text:
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes cardiomyocyte survival and contributes to ischemic preconditioning. S1P lyase (SPL) is a stress-activated enzyme responsible for irreversible S1P catabolism. We hypothesized that SPL contributes to oxidative stress by depleting S1P pools available for cardioprotective signaling. Accordingly, we evaluated SPL inhibition as a strategy for reducing cardiac ischemia-reperfusion (I/R) injury. We measured SPL expression and enzyme activity in murine hearts. Basal SPL activity was low in wild-type cardiac tissue but was activated in response to 50 min of ischemia (n = 5, P < 0.01). Hearts of heterozygous SPL knockout mice exhibited reduced SPL activity, elevated S1P levels, smaller infarct size, and increased functional recovery after I/R compared with littermate controls (n = 5, P < 0.01). The small molecule tetrahydroxybutylimidazole (THI) is a Federal Drug Administration-approved food additive that inhibits SPL. When given overnight at 25 mg/l in drinking water, THI raised S1P levels and reduced SPL activity (n = 5, P < 0.01). THI reduced infarct size and enhanced hemodynamic recovery in response to 50 min of ischemia and to 40 min of reperfusion in ex vivo hearts (n = 7, P < .01). These data correlated with an increase in MAP kinase-interacting serine/threonine kinase 1, eukaryotic translation initiation factor 4E, and ribosomal protein S6 phosphorylation levels after I/R, suggesting that SPL inhibition enhances protein translation. Pretreatment with an S1P1 and S1P3 receptor antagonist partially reversed the effects of THI. These results reveal, for the first time, that SPL is an ischemia-induced enzyme that can be targeted as a novel strategy for preventing cardiac I/R injury.
- sphingosine-1-phosphate
- sphingolipid
- Sgpl1
sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that promotes cell survival and inhibits apoptosis through activation of its cognate G protein-coupled receptors, resulting in the induction of multiple cell survival signaling pathways (4). S1P signaling contributes to cardiac development, angiogenesis, HDL-mediated effects, and regulation of vascular tone and permeability (7, 17, 21, 28). Recent studies (8–13, 15–18, 21, 29, 31, 32, 36) have implicated sphingolipid signaling in protection from ischemia-reperfusion (I/R) injury in the heart and other tissues as well as activation by pre- and postconditioning regimens. These studies collectively indicate that reduced S1P synthesis and signaling contribute to I/R injury, whereas increasing S1P signaling through specific S1P receptors may provide therapeutic benefits in the setting of I/R. Unfortunately, delivery of S1P is challenging due to binding by carrier proteins, ubiquitously expressed receptors, and rapid metabolism. S1P receptor agonists, such as FTY-720, enhance functional recovery after I/R (6). However, FTY-720's clinical utility may be limited by bradycardia stemming from a lack of receptor specificity. Thus, the development of alternative methods for modulating S1P signaling for therapeutic benefits is warranted.
S1P lyase (SPL) catalyzes the irreversible degradation of S1P (14). By reducing S1P pools available for autocrine and paracrine signaling, SPL promotes apoptosis under stress conditions, whereas SPL downregulation promotes cell survival. We hypothesized that modulation of SPL would affect the outcome of I/R injury in the heart. Accordingly, we measured SPL protein expression and activity in cardiac tissue at baseline and during ischemia. We further tested the contribution of SPL to cardiac injury after I/R using a genetic SPL knockout mouse model and a chemical SPL inhibitor. Our results suggest that SPL contributes to I/R injury and that SPL inhibition represents a promising strategy to mitigate cardiac I/R injury.
Animals and drug treatment.
This investigation conformed with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals (NIH Pub. No. 85-23, Revised 1996). This study was approved by the Institutional Animal Care and Use Committees of the Veterans Affairs Medical Center and Children's Hospital Oakland Research Institute. Male wild-type (WT) C57Bl/6 mice weighing 19–25 g were from Charles River (Hollister, CA). SPL gene-trap knockout mice were a kind gift from Philippe Soriano (Mount Sinai School of Medicine, New York, NY) (22). These mice were maintained on a mixed C57BL6/129sv background by mating of heterozygotes, and WT littermates were used as controls. Genotyping was performed as previously described (3). All mice received standard rodent chow. WT C57Bl/6 mice received vehicle or 25 mg/l tetrahydroxybutylimidazole (THI; ∼200-fold more than would be ingested in a normal human diet per day) administered ad libitum in water containing 5.5 mmol/l glucose for 24 h before euthanasia (23). Glucose was added to the water to improve palatability of the THI solution; water intake was not different between vehicle- and THI-treated groups. SPL knockout mice received only vehicle.
