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Peroxisome proliferator-activated receptor-γ coactivator-1α and -1β (PGC-1α and PGC-1β) were overexpressed by adenovirus-mediated gene transfer in cultures of primary rat skeletal muscle cells derived from neonatal myoblasts. Effects on muscle fiber type transition and metabolism were studied from days 5 to 22 of culture. PGC-1α and PGC-1β overexpression caused a three- to fourfold increase in mRNA level, a doubling of enzymatic activity of citrate synthase, a slight increase in short-chain acyl-CoA dehydrogenase mRNA, a doubling of the mRNA level, and a 30–50% increase in enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase. Lactate dehydrogenase or creatine kinase activity was unchanged. PGC-1α enhanced glycogen buildup twofold at 5 or 25 mM glucose, whereas PGC-1β caused a decrease. Both PGC-1α and PGC-1β overexpression caused a faster maturation of myotubes, as seen by mRNA downregulation of the immature embryonal and perinatal myosin heavy-chain (MHC) isoforms. PGC-1α or PGC-1β overexpression enhanced mRNA of the slow oxidative-associated MHC isoform MHCIb and downregulated mRNA levels of the fast glycolytic-associated MHC isoforms MHCIIX and MHCIIB. Only PGC-1β overexpression caused an increase in mRNA of the intermediary fast oxidative-associated MHC isoform MHCIIA. PGC-1α or PGC-1β overexpression upregulated GLUT4 mRNA and downregulated myocyte enhancer factor 2C transcription factor mRNA; only PGC-1α overexpression caused an increase in the mRNA expression of TRB3, a negative regulator of insulin signaling. These results show that both PGC-1α and PGC-1β are involved in the regulation of skeletal muscle fiber transition and metabolism and that they have both overlapping and differing effects.
- skeletal muscle cell culture
- peroxisome proliferator-activated receptor γ coactivator-1
- myosin heavy chain
- enzyme activities
- glycogen
the beneficial effect of exercise on various diseases is widely acknowledged (7), and exercise has proven particularly successful as a treatment for the metabolic syndrome, including type 2 diabetes (48); however, the exact molecular pathway responsible for the effect is largely unknown. Recently, genes involved in oxidative phosphorylation in skeletal muscle were found to be downregulated in patients with type 2 diabetes (37, 43), and speculations about type 2 diabetes being caused by mitochondrial dysfunction, primarily in the type I skeletal muscle fibers, have surfaced (13, 31, 51). Regular exercise has been shown to induce changes in both skeletal muscle metabolism and muscle fiber type over time, most notably an increase in mitochondrial content and oxidative metabolism as well as a shift toward a more slow oxidative fiber type (8, 44). Single bouts of exercise transiently change the mRNA expression levels of a vast amount of genes both during and immediately after exercise (3, 10, 45). It has been speculated that it is the repeated transient induction of these genes, leading to an average higher gene expression over time that is ultimately responsible for the changes seen in skeletal muscle phenotype after regular exercise (57).
One of the genes induced in skeletal muscle after exercise is the peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α; see Refs. 1, 2, and 10). PGC-1α, a coactivator of several nuclear receptors and other transcription factors, has been shown to be involved in the regulation of mitochondrial biogenesis, adaptive thermogenesis, and enzymes involved in oxidative metabolism as well as glucose transport in skeletal muscle (27, 46). Furthermore, PGC-1α was recently shown to be involved in muscle fiber-type switching during development (29). Peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β), another family member of the PGC-1 family of transcriptional coactivators, has been less extensively studied than PGC-1α, but like PGC-1α it seems to be involved in the regulation of energy metabolism and energy expenditure, although with subtle differences compared with PGC-1α (21, 27–29). Even though PGC-1β is highly expressed in skeletal muscle, it does not seem to be regulated by endurance exercise (34). The involvement of PGC-1β in skeletal muscle fiber plasticity has not been studied, although overexpression of PGC-1α and PGC-1β in skeletal muscle cells suggests a different role of these coactivators in controlling mitochondrial function (52). Both PGC-1α and PGC-1β have been shown to be downregulated in skeletal muscle in type 2 diabetes (43), and a correlation to the downregulation of genes involved in oxidative phosphorylation has been established (37).
By using adenoviral-mediated overexpression of either PGC-1α or PGC-1β, we examined the different effects of increased levels of these coactivators on the metabolic and contractile phenotype of skeletal muscle cells. PGC-1α and PGC-1β induced similar changes in both the metabolic and contractile phenotype of primary rat skeletal muscle cells, with subtle differences between PGC-1α and PGC-1β overexpression.
FCS and horse serum were from In Vitro (Fredensborg, Denmark). Matrigel was from BD Biosciences (Bedford, MA), accutase was from Cytotech (Hellebaek, Denmark), and all plasticware was from Nunc (Roskilde, Denmark). ADP, NADH, creatine phosphate, glucose-6-phosphate dehydrogenase, and hexokinase were from Roche (Basel, Switzerland). AMP was from Calbiochem (La Jolla, CA); gentamicin, acetyl-CoA, BSA, DTT, and NADP+ were from Gerbu (Gaiberg, Germany); and bovine insulin was from Novo Nordisk (Gentofte, Denmark). Adeno-X Virus Purification Kit and Adeno-X Rapid Titer Kit were from Clontech (Mountain View, CA). Omniscript RT, Quantitect SYBR Green Master Mix, and Quantitect SYBR Green RT-PCR kit were from Qiagen (Valencia, CA), and the QuantumRNA 18S internal standards kit was from Ambion (Cambridgeshire, UK). All other chemicals and enzymes were from Sigma-Aldrich (St. Louis, MO).
Primary skeletal muscle cell culture preparation.
Primary cultures of rat myotubes were prepared from the hindleg muscles from <24-h-old Wistar rats by a modification of a previously described method for rabbits (24). On day 0, 25 newborn rats were decapitated, and the bodies were carefully rinsed in 70% ethanol and allowed to dry for 15 min, after which the hindlegs were cut off. With the use of a stereomicroscope, the legs were skinned, washed two times in ice-cold Dulbecco's PBS without Ca2+ and Mg2+ (CMf-DPBS), and carefully trimmed for muscle tissue in a few drops of CMf-DPBS. The muscle tissue was cut with a pair of iris scissors for ∼10 min in a few drops of CMf-DPBS, transferred to an extraction beaker, and incubated for 5 min at 37°C with magnetic stirring at 300 revolutions/min (30 s left, 30 s right) in 40 ml of a trypsin solution (1.25 mg/ml). The tissue was allowed to sediment, the supernatant was discarded, and 40 ml of fresh trypsin solution (as above) were added together with 1 ml of collagenase I solution (32 mg/ml); the suspension was incubated at 37°C for 25 min with stirring as above. The suspension was triturated every 10 min at least 15 times with a wide mouth pipette. After 25 min of digestion, the suspension was again triturated at least 15 times, and the undigested tissue was allowed to sediment for a few minutes. The supernatant was filtered through a stainless steel sieve (0.2-mm pore size) into a 50-ml tube containing 1 ml plating medium (DMEM containing 5 mM glucose, 2 × 105 IU/l penicillin, 50 mg/l gentamicin, 1.25 mg/l amphotericin B, and 20% FCS). The volume of filtrate should not exceed 15 ml/tube. CMf-DPBS (35 ml) was added to each tube, and the tubes were gently mixed and centrifuged at 778 g for 8 min at room temperature. The supernatant was discarded, and the pellets were resuspended in 10 ml plating medium/tube. Meanwhile, 40 ml fresh trypsin solution plus 1 ml of collagenase I solution (as above) were added to the remaining tissue in the extraction beaker, and the tissue was incubated for a further 20 min, after which the cells were collected as described above. The combined cell suspensions were filtered through a Millipore filter (20 μm pore size) in a total volume of 180 ml plating media, after which the cell suspension was transferred to three 75-cm2 culture flasks (60 ml/flask) and placed in the incubator for 50 min to allow fibroblasts to attach to the surface. The myoblasts still in suspension were carefully poured into a sterile bottle and counted, and plating medium was added to a final cell concentration of ∼0.5 × 106 cells/ml. Cell suspension (2 ml) was plated on 35-mm culture dishes precoated overnight in the incubator with a 1:100 dilution of Matrigel in DMEM. The culture medium was changed to fusion medium on day 3 (DMEM containing 5 mM glucose, 2 × 105 IU/l penicillin, 50 mg/l gentamicin, 1.25 mg/l amphotericin B, and 10% horse serum) and transduced with adenovirus on day 5, as described below. On day 7, the culture medium was changed to differentiation medium (DMEM containing 5 mM glucose, 2 × 105 IU/l penicillin, 50 mg/l gentamicin, 1.25 mg/l amphotericin B, 10% horse serum, and 1 μM dexamethasone) in which the cells were kept for the remainder of the experiment. The medium contained 10 μM cytosine β-d-arabinofuranoside from day 5 to day 9. All cultures had their medium changed every 2nd or 3rd day.
Fibroblast cultures were prepared from the cells, which adhered to plain plastic in the purification step described above. After removal of the medium containing myoblasts, the fibroblasts were washed one time with CMf-DPBS and loosened from the culture flask by addition of 10 ml accutase. Cultures from this fibroblast suspension were prepared exactly as described for myoblast cultures.
Transduction of primary skeletal muscle cell cultures with adenovirus.
Immediately before transduction, all dishes were changed to serum-free plating medium, and adenovirus, diluted in serum-free plating medium, was added to a final virus concentration of 108 infectious units/35-mm dish (resulting in a multiplicity of infection of ∼25). The dishes were gently shaken and incubated at 37°C in the incubator for 3 h, shaking the dishes gently one time per hour, after which the medium was changed to fusion medium as described above.
Preparation of cell lysates for enzyme assays.
