent with her evil plan to seduce him away from Jade. So her appearance out of the blue was a bit of a surprise yesterday, as was today's update as well.
We catch Brent and Jade on the tale-end of an argument about Brent "cupping Miranda's breast" and with no real knowledge of what Jade had accused him of. It's easy enough to understand, though, even without hearing each word of the argument. The masterstroke, of course, is the final panel. Just about any guy out there knows what it's like to accidentally catch a feel of a girl's breast, whether it's from catching the girl when she trips or tickling her ribs or even just rough-housing around. And despite Brent's devotion to Jade and knowledge of Miranda's motives… he can't help but remember what it felt like to be holding Miranda, and feeling that breast in his hand. Most funny. And most real. Congratulations, Scott, you continue to excel.


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1. Which of the following search belongs to totally ordered plan search?
a) Forward state-space search
b) Hill-climbing search
c) Depth-first search
d) Breadth-first search
View Answer
Explanation:Forward and backward state-space search are particular forms of totally ordered plan search.
2. Which cannot be taken as advantage for totally ordered plan search?
a) Composition
b) State search
c) Problem decomposition
d) None of the mentioned
View Answer
Explanation:As the search explore explore only linear sequences of actions, So they cannot take the advantage of problem decomposition.
3. What is the advantage of totally ordered plan in constructing the plan?
a) Reliability
b) Flexibility
c) Easy to use
d) All of the mentioned
View Answer
Explanation:Totally ordered plan has the advantage of flexibility in the order in which it constructs the plan.
4. Which strategy is used for delaying a choice during search?
a) First commitment
b) Least commitment
c) Both a & b
d) None of the mentioned
View Answer
Explanation:The general strategy of delaying a choice during search is called a least commitment strategy.
5. Which algorithm place two actions into a plan without specifying which should come first?
a) Full-order planner
b) Total-order planner
c) Semi-order planner
d) Partial-order planner
View Answer
Explanation:Any planning algorithm that can place two actions into a plan without specifying which should come first is called partial-order planner.
5. How many possible plans are available in partial-order solution?
a) 3
b) 4
c) 5
d) 6
View Answer
Explanation:The partial-order solution corresponds to six possible total-order plans.
6. What is the other name of each and every total-order plans?
a) Polarization
b) Linearization
c) Solarization
d) None of the mentioned
View Answer
Explanation:Each and every total order plan is also called as linearization of the partial-order plan.
7. What are present in the empty plan?
a) Start
b) Finish
c) Modest
d) Both a & b
View Answer
Explanation:The 'empty' plan contains just the start and finish actions.
8. What are not present in start actions?
a) Preconditions
b) Effect
c) Finish
d) None of the mentioned
View Answer
Explanation:Start has no precondition and has as its effects all the literals in the initial state of the planning problem.
9. What are not present in finish actions?
a) Preconditions
b) Effect
c) Finish
d) None of the mentioned
View Answer
Explanation:Finish has no effects and has as its preconditions the goal literals of the planning algorithm.
10. Which can be adapted for planning algorithm?
a) Most-constraint variable
b) Most-constraint literal
c) Constraint
d) None of the mentioned
View Answer
Explanation:The most-constraint variable heuristic from CSPs can be adapted for planning algorithm and seems to work well.
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When I realized that there were far too many discussions and questions floating around in free Facebook groups than I could possibly have time to answer, I decided to narrow my attention down to people that were truly serious about starting up their dog training businesses in the next 12 or so months. Those that want to make their hobby into a career. Those that are ready to invest in the business side of their profession as well as their dog training education. I offer online email courses, but nothing beats personal, productive discussions amongst like-minded individuals and weekly coaching like I'm offering through this community.
This is the community I wish I had when I was first starting out.
Features of The Modern Dog Trainer Society – A Dog Training Business Support Group (Only $9.99/Month)
Weekly 1-Hr AMA (Ask Me Anything) Coaching Thread – In this weekly Q&A I'll sit down for one hour and you'll have my undivided attention so I can answer your most pressing questions. I'll help guide you through important decisions with step-by-step advice so you'll have the right information you need to make decisions for your business with confidence. Of course, you can brainstorm, discuss ideas, and ask questions with everyone else in the group the rest of the week as well!
Brainstorm & Collaborate with Other Like-Minded Professional Dog Trainers – The Modern Dog Trainer blog and podcast has a wonderful following of dedicated dog trainers that you'll be able to connect and network with. We're a positive bunch and we all want to see each other succeed. This group is closely monitored to ensure it continues on this way, too! You'll never hesitate to share your challenges with this supportive group of like-minded trainers so you can answers, stay motivated, and reach your goals.
Monthly Focus Discussion Topic – Each month we'll vote on a topic or challenge that everyone is experiencing in their businesses so we can address it head on. I'll share exclusive articles and resources for you to look at and we'll talk about this topic in the weekly AMA.
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Eligibility to Be Interviewed on The Modern Dog Trainer Podcast – Once a month we'll draw a name at random and invite them onto the Podcast for an interview. Talk about your process, current challenges, and promote your dog training business.
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A:Sorry we cannot give you the broker's number. Contact the live help person as she might have answers to your questions about Daniel Tosh Tickets.
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New Nats 1st baseman Adam LaRoche looks like Bryce Harper, but only during deer season
(I grabbed this photo from Nationals Enquirer (with love!) who grabbed it frin BuckCommander.com.) The Washington Nationals signed free agent 1B Adam LaRoche to a 2 year contract that will pay him at $16 million. They probably overpaid, which Thomas Boswell says is the cost of being cheap in the past. Whatever. As Nationals


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We have put together this great range of Private Area Screens at Panel Warehouse which are perfect for creating additional areas within a larger space. These spaces can be used for a variety of activities or uses, including office areas, reception areas and school areas. All of these Screens for Private Areas have been built to withstand the rigours of busy environments so you are assured of the high durability and long-lasting performance from all Panel Warehouse products. No matter what your requirement or environment we have a screen to suit your needs, each of these Private Area Screens are available in a range of sizes and colours to fit into any space. Take a look at this great collection of Private Area Screens at Panel Warehouse all available to buy online.
You may also be interested in our other collections of Screens and Dividers that may suit your requirements including Displays for Exhibitions and Folding Display Boards, all of which are ideal for creating additional areas within an environment.
When it comes to dividing space in the classroom we have a room divider and partition solution to suit your requirements. All Panel Warehouse Screens are manufactured in our Manchester factory in 3-5 working days, we also offer a Next Working Day service on select range of our most popular sizes and colours. All screens have a pinnable surface and can be used to display school course work at exam presentations as well as displaying posters at Open Days and Events. We offer a wide range of sizes and colours and all screen and partitions include free support feet. Delivery to all UK Mainland destinations on orders over £100 + VAT is free of charge. We accept School, College and Local Authority Purchase Orders.