I/R injury.
Ex vivo I/R experiments were performed essentially as previously described (8). WT and heterozygous SPL-null mice (males, weight: 22–25 g) were heparinized (500 U/kg ip) and anaesthetized with pentobarbital sodium (60 mg/kg ip). Hearts were rapidly excised, washed in ice-cold arresting solution (120 mmol/l NaCl and 30 mmol/l KCl), and cannulated via the aorta on a 20-gauge stainless steel blunt needle. Hearts were perfused at 70 mmHg on a modified Langendorff apparatus using Krebs-Henseleit solution containing (in mmol/L) 118 NaCl, 4.7 KCl, 2.5 CaCl2, 1.2 MgSO4, 1.2 KH2PO4, 24 NaHCO3, 5.5 glucose, and 5.0 sodium pyruvate bubbled with 95% O2-5% CO2 at 37°C.5 Platinum electrodes connected to a stimulus generator (Grass Instruments, West Warwick, RI) were used to pace hearts at 360 beats/min. An isovolumic balloon filled with degassed distilled water was inserted into the left ventricle (LV) to record hemodynamics as previously described (9–11). The protocol consisted of a 20-min equilibration period followed by 50 min of global ischemia and 40 min of reperfusion. In some experiments, the index ischemia time was reduced to 40 min. For ischemic preconditioning (IPC), hearts were equilibrated for 16 min and then subjected to two short cycles of I/R, each consisting of 2 min of global ischemia and 2 min of reperfusion followed immediately by prolonged I/R as described above. Some hearts received the S1P1 and S1P3 receptor antagonist VPC-23019 (Avanti Polar Lipids, Alabaster, AL) administered at 1 μmol/l for 20 min during the 20-min equilibration period.
For the measurement of infarct size after I/R ± IPC, hearts were infused with 15 ml of 1% triphenyltetrazolium chloride (TTC; Sigma) in PBS at a rate of 1.5 ml/min as previously described (9–11). Hearts were then removed from the cannula, weighed, and fixed overnight in 10% formalin. Hearts were removed from formalin and stored at −20°C until being sectioned for the analysis of LV infarct size as previously described by our laboratory (9–11). The infarct size of each section was expressed as a fraction of the area at risk, which was defined as the total area of the LV in this global ischemia model.
Antibodies and reagents.
Antibodies were raised against the murine SPL COOH-terminal peptide VTQGNQMNGSPKPR. Anti-ribosomal S6 protein-phosphoprotein (S6), anti-phospho-eukaryotic translation initiation factor 4E (eIF4E), anti-phospho-MAPK-interacting serine/threonine kinase 1/2 (Mnk1/2), and horseradish peroxidase-linked anti-rabbit IgG were from Cell Signaling (Danvers, MA). Anti-actin and TTC were from Sigma-Aldrich. Rabbit polyclonal anti-β-galactosidase was from Abcam. THI was from Albany Molecular Research. ω-(7-Nitro-2–1,3-benzoxadiazol-4-yl)-d-erythro-S1P (NBD-S1P) and VPC-23019 were from Avanti Polar Lipids.
Western blot analysis and immunohistochemistry.
Measurements of SPL, phospho-eIF4E, phospho-S6, and phospho-Mnk1/2 were performed using standard SDS-PAGE and Western blot analysis as previously described by our laboratory (20). Immunoreactive bands were detected by enhanced chemiluminescence (Amersham Bioscience, Piscataway, NJ) and quantified by the densitometric analysis of digitized autoradiograms with NIH Image 1.61 software.