The dishes were placed on ice, and the media were removed. Five hundred microliters of ice-cold buffer (25 mM glycyl-glycin, 150 mM KCl, 5 mM MgSO4, 5 mM EDTA, 1 mM DTT, 0.02% BSA, and 0.1% Triton X-100, pH 7.5) were added to each dish. The cell lysate was scraped off, and the resulting lysate was transferred to an Eppendorf tube, whirl mixed, frozen in liquid nitrogen, thawed on ice, and whirl mixed once again. The lysate was then centrifuged at 22,000 g for 2 min at 4°C. The supernatant was stored at −80°C for later determination of enzyme activities. Two separate 35-mm dishes were harvested for each time point.
Preparation of cell lysates from adult muscle tissue.
Male Wistar rats were sedated using thiomebumal and killed by neck dislocation. Extensor digitorum longus (EDL) or soleus muscles were dissected and freeze-clamped in liquid nitrogen. Frozen muscle tissue was stored at −80°C until time of analysis. A 5% (wt/vol) homogenate was prepared in a 2-ml Potter-Elvehjem homogenization glass on ice in 25 mM glycyl-glycin, 150 mM KCl, 5 mM MgSO4, 5 mM EDTA, 1 mM DTT, 0.02% BSA, and 0.1% Triton X-100, pH 7.5, using a Teflon piston for 1 min. The homogenate was frozen in liquid nitrogen, thawed on ice, whirl mixed, and centrifuged at 22,000 g for 2 min at 4°C. The supernatant was stored at −80°C for determination of enzyme activities.
Protein concentration.
Protein content was measured using BSA (fraction V) as standard (32).
After the medium was removed, the cells were extracted with 500 μl of 0.5 M KOH at room temperature for 10–15 min. The lysate was boiled for 10 min and frozen at −20°C for later determination of protein and glycogen content. Glycogen was measured as glucose after hydrolysis in 1 M HCl at 100°C for 2 h. Glucose was determined enzymatically in the neutralized hydrolysate using glucose oxidase as described previously (25).
Citrate synthase.
Citrate synthase (CS, EC 126.96.36.199) activity was determined spectrophotometrically at 409.5 nm and 30°C by measuring the reduction rate of DTNB in a reaction mixture with 100 mM glycyl-glycin, 0.5 mM EGTA and 2 mM MgCl2, 100 μM DTNB, and 50 μM acetyl-CoA, pH 8.2, as described previously (42). The reaction was initiated by adding oxaloacetate to 50 μM.
Creatine kinase.
Creatine kinase (CK, EC 18.104.22.168) activity was determined spectrophotometrically at 340 nm and 37°C in a reaction mixture with 100 mM glycyl-glycin, 10 mM MgCl2, 0.02% BSA, 5 mM DTT, 1 mM ADP, 5 mM AMP, 2 mM glucose, 1.5 mM NADP+, 3 U/ml hexokinase, and 0.175 U/ml glucose-6-phosphate dehydrogenase, pH 7.0, as described previously (42). The reaction was initiated by adding phosphocreatine to 25 mM.
Lactate dehydrogenase.
Lactate dehydrogenase (LDH, EC 18.104.22.168) activity was determined spectrophotometrically at 340 nm and 37°C in 100 mM triethanolamine, 2.5 mM DTT, and 0.154 mM NADH, pH 7.4, as described previously (42). The reaction was initiated by addition of pyruvate to 5 mM.
Glyceraldehyde-3-phosphate dehydrogenase.
The glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 220.127.116.11) activity was determined spectrophotometrically at 340 nm and 37°C by measuring the rate of NAD+ reduction. To take into account possible interference from LDH, the activity was measured as (GAPDH + LDH) activity − LDH activity. LDH activity was measured in a reaction mixture with 100 mM HEPES, 2 mM MgSO4, 1 mM EDTA, 1 mM ATP, 20 μM NADH, 0.15 U/ml 3-phosphoglycerate kinase, 0.15 U/ml α-glycerophosphate dehydrogenase, and 1.5 U/ml triosephosphate isomerase, pH 7.5. The reaction was initiated by addition of pyruvate to 5 mM. GAPDH + LDH activity was measured in the same reaction mixture, and the reaction was initiated by addition of pyruvate and 3-phosphoglycerate to 5 mM each.
RNA isolation.
Total RNA was isolated from the cell cultures with TriReagent as previously described (18). Intact RNA was confirmed by denaturing agarose gel electrophoresis.
Northern blotting.
mRNA levels were determined by Northern blotting using cloned PCR products as described previously (20). The PCR primers are shown in Table 1. Total RNA (500 ng) was used per lane, and 28S rRNA was used for normalization.
Quantitative real-time RT-PCR (excluding tribbles 3).
Total RNA (500 ng) was converted to cDNA in 20 μl using the OmniScript RT (Qiagen) and poly(dT) according to the manufacturer's protocol. For each target mRNA, 0.25 μl cDNA was amplified in a 25-μl SYBR Green PCR reaction containing 1× Quantitect SYBR Green Master Mix (Qiagen) and 100 nM of each primer (Table 1). The amplification was monitored real-time using the MX3000P Real-time PCR machine (Stratagene). The threshold cycle values were related to a standard curve made with the cloned PCR products. The quantities were normalized to mRNA for the large ribosomal protein P0 (RPLP0; see Ref. 11). No statistically significant difference was found between RPLP0 mRNA levels of all samples when RPLP0 were normalized to 18S RNA levels (data not shown).
Quantitative real-time RT-PCR of tribbles 3.
Tribbles 3 (TRB3) mRNA was measured with 18S rRNA as internal standard on a Rotor-Gene 3000 (Corbett Research) employing quantitative real-time RT-PCR using the QuantiTect SYBR Green RT-PCR kit according to the manufacturer's instructions. The primers used to measure 18S rRNA were part of the QuantumRN 18S Internal Standards kit (Ambion). The primers used to measure TRB3 mRNA are shown in Table 1. All quantitative RT-PCR determinations were done in duplicate, and TRB3 mRNA levels were normalized to 18S rRNA levels.
Recombinant adenoviruses.
Ad-CMV-GFP, Ad-CMV-mPGC-1α, and Ad-CMV-mPGC-1β are all recombinant adenovirus vectors (6) capable of expressing either green fluorescent protein (GFP), mouse PGC-1α, or mouse PGC-1β (52). The preparation of purified adenovirus was carried out using the Adeno-X Virus Purification Kit according to the manufacturer's instructions. Recombinant adenoviruses were titered using the Adeno-X Rapid Titer Kit (Clontech).
mRNA and glycogen data were log-transformed before statistical analysis. All graphs depict the mean (geometric mean for mRNA and glycogen) of three independent experiments done in duplicate ± SE (backtransformed for mRNA and glycogen) unless otherwise noted. All data were analyzed using mixed-model statistics on each day, with post hoc tests being Bonferroni adjusted (SAS 9.1.2; The SAS Institute). The experiments were considered to be a randomized complete block design. Statistically significant differences between GFP and control, PGC-1α, or PGC-1β or between PGC-1α and PGC-1β are indicated in the legends for Figs. 1–5.
Primary rat skeletal muscle cell cultures.
The cultures matured from single dispensed myoblasts on day 0 into myotubes exhibiting a morphology resembling striated muscle and showing spontaneous contractile activity from day 6. By visual assessment, it was estimated that >90% of the single myoblasts fused into myotubes. The cultures were readily transduced with adenoviruses on day 5 postisolation when infected with adenoviruses at a multiplicity of infection of ∼25. The level of infection could be observed visually by the expression of GFP (Fig. 1), and, judging from GFP expression, >90% of the cells were successfully transduced. The cultures showed a significant increase in PGC-1α mRNA levels in the PGC-1α-transduced cultures and a significant increase in PGC-1β mRNA levels in the PGC-1β-transduced cultures (see Fig. 4), whereas no increase in PGC-1α nor PGC-1β expression was seen in the GFP-transduced cultures. No direct visual difference between nontransduced cultures and cultures transduced with adenoviruses capable of driving the expression of either GFP, PGC-1α, or PGC-1β was observed (Fig. 1). However, a marked increase in the spontaneous contractile activity of the PGC-1α-overexpressing cultures was observed visually.
Effects of PGC-1α and PGC-1β overexpression on the activities and mRNA levels of metabolic enzymes.
The activities of four different metabolic enzymes (CS, LDH, CK, and GAPDH) were measured in the skeletal muscle cell cultures at the indicated days (Fig. 2). For comparison, the activities of LDH, CS, and CK were measured in two different rat hindleg muscles (EDL and soleus) in 3-wk-, 8-wk-, and 4-mo-old rats as well as in rat primary fibroblast cultures (Table 2).
Both PGC-1α and PGC-1β overexpression enhanced CS activity approximately twofold from days 14 to 22 (Fig. 2), indicating a shift toward a more oxidative metabolism. This corresponds well with previous observations that both PGC-1α and PGC-1β stimulate mitochondrial biogenesis and oxidative metabolism (28, 29, 37, 43, 47). As expected, the mRNA level of CS was increased in both the PGC-1α- and PGC-1β-overexpressing cultures from days 9 to 22 (see Fig. 4). The highest increase in CS mRNA levels was observed on day 9, with a three- to fourfold upregulation compared with both controls. The level of CS activity in the skeletal muscle cell cultures was comparable to the CS activity observed in adult muscle (Table 2). Fibroblast cultures, however, had about fourfold lower CS activity than the skeletal muscle cell cultures.
Transduction of the skeletal muscle cell cultures with an adenovirus expressing GFP increased the CK activity compared with the nontransduced control on days 14 and 22 (P < 0.05 and P < 0.01, respectively). This effect was, however, negated to some extent by the overexpression of PGC-1α and PGC-1β, suggesting a negative regulation of CK activity by PGC-1α and PGC-1β (Fig. 2). The levels of CK activity measured in the skeletal muscle cell cultures were ∼35-fold higher than in fibroblasts, but approximately sixfold lower than the lowest activity measured for adult muscle tissue (Table 2).