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Alistair Croll, VP
CloudOps Research, co-hosts t…
Parlons-en du Cloud
Alistair Croll, VP
WebCom Montreal
Cloud Adoption Conference
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November 13, 2012
CloudOps vice president of business development Pierre-Luc Bisaillon will present on the panel "Data in the Cloud — Economical and Secure". For more information and registration visit…
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October 15-16, 2012
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CloudOps vice president of Research, Alistair Croll, and CloudOps CEO, Ian Rae will join a panel of Cloud industry experts and top CIOs for a panel discussion on Cloud technology innovation and its impact on the Canadian economy. Register for the event her…
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Elveden Inn
Select your stay dates to check availability at Elveden Inn
Elveden Inn
About the Hotel
Property Location
When you stay at Elveden Inn in Thetford, you'll be within the vicinity of Go Ape Thetford. This 5-star inn is within the region of Bury St Edmunds Art Gallery and Abbeygate.
Stay in one of 4 guestrooms featuring flat-screen televisions. Complimentary wireless Internet access keeps you connected, and digital programming is available for your entertainment. Private bathrooms have complimentary toiletries and hair dryers. Conveniences include coffee/tea makers, and cribs/infant beds can be requested.
Rec, Spa, Premium Amenities
Take in the views from a garden and make use of amenities such as complimentary wireless Internet access and wedding services. Additional amenities include a picnic area and barbecue grills.
Enjoy a satisfying meal at a restaurant serving guests of Elveden Inn. Quench your thirst with your favorite drink at a bar/lounge.
Business, Other Amenities
The front desk is staffed during limited hours. Free self parking is available onsite.
Hotel Facilities
- Wedding services
- Front desk (limited hours)
- Garden
- Free self parking
- Bar/lounge
- Smoke-free property
- Free breakfast
- Free WiFi
- Number of floors - 2
- Barbecue grill(s)
- Total number of rooms - 4
- Restaurant
- Picnic area
Room Facilities
- Coffee/tea maker
- Digital TV service
- Flat-panel TV
- Cribs/infant beds available
- Hair dryer (on request)
- Free toiletries
- Private bathroom
- Free WiFi
Hotel Policy
Know Before You Go
- Guests can arrange to bring pets by contacting the property directly, using the contact information on the booking confirmation.


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- Please select a date to see the proper prices!
Description of the accommodation:
Rooms, services Are you looking to reserve a room in Mexico? Hotel Portonovo Plaza Puerto Vallarta is pleased to host guests booking on RevNGo.com. Guests looking for accommodation in Puerto Vallarta are welcome to book 45 nicely furnished rooms at the hotel. The bar provides a nice atmosphere for a romantic evening talk or a personal meeting. You can secure your valuables in the safe. You can find the exact list of services provided by Hotel Portonovo Plaza Puerto Vallarta (including those for extra fees) and the exact equipment of the rooms on the information sheet below.
Payment Advance bank card payment or credit card guarantee may be required for the reservation, depending on the chosen date, room and price.
Arrival, opening hours The earliest arrival time is 15:00, the latest time to leave the rooms is 12:00. You will be able to speak with the personnel in Spanish and English languages.
Hotel Portonovo Plaza Puerto Vallarta rooms Rooms
- Please select a date to see the proper prices!
Accommodation services
- Pool (Outdoor - seasonally open)
Bar, Elevator, Safe deposit box, Roof garden
Hairdryer, Desk in the room


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Kettle Kin
EditBOSS - KETTLE KIN
Kettle Kin is a pretty easy boss. He only has about 1200 hp, which is nothing at this point in the game. Hit him with a couple of physical attacks quickly though, because he casts Lucid Barrier early on in the fight, and then will continue to do so. This makes him invulnerable to physical attacks, so you'll have to kill him with magic. He has no elemental weakness, so use whatever you have at the highest level. He'll go down after just a few spells, and rewards you with a Bow's orb.
Top Wiki Contributors
Need assistance with editing this wiki? Check out these resources:


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- Please select a date to see the proper prices!
Description of the accommodation:
Rooms, services Super 8 Gardner would be glad to host you for a memorable journey in Gardner. The hotel is offering 56 comfortable rooms to guests looking for accommodation in Gardner. To learn more about the exact range of services of Super 8 Gardner (including services for an extra fee) and the exact equipment of the rooms, please check the information sheet below.
Payment Advance payment by credit card or providing credit card guarantee may be necessary for finalizing the reservation, depending on the chosen date, room and price.
Arrival, opening hours The earliest check-in time is 14:00, the latest check-out time is 11:00. The personnel is at your service in English.
Super 8 Gardner rooms Rooms
- Please select a date to see the proper prices!
General Policies
from 14:00 o'clock
Check out
until 11:00
Spoken languages
Accepted bank cards
MasterCard, VISA, Diners Club, Amex
Local tax
Please check the details of the selected price.


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Among the Easter festivities at the Shop Teacher household yesterday, was a nice play session with a whole big bin of diecasts, both my daughters, and myself. It was pretty great. I thought I had cleaned them all up, but the wee one apparently absconded with these two Micros. The blue '59 Chevy convertible was mine from childhood, but the big one charmed me out of it.
The pink disco-Camaro was actually my mom's. She was a huge enabler of my diecast collection as a kid, especially my Micro Machines. The pink ones always went to her. After she passed away, my wife put her Mom's collection on our kitchen window sill. When my daughter got old enough to ask for them, they became hers. Nothing makes me smile more than seeing one of my daughters play with a pink Micro Machine. I sure wish they could've met their grandma.
Here they were as I found them last night.
And then again when I got home today, I found them slightly rearranged.
I think they make an interesting pair.


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The Daytona 100 – 1959
J Louis Frey
Smashwords Edition
Text copyright 2012 J Louis Frey
All Rights Reserved
Smashwords Edition, License Notes
This ebook is licensed for your personal enjoyment only. This ebook may not be re-sold or given away to other people. If you would like to share this book with another person, please purchase an additional copy for each recipient. If you're reading this book and did not purchase it, or it was not purchased for your use only, then please return to Smashwords.com and purchase your own copy. Thank you for respecting the hard work of this author.
To those who drove open wheel auto racing cars during the 1950's and 1960's.


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We are just days away from the official launch of Realm of the Underworld as the toy line goes up for pre-order on Friday. You may recall me talking about this line several times in the past few months, back when it was called Warlords and Warriors. The line has underwent a few name changes, but ultimately it remains the same. Great old school styled figures, with improved modern construction. The best part is that it's just about here! And today have I got an exclusive for you.
It's a sneak peek at the front of the card. This is what the figures will come packed on. Zoloworld has already revealed the back of the card, but we got the first look at the new front of the card. It looks incredible. Very retro and in with the vibe that they're trying to attain. I particularly like that it mentions that it "plays with all other 5 3/4 fantasy figures" which is something Remco would often put on their cards.
These dudes go up for preorder on Friday at UnderworldFigures.com. They have a lot of neat stuff planned for this line and orders are expected before Christmas. I can't wait!
One Response to Realm of the Underworld Exclusive Reveal
These are cool, not psyched about Hercules, but these three above are nice. I'm big fan of MOTU from the beginning and I had a couple of Remco's Warlord figures. I'm glad folks are keeping this style alive.