For immunohistochemistry, β-galactosidase antibody was diluted to 1:500 and incubated for 1 h with fixed cardiac tissue from SPL reporter mice or littermate control mice lacking the reporter. Incubation with secondary antibody (anti-rabbit IgG, diluted 1:1,000) followed for 1 h. Paraffin-fixed sections (4 μm thick) were stained with Mayer's hematoxylin-eosin or immunostained. Dectection of the secondary antibody was performed with the Vectastain ABC Elite Kit (Vector Laboratories). Images of slides were captured using ×20 and ×10 objectives on a Carl Zeiss (Thornwood, NY) AxioScope microscope with an AxioCam camera and processed using Adobe Photoshop (Adobe Systems, San Jose, CA) software.
SPL activity.
SPL activity was determined using a fluorescent assay as previously described by our laboratory (2). Briefly, 20 μM of NBD-S1P in SPL reaction buffer (0.6 mM EDTA, 0.4 mM pyridoxal 5′-phosphate, 3 mM DTT, 70 mM sucrose, 36 mM potassium phosphate buffer, and 36 mM NaF) were mixed with 0.08% of Triton X-100 and briefly sonicated. The reaction was carried out by adding 25–50 μg protein at 37°C for 30 min. At the end of the reaction, lipids were extracted into the organic phase by two-phase separation. The lower organic phase was dried, resuspended in methanol, and injected onto a 4.6 × 75-mm Luna C18 HPLC column (Phenomenex, Torrance, CA). The mobile phase consisted of solvent A (water) and solvent B [methanol-5 mM acetic acid in water-1 M tetra-n-butylammonium dihydrogen phosphate at 95:4:1 (vol/vol/vol)]. The peaks corresponding to fluorescent NBD-containing compounds were integrated for quantification.
S1P quantification.
For S1P measurements, mouse heart tissue, equivalent to 25% of a whole heart, was homogenized in 0.5 ml methanol using a glass homogenizer and a tip sonicator. After homogenization, 1.0 ml chloroform-methanol (1:1) was added, and the sample was incubated over night at 48°C. The sample was dried down and resuspended in 3 ml chloroform-methanol (2:1), and the extract was made basic by adding 50 μl of 1 M KOH in methanol. A two-phase separation was obtained by adding 0.5 ml water. The aqueous phase was recovered and made acidic by adding 0.1 ml concentrated acetic acid. Another two-phase separation was obtained by adding 1 ml chloroform-methanol (2:1), and the organic phase was recovered. S1P was extracted from 10 μl mouse plasma by adding 0.4 ml methanol followed by vortexing and incubation for 30 min at 30°C. The sample was spun in a tabletop centrifuge at 14,000 g, and the supernatant was recovered. [17C]S1P was used as an internal standard. Lipids were separated on a C18 column (2.1 × 50 mm, Kinetex, Phenomenex) at a flow rate of 0.25 ml/min. The gradient used was from 45% to 99% methanol containing 1% acetic acid and 5 mM ammonium acetate. Data were acquired in positive mode on a Micromass Quattro LCZ (Waters) mass spectrometer. Lipids were identified based on their specific precursor and product ion pair and quantitated using multiple reaction monitoring as previously described (27).
Statistical analysis.
Statistical significance was determined by a Student's two-tailed t-test for comparison of the means of two samples. Significance was set at P < 0.05.
SPL expression and activity in the mammalian heart.
The SPL gene Sgpl1 is transcriptionally active in murine heart tissues (37). Therefore, we compared immunohistochemical detection of a β-galactosidase reporter in hearts of SPL gene-trap knockout mice and WT littermate controls. Our results revealed specific signals in the endothelium, endocardium lining the valve, and cardiomyocytes (Fig. 1A). In contrast, fibroblasts comprising the valve stroma and scattered throughout the myocardium appeared negative. To confirm SPL expression in WT cardiomyocytes, immunoblot analysis of isolated adult murine cardiomyocytes was performed. As shown in the three control lanes in Fig. 1B, SPL protein was readily expressed in isolated heart cells. Consistent with this finding, SPL activity of 2–5 pmol·mg−1·min−1 was detected in adult cardiac tissues.
SPL activity is induced during ischemia.