No significant change in LDH activity was observed upon overexpression of either PGC-1α or PGC-1β in the skeletal muscle cell cultures (Fig. 2). The level of LDH activity measured in the skeletal muscle cell cultures was comparable with the level of LDH activity in adult rat muscle and about twofold higher than the activity measured in fibroblasts (Table 2).
The activity of GAPDH was found to be slightly elevated by PGC-1α overexpression at the end of the culture period (Fig. 2), whereas the relative differences in the mRNA levels of GAPDH varied a lot more (Figs. 3 and 4). Most notably, a significant upregulation of GAPDH mRNA of about fourfold by PGC-1α was detected by both quantitative RT-PCR and Northern blot, but also PGC-1β overexpression upregulated GAPDH mRNA expression. The levels of GAPDH activity measured in the skeletal muscle cell cultures were comparable with the GAPDH activity observed in adult muscle (30).
The mRNA levels of short-chain acyl-CoA dehydrogenase were increased by PGC-1α and PGC-1β overexpression, although statistically significant on day 9 only (Fig. 4).
Both PGC-1α and PGC-1β cause an increase in GLUT4 mRNA levels, but only PGC-1α causes an increase in glycogen accumulation.
PGC-1α overexpression caused an increase in GLUT4 mRNA levels (Fig. 4), as has previously been reported (35). Interestingly, we observed a similar increase in GLUT4 mRNA levels in the cultures overexpressing PGC-1β (Fig. 4). PGC-1α overexpression significantly increased the glycogen content by ∼100% at both 5 and 25 mM glucose on day 9 (Fig. 5), whereas PGC-1β seemed to have the opposite effect, decreasing glycogen content, on days 14 and 22 (Fig. 5). The cultures were found not to be insulin sensitive, since treatment with or without 10 nM insulin at both 5 and 25 mM glucose resulted in no difference in glycogen accumulation (data not shown).
Both PGC-1α and PGC-1β overexpression quicken the maturation of muscle myotubes and induce a more oxidative muscle fiber type.
To determine the fiber type composition of the primary skeletal muscle cell cultures, the mRNA levels of different myosin heavy-chain (MHC) isoforms (44) were measured in the skeletal muscle cell cultures (Fig. 3). The skeletal muscle cell cultures contained up to 13% of the amount of adult MHC mRNA found in adult rat skeletal muscle (Schjerling, unpublished observation) and expressed all adult MHC isoforms normally found in adult skeletal muscle tissue. The mRNA levels of embryonal MHC (MHCemb) and perinatal MHC (MHCperi), both developmental and immature MHC isoforms, were significantly faster downregulated in the cultures overexpressing PGC-1α and PGC-1β, indicating that these cultures matured faster than the control cultures. Both PGC-1α and PGC-1β overexpression increased the mRNA levels of the slow oxidative associated MHCIb isoform, whereas only PGC-1β significantly increased the mRNA level of the intermediate fast oxidative-associated MHCIIA isoform. PGC-1α and PGC-1β overexpression both decreased the mRNA levels of the fast glycolytic-associated MHC isoforms, MHCIIX and MHCIIB, throughout the culture period. All in all, the overexpression of either PGC-1α or PGC-1β leads to a more mature and oxidative MHC isoform mRNA expression pattern in the skeletal muscle cell cultures.
PGC-1α and PGC-1β overexpression alter myocyte enhancer factor 2C and TRB3 mRNA levels.
In this study, PGC-1α and PGC-1β overexpression caused an ∼50% downregulation of myocyte enhancer factor 2C (MEF2C) mRNA levels throughout the culture period (Fig. 4). The transcription factor MEF2C has been implicated in myofiber plasticity (41) and in PGC-1α regulation of GLUT4 expression in skeletal muscle (29, 33).
PGC-1α overexpression was recently shown to enhance the expression of TRB3, a negative regulator of insulin signaling, in hepatocytes (12, 22), although some controversy exists (19). In the present experiment, TRB3 mRNA levels increased ∼25-fold from day 5 to day 9, suggesting a regulation of TRB3 expression by mechanisms involved in myotube maturation (Fig. 3). Notably, only PGC-1α overexpression was found to significantly increase the TRB3 mRNA levels on days 9 and 14, whereas no significant effect on TRB3 mRNA levels was observed in the PGC-1β-overexpressing cultures. The TRB3 mRNA levels observed on days 9, 14, and 22 were ∼10% of the level present in primary hepatocytes (data not shown).
The PGC-1 family of transcription factors comprises three members [PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC)], with both PGC-1α and PRC being upregulated in skeletal muscle by acute bouts of exercise (2, 45, 49) and PGC-1β being unaffected (34). PGC-1α and PGC-1β have furthermore been shown to be differentially regulated in oxidative and glycolytic skeletal muscle tissue, with PGC-1α having a high expression level in oxidative type 1 muscle and a low expression level in type 2 glycolytic muscle, whereas the opposite holds true for PGC-1β (23, 29). PGC-1α transgenic mice expressing the coactivator specifically in skeletal muscle tissue show a distinct muscular phenotype, with all skeletal muscle becoming more oxidative (29). The effect of enhanced PGC-1β expression in vivo on skeletal muscle phenotype has not been examined (21). Overexpression of PGC-1α or PGC-1β in vitro has shown that both coactivators are able to alter mitochondrial metabolism by increasing the level of proton leak rates in mitochondrial respiration, with PGC-1α being the most potent (52). Even though PGC-1α and PGC-1β share many target genes (27), PGC-1β is unable to compensate for the loss of PGC-1α as seen in PGC-1α knockout mice, who exhibit deficits in oxidative metabolism in multiple tissues and exercise intolerance (26). Here we show that PGC-1β also contributes to the regulation of the skeletal muscle contractile and metabolic phenotype.
Effect of PGC-1α and PGC-1β overexpression on metabolic phenotype.
The present study confirms the stimulating effect of both PGC-1α and PGC-1β expression on oxidative metabolism (21, 29, 52). This is most obviously seen by the increase in CS activity and mRNA expression and is corroborated by the enhanced expression of short-chain acyl-CoA dehydrogenase on day 9 of culture (Figs. 2 and 4). The decrease in CK activity in PGC-1α- and PGC-1β-transduced cultures may also suggest a change toward a slow oxidative phenotype, since the CK activity was found to be lower in slow oxidative soleus muscle than in fast glycolytic EDL muscle of young rats (Table 2). Although this difference diminished with age, the properties of the muscle cell cultures prepared from neonatal myoblasts probably reflect those of younger rather than older rats. CK activity has also been reported to be significantly higher in fast glycolytic than in slow oxidative muscle fibers (59), although others find no difference (9). This discrepancy might be explained by our observation that CK activities in rat skeletal muscles change with age in soleus muscle (Table 2).
Neither PGC-1α nor PGC-1β appears to downregulate glycolytic metabolism as one might have anticipated. Thus only a slight effect was found on the activity of GAPDH, and both coactivators caused an unexpected increase in GAPDH mRNA levels (Figs. 2–4). In adult rats, the activity of GAPDH has been reported to be fourfold higher in glycolytic than in oxidative muscles (30). Similarly, the activity of LDH, which is often taken as a measure of glycolytic metabolic activity (53), was not affected by PGC-1α or PGC-1β overexpression (Fig. 2), although the enzyme activity was higher in EDL than in soleus muscle of young rats (Table 2). Furthermore, the expression of GLUT4 was enhanced by PGC-1α or PGC-1β overexpression (Fig. 4). Interestingly, glycogen accumulation was increased, and the effect appeared specific for PGC-1α overexpression (Fig. 5). This corresponds with the observation that endurance training, which is known to upregulate PGC-1α (45), increases the maximum glycogen content of skeletal muscle (16, 38, 50). The observation that PGC-1β seems to cause a decrease in glycogen accumulation has not been shown before, and the possible involvement of PGC-1β in skeletal muscle glucose metabolism warrants further investigation, since it has only been thoroughly examined in the liver (28). It may be suggested that PGC-1α causes a diversion of glucose metabolism from oxidation to deposition in accordance with the lowered pyruvate oxidation, as reflected by enhanced expression of pyruvate dehydrogenase kinase-4 in C2C12 myotubes overexpressing PGC-1α (56).
GLUT4 expression is known to be enhanced by PGC-1α via coactivation of MEF2C (35); however, regulation of MEF2C by PGC-1α and PGC-1β as seen in this study (Fig. 4) has previously only been reported for PGC-1α (36) and not for PGC-1β. Despite the downregulation of MEF2C, we still observed an increase in GLUT4 expression, in contrast to a previous in vivo finding where overexpression of PGC-1α in skeletal muscle of mice prompted both a downregulation of MEF2C and GLUT4 (36). This apparent discrepancy in the results of PGC-1α overexpression in vivo and in vitro is not easily explained; however, others have found a similar increase in GLUT4 mRNA expression after PGC-1α overexpression in myotubes in vitro (35). Interestingly, PGC-1α expression is regulated by MEF2C as well in a feedforward autoregulatory loop (15). One might speculate that the downregulation of MEF2C expression seen in both PGC-1α and PGC-1β overexpression constitutes a failsafe mechanism to control their runaway expression.
The upregulation of TRB3 mRNA after myotube formation from day 5 to 9 of culture (Fig. 3) suggests a possible role for TRB3 in myogenesis. TRB3 binds to and inhibits the activation of Akt1 and Akt2 (12), which are both implicated in signal transduction events by insulin and insulin-like growth factor I (IGF-I; see Ref. 14). IGF-I has been shown to be involved in muscle fiber growth (39), and the marked upregulation of TRB3 after myofiber formation might be one mechanism by which myogenesis prevents excessive skeletal muscle hypertrophy. PGC-1α and to some extent PGC-1β overexpression in the skeletal muscle cell cultures caused an increase in TRB3 mRNA (Fig. 3) in accordance with the observation that TRB3 upregulation in liver is caused by PGC-1α (22). The observed increase is comparable with the relative increase observed in fasted liver (12).