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Thread: how to autologin xdmcp display
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02-19-2010 #1
- Join Date
- Oct 2008
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- 9
how to autologin xdmcp display
I am building a thin-client like an X-terminal which boots from PXE, runs an X server, opens gdm session and displays some statistics page in a browser.
So far it boots and runs X server and gets the screen attached to server by XDMCP and displays Gnome logon screen but I want it to log in automatically or attach to some session and I dont know how to do this
The idea is to have a bunch of such dumb devices, like a platform to run various info displays, barcode access stations, etc - plug it in, it boots small linux from PXE and after 30 seconds it comes up and displays a screen with specific app or a full screen browser page according to configuration for each MAC address of the device.
I dont want to run apps locally as the thin-clients themselves are too old and too weak for other than presenting a screen.


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General Details
Bel Canto Singing and Music Academy is celebrating it's 12th year of operation in Rockhampton. Owner Linda Coombes is joined by a team of professional, Conservatorium trained staff; Liz McNally (Singing), Karen Clifford (Singing), Lee Dawson (Singing), Zoe H (Singing) Gabby Hanlon (Acting & Drama), Danielle Boto (Violin & Keyboard), Tauren Vincent (Guitar), Tom K(Percussion), Steve Kumar (Jazz & Modern Keyboard/Piano) and Mary Steer (Classical Piano).
Lessons are usually individual (one on one) for 30 minutes or 1 hour sessions. Group lessons of 3 or more are available with prior arrangement with the teacher of the instrument.
Drama classes are for ages 5 – 9, 10 – 13 and 14 – 18 year. 5 – 9 years is a half hour class and cost $7 per person per half hour session. Ages 10 – 13 and 14 – 18 are one hour class and cost $10 per person per 1 hour session.
These details were last updated on May 2, 2012


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Skip to comments.Robert Redfords Terrorist Heroes
Posted on 04/16/2013 9:28:32 AM PDT by Perseverando
ALL OF IT, said Robert Redford, when asked if he supported the bombings by The Weather Underground.
Redford came out for terrorism on a mainstream morning television show in an interview with democrat-operative-leftist-hack George Stephanopoulos, who was slobbering over Redfords pro-terrorist movie, The Company You Keep. I drew my illustration of Redford, below, days ago, and I wonder if hes for the terrorist attack in Boston today. Or maybe he wants to wait and see if its leftist terrorists before he decides hes all for it. Below is a list of what Robert Redford was for, via Sean Hannity on FOX News.
The Weather Undergrounds history of terrorism consisted of:
1970: SFPD Bombing (1 Killed)
1970: NYPD Bombing (7 Hurt)
1970: NYC Explosion (3 Killed)
1971-72: Capital & Pentagon Attacked
1981: Armed Robbery (3 Killed)
(As John Boot at PJ Media notes: The Vietnam War, of course, had been over for years, [by 1981] which gives the lie to the films claim that the Southeast Asia conflict was anything but a pretext for the terrorist network.)
As Larissa Atbashian wrote in FrontPage recently:
Variety magazine has already created sympathetic buzz with a barrage of articles, calling the movie an unabashedly heartfelt but competent tribute to 1960s idealism, adding that [t]here is something undeniably compelling, perhaps even romantic, about Americas 60s radicals and the compromises they did or didnt make.
What Variety is saying is that Redfords film is an: unabashedly heartfelt but competent tribute to 1960s terrorism, adding that There is something undeniably compelling, perhaps even romantic, about American terrorists and the compromises they did or did not make.
To fully appreciate who Robert Redfords heroes are, Obamas friend and co-founder of The Weather Underground, Bill Ayers, planned to murder 25 million Americans.
(Excerpt) Read more at frontpagemag.com ...
How soon can he put together a film about the wonderful folks who gave us boston yesterday. He'll be the toast of the town. Too bad he ain't just toast.
Hey, Red.....go climb back into that Vodka bottle. You're more at ease and sensible there.
Gotta love those Columbians. They took care of Che as well.
Wonder if he considers the Bath school bomber, the Wall Street Bomber, or the LA Times bombers to also be his heroes.
Maybe he got a thrill yesterday.
Rush was just talking about Bill Ayers and the Weather Underground.
Just another pretty-boy traitor .. dime a dozen.
This is what Redford supports: http://www.liveleak.com/view?i=072_1366065507
Mexican cartels dispatch agents deep inside US - spread into non-border states
CHICAGO (AP) Mexican drug cartels whose operatives once rarely ventured beyond the US border are dispatching some of their most trusted agents to live and work deep inside the United States an emboldened presence that experts believe is meant to tighten their grip on the world's most lucrative narcotics market and maximize profits. If left unchecked, authorities say, the cartels' move into the American interior could render the syndicates harder than ever to dislodge and pave the way for them to expand into other criminal enterprises such as prostitution, kidnapping- and-extortion rackets and money laundering.
Some cartels even have Mexican operatives fill out job applications before being dispatched to the US, Riley added.
In Mexico, the cartels are known for a staggering number of killings more than 50,000, according to one tally. Beheadings are sometimes a signature. So far, cartels don't appear to be directly responsible for large numbers of slayings in the United States, though the Texas Department of Public Safety reported 22 killings and five kidnappings in Texas at the hands of Mexican cartels from 2010 through mid- 2011. Still, police worry that increased cartel activity could fuel heightened violence.--SNIP--
In Chicago, the police commander who oversees narcotics investigations, James O'Grady, said street-gang disputes over turf account for most of the city's uptick in murders last year, when slayings topped 500 for the first time since 2008.
Although the cartels aren't dictating the territorial wars, they are the source of drugs. Riley's assessment is stark: He argues that the cartels should be seen as an underlying cause of Chicago's disturbingly high murder rate. "They are the puppeteers," he said. "Maybe the shooter didn't know and maybe the victim didn't know that. But if you follow it down the line, the cartels are ultimately responsible."
SOURCE http://www.nypost.com/p/news/national/mexican_cartels_dispatch_agents_ZsKwR5wQCvQvpBXnejs1TJ
Thought it was Bolivia. What a commie hole that's become. Thanks evo.
I guess him and HAnoi Jane got closer than we thought!
Another asinine Hollywood Type that has no clue of what they say!
You can look @ Boston and see what Ayers was all about !
RR then had to support the actions of the Boston Bombers!
Support of Terrorism means all Terrorism!
Yo have to remember an actor only conveys what the dorector wants you to see!
However when the Actor speaks of free will, the accolades do not come, their ignorance shows!
Ask Mr Ayres of his thougts of collateral damage! Was the death of an innocent 8 year old child yesterday just collateral damage!
Mr Redford's mouth seems to have overloaded his ass!
And you Sir can rot in hell!
"Rush was just talking about Bill Ayers and the Weather Underground."
Good, I hope he mentioned that Ayers girlfriend and cronies were building similar anti personal bombs that they planned to detonate on a crowded dance floor at a Dance at Ft Dix New Jersey. Lucky for their targeted victims the bomb exploded when it was being constructed.
Ayers close relationship with Obama before Obama found it politically expedient to distance Ayers from his political career should be also emphasized.
Actually it was Bolivians.
I'm hopin' you meant bobby can rot in hell and not me. LOL!
YEs and so sorry for the typo's!
I had thought I should used RR's name after hitting the post button. Also sorry for the typos.
For anyone to embrace Bill Aryes and anyone who associates himself with this psycopath riles me! That was my first red flag on 0 other than his Share the wealth plan in the early stages of the 08 election! To be a candidate for POTUS and assoiciate with ones who perpetrate Murder and have a connection with is not who one would think as a viable candidate and last week Ayres confirmed he was more than an aquiantance with 0!
Rush mentioned the girlfriend and the accidental detonation, but did not mention the Ft. Dix target.
Redford likes that stuff because he's attracted to and entertained by things as dramatic and flamboyant as bombings. He finds them interesting and thinks it makes himself to be a more interesting person, actor and "artist".
Same thing with guys like Sean Penn. He's a "life imitating art" kind of guy...
And they don't mind letting the world know what they think.
My bad. I was giving Columbia credit due to Bolivia for offing both POS jerks. Che was at least 1000 times worse than Butch Cassidy, however.
Roger that.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.