To determine whether cardiac SPL activity is affected by ischemia, the Langendorff model was used to induce ischemia and I/R in ex vivo WT murine hearts using the treatment scheme shown in Fig. 2A. We have previously shown that IPC enhances the biosynthesis of S1P by increasing sphingosine kinase activity (11). Considering these previous findings, we also examined whether IPC influences the activity of the major enzyme responsible for S1P degradation, namely, SPL. As shown in Fig. 2B, SPL activity in ischemic tissues increased threefold over baseline. SPL activity returned to near baseline levels in I/R-treated tissues during reperfusion. SPL activity was lower in IPC plus ischemia-treated tissues than baseline, although the results did not reach statistical significance. In contrast to the dynamic response of SPL activity, SPL protein expression remained constant under these conditions (Fig. 1B). Based on these results, we conclude that SPL is activated by ischemia and may be inhibited by IPC.
SPL loss-of-function mutant mice are resistant to I/R-induced cardiac injury.
To ascertain whether SPL activation contributes to cardiac I/R injury, we used a genetic model of SPL deficiency. Because mice homozygous for a targeted deletion of the murine SPL gene Sgpl1 do not survive beyond ∼1 mo after birth, we compared mice heterozygous for the Sgpl1-null allele to age- and sex-matched WT littermate controls. Furthermore, to evaluate the importance of SPL in regulating cardiac S1P, we quantified S1P levels in WT and SPL-deficient mouse hearts at baseline and after I/R. As shown in Fig. 3A, tissue SPL activity in heterozygous SPL-null mice is approximately half that of littermate controls. Hearts were isolated from heterozygotes and WT littermate control mice, mounted on a Langendorff apparatus, equilibrated, and subjected to I/R. Hemodynamic function was followed by the continuous monitoring of LV developed pressure (LVDP), and infarct size was measured at the end of the experiment, as described in methods. As shown in Fig. 3B, SPL heterozygotes showed a twofold increase in cardiac S1P levels compared with WT littermates under baseline conditions. After I/R, S1P levels decreased in both heterozygote and WT hearts, consistent with SPL activation. Importantly, as shown in Fig. 3, C and D, mice constitutively deficient in SPL demonstrated significantly reduced infarct size and increased hemodynamic recovery from I/R injury compared with controls.
Brief oral THI pretreatment affords cardioprotection from I/R-induced injury.
To address whether the cardioprotective effects afforded by SPL reduction observed in a genetic model have translational relevance, it became important to assess the potential cardioprotective effects of pharmacological SPL inhibition. Recently, THI, an imidazole compound found in Federal Drug Administration (FDA)-approved caramel food coloring no. 3, was shown to inhibit SPL when administered orally to mice (23). The only other small-molecule SPL inhibitor that could be used safely in vivo is the vitamin B6 analog deoxypyridoxine, which has nonspecific activity against all vitamin B6-dependent enzymes. Therefore, we used THI to achieve pharmacological SPL inhibition and tested the effect of this strategy on ischemic heart injury in WT hearts. To that end, THI was placed in the drinking water for 24 h before euthanasia. Initially, we tested several different regimens of THI administration, including 24-h treatment with 25 mg/l, 24-h treatment with 50 mg/l, and 3 days of treatment at both 25 and 50 mg/l concentrations. Surprisingly, maximal cardioprotection was obtained using the lower dose of THI for 24 h, whereas increasing the concentration or the length of exposure resulted in diminished treatment efficacy (data not shown).
As shown in Fig. 4, A and B, THI at 25 mg/l given for 24 h reduced tissue SPL activity and raised cardiac and plasma S1P levels. THI treatment reduced the size of infarction from an average of 29.6 ± 2.4% of the risk area in control hearts to 15.1 ± 4.0% in hearts from mice treated with THI (Fig. 4, C and E). Functional recovery was also improved by THI treatment. As shown in Fig. 4D, LVDP at the end of the experiment averaged 27.8 ± 4.1 mmHg in control hearts versus 52.3 ± 7.5 mmHg in THI-treated hearts.
S1P cell surface receptor antagonism reduces the effect of THI.
We next asked whether inhibition of cell surface S1P receptors would blunt the effects of THI. In isolated mouse hearts, we infused the S1P1 and S1P3 receptor antagonist VPC-23019 at a concentration of 1 μmol/l for 20 min during 20 min of equilibration. Hearts (n = 4 hearts/group) were then subjected to 50 min of ischemia and 50 min of reperfusion. Hearts were from mice treated with THI with or without VPC-23019 or controls treated with the S1P receptor antagonist alone. As shown in Fig. 5, A and B, VPC-23019 alone had no effect on infarct size and hemodynamic recovery compared with hearts from mice not treated with this agent (compare with Fig. 4, C and D). As expected, THI treatment by itself dramatically reduced infarct size and markedly improved hemodynamic recovery, also consistent with the data shown in Fig. 4, C and D. VPC-23019 pretreatment of hearts from mice that received THI showed an intermediate response: infarct size was significantly reduced but not to the level of THI alone. The same was true for LVDP, which was augmented but not to the level of the hearts treated with THI alone. These data establish receptor involvement in THI-mediated cardioprotection but do not exclude an intracellular role for S1P.