In several cases, an effect of the GFP-expressing adenovirus alone was noted. This was most pronounced in the case of CK activity but was also observed in LDH activity and GAPDH measurements as well as in MHCemb, MHCperi, MHCIb, and MHCIIA mRNA levels; however, the majority of parameters measured showed no significant difference between nontransduced controls and GFP-transduced controls. Similar effects were observed in skeletal muscle cell cultures transduced with an adenovirus expressing β-galactosidase (data not shown), which has led us to conclude that the effect is not caused by the overexpression of GFP but is rather an effect inherent in the adenovirus expression vector. Most of the changes caused by transduction with the GFP-expressing adenovirus perturbs the skeletal muscle cell culture toward a more glycolytic phenotype, something that has previously been observed to happen upon infection of cells with adenovirus (4, 17).
Effect of PGC-1α and PGC-1β overexpression on contractile phenotype.
Both PGC-1α and PGC-1β seem to be involved in myofiber maturation, since overexpression of either coactivator causes a downregulation of MHCemb and MHCperi (Fig. 3).
Overexpression of both PGC-1α and PGC-1β causes a downregulation of the fast glycolytic-associated MHC isoforms, MHCIIX and MHCIIB, and an upregulation of the slow oxidative-associated MHC isoforms, MHCIb and MHCIIA (Fig. 3). PGC-1β, which has not previously been shown to be involved in skeletal muscle plasticity, increases the levels of the fast glycolytic oxidative-associated MHCIIA mRNA both sooner and to a higher degree than PGC-1α, indicating a difference in MHCIIA regulation by the two coactivators. Interestingly, transgenic mice overexpressing either PPARδ or calcineurin in skeletal muscle have a similar phenotype to mice overexpressing PGC-1α in skeletal muscle (40, 54). We have previously shown that calcineurin signaling is involved in regulation of an oxidative muscle fiber phenotype (18), whereas others have shown involvement of MEF2D and PGC-1α in calcineurin regulation of skeletal muscle phenotype (29). With the regulation of MEF2C expression by PGC-1α and PGC-1β shown here and the knowledge that MEF2 transcription factors act downstream of calcineurin signaling (5), one might speculate that a shift toward more oxidative phenotype in skeletal muscle is carried out by the combined transcriptional regulation of PGC-1α, PGC-1β, PPARδ, and calcineurin signaling, e.g., MEF2 transcription factors.
PGC-1α has been shown to cause a dramatic shift toward a slow oxidative muscle fiber type in transgenic mice when expressed from about embryonic day 14 in skeletal muscle (29, 55). Because PGC-1α in these mice was expressed throughout both primary and secondary myofiber formation, it cannot be ruled out that the observed effects were the result of a role of PGC-1α in myogenesis. The effects seen by PGC-1α and PGC-1β overexpression in the present experiments cannot be purely developmental and may indeed be the result of true adult myofiber plasticity, since the PGC-1α and PGC-1β overexpression in the skeletal muscle cell cultures starts at ∼days 6–7. This corresponds to a time when myotubes have already been formed and some maturation toward myofibers has begun. On the other hand, the gradual downregulation of MHCemb mRNA during culture suggests that the cultures are not yet fully adult in nature.
The myotubes in the skeletal muscle cell cultures exhibited plenty of spontaneous contractions. PGC-1α has been shown to be induced in skeletal muscle by exercise (1, 2), and exercise is known to cause a shift in skeletal muscle fiber phenotype from fast glycolytic to slow oxidative. It can therefore not be excluded that the spontaneous contractions of the muscle cell cultures are required for the myofiber-type switch caused by PGC-1α or PGC-1β overexpression and that the effect might be more pronounced in the PGC-1α-overexpressing cultures, since these qualitatively seemed to spontaneously contract more frequently. However, if the differences in spontaneous contractile activity had a major impact on the metabolic properties of the myotubes, one might also expect the more active myotubes to store less glycogen, since the energy would be required for contraction. This does, however, not seem to be the case, since the more active myotubes, the ones overexpressing PGC-1α, stored more glycogen than the cultures that were less active, indicating that the contribution from spontaneous contractions most likely can be dismissed.
In conclusion, both PGC-1α and PGC-1β were shown to have an effect on skeletal muscle fiber metabolism and fiber type. Both upregulated oxidative metabolism, with no apparent effect on glycolytic metabolism, and both conferred a switch toward a more slow myofiber phenotype. The switch in myofiber phenotype was, however, differently regulated by PGC-1α and PGC-1β, since both caused a decrease in fast glycolytic-associated MHCIIB and MHCIIX, with PGC-1β having a more profound effect on the glycolytic oxidative MHCIIA. The differences between PGC-1α and PGC-1β became more apparent when the glycogen content of the myofibers was measured, since only PGC-1α upregulated cell glycogen content and only PGC-1α was able to upregulate TRB3. All in all, PGC-1α and PGC-1β seem to have both overlapping yet distinctively different effects on the phenotype of skeletal muscle fibers.
The adenoviruses used were a generous gift from Dr. Christopher Newgard (Duke University). This work was supported by the Danish Academy of Technical Sciences, Novo Nordisk, Novo Nordisk Foundation, Rigshospitalet, Hovedstadens Sygehusfællesskab, University of Copenhagen, and Savværksejer Jeppe og Hustru Ovita Juhls Mindefond.
We are grateful for the excellent technical assistance by Tina Kisbye Rasmussen and Christina Bøg Sørensen.
The current address for O. Hartvig Mortensen is Centre of Inflammation and Metabolism, Rigshospitalet (Copenhagen, Denmark).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2006 by American Physiological Society


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Herald Extra: Marvel icon Stan Lee, 'Weird Al,' 'Princess Bride' actors among guests announced for Salt Lake Comic Con FanX
(Daily Herald) With Marvel films dominating the box office year after year, and characters such as Spider-Man and The Fantastic Four coming in on multiple big screen incarnations, it's safe to say Salt Lake Comic Con's founders are paying attention to what fans want when it comes to their conventions. Just check the guest list announced this week at a preliminary press conference for the upcoming Salt Lake Comic Con FanXperience if you need proof.
When it comes to Marvel Comics, there's no one more iconic or acclaimed than the Marvel Universe's founder himself, Stan Lee, who marked only the beginning of a pretty diverse guest lineup pegged for attendance at the March 17-18 convention.
Also scheduled to attend are previously announced guests John Rhys-Davies, Wallace Shawn and Michael Cudlitz, with the 11 a.m. press conference at the Utah State Capitol Rotunda announcing the addition of "Weird Al" Yankovic, Judge Reinhold, Chris Sarandon, Cary Elwes, Adrian Paul, Khary Payton and Tara Strong.
Though Lee's reputation tends to speak for itself — the Comic Con alum is behind the creation of an entire comic book universe and is well-known for his popular cameo appearances in Marvel films — the rest of the guest lineup lends itself to a wide variety of other fandoms, including Utah favorite "The Princess Bride," which according to Salt Lake Comic Con Show Producer and Co-Founder Dan Farr, is one of the highlights of the upcoming event.


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As a high school counselor for over fifteen years, I have tutored students in all humanities subjects using logical sequencing to enhance the learning experience and relevance to the student. If we are covering biology vocabulary, for instance, we start with the first item that happens, then continue on in sequence so that each item (vocabulary word) follows logically from the one before. That helps the student remember the words and their meanings. If we are covering English literature, I ... ... More
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Hello, and welcome to my page! Thank you for considering me as a tutor. More than that, though, thank you for being mature enough to admit when you need a helping hand. Even if I don't seem like quite what you're looking for, I hope you won't get discouraged. I guarantee that there are a lot of great tutors out there that want nothing more than to see you succeed. Ultimately, my goal is to work myself out of a job. I don't want anybody becoming reliant on a tutor to do their work for them. I ... ... More
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I am a certified mentor through the College Reading and Learning Association. I have a few years of experience with mentoring roles throughout high school and college. These roles have allowed me to pass on valuable study skills and information retention strategies. I am also very compassionate and patient and I really love helping people one on one to master subjects of difficulty.
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From the International AIDS Conference 2012: Living 2012 Summit
Posted on: 27th July 2012
Posted by: Body & Soul
This post comes from 'M', a member of The Teen Spirit Board of Directors, a peer mentor at Body & Soul, St George's and St Thomas' Hospitals and a Life in my Shoes Ambassador at the AIDS 2012 Conference in Washington DC
Finally the day arrived and I was on my way to the
'Living 2012 Conference'
. I honestly did not know what expect, but I did anticipate leaving the conference feeling inspired by many people across the world.
As the only representative from Body & Soul at the conference I felt a sense of responsibility for youth living with HIV in the UK. As this was not a youth
conference many elders and experienced professionals in their field surrounded me. The majority had visited previous conferences before hand. Automatically I decided to take the stance to learn from these individuals so when I return to the UK I can talk to young people, at Teen Spirit and further afield, about what I learnt.
Whilst waiting for the conference to start, a Church leader from Senegal greeted me. He informed me of the battle he faced in Africa living with HIV and how it has developed him into a stronger person, leading him to Washington D.C.
I left the conversation inspired and hopeful. Inspired by such a wise and articulate man, and hopeful for those living with HIV, that they had such advocates all over the world.
The day was split into talks and mini workshops/break out sessions. Cornelius Baker spoke about
and the history of the Living conferences. He stated that, "addressing the HIV epidemic is more than addressing cells, it's about addressing peoples lives…" He challenged us to be creative and to "turn the tide". Their were also talks from
Anna Zakowicz
and Kate Thompson.