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I had to go to Cabo San Lucas in Mexico for a conference and I also took my wife along with me on this trip. I routed my flight in such a way whereby I can have a stop over in Seoul as my wife has not been there and I have also got a friend who is stationed there so ...I should just kill 2 birds with 1 stone huh!!
1 Feb 2007
Flight time 2 hrs
Cruising altitude: 34,000ft
Pre Flight:
I am sure all of you heard about the floods in Jkt, will the downpour actually started on the Thursday I left....my car had to thread thru water which is starting to rise up halfway of the width of my rims !! ... oh well...not too much of a hassle....made it to the airport @1415 for my 1545 flight. Boarding was efficient at check in and no one was in the Golden Club Class line, even Y line was pretty empty. I was assigned my pre-requested seats and the agent fumbled for awhile as she had ran out of Business Class luggage tags, so in the end, she gave me First class tags instead (interesting they should have these as none of MH flights to CGK has F seats !!!) Afterwhich I went on to the fiscal and then cleared thru immigration in 15 secs !! (I love that Saphire Program and I definitely reccomend it to everyone) Decided that the common use lounge is boring, I decided to go to the food court to have a quick bite to eat and also do some spotting (Empty tarmac at this time of the day, saw an SQ 772 departing and some domestic GA 737's) as the smoking area has a great view of the tarmac. We then decided to go to the lounge and had a drink and more cigarettes (for me) b4 we proceeded to the gate.
Flight of the day- MH720 (B737-400) 9M-MQO
Photo © JKSC
Seats of Business Class on MH's 737-400
Empty Tarmac @ CGK
What can I say, typical great MH inflight service, attentive and super polite FAs!! A most importantly, alwats ready to serve with a smile. MH 734's generally are in great condition, only thing is the seat pitch is pretty tight (vs GA's 737's) Anyone know about upgrade plans of MH's short haul fleet? New interiors or perhaps a/c?
Some Corsair B744 on charter at the Haj terminal
C Class on MH B734
Light Meal for CGK-KUL
Marinated Garoupa with Avocado
Main Course
Beef Rendang
Szechuan Chicken
Gratinated Penne Pasta
Mocha Cream Cake
Szechuan Chicken ..YUMMY !!!!
Our routing took us as usual over Sumatra, Singapore, Johor Bahru, Meleka and then straight into KUL. Nice smooth landing. Overall, another great MH flight (come to think of it, have yet to have a bad MH flight)
Load: 90% in C, 80% in Y
1 Feb 2007
B777-200 - HS-TJB "Uthai Thani"
Flight time: 1hr 41 min
Seat: 11K
After getting off the MH flight, we took a quick walk and managed to quickly clear immigrations because of the Premier Lane. Afterwhich we walked to the caroudel and bags were out within 3 mins (not bad huh!!!) We picked out bags, went out to the arrivals hall, and then up the escalator to the departure hall to check-in for our TG flight. Had to wait for 1 person in front of me at the check in but that didn't take too long ...but was kept amused with a Canadian guy in the Y line who was complaining about TG not letting him get off with his bags which was 5 kgs overweight, and he was argueing about the pieces rule in North America, well, sometimes I really can't understand these people, we in asia always adapt to the pieces rule when we are in North America, so they should just do the same with our Kgs rule in Asia (or most part of the world in that case), ok, but maybe TG was also being a little strict and should just let him check in the slightly overweight bags. i checked my bags straight thru to ICN and then got boarding passes for both sectors. I left for immigration (with that Canadian guy still argueing his case) again quick with the Premier Lane in operating and made out way by the sky train to C gates. C3 was the gate in use today. Was getting pretty tired by now, so me and the mrs decided just to browse the book store before proceeding to the TG lounge. The lounge still looks nice but very crowded!! t was about 90% full and certaining needs several of the seats changed due to torn upholstery.
Our B772 to BKK - HS-TJB
Photo © Raymond Ngu
Retrofit Seats and new c/s on this baby
This a/c was generally in good condition even after the renovation, its a good thing to note that this a/c is a non er version of the 772. But starting to get used to the new seats in Royal Silk, although they are actually pretty hard. But no hassle about hard seats as this is going to be a flight under 2 hrs. And with AVOD, the flight seem to take 30mins!! ehehhehe. Flight crew was polite as usual but there were 1 or 2 sour faces, this is the problem I contanstantly get with TG's C class. A mixed set of crew on the regional flights but overall, much better and cheerful crew on the long hauls...explanations anyone?? in C, MH will kick ass anytime, be in regional or long haul.
Smoked Salmon & Halibut
Main Course
Pan-Fried Veal Loin w/ Cheasseur Sauce
Stir-Fried Chicken w/ Thai Herbs
Siam Perch in Thai Mushroom & Giner Sauce
Sweet Jelly w/ Thai Herbs
Main - Veal Loin
Sweet Jelly w/ Thai Herbs
Flight was pretty uneventful and over in a breeze! But food was really bad!! But I am not complaining, my next leg will be on a B772er, TG's newest baby (so they say online, but with TG you never know, my last trip to ICN in late 2002 was on a B773 with C class seats w/ the worst recline angle ever)
1 Feb 2007
B777-300 - HS-TKB New C/S but not yet fit out with new seats
Flight time: 4hr 15 min
Seat: 12A
Pre Flight
Although we arrived early from KUL, it still took sometime to park the a/c as due to refurbishment of the cracks on the taxi and runways, one concourse was closed, so our a/c had to park at a remote stand. By the time the stars got to the a/c the buses did not!! Oh well, not much of a hassle as we had time to kill before the next flight. We just spent time walking around concourse C & D and afterwhich we went into the Royal Silk Lounge at concourse C. As usual for this time of the day, the lounge was almost at full capacity.
We decided to walk to the gate just before boarding was called as it was another remote gate C1A being used for this flight. Noticed that most of the passengers on this flight to ICN were Koreans.
We were on the 1st bus to the a/c and as we approached from the distance, I saw the B777 in here gleaming new paint!! I was excited but not for long, as the closer I got I noticed it was not the new B772er but was a B773 which has just been repainted a week prior to my trip!!
HS-TKB (B4 her new c/s)
Photo © Giovanni Verbeeck
In Flight
Oh well, as I thought, TG likes to change their equipment at a moments notice. This a/c still had the new seats which I was complaining earlier about. The C seats has terrible recline.
I asked the lead stewardess and she said that all TGs B773s will be retrofitted by July 2007 even including PTVs in Y. So I guessed I looked at the bright side that I am traveling on one of the last few flights in the old interior of the B773er.
Amenity Kit
TG AB6 next to us, ready to go to, I don%u2019t know where !!
We had a slight delay to depart due to the fact a Korean rock band who were also traveling in C were the last to board, did not know which band they were, but at least they are not noisy or intrusive. Load was 50% in C, and 100% in Y. The last people to board was actually 3 Y passengers, gosh, really hate them, there were last to be bussed to the a/c and still had the nerve to ask the ground agent to take a few pictures of them before the ascended the stairs to board the aircraft, I was giving them death looks from my window !!!
PTV w/ touch screen but not AVOD
Menu for the flight
Cold cuts w/ sushi
2nd Serving
Fresh fruits, juice & yoghurt
Main course
Cheese Omelette w/ veal sausage
Chinese Yang Chao w/ prawn & chicken sausage
Roast duck w/ gravy & yellow noodles
The 2nd serving was actually done about 1.5 hrs before landing
Roast duck
Getting there!
Well, its another uneventful flight for me, but this time, the crew was definitely an improvement than the previous leg!!
3 Feb 2007
B747-400 HL7418 old c/s
Flight time: 10hrs
Cruise: 39,000ft
Seat: 21K
Pre Flight
We spent just over 24hrs in Seoul. Managed to have dinner with an old friend, and we also visited one of the palaces near our hotel (Westin Chosun) and took the wife shopping and eating around the Myeong Dong area. ICN airport si quite a distance from the city but I was not complaining as my friend has arranged his chaeuffer to both pick and send us to the airport. We reached the airport in time at around 1430, plenty of time for the 1630 departure to LAX.
Landside @ ICN
Premium check in of OZ which I just came out from
Check in was a breeze and I got my preassigned seats, plus point to note, this is my first time on OZ but great courteous staff all round!! Good first impression!! I was seated in 21J & 21K, lower deck of the 747. We went thru immigration and then we walked around the duty free, had lunch at a nice café where they served kick-ass Beef Kalbi (opposite Gate 30) After the meal, it was not long to go before boarding, but we decided to go and have a quick look at OZ lounge. My previous trips into ICN were by SQ and TG and they both used the Silver Kris lounge which was great. The OZ lounge was nice too, but I still think the Silver Kris lounge is better, but this maybe due to the fact that the OZ lounge running really full!