SPL inhibition potentiates the activation of key regulators of protein translation after I/R.
Cell survival and containment of tissue damage after I/R are facilitated by stress-induced signaling pathways that activate the protein translational machinery. To explore whether SPL inhibition influences this process, we measured the activation status of two key components of the translational machinery, ribosomal S6 protein and eIF4E, by monitoring their phosphorylation status in the hearts of WT THI-treated and vehicle-treated WT mice. As shown in Fig. 6A, phosphorylation of eIF4E and S6 were both elevated after I/R in control and THI-treated hearts. However, phosphorylation of both these proteins was significantly higher in THI-treated hearts. Similarly, hearts of THI-treated mice subjected to I/R exhibited elevated levels of phosphorylated Mnk1/2, the protein kinase responsible for eIF4E phosphorylation, compared with vehicle-treated I/R control hearts. Quantitative analysis of this immunoblot is shown in Fig. 6B. Quantitated differences in protein levels between THI-treated and vehicle-treated hearts reached statistical significance (P < 0.05) except for eIF4E (P = 0.05). Based on these results, we conclude that THI treatment activates a signaling pathway that involves Mnk/eIF4E and ribosomal S6 protein.
Importantly, we found that the levels of eIF4E, Mnk1/2, and S6 phosphorylation observed in heart tissues exposed to the combination of THI pretreatment administered in vivo and VPC-23019 given ex vivo before I/R were markedly lower than those observed in heart tissues exposed to THI alone. In the case of eIF4E, phosphorylation was almost completely blocked, whereas Mnk1/2 and S6 phosphorylation levels were intermediate between those observed in hearts receiving either agent alone, as shown in Fig. 6, C and D. We observed some variability in our results, some of which may be accounted for by the use of different antibody lots between the two experiments. Despite these variations, our results clearly show that THI effects on the protein translational machinery are attenuated by VPC-23019. These results demonstrate that the activation status of the Mnk/eIF4E and S6 signaling pathway correlates with THI-mediated cardioprotection. Furthermore, both THI-mediated cardioprotection and its effects on the protein translation machinery appear to be at least partially dependent on S1P receptor signaling.
The principal and most remarkable finding of this study is that we show, for the first time, that short-term inhibition of SPL protects mouse hearts against I/R injury. Our study also reveals that SPL is expressed in the murine heart. Although cardiac SPL protein levels remained constant under different ex vivo conditions, SPL activity was rapidly induced in hearts subjected to I/R, presumably through a posttranslational mechanism. This possibility is consistent with the identification of SPL in a screen for nitrosylated proteins and with the presence of potential sites for protein kinase phosphorylation within mammalian SPL protein sequences and the recent identification of SPL as a target of phosphorylation by ataxia telangiectasia mutated/ ataxia telangiectasia and Rad3 related (ATM/ATR) (19, 24, 35).
In our study, a combination of genetic and pharmacological models of SPL inhibition was used to test the role of SPL in I/R, since no specific inhibitor of SPL is available to date. We observed cardioprotection in a genetically altered mouse model exhibiting reduced SPL expression and activity and increased S1P levels. This model was generated by gene-trap mutagenesis, resulting in a null allele (22). In the homozygous state, SPL mutants are runted and die early, whereas heterozygotes are reproductive and live a normal lifespan. In this mouse model, reduced SPL activity observed in the heterozygote does not confer a phenotype in the heart under resting conditions, but hearts from these mice exhibit diminished susceptibility to I/R injury.