For me, the most enjoyable part were the 'break-out' sessions. We were challenged with a topic and we had to identify the problem and construct solutions.
Sometimes the solutions were very optimistic, but I still admired the passionate responses to each problem.
As a mentor at Body & Soul and both St George's and St Thomas' hospital in London, I have witnessed first-hand the effectiveness of psychosocial support.
This was a major topic and we identified the need for more people to support those living with HIV. We realised that there are issues with this specific
support system, for example presenting sufficient evidence for funding purposes, whilst battling with the confidentiality agreement made between the
mentee and patient.
We also discussed that 'adherence increases when people have support around them' and how 'HIV is more than a health issue. It should be dealt in a social aspect to help health'.
On day two we collected various information and ideas. We were now ready to construct a documentation for those in power to read. We spent the morning
splitting into break out sessions, but this time each session had a specific topic. I chose to go into the group discussing Religion and HIV and Funding.
As a Christian this interested me and also gave me insight into how many people are actually dying due to mis-informed messages from religious leaders. Also there are people who were rejected from their religious groups due to their HIV status and sexual orientation. Their stories were very painful.
Body & Soul is based in London and working with Body & Soul I have become very accustomed to identifying issues in regards to United Kingdom. The Living conference brought the world's issues into perspective, identifying problems which I had never anticipated. Each country has its own issue and it would be wrong of me to say which issue takes priority above another, because all these problems narrow down to the health of a fellow being. The living conference has existed for many years and HIV is still an issue in the lives of all the people of the world.
I wouldn't be surprised if the discussions we were having today were similar to the last conference. Those living with HIV should be ready to speak up to those in in an influential position, or no change will occur. But for this to happen, something must be done to address the stigma surrounding the virus.
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Results 1 to 2 of 2
05-19-06, 20:47 #1Registered User
- Join Date
- May 2006
- Posts
- 2
Unanswered: Oracle 10g HTMLDB,.. How to EDIT TABLEs
Can someone please tell me the following:
1) How edit tables
I have created Tables in Oracle 10g using the wizard but dont know how edit them to change something. Moreover, how can i make the tables manually using the CREATE table command. I know the syntax but dont know where to write it.
2) Moreover, how to add constraints in the table made by wizard,...
Workspace>SQL Workshop>Create Table
05-20-06, 06:26 #2Registered User
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- May 2006
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Never mind,.. i got the answer,..


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Parent or a teacher, whose role is more important? Score:5 November 12th, 2017 by varun upadhye
The statement given by the author itself is a debatable one as it won't have any definite answer as many people would have different opinions. Parents are the two most important building blocks fo... Read more
Teacher were more valued in the past than now Score:5 October 26th, 2016 by sadik
Throughout history, teachers have played a pivotal role on forming societies. A controversial question which is raised regarding their importance is whether nowadays they are less considered to be ... Read more
No title Score:4 August 15th, 2016 by findscore.com=> 5 or 6 Essays, Click Here <=
I disagree with the idea. Academic progress is not as important as forming moral sense and communication skills. Children acquire them much more from good parents than good teachers. I have two rea... Read more
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toefl3 Score:5 June 12th, 2016 by findscore.com
Children are the unlimited source of possibilities. I have a three-year-old daughter. Every day when she comes home from kindergarden, she tells me what she did, saw, and heard in the school. I am ... Read more
study Score:4.5 May 13th, 2016 by findscore.com
Some people might contend that studying and playing is more recommendable for children than helping their parents with the household chores. Others might argue that the opposite is true. If asked, ... Read more
Better parents than teachers Score:2 May 2nd, 2016 by findscore.com
Some people argues that good teachers are more important to a child's development than good parents. From my expierences, I don't agree with it. Why? Because parents stay with the child much longer... Read more
test of toefl Score:5 April 17th, 2016 by findscore.com
It is one of the most controversial topics whether when you have a chance to get a job, you should wait for another chance or taking it right away. The way I see it, some may concur with the propos... Read more
Child Development Score:3 March 29th, 2016 by findscore.com=> 5 or 6 Essays, Click Here <=
It can not be denied that teachers play a very important rule in child's development, but a teacher can never replace the part that parents have in a child's development.a child's mid function ... Read more
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practice_teachers Score:4.5 December 10th, 2015 by findscore.com
I disagree with the idea that great teachers are more important to a child's development than good parents. In my opinion, good parents have more positive effects on their children. There are two r... Read more
teachers vs parents in child's development Score:4 October 19th, 2015 by findscore.com
I don't agree with the statement, as I agree that teachers have great impacts on child's behaivior and beliefs and as a consequence the way they would develop throught years, it is completely far l... Read more
Whether parents are the best teachers or not Score:4.5 September 30th, 2015 by findscore.com
I do believe that parents can give us a lot of important and useful knowledge about moral and ethical rules of life, but it is quite doubtful that any parent can teach its child physics or informat... Read more
Good teachers are more important to a child's development th Score:3.5 September 17th, 2015 by findscore.com
If you ask people are their parents their best teacher, you will receive different answers. Some of them may say that their parents are their best teachers and others disagree. You will not receive... Read more
Good teachers are more important to a child's development th Score:4 July 13th, 2015 by findscore.com
Parents have an important role in the children's life, and their great impact on their development is undeniable. Even though teachers can be so helpful in broadening their knowledge, they are not ... Read more
Education from teachers Score:3.5 May 31st, 2015 by findscore.com
Those who value families might say that good parent are more necessary than good teachers when it comes to a child's development. However, I strongly agree with the idea that children need good tea... Read more
Good teachers are more important to a child's development th Score:4 April 22nd, 2015 by findscore.com
While some are inclined to consider the role of the good teachers as the most important in the development's process of children, I disagree with this point of view. Personally, I believe that the ... Read more
Are good teachers important than parents? Score:4 February 16th, 2015 by findscore.com
parents are probably the ones who we first when we open our eyes after our birth. They are part of our lives even before our teachers enters in our academic lives. I truly believe that no one can b... Read more
teachers v/s parents Score:3 January 31st, 2015 by findscore.com
Development of a child starts long before he or she starts going to school in fact a child starts learning the day he opened his eyes for the first time. So to say that teachers are more important ... Read more
Parents Role in child Development. Score:3 January 2nd, 2015 by findscore.com
Both Parents and Teachers are play important role in children development. Parents born child and thought him every day life style.However, teachers taught him Languages, mathematics ,Ethics of lif... Read more
No title Score:4 December 5th, 2014 by findscore.com
We are always been taught that parents are the first teacher of any children. For me, my first teacher is always my parents. I strongly agree with the statement. Parent plays major role in the deve... Read more
Good parents mean good children Score:4 November 3rd, 2014 by findscore.com
I disagree with the statement that good teachers are more important to child's development than good parents because it is not crystal clear as it is claimed.In my opinion good parents are more imp... Read more
tasks Score:4 October 10th, 2014 by findscore.com
The question about what characterizes the good teachers is complex. I totally disagree with the statement that a good teacher set challenging tasks for their students. This is just one point betwe... Read more
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At the first glance, it seems too difficult to draw a quick conclusion about whether teachers are have more influence on children than their parents. Howver, after enough pondering and reflection, ... Read more
A teacher Score:5 July 1st, 2014 by findscore.com
Some children consider their good teacher to contribute in the formation of their development, which I consider in some aspects true, however personally I don't agree that good teachers are more im... Read more
good teacher is important for a child's development Score:2.5 June 24th, 2013 by findscore.com
"parents are the good teachers" is an excellent proverb that we are listening since we were kids. good teachers are important for child's development than good parents. i disagree with this statem... Read more
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The development of a child depends on various things. However, parents or teachers work as a piller of their developement. I strongly believe that parents are more important than teachers in a chil... Read more
Good parents are more important than good teachers to a chi Score:5 April 2nd, 2012 by findscore.com
It is sometimes difficult to discuss people's view about the influence on child's development because it is such an multifaceted topic. Although some people think that good teachers are more import... Read more


text:
When Americans were introduced to the Buena Vista Social Club in 1999, Cuban oldies suddenly were hot. But behind the scenes, a legal battle over who owns rights to those songs was born. Dan Grech explains.
Two investment firms have teamed to make an $8.5 billion offer for Australia's Qantas Airways.
A new consumer confidence survey comes out today, just in time for the traditional start of the holiday shopping season. John Dimsdale has a preview.
The plane tickets, the hotel, gasoline — getting to Grandma's house is more expensive than ever this year. Amy Scott breaks it down.
The U.S. wants India to open up its markets to U.S. farm products. India has a wheat shortage but says ours doesn't meet its strict health standards. Where does that leave us? Miranda Kennedy reports.
Commentator Robert Reich says Treasury Secretary Henry Paulson is wrong when he blames strict accounting rules in the U.S. for fueling private acquisition of publicly-held companies.
While the U.S. attempts to squelch online gaming, the Philippines and other countries are welcoming it with open arms. Miranda Kennedy reports.
The U.S. ranks 22nd out of 115 nations in narrowing the economic and political differences between the sexes. Steve Tripoli has details.
Speculative investors, led by American corporate raider Samuel Heyman, have been buying up stock in the London Stock Exchange. Stephen Beard tells us what that means for NASDAQ's bid for a takeover.
Hollywood's holiday film season moves into full swing this week. Ashley Milne-Tyte looks at what's at stake.


text:
Chasing Wild Horses Trailer (2008)
15 December 2008 Factual 48 mins
Roberto Dutesco, New York City's top fashion photographer, captures human beauty everyday. His work graces the covers of everything from Vogue to Victoria's Secret. Since his childhood in Montreal he has carried with him a singular artistic vision. Wild, long-maned dark horses running though white sand dunes. It took him nearly a lifetime to learn where his vision came from. When he discovered Sable Island he became obsessed with the natural beauty of the untouched and unclaimed wild horses. Through his art, and his Manhattan gallery, dedicated solely to the wild horses of Sable Island, Roberto wants to bring support the various organizations dedicated to preserving the beauty of an island untouched.