Empty Tarmac
It was soon time to board and we got into the C and F line, was quite a long wait before the line started moving.
Our a/c HL7418
Photo © David James Clelford
In Flight
Ancient seats in C
Looking out the window
Nice looking safety card though
PTV, Amenity Kit & Menu
We were already seated for around 20 mins and still be pre-take off drinks were not served, not looking good! So I decided to walk around the cabin, F was 50% load, C was 100% and Y 100%. The inflight product of this a/c is really looking very very old indeed and needs a desperate upgrade. The seats are similar to TGB744s pre-retrofit , especially the similarity can be seen in the F seats. Thanks god TG was upgraded their B744 fleet. PTV had 3 movies, and 2 short features all playing in a loop, BORING! Thank god I had my laptop and a couple of DVDs with me.
Selections of canapés
Mixed beans w/ parma ham
Mixed garden salad
Beef tenderloin steak
Grilled Salmon
Fresh fruit & assorted cheese
Selection of canapés
Korean Bi Bim Bap
Fresh fruit & assorted cheese
Fresh fruit & juice
Fruit flavoured yoghurt
Stir fried beef w/ leek
Cream cheese pancake
Beef tenderloin
Cheese anyone??
Service I find was really efficient (only hiccup was really slow in offering pre take off drinks) they really smiled a lot and some of them were pretty cute %uF04A
I was hungry nearing breakfast time when I got up so I decided to have a Korean instant noodle soup it was greatbut SPICY!!
So by the time breakfast was served, I was not that hungry so just had the fruits instead.
Just hitting the California coast
About 20 mins to descend
Overflying LAX
The LA urban sprawl!
Well, we got off the a/c and its the usual mad dash to LAX immigration, waited in line for 10 mins, seems like ages to go, and yippee they opened up a new counter and I was told to stand in that new line with only 2 pax in front of me, for one, I got an unusually chatty immigration officer. He did his work quick, but spent another 2 mins or so chatting with me! We then got our bags and then went landside to get to the Hertz shuttle to pick up our rent a car b4 checking in to our hotel, the Beverly Hilton.
Overall I find OZ a good airline with great service, but my only problem is the ageing inflight product. I would probably wait for them to upgrade their inflight product before I fly them again. Although I know some of their a/c has been upgraded.
4 Feb 2007
LAX-SJD (Cabo San Lucas Baja California)
MD-80 or S-80 as marketed by AA
Seat: 6 F
Flight time: 1hr 53min
Cruise: 35,000ft
Pre Flight
After spending a nice 24hrs in LA, we left our hotel at 0715 for our 1010 departure. I reckon that will just be right since I had to drop off the rent a car at Hertz and then catch the shuttle to AAs terminal. By 8am I was already at the terminal and managed to checked my bags in, but had a little trouble due to the fact that my agent messed up and entered both me and my wifes surnames as first names !!...but it didnt take too long to sort that out. Was also amazed that AA does not give priority tags to business class passengers. Well, 1st impressions already not that great (I would rather take UA or US coz of *A) at least my QF FF number still can be used, although I barely have any mileage as all my travels are on *A.
After a quick security check we went into the terminal, wanted to enter the lounge but guess what, business class passengers are not entitled to the lounge, only admiral club members?!! What the *^%^&@( !!!!! This is starting to get pretty bullsh*t and really not starting to make a lasting impression). At least its making me appreciate *A more now. 1st time I ever heard that premium passengers cant use the lounge. So what did I do for the rest of the time, browsed the magazine store, grabbed a coffee, and then sat at the gate and stared at the ceiling with my wife staring at me and looking at me curse and swear to myself about the lounge incident (mind you, not once did I complain to any of the AA staff, I did all the cursing and swearing within myself, pretty good huh)
Our MD S-80 to SJD , did not manage to get the rego due to the angle it was parked to the gate
In Flight
I was one of the 1st to board the a/c and at least the very cheerful purser that greeted us was making my experience with AA a little better, I then settle in my seats. And guess what, impression started to go down again, seats were filthy!! Blanket was smelly and reused dont know how many times. Trust me, UA is starting to seem much better at this stage.
Legroom just enough for C
What is that ground staff doing?
Safety card
Mexicana A319 taking off just before us
Views on the take off run
Santa Monica
There was only 1 guy in charge of the 90% full C cabin. But he did his job in a very professional, but still with a nice touch of humour.
Roasted nuts, not bad
Of course there was no menus handed out, with the lunch choice of either chicken tenders or Vegetable Pizza.
I took the Pizza
Wife took the chicken tender which was better, so in the end I also ate most of it well I was starving!! Too much cursing and swearing at myself b4 take off I guess over that lounge thing heeheheh, hey, a guy needs his lounge and food in the morning!!
On descend to SJD
SJD Airport, full of Biz Jets
My overall impression of AA was mixed, the only bright side was the really great cabin crew and above average catering.
We spent the next 3 days mainly at the Sheraton Hacienda where my conference was held, great beach though.
View from my room
Managed to visit the famous Hotel California which is the name of the Eagles song
7 Feb 2007
Flight time: 2hr 5 min
Seat: 4A
Cruise: 36,000ft
Pre Flight
Time in Mexico really passed by quickly it was really nice, especially since it was the migrating & mating season of the Grey Whales, we managed to see many of them from the hotel balcony.
We arrived at the airport with a little over an hour to spare, really nothing much to do at the airport, some of my colleagues were in the C line at the check in but soon enough it was my turn, by the way, the conducted baggage check manually at table right before the check in counter. When it was my turn to check in, the agent disappeared!! Had to wait several minutes of me signaling the other agents attending to the Y line before a female agent gestured to me to come over. After a short check in process and me getting my assigned seats, we decided to grab a bite at Burger King which is located right before the security check
We then went thru security and waited at the departures area
Observed an AA B752 from DFW unloading, also America West A320 and Interjet A320
Not too long later, our MD-S80 arrived and boarding commenced with C passengers being called first, another make shift security check was done at the gate and they did not allow me to carry my matches on board!! I told them in a nice way that TSA allows matches but not lighters%u2026and guess what, the security guy did not speak English, I just gave up and walked to the plane as I had a plane load of people behind me.
N297AA taking us back to LAX
In Flight
After the last filthy interior on the inbound flight, this time its better, maybe by about 25% in terms of cleanliness
Because of my size, legroom in C still looks tight huh, btw, the bag u see is my wifes not mine !! ahahhaha
Seats, pardon me for this, I forgot to invert the pix
Push Back
America West A320
The Baja coastline
Meal choice, I really can%u2019t remember as it was not that good, wait, terrible!
Anyone know which airport is this I overflew on approach to LAX?
This was yet another uneventful flight and service is acceptable but the purser on the inbound flight still kicks ass with his service style and humour
Overall my impressions of AA was ok with good staff making up for the lack of product substance. But my 1st choice in the US will still be UA.
We disembarked to an empty AA terminal and I was 1st to be at immigrations with no one in front of me (what a shocker in contrast to Tom Bradley Terminal). We then got our bags and headed to Hertz to pick up our car, as I had some colleagues with us, I rented a Hummer H2..woohoo.
10 Feb 2007
Seat: 16K
Pre Flight
After spending a few days shopping and eating in LA, I spent my afternoon at Long Beach before heading back to the Beverly Hilton to check out for my evening flight to BKK. The hotel was packed with security personnel and many stars were there was Clive Davis (famous record producer) was having his Pre-Grammy award party there. I managed to sport Christina Aguilera. But as it fast approached the tiem of the party, I decided to leave the hotel asap to avoid the crowd at the hotel. So before heading to the airport, we had a quick meal at McDonalds and then we drove-by to Grummans Chinese Theatre and the walk of fame to kill some time.