Importantly, in WT C57/Bl6 mice, inhibition of SPL by placing the FDA-approved food additive THI (caramel coloring no. 3) in drinking water for 24 h increased S1P levels, reduced infarct size, and improved functional recovery after I/R. The results we obtained using both of these models strongly implicate SPL as the target of THI that is responsible for mediating cardioprotection. Some differences in the extent of responses between THI administration and SPL heterozygosity were noted. This may be accounted for by the fact that these two experiments were performed in mouse lines of different genetic backgrounds. However, the most likely explanation for this difference is that the heterozygous SPL-null mouse represents a chronic state of inhibition of the sphingolipid degradative pathway. In homozygotes, this has been shown to result in the accumulation of other sphingolipid intermediates upstream of S1P that may be damaging to the myocardium, such as ceramide or sphingosine (3). We suspect that targeting SPL using a small-molecule inhibitor for a brief time period avoids the potential untoward complications of the genetic model, thereby unmasking the full effect of S1P as a cardioprotectant.
The Langendorff system we used for these experiments is a constant-pressure system set at 70 mmHg (11). Since coronary perfusion pressure was constant, coronary flow reflects coronary vascular resistance. At baseline, coronary flow, as measured by the coronary sinus effluent over time, did not differ between the control and THI-treated groups (2.9 ± 0.04 vs. 2.92 ± 0.03 ml/min). After recovery from I/R injury, the coronary flow was higher in the THI-treated group (1.88 ± 0.07 vs. 1.52 ± 0.06 ml/min, n = 6, P < 0.01). The following factors may be involved: control hearts had a larger infarct size, which leads to a larger area of no flow and, hence, an overall reduction in coronary flow. Also, as shown in Fig. 4, I/R injury resulted in higher diastolic pressures and lower systolic pressures in control versus THI-treated hearts. The marked reduction in developed pressure would also be expected to contribute to a reduction in coronary flow. Similar results were found in the heterozygous SPL hearts subjected to I/R injury compared with WT controls.
As noted above, there is substantial evidence that the administration of S1P acutely is cardioprotective (8–12, 17, 21, 29, 31, 32, 36). Although the degree of S1P elevation in response to THI pretreatment was modest, it exceeded endogenous levels relative to baseline achieved by IPC. These levels are sufficient to mediate cardioprotection in rat models of I/R, as we have previously reported (32, 33). We observed that pretreatment of mice with a low concentration of THI for 24 h afforded greater protection than did a higher dose and/or longer treatment periods, such as those used by Schwab et al. (23) to induce lymphocyte depletion. In this connection, it has recently been reported that acute in vitro S1P degradation is primarily driven by lyase cleavage, a process that takes only 40–100 min (25). The translational relevance of these findings will require further testing using SPL inhibitory strategies in postischemic delivery regimens and/or through the use of inducible SPL knockout mouse models.
The shortened lifespan and congenital anomalies observed in homozygous SPL-null mice demonstrate that complete SPL inhibition is not well tolerated and that SPL is an essential protein (3, 22, 34). In contrast, mice exhibiting low levels of SPL expression and activity do not exhibit notable phenotypes, and pharmacological inhibition of SPL has proven useful for immunomodulation (1, 34). Thus, we interpret our data to indicate that brief and incomplete inhibition of SPL may serve to raise and maintain S1P during I/R injury at levels sufficient to capitalize on the protective effects of S1P signaling. Accordingly, the complications that may be associated with long-term total inhibition of sphingolipid degradation can be avoided.
We hypothesize that cardioprotection associated with SPL inhibition or reduced SPL expression can be attributed primarily to the accumulation of S1P and the resulting intracellular and/or receptor-mediated effects. Because THI increases S1P levels both in tissue and plasma, we sought to determine whether cell surface S1P receptors are involved in its beneficial effects. We found that the S1P1 and S1P3 receptor antagonist VPC-23019 significantly reduced the cardioprotective effects of THI feeding. However, there was still a residual reduction of infarct size and an increase in hemodynamic recovery. One possibility is that there is an additional effect of THI on intracellular or even on mitochondrial S1P. Recent evidence has identified a pool of S1P generated by sphingosine kinase-2 that regulates gene transcription (5). Of direct pertinence to the present study is that S1P produced by sphingosine kinase-2 in the mitochondria interacts with prohibitin 2 to regulate the assembly and function of a key member of the electron transport chain, complex IV, or cytochrome c oxidase (26). By raising intracellular S1P levels, THI might affect one or both of these processes. Whether this is the case awaits future investigation.