Watch the official Chasing Wild Horses 2008 trailer in HD below or find more Chasing Wild Horses videos on Vidimovie.


text:
Sometimes I seriously wonder how He does it. How does He, right in the middle of Mass, find a way to talk to me?? With everything going on (the praying, the singing, the reading, the learning), He takes the time to talk with little, old, insignificant me. Not that this happens every Sunday...or maybe it does, but I choose not to listen. But it happens enough that I wonder what I ever did deserve to hear Him speak to my heart.
I don't know if you know what I'm talking about. But attending Mass is a powerful thing (well, of course you all know that!)! And last Sunday, the heavens parted for me and I was like "Duh!" Of course He can talk to me! He talks to all those who are willing to open their hearts! What's funny to me, is that He always says what I need to hear at that moment. Whether I hear it being read from the Bible, or if it's coming through the homily. It's like a big slap in the face (in a good way!)...WHAM!! "Here ya go, Liz! You got questions...I got answers!"
I started getting suspicious when 2-3 times out of the month, it felt like Mass had been rearranged and said specifically for me, my worries, my thoughts, my questions. Seriously. It was too much to go unnoticed. I'm a cry-baby to start with and I tend to get emotional at Mass to begin with...this made it all the more reason for me to bawl like a baby. But this is crying in a good way. "THANK YOU!" How can you ever say that enough to Him?
I'm not usually all about my feelings and emotions on this blog. But I have to get the word out.
LISTEN!!! He is talking to all of us!!! We just need to listen. And perhaps I should take my own advice, for I know that I don't need to wait until Sunday Mass to strike up a conversation with Him. He's available 24/7. My thing is that sometimes...I just go off and talk, talk, talk. Perhaps on Sunday's He's like, "OK...I've listened to you all week long. Now it's my turn and here's what I have to say."
I'm in constant awe.


text:
Our Vision
To serve our partners with unrivaled performance inspiring those we serve to be of service to others, creating a positive impact.
Company Milestones
- SDP established since 1986
- SDP processes over 1.37 billion dollars in transactions each year
- SDP handles tax filings in all 50 states from our CA office
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text:
CosmiQ Works, a firm closely associated with the US intelligence agency, is working with the online retail giant Amazon and the satellite mapping firm DigitalGlobe to train algorithms to work out what's happening on the surface of our planet.
Satellites can already capture astonishingly detailed images from up in space, but the CIA-linked project wants to go one step further and use artificial intelligence to analyse these pictures.
The partners hope to collect 60 million satellite images and store them in a database called SpaceNet which will be open and accessible by members of the public.
Programmers will then design algorithms which can work out what's happening in the images or highlight the buildings, objects and natural features in the photos. The project will be "fuelled by the massive amount of information about our changing planet that DigitalGlobe collects every day".
However, the news is likely to send a chill down the spine of privacy campaigners and conspiracy theorists alike, because it conjures images of a world where surveillance satellites keep a watchful eye on all of us.
"Each minute something is happening in the world," said Tony Frazier, senior vice president at DigitalGlobe.
"While commercial constellations are poised to collect imagery at global scale, we must advance our ability to analyse data to realise its full potential.
"SpaceNet is key to unlocking a huge explosion of new AI-driven applications that ultimately will help us better respond to natural disasters, counter global security threats, improve population health outcomes, and much more.
"The industry is coming together to power smarter algorithms so we can see and learn things from imagery about our planet that we simply cannot know today through manual techniques." source
Geoffrey Grider
NTEB is run by end times author and editor-in-chief Geoffrey Grider. Geoffrey runs a successful web design company, and is a full-time minister of the gospel of the Lord Jesus Christ. In addition to running NOW THE END BEGINS, he has a dynamic street preaching outreach and tract ministry team in Saint Augustine, FL.
- Ky
Where have I heard that Before???
Oh, that's right, Terminator 3: Rise of the Machines!
Come On, Jesus!
OK KY. Here is a quote from Terminator 3 about Skynet:
Terminator 3: Rise of the Machines (2003)
"John Connor: By the time Skynet became self-aware it had spread into millions of computer servers across the planet. Ordinary computers in office buildings, dorm rooms; everywhere. It was software; in cyberspace. There was no system core; it could not be shutdown. The attack began at 6:18 PM, just as he said it would. Judgment Day, the day the human race was almost destroyed by the weapons they'd built to protect themselves. I should have realized it was never our destiny to stop Judgment Day, it was merely to survive it, together. The Terminator knew; he tried to tell us, but I didn't want to hear it. Maybe the future has been written. I don't know; all I know is what the Terminator taught me; never stop fighting. And I never will. The battle has just begun."
Self fulfilling prophesy it seems.
- 01e1ngvar
From last Terminator movie – SkyNet will be launch at the end of September 2017.
- Daniel
Interesting. 6:18pm is 18:18 = 36 or 666. Interesting.
- 01e1ngvar
All sci-fi movies has huge portion of truth. Most technologies what you see there – real. That's what said John Coleman, ex-FBI officer.
- Lucienne
but the CIA-linked project wants to go one step further and use artificial intelligence to analyses these pictures.
This is already being done. Ask me how I know, wink. Targeted Individual, Brain mapping through DARPA, Direct Energy Weapons, Mind Control. ( search terms) Preparations for satans one world govt/religion. How do I beat it? Jesus.
Praise The Lord!
- Ky
"All sci-fi movies has huge portion of truth."
This is very true. If you go back to some of the oldest stuff out there, say "Buck Rogers in the 21st Century", they always looked far fetched at the time, but years later the technology many times appears and surpasses what was in the movie! Sooner or later the military always turns it into a weapon. Isaac Asimov's novels and Star Trek are also good examples of technology that is being pursued. The question I always have is, who is the inspiration for this stuff, the scientists or people with fertile imaginations? (The chicken or the egg?)
- George W
I wonder if they will be able to see me take a piss in the back field at night?
- George W
Soon the androids will be coming for us!
- Ky
Why yes, yes they will…
- DeniseC
Interesting that Muslim prophecy, as interpreted by Grand Ayatollah Shirazi, ties in with this.
"The comments came from Grand Ayatollah Naser Makarem Shirazi, who operates his own website to promote his views."
"Today we use satellites [and by means of them] cover extensive areas, so that anyone with a receiver can use them… In the time of the Mahdi's arrival, there will be a powerful apparatus, that may be difficult for us to imagine today, for transmitting images so that the entire world is visible like the palm of a hand. Without worldwide control by an intelligence [apparatus], there can be no unified global regime [as foretold that there will be when the Mahdi arrives], and no peace, security, and decency… Therefore, God grants him this tool… Once again I stress that this is a routine matter, and that it is inconceivable that it will come about based on a miracle; rather [it will come about] by means of ordinary tools that are based on scientific and industrial advances."
"When the Mahdi rules, the pure will have the height of freedom, and the criminals will be monitored – maybe so much so that sound waves will be detected from the walls of their houses, and when necessary it will be possible to understand what they say at home."
"Perhaps a century ago, this statement [about detecting sound waves] would have seemed like an unimaginable miracle. Yet today, some countries monitor traffic on the roads using radar, with no police present. Therefore, it is clear that during the global revolution of the Mahdi… there will be an unprecedented expansion of industry and technology."
Read more at http://www.wnd.com/2016/08/ayatollah-mahdi-coming-back-in-spaceship/#FJBAgdRuHfbZ1RiG.99
I think it's all part of the Great Delusion: the Vatican is tied to Muslims and also believes in aliens. I think something is going to be revealed very soon. Whether we are here or not for it is up to God.


text: Search Results Studies Variables Publications (1) Your query returned 1 citations. Sort by: Pub Date (newest) Title Recent Additions Author Clear All Pub. Year Citation 1. 1987 Amin, Ruhul, Mariam, A.G. . Racial Differences in Housing: An Analysis of Trends and Differentials, 1960-1978. Urban Affairs Quarterly. 22, (3), 363-376. Full Text Options: DOI Worldcat Google Scholar Export Options: RIS EndNote XML Results 1 - 1


text: I just set up my new web site, which I cannot link to, but I can PM the URL if anyone is interested.. Have added it to web directories, doing forum profiles, and social bookmarking. Gonna have an article written and submitted soon. Do you guys think a campaign for $100 with directcpv.*o* would help my site get some sales or am I wasting my money? Cost for a RON campaign with them is 0.4 cents per view.. Any kind of advice is appreciated, wouldn´t like to throw away $100, I´m in a situation where I need to start making money or end up on the street soon basically.


text:
for Student Mental Health
Student Minds has compiled a report aiming to provide more universities and Students' Unions with information on how peer support for mental health works. The report reviews how peer support can be used safely and effectively within university settings, and includes examples of best practice from around the country to showcase some of the amazing work that is already going on - thank you to all of you who have shared examples of what's happening on your campus!
To take a look at the full report, click on the button to the right.


text:
The Basic Data Types
|The smallest type on an architecture. Usually 8-bits wide. Sign depends on implementation.
|The only type that the modulus operation can be applied on. At least 16-bits in size. Usually 32-bits on 32-bit systems.
|Single precision floating point number. Typically 32-bits wide.
|Double precision floating point number. Typically 64-bits wide, although can be analogous to float (i.e. 32-bits wide) on smaller systems such as 8-bit microcontrollers.
|long double
|Not normally supported on embedded platforms. 128-bits.
|Special case data-type.
Using sizeof()
sizeof() can be used to return the number of bytes each type uses.
"There was a young man named Wight,
Who invented the thirteen bit byte.
You'll get so much more,
from your memory, I'm sure.
But sadly your sizeof ain't right."