After returning the car and taking the Hertz shuttle to Tom Bradley, we had to line up for 20mins for TSA screening before we checked-in, there was only 2 persons in the Royal Silk line. Again check-in was swift with my bags checked thru to KUL. Agent told me flight was 95% full in C, and 100% in Premium Y and Y.
After getting my boarding pass for both legs of the journey, we went to the common use lounge which was packed on my trip a mth ago, but not too bad this time. Was told the proper airline lounge will only finish renovations sometimes in August this year.
We only stayed at the lounge for 20mins and proceeded through security. It was pretty full but the lines moved pretty quick. Our gate today was a remote gate so meaning we had to take a nice long bus trip to the remote pier where this bunker looking building are located where our a/c was parked
HS-TLC our A345 to BKK
Photo © Giovanni Verbeeck
In Flight
Nice Legroom on A345 in C, but I wish the A346 comes to this route so we get F class
This is my 3rd time on board a A345 on my 2nd time on HS-TLC, she still looks sparkling clean and all seats still in great condition, by the way, have I already mentioned how I love the lavatory with the windows?!!!
Everything about TGs A345 product is good, only perhaps the seat needs more cushioning, little hard as it is, but when my back gets sore, all I need to do is press the massage function
1st Serving
Hot Savouries
1st Course
Salmon Rolled w/ cream cheese
Salad w/ olive oil and vinegrette dressing
Main Course
Grilled duck breast w/ mushroom cream sauce
Sauteed prawns and scallops provencale
Chicken of Friscassee w/ mushroom
Stir fried prok with chilli, basil & minced garlic
Pineapple Tarte
I was having a really bad stomachache (much be from the double quarter pounder I had at McDonald) The lead FA was really nice to me and offered me some carbon pills (charcoal). After take-off it was a mad dash to the lavatory once the seat belt signs were off. After I took my seat again, I decided to skip dinner but my wife still had hers so I took pics of her meal.
Hot Savouries
Salmon & Salad
My wife had the prawn dish, she actually started eating and I was starting to fall asleep, hence the partially eaten dish :p
I managed to sleep most of the 1st half of the flight, letting my stomach recover, the lead FA all this while kept checking on me if I was ok. I got up just about the time they were serving the 2nd meal.
2nd serving
1st Course
Fresh fruit & yoghurt
Main Course
Cheese Omelette
Boiled rice w/ chicken,coriander & spring onions
Thai fried rice w/ prawns
I had the latter
After the meal, I watched the Fast & the Furious Tokyo Drift on the AVOD before going back to sleep (by the way, I bought the BOSE noise canceling headset when I was in LA, and boy was it a great investment!!) Again to my stomach natural clock, I woke up before they starting serving the 3rd and final meal for the flight
Slowly but surely we are getting to BKK
3rd Serving
1st Course
Mixed green salad w/ Italian dressing
Main Course
Mushroom risotto w/ grilled yellow spinach
Chicken & eggplant w/ black bean sauce
Assorted petit fours
Chicken &Eggplant
Time passed quickly as I slept most of the journey and soon enough we touched down at BKK. This time we did not have to park at the remote bay.
And as I always said before, the crew on this flight were great, still cant understand why the crew on C class seems much better on the long haul than the short haul flights on TG? Can somebody please explain this?
12 Feb 2007
A330-300 HS-TED old c/s
Flight time: 1hr 45min
Once I got off, I really didnt feel like doing anything much and just stopped by the smoking rooms for a puff or two. We then stretched our legs and had a look at the duty free before going into the Royal Silk lounge at C concourse. Wanted to check my email but the pcs werent running and I had to go to the other lounge. I was so dead tired by now I couldnt be bothered and just decided to chill out. At 0830, I started to walk to the gate and by this time boarding already commenced so I walked to the gate and straight into the a/c. Today being operated by HS-TED and this is probably my 8th time in this a/c and also my 8th time in 11K on this aircraft!! Fancy that!!
Photo © M Radzi Desa
Old but comfy seats on this baby although not on my trip to PER but great for short haul
*A c/s A333 next to us
PB Air E145 ready to take off in front of us
Fresh fruits & juice
Main Course
Seafood yakisoba
Omelet w/ tomato & onion
Roast chicken Chinese style, w/ hainan chicken rice
I was not hungry, just tired so took the fruits part of the meal
The flight was smooth with a fuss free service. But typical service as I always said for the short haul crew which stands in contrast to the long haul crew.
12 Feb 2007
MH723 B737-400 9M-MMQ later to be 9M-MMB
ETD:1630 later to be 1905
ATA:What a mess!!
ETA:1730, now 2005
ATA: Got no idea, at least I finally made it back to CGK
Seat:1F later to be 4F
As we landed a little early, I decided to make the dash to immigration, pick my bags and rushed to the MAS Golden Club check-in to see if I can get the 1345 flight to CGK instead of the 1630 I was booked on. But alas, the agent said only 1 seat in C was available with my wife or me having to seat in Y. My wife said she didnt mind to seat in Y as we can reach CGK earlier, but I told her its ok, we will just wait for our 1630 flight as we already paid to fly in C, we should just wait for the next flight. This was a mistake as later you guys will find out why.
Since we had so much time, I decided to check into the transit hotel airside to have a look and also take a quick nap and shower. Although we can also do that at the Golden Club Lounge, at least the transit hotel gives us a little more privacy. While the wife took her shower, I decided to walk around the airport and also had a quick 30min foot reflexology relaxing indeed. I then went back to the room and had a shower and a quick nap. We checkout at around 1545 and took a nice slow walk and skytrain back to G gates for our flight to CGK. It was now 1610, but no security staff were at the xray machine so we had to wait with the MH ground staff hassling the security to hurry up. The security started the xray at 1620 and we were all told to board the a/c immedietly, dorrs of a/c was closed at 1633. Efficient huh!! We then taxied and waited for ok to take off.
SQ to SIN departing before us
Legroom & seats (again I forgot to invert the pic, sorry)
Once we turned onto the runway for take off, instead of full thrust, only minimal thrust was applied and the aircraft turned off the 1st taxiway, ok, I sense a problem. We then pulled back into the gate where the captain took a long time before coming onto the PA to mentioned they had flaps and also an aircon compressor problem on the a/c therefore parts have been dispatched and we should be able to be on our way in 30 mins. Ok, not a problem in my case. But after 45mins on the a/c, some irate passengers in Y decided just to walk off the a/c and wait at the gate as it was hot (aircon not functioning due to faulty compressor). After about 1 hr of returning to the gate, the captain then said that we should all just disembark and wait at the gate. Now I really wished I listened to the wife and take the 1345 flight instead although meaning 1 C ticket had to be sacrificed and she or I traveled in Y.
The box I guessed contained the spare parts
After another 10 mins at the boarding lounge, the MH agent then told all of us to go to the transfer counter so we could all be accommodated on the 1900 flight to CGK and this MH723 will be cancelled. GREAT!! Another mad dash to transfer counters were everyone was pushing each other out of the way. I decided to play the ignorant game and just walked straight to the gate leaving everyone pushing and shoving at the transfer counter. I got to the gate and when the MH agent asked me why I did not go to the transfer counter I just said I was not told not to do so, so she got on her walkie talkie and 3 mins later I got my boarding pass for my flight heehhehe all this while everyone was still pushing and shoving at the transfer counter.
Still amazed that all the pax on my original flight in both Y and C can be accommodate on this flight, this flight must be pretty empty!! Once I got on the a/c. so did the whole world behind me, this flight is now 100% full after combining both flights pax.
Prawns w/vermicelli
Main Course
Chicken stew
Beef rending
Pumpkin ravioli
Banana cherry gateau
Chicken for me
Over Sumatra
There was only 1 FQ for C but she did an amazing job for the full load of passengers. That why MHs FA will always beat TG everytime, the only pity is that MH has a lack of alliance.
Does MH have any plans to change their B734s?
Overall and interesting end to a great journey. Hope you guys enjoy your read. My next post will be up in 24 hrs which is a domestic trip w/ GA from CGK-SUB-CGK. I will be on my next long haul trip in 2 weeks on MH, TG & JK to Madrid, Valencia and Barcelona in C for MH, F in TG and Y for JK.