However, it is possible that other factors may be involved. For example, SPL catalyzes the formation of the reactive long-chain aldehyde hexadecenal. The latter could enhance oxidant stress produced by I/R, thereby potentiating tissue injury. Conversely, oxidant stress during ischemia may be equivalent or even additive to pharmacological postconditioning with S1P, which is cardioprotective (8, 32). Future studies will be required to clarify how modulation of SPL expression and activity influence the heart in the context of I/R and whether S1P and S1P receptors are necessary for mediating the cardioprotective effects of THI. SPL is expressed in cardiomyocytes, fibroblasts, and endothelial cells as well as in other cells and tissues extrinsic to the heart. Further studies using tissue-specific SPL knockout models may be helpful in identifying the specific tissue source of SPL that is required for modulating the cardiac response to I/R.
We observed no obvious differences in apoptotic or autophagic programmed cell death between THI- and vehicle-treated ischemic heart tissues, based on levels of the cleaved form of the caspase-3 substrate poly(ADP-ribose) polymerase as a marker of apoptosis and the processed form of the autophagy marker LC3 by immunoblot analysis (data not shown). These were not unexpected findings, since it would be unlikely for either intrinsic or extrinsic apoptotic pathways to be activated within the short time frame in which our experiments were conducted. Based on our results, we attribute the protection from myocardial tissue injury afforded by THI to the prevention of necrotic cell death.
The effects of THI pretreatment on I/R recovery and infarct size correlated with elevated levels of phosphorylated S6, Mnk1/2, and eIF4E. Furthermore, both THI-mediated cardioprotection and protein phosphorylation effects were partially reversed by inhibition of signaling through S1P1 and S1P3 receptors. Thus, the effects of THI on S1P receptor signaling appear to contribute to its effects on the protein translational machinery. All three of these proteins are downstream targets of stress-activated prosurvival signaling pathways that are influenced by S1P, including phosphatidylinositol 3-kinase, and MEK/ERK MAPK pathways (29, 30, 36). Our cumulative findings suggest that pretreatment with THI primes specific stress-activated signaling pathways, thereby preparing tissues to respond to ischemic injury and contributing to its cardioprotective effects. Preservation of protein translational activity may contribute to the ability of THI to mediate cardioprotection, but it is likely that other factors affected by the immediate response to stress signaling are also involved.
In summary, our findings demonstrate that short-term SPL inhibition may be a novel strategy to protect against acute cardiac I/R injury. Small-molecule inhibitors of SPL are currently in clinical trials as immunomodulatory agents. Based on our findings, we hypothesize that these agents could potentially mitigate I/R injury and other forms of cardiac insult or ischemic tissue damage. In conclusion, this is the first demonstration that short-term SPL inhibition using an FDA-approved food additive is cardioprotective.
This work was supported by National Institutes of Health Grants GM-66954 and CA-77528 (to J. D. Saba), HL-090606 (to J. S. Karliner), and K26-RR-0243037 (to A. D. Borowsky).
No conflicts of interest, financial or otherwise, are declared by the author(s).


text:
ELMONT, N.Y. -- After Eugene Melnyk had watched his horse finish second in the Breeders' Cup Classic, little did he know it was just the start of a big sporting day.
The Ottawa Senators owner made a bee-line from Belmont Park, where Flower Alley was runner-up in the $4.2 million US race, to his favourite Manhattan sports bar.
When he arrived, Melnyk saw that his Senators were handing it to the Maple Leafs, already up 5-0.
"This day just keeps on getting better," said Melnyk, whose horse earned more than $900,000 US for finishing second to Saint Liam.
"I live for days like this. To have a horse finish second in the biggest race of the year is just an incredible, incredible feeling."
And having his hockey team beat the rival Leafs was icing on the cake.

subset: commoncrawl


text:
Content count2,572
Last visited
About Benzine
Socratic Potter
Profile Information
The Hawkeye State
The Arts (Drawing, Painting, Ceramics, Graphic Design), Running, Music (Mostly Rock), Movies, Technology
nancylee liked a post in a topic: Ways To Make Square Forms\Urns
Babs liked a post in a topic: Drying Pots developing mold?
D.M.Ernst liked a post in a topic: Drying