Fixed-width Integral Types
The problem with using int and all of it's derivatives ( short int, long int, long long int , e.t.c) is that the width of the integer is platform specific. It is normally the same width as the platforms bus, but at least 16-bits. It is also called the natural width. For example, on an 8-bit system, an int will be 16 bits wide (remember, the C standard specifies it can't be less than 16 bits). On a 16-bit platform, it will usually be 16 bits, 32 bits for a 32-bit platform, 64 bits for a 64-bit platform, and so on, you get the idea!
To write portable code, it is usually better to use fixed-width integral types.
Fixed-width integral types also need special symbols for printf() statements. These are specified in <cinttypes.h>. They begin with the lettters PRI.
Posted: June 14th, 2013 at 7:25 pm
Last Updated on: August 15th, 2017 at 10:50 am


text:
Multiple Reactions. 授課教師:林佳璋. Definitions. There are four basic type of multiple reactions: series, parallel, complex, and independent. These types of multiple reactions can occur by themselves, in pair, or all together. When there is a combination of parallel and series reactions, they
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There are four basic type of multiple reactions: series, parallel, complex, and independent. These types of multiple reactions can occur by themselves, in pair, or all together. When there is a combination of parallel and series reactions, they
are often referred to as a complex reactions.
Parallel reactions (competing reaction)
The reactant is consumed by two different reaction pathways to form different products.
Series reactions (consecutive reaction)
The reactant forms an intermediate product, where reacts further to form another product.
formation of butadiene from ethanol
Involving a combination of both series and parallel reactions
Independent reactions
cracking of crude oil to form gasoline
Occurring at the same time but neither the products nor reactants react with themselves or one another.
Desired and Undesired Reactions
Of particular interest are reactants that are consumed in the formation of a desired product, D, and the formation of an undesired product, U, in a
competing or side reaction.
For a parallel reaction sequence
For a series reaction sequence
We want to minimize the formation of U and maximize the formation of D because the greater the amount of undesired product formed, the greater the cost of separating the undesired product U from
the desired product D (Figure 6-1).
As the cost of a reactor system increases in a attempt to minimize U, the cost of separating species U from D decreases.
Selectivity tells us how one product is favored over another when we have multiple reactions. We can quantify the formation of D with respect to U by
defining the selectivity and yield of the system.
The instantaneous selectivity of D with respective to U is the ratio of the rate formation of D to the rate of formation of U.
Overall selectivity
for a batch reactor
Example 6-1 when we have multiple reactions. We can quantify the formation of D with respect to U by
Develop a relationship between SD/U and for a CSTR.
Consider the instantaneous selectivity for the two parallel reactions just discussed:
Overall selectivity
For a CSTR the overall and instantaneous selectivities are equal.
Carrying out a similar analysis of the series reaction
instantaneous yield when we have multiple reactions. We can quantify the formation of D with respect to U by
overall yield
~Instantaneous yield and overall yield are identical
for a CSTR.
~From an economic standpoint, the overall selectivities
and yields are important in determining profits.
However, the rate-based selectivities give insights in
choosing reactors and reaction schemes that will help
maximize the profit.
~There often is a conflict between selectivity and
conversion (yield) because you want to a lot of your
desired product (D) and at the same time minimize
the undesired product (U). However, in many
instances, the greater conversion you achieve, not
only do you make more D, but you also form more U.
for a batch system
for a flow system
Parallel reactions when we have multiple reactions. We can quantify the formation of D with respect to U by
rate of disappearance of A is
instantaneous selectivity is
Case 1:1>2
To make this ratio as large as possible, we want to carry out the reaction in a manner that will keep the concentration of reactant A as high as possible during the reaction.
A batch or plug flow reactor should
be used in this case.
CSTR should not be chosen under these
If the reaction is carried out in the gas phase, we should run it without inerts and at high pressures to
keep CA high.
If the reaction is in the liquid phase, the use of diluents
should be kept to a minimum.
Case 2: when we have multiple reactions. We can quantify the formation of D with respect to U by 2>1
For this ratio rD/rU to be high, the concentration of A should be as low as possible
This low concentration may be accomplished by diluting the feed with inerts and running the reactor at low concentrations of A.
A CSTR should be used because the concentrations of reactants are
maintained at a low level.
A recycle reactor in which the product stream acts as a diluent could be used to maintain the entering concentrations of A at a low
Because the activation energies of the two reactions in case 1 and 2 are not given, it cannot be determined whether the reaction should be run at high or
low temperatures.
The sensitivity of the instantaneous selectivity to temperature can be determined from the ratio of the specific reaction rates,
A is the frequency factor
E is the activation energy
Case 4:EU>ED
Case 3:ED>EU
The reaction system should be carried out at a low temperature to maximize SD/U.
The reaction system should be operated at the highest possible temperature to maximize SD/U.
Example 6-2 1 and 2 are not given, it cannot be determined whether the reaction should be run at high or
Reactant A decomposes by three simultaneous reactions to form three products, one that is desired, B, and two that are undesired, X and Y. These gas-phase reactions,
along with the appropriate rate laws, are called the Trambouze reactions.
The specific reaction rate are given at 300 K and the activation energies for reactions (1), (2), and (3) are E1=10000 kcal/mol, E2=15000 kcal/mol, and E3=20000 kcal/mol. How and under what conditions (e.g., reactor type(s), temperature, concentrations) should the reaction be carried out to maximize the selectivity of B for an entering
concentration of A of 0.4M and a volumetric flow rate of 2.0 dm3/s.
maximum 1 and 2 are not given, it cannot be determined whether the reaction should be run at high or
The selectivity with respect to B is
Because the concentration changes down the length of a PFR, we cannot operate at this maximum. As a result, a CSTR would be used and operated at this maximum.
The corresponding selectivity at CA* is
The net of formation of A from reactions (1), (2), and (3) is
The mole balance on a CSTR for this liquid-phase reaction (v=v0) is
Maximize the selectivity wrt temperature is
Run at as high a temperature as possible with existing equipment and watch out for other side reactions that
might occur at high temperatures.
Case 1: If
Run at low temperatures but not so low that a significant conversion is not achieved.
Case 2: If
For the activation energies given above
The selectivity for this combination of activation energies is independent of temperature!
What is the conversion of A in the CSTR? is
If greater than 72% conversion of A is required, then the CSTR operated with a reactor concentration of 0.112 mol/dm3 should be followed by a PFR because the concentration and hence selectivity will decrease continuously from CA* as we move down the PFR to
an exit concentration CAf. Hence the system
would give the highest selectivity while forming more of the desired product B, beyond
what was formed at CA* in a CSTR.
Optimum CSTR followed by a PFR is
The exit concentrations of X, Y, and B can be found from the CSTR mole balances
If 90% conversion were required then the exit concentration would be CAf=(1-0.9)/(0.4 mol/dm3)=0.04 mol/dm3.
The PFR mole balances for this liquid-phase reaction (v=v0) are
At τ=0, the values of the entering concentrations to the PFR are the exit concentrations from the CSTR.
maximizing S would be CD/U
The two reactions with recycle shown in (i) and (j) can be used for highly exothermic reactions. Here the recycle stream is cooled and returned to the reactor to dilute and cool the inlet stream thereby avoiding hot spots and runaway reactions. The PFR with recycle is used for gas-phase reactions, and the CSTR is used for liquid-phase reactions.
The last two reactors, (k) and (I), are used for thermodynamically limited reactions where the equilibrium lies far to the left (reactant
and one of the products must be removed (e.g., C) for the reaction to continue to completion.
The membrane reactor (k) is used for thermodynamically limited gas-phase reactions, while reactive distillation (I) is used for liquid-phase reactions when one of the products has a higher volatility (e.g., C) than
the other species in the reactor.
Example 6-3 would be C
For the parallel reactions
Consider all possible combinations of reaction orders and select the reaction scheme that will maximize SD/U.
Case I:1>2, 1>2
To maximize the ratio rD/rU, maintain the concentration of both A and B as high as possible. To do this, use
~A tubular reactor (Figure 6.3 (b))
~A batch reactor (Figure 6.3 (c))
~High pressures (if gas phase), and reduce inerts
Case II: would be C1>2, 1<2
To make SD/U as large as possible, we want to make the concentration of A high and
the concentration of B low. To achieve this result, use
~A semibatch reactor in which B is fed slowly into a large amount of A (Figure 6.3(d))
~A membrane reactor or a tubular reactor with side streams of B continually fed to
the reactor (Figure 6.3(f))
~A series of small CSTRs with A fed only to the first reactor and small amounts of B
fed to each reactor. In this way B is mostly consumed before the CSTR exit stream
flows into the next reactor (Figure 6.3(h))
Case III: would be C1<2, 1<2
To make SD/U as large as possible, the reaction should be carried out at low concentrations of A and B. To achieve this result, use
~A CSTR (Figure 6.3(a))
~A tubular reactor in which there is a large recycle ratio (Figure 6.3(i))
~A feed diluted with inerts
~Low pressure (if gas pressure)
Case IV: would be C1<2, 1>2
To make SD/U as large as possible, run the reaction at high concentration of B and low concentration of A. To achieve this result, use
~A semibatch reactor with A slowly fed to a large amount of B (Figure 6.3(e))
~A membrane reactor or a tubular reactor with side streams of A (Figure 6.3(g))
~A series of small CSTRs with fresh A fed to each reactor (Figure 6-3(h))
Maximizing the Desired Product in Series Reactions would be C
For series of consecutive reactions, the most important variable is time: space-time for a flow reactor and real time for a batch reactor. To illustrate the
important of the time factor, we consider the sequence
B is the desired product
~If the first reaction is slow and the second reaction is fast, it will be extremely
difficult to produce species B.
~If the first reaction (formation of B) is fast and the reaction to form C is slow,
a large yield of B can be achieved.