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Stunt Cycle
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Genre: Arcade, Racing, Simulator
The game is housed in a custom cabinet that includes a simulated motorcycle steering column mounted on the control panel. The right side handle grip is twisted for acceleration. The monitor is a 19-inch black and white CRT monitor with a black and white overlay that adds giant tubes to the play field used to traverse from one split level to another. Sounds include a motorcycle roar, crash sounds, and crowd cheers.
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ECCO2017 Symposium
Treatment evolution in advanced GI malignancies
Official Sponsored Satellite Symposium at ECCO 2017: European Cancer Congress. 29 January 18:45 – 20:15
During this symposium, a distinguished faculty of experts engaged the audience in an interactive discussion on how to optimize the day-to-day management of patients with gastrointestinal malignancies. Using patient cases from their clinical practices, the experts exemplify how treatment has evolved over the years into the current best-treatment strategies. The final presentation covers the latest clinical evidence of how these strategies may continue to evolve in the future.
Learning objectives based on identified educational needs
- Describe the evolution of metastatic colorectal cancer (mCRC) management and progress in treatment of advanced/metastatic gastric and gastro-oesophageal junction (GEJ) cancer to its current status in recent years
- State the evidence supporting the design of current optimal treatment strategy for patients with advanced/metastatic GEJ cancer and mCRC
- Develop a care plan that aims to achieve optimal treatment benefits and maximize individual patient outcomes in patients with advanced/metastatic GEJ cancer and mCRC in daily clinical practice
- Formulate the remaining unmet needs in the treatment of patients with locally advanced or metastatic gastric/GEJ cancer and mCRC and understand how ongoing research could further improve outcomes in patients with advanced/metastatic GEJ cancer and mCRC
Welcome and introduction
Florian LordickThis symposium focuses on gastric cancer and colorectal cancer in the advanced stages and looks at clinical trial data, multi-disciplinary...
Knowns and unknowns in management of advanced/metastatic gastric and GEJ cancer
Naureen StarlingNew ESMO clinical practice guidelines on gastric cancer were published in 2016. Dr Starling takes the audience on a journey that addresses: the advances in chemotherapy treatments over the past 2 decades, the impact of targeted therapies, and the relatively new area of checkpoint inhibitors. She summarises many of the negative clinical trial results and highlights emerging areas of clinical research in advanced/metastatic gastric and gastroesophageal junction (GEJ) cancer.
Overcoming challenges in management of mCRC
Eric Van CutsemNew ESMO clinical practice guidelines on metastatic colorectal cancer were published in 2016. Dr Van Cutsem builds real-life scenarios around these guidelines using case studies and interactive questions where he asks the audience to select a treatment option for each case study. Based on the answers, he then engages the panel to contribute their expertise to explain why they would select a particular option over another in their practices.
Looking into the future of GI cancer management
Nicole van GriekenDr van Grieken, a pathologist, presents the past, present and future status of molecular biology in tumour research. She reviews the history of technological development that has led to molecular markers, comments on how comprehensive molecular analyses is improving our understanding of tumour biology and clinical behaviour, and addresses the challenges that remain in making molecular markers useful predictive tools. She also reviews the exciting potential value of liquid biopsies for diagnosis and follow up in cancer patients.


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|29 May 2012
windows vista
Buying a netbook with no OS?
I'm in Bangkok and thinking of buying a netbook here. only thing is is that they dont come with an OS already installed and charge you to put one on.
i wanted to know if its possible to put one on myself. i know very little about computers, only how to use them and the netbooks do not come with a cd drive.
am i right in asuming that even if computer doesnt have a OS it can still turn on and you can acess internet?
thanks for your help.
|My System Specs
|29 May 2012
Ubuntu is probably the easiest free OS around. easy to install and get used to.
Otherwise Windows for a netbook would probably be best to use windows 7 starter
Compare Windows 7 Editions
This is usually pre-installed from the manufacturer tho...
Here is a comparison of the windows 7 versions:
Compare Windows 7 Editions
|My System Specs
|29 May 2012
Also, it is possible to create a bootable Thumb-drive to install the OS.
Here is the tutorial for Ubuntu: http://www.ubuntu.com/download/help/...ick-on-windows
Ah and here is the tutorial for creating a win7 flash drive: USB Windows 7 Installation Key Drive - Create
These might be a little daunting at first glance, but with the help of people on this forum, downloading and installing Ubuntu should be no problem.
If you are tight on money it is a great option.
|My System Specs
|29 May 2012
What I would do in that position if I don't like Linux as well as Windows is to install the Consumer Preview of Windows 8. It's not supposed to be for production use but it is as rock solid as Win7, just with a bit different start page which actually starts with windows and allows you to configure it as buttons. It takes some getting used to, but is much easier than Linux. And it's free.
Visit our sister site Windows 8 Forums to find out all about it.
If it unfolds like Win7 did, you'll have opportunities for half-price pre-purchase and freebies when it is released which likely won't be for at least a year.
|My System Specs
|29 May 2012
Windows 7 Ultimate x64
|My System Specs
|30 May 2012
W7 Ultimate x64/W10 Pro x64 dual boot main build-remote pc W10 Pro x64 Insider Preview/W7 Pro x64
Welcome to SF! alicedolan
You have a few option as far as which OS or which edition of Windows you can go with. If you want to stay with Windows besides getting familiar with how to create a USB Install Key as pointed to in the guide Thorsen posted you may want to read how to see 7 installed with an upgrade disk. Clean Install with a Upgrade Windows 7 Version
As for which Linux distro to go with if you decide on the other OS there are other more user friendly distros besides ubuntu which sees a new version every six months or so! Linux Mint or Linut Mint Debian being a little larger in size will include options to install numerous Linux type desktop apps.
As for 7 generally the 7 Home Premium or Basic edition would be the lower cost options as far as which edition to run on a netbook. The Starter edition mainly the stripped down to basics edition. When considering buying a netbook here for a family member if not for my own use I would have likely gone with the Home Premium.
With any Windows installation you follow the onscreen instructions and options. With a usb key you would select the Custom install option and then select the one drive on the netbook itself. With 7 you would use the drive tools option to partition and format the drive during the installation.
With any any Linux distro the home site will have it's own tutorials for installation to follow. With 7 or the upcoming WIndows 8 Release Preview discussed over at the eightforums.com site Windows will include native usb support since any new apps you install may have to go on by way of a usb optical drive if not downloaded from the web.
In general for someone just starting out Windows is the preferred OS to learn since most softwares are written with Windows in mind. And as Thorsen also pointed out there's plenty of Windows users that can help out here at SF and over at eightforums.
|My System Specs
|30 May 2012
Windows 7 Professional x64 Service Pack 1
Does the netbook have a product key on the bottom? we could use that and get you the version of widnwos you need. I generally don't advise people use Linux, because if something goes wrong, it isn't a simple system restore or something. It is getting into nitty-gritty terminal stuff. Linux is a geek's toy, not a consumer os.
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|General Discussion
Need help in buying new pc...
My friend wants to buy a new pc..but he is tight on budget..i have suggested the following config is it good... Mo bo-Gigabyte GA -880 g-ud 3h... processor-Amd Athlon II x 4 645... monitor-dell d1920.. 2g ddr3 ram... 450w psu... no graphics card..
|Hardware & Devices
Buying PS3 used
My local Gamestation does Pre-owned Ps3s (The older fat type)Some 40Gb models,Some 80Gb models quite cheap...one i seen was only £99 for the 40Gb model. Ive been wanting to pick up a PS3 for ages now for Blu-Ray and games like GTA IV to run properly but dont really want to splash out £249 for a...
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