~However, if the reaction is allowed to proceed for a long time in a batch
reactor, or if the tubular flow reactor is too long, the desired product B will be
converted to the undesired product C.
Example 6-4 would be C
The oxidation of ethanol to form acetaldehyde is carried out on a catalyst of 4 wt % Cu-2 wt % Cr on Al2O3. Unfortunately, acetaldehyde is also oxidized on this catalyst to form carbon dioxide. The reaction is carried out in a threefold excess of oxygen and in dilute concentration (ca. 0.1% ethanol, 1% O2, and 98.9% N2). Consequently, the volume change with the reaction can be neglected. Determine the concentration of
acetaldehyde as a function of space-time,
The reactions are irreversible and first order in ethanol and acetaldehyde, respectively.
O2 in excess
Mole balance on A: would be C
Mole balance on B:
integrating factor
Mole balance on C: would be C
Optimum yield
The yield has been defined as would be C
shown as a function of conversion in Figure E6-4.2
Another technique is often used to follow the progress for two reactions in series. The concentrations of A, B, and C are plotted as a singular point at different space time (e.g., 1', 2') on a triangular diagram (see Figure 6.-4). The vertices correspond to
pure A, B, and C.
For (k1/k2)>>1, a large quantity of B can be obtained.
For (k1/k2)<<1, very little B can be obtained.
Algorithm for Solution of Complex Reactions would be C
~In complex reactions systems consisting of combination of parallel and
series reactions, the availability of software packing (ODE solvers) makes
it much easier to solve problems using moles Nj or molar flow rates Fj
rather than conversion.
~For liquid systems, concentration is usually the preferred variable used in
the mole balance equations. The resulting coupled differential mole
balance equations can be easily solved using an ODE solver.
~For gas systems, the molar flow rates are usually the preferred variable in
the mole balance equation.
Mole Balances would be C
Table 6-1 gives the forms of the mole balance equation we shall use for complex reactions where rA and rB are the net rates of formation of A and B.
We find the net rate of reaction for each species in terms of the concentration of the reacting species in order to combine them with their respective mole
Net Rates of Reaction of the concentration of the reacting species in order to combine them with their respective mole
Consider the following reactions
Example 6-5 of the concentration of the reacting species in order to combine them with their respective mole
Consider the following set of reactions:
Write the rate law for each species in each reaction and then write the net rates of formation of NO, O2, and N2.
Net Rates of Reaction
Relative Rates of Reaction of the concentration of the reacting species in order to combine them with their respective mole
Net rate NO of the concentration of the reacting species in order to combine them with their respective mole
Net rate N2
Net rate O2
Stoichiometry: Concentration of the concentration of the reacting species in order to combine them with their respective mole
for liquid-phase reactions, v=v0
for gas-phase reactions
where fn represents the functional dependence on concentration of the net rate of formation
Multiple Reactions in a PFR/PBR of the concentration of the reacting species in order to combine them with their respective mole
We now insert rate laws written in terms of molar flow rates into the mole balances. After performing this operation for each species, we arrive at a coupled set of first-order ordinary differential equations to be solved for the molar flow rates as a
function of reactor volume.
In liquid-phase reactions, incorporating and solving for total molar flow rate is not necessary
at each step along the solution pathway because there is no volume change with reaction.
for gas-phase reactions
Combing mole balance, rate laws, and stoichiometry
solved simultaneously with a numerical package or by writing an ODE solver.
Example 6-6 of the concentration of the reacting species in order to combine them with their respective mole
Consider again the reaction in Example 6-5. Write the mole balances on a PFR in terms of molar flow rates for each species.
total molar flow rate of all the gases is
mole balance on NO of the concentration of the reacting species in order to combine them with their respective mole
mole balance on NH3
mole balance on H2O
mole balance on N of the concentration of the reacting species in order to combine them with their respective mole 2
mole balance on O2
mole balance on NO2
ODE solver algorithm is shown in Table E6-6.1 of the concentration of the reacting species in order to combine them with their respective mole
Table 6-2 shows the equation for species j and reaction i that are to be combined when we have q
reactions and n species.
Example 6-7 that are to be combined when we have q
The production of m-xylene by the hydrodealkylation of mesitylene over a Houdry Detrol
catalyst involves the following reactions:
m-xylene can also undergo hydrodealkylation to form toluene:
The second reaction is undesirable, because m-xylene sells for a higher price than toluene ($1.32/lb vs. $0.30/lb). Thus we see that there is a significant incentive to maximize the
production of m-xylene.
The hydrodealkylation of mesitylene is to be carried out isothermally at 1500R and 35 atm in a packed-bed reactor in which the feed is 66.7 mol% hydrogen and 33.3 mol% mesitylene. The volumetric feed rate is 476 ft3/h and the reactor volume (i.e., V=W/b) is
238 ft3.
The rate laws for reactions 1 and 2 are, respectively that are to be combined when we have q
where the subscripts are: M=mesitylene, X=m-xylene, T=toluene, Me=methane, and
H=hydrogen (H2).
At 1500R, the specific reaction rates are
The bulk density of the catalyst has been included in the specific reaction rate (i.e, k1=k1'b).
Plot the concentration of hydrogen, mesitylene, and xylene as a function of space time. Calculate the space time where the production of xylene is a maximum (i.e., opt)
Solution that are to be combined when we have q
1.Mole balances:
2.Rate laws and net rates:
3.Stoichiometry: that are to be combined when we have q
4.Combining: that are to be combined when we have q
If we know CM, CH, and CX, then CMe, and CT can be calculated from the reaction
5.Parameter evaluation:
These equations can be solved analytically. that are to be combined when we have q
Multiple Reactions in a CSTR that are to be combined when we have q
~If there is no volume change with reaction, we use concentration, Cj, as variables.
~If the reactions are gas phase and there is volume change, we use molar flow rates,
Fj, as variables.
The total molar flow for n species is
Example 6-8 that are to be combined when we have q
For the multiple reactions and conditions described in Example 6-7, calculate the conversion of hydrogen and mesitylene along with the exiting concentrations of mesitylene, hydrogen,
and xylene in a CSTR.
The moles of hydrogen consumed in reaction 1 are equal to the moles of mesitylene
consumed. Therefore, the conversion of hydrogen in reaction 1 is
The conversion of hydrogen in reaction 2 is just the overall conversion minus the
conversion in reaction 1; that is,
The yield of xylene from mesitylene based on molar flow rates exiting the CSTR for
=0.5 is
The overall selectivity of xylene relative to toluene is
Membrane Reactor to Improve Selectivity in Multiple Reactions
~In addition to using membrane reactors to remove a reaction product in order to
shift the equilibrium toward completion, we can use membrane reactor to
increase selectivity in multiple reactions.
~This increase can be achieved by injecting one of the reactants along the length of
the reactor.
~It is particularly effective in partial oxidation of hydrocarbons, chlorination,
ethoxylation, hydrogenation, nitration, and sulfunation reactions.
By keeping one of the reactants at a low concentration, we can enhance selectivity. By feeding a reactant through the sides of a membrane reactor, we can keep
its concentration low.
Example 6-9 Reactions
The reactions
take place in the gas phase. The overall selectivities, , are to be compared for a membrane reactor (MR) and a conventional PFR. First, we use the instantaneous selectivity to determine
which species should be fed through the membrane
We see that to maximize SD/U we need to keep the concentration of A high and the concentration of B low; therefore, we feed B through the membrane. The molar flow rate of A entering the reactor is 4 mol/s and that of B entering through the membrane is 4 mol/s as
shown in Figure E6-9.1 For the PFR, B enters along with A.
The reactor volume is 50 dm3 and the entering total concentration is 0.8 mol/dm3. Plot the molar flow rates and the overall selectivity, , as a function of reactor volume for both the MR
and PFR.
Solution Reactions
Mole Balances for both the PFR and the MR
Net Rates and Rate Laws
Transport Law Reactions
The volumetric flow rate through the membrane is given by Darcy's Law:
K is the membrane permeability (m/skPa) and Ps (kPa) and Pt (kPa) are the shell and tube side pressures, and At is the membrane surface area (m2).
The molar flow rate of B per unit volume of reactor is
no pressure drop
isothermal operation
Fi vs. V
SD/U vs. V
We can easily modify the program, Table E6-9.1, for the PFR simply by setting RB equal to zero (RB=0) and the initial condition for B to be 4.0.
Notes that the enormous enhancement in selectivity the MR has over the PFR.
Example 6-10 simply by setting R
The following gas-phase reactions take place simultaneously on a metal oxide-supported catalyst:
Writing these equations in terms of symbols yields
Determine the concentrations as a function of position (i.e., volume) in a PFR.
Addition information: Feed rate = 10 dm3/min; volume of reactor = 10 dm3; and CA0 =
CB0 = 1.0 mol/dm3, CT0 = 2.0 mol/dm3
Solution simply by setting R
Mole Balances
no pressure drop
relative rates
isothermal operation
Notes that there is a maximum in the concentration of NO (i.e., C) at approximately 1.5 dm3.
Closure (i.e., C) at approximately 1.5 dm
~After completing this section, the student should be able to describe the
different types of multiple reactions (series, parallel, complex, and independent)
and to select a reaction system that maximizes the selectivity.
~The student should be able to write down and use the algorithm for solving
CRE problems with multiple reactions.
~The student should also be able to point out the major differences in the CRE
algorithm for the multiple reactions from that for the single reactions, and then
discuss why care must be taken when writing the rate law and stoichiometric
steps to account for the rate laws for each reaction, the relative rates, and the
net rates of reaction.
~Finally, the student should feel a sense of accomplishment by knowing they
have now reached a level they can solve realistic CRE problems with complex
Homework-4 (i.e., C) at approximately 1.5 dm
Due 2007.11.26
In Int. J. Chem. Kinet., 35, 555 (2003), does the model overpredict the orthodiethyl benzene concentration? Please give a reason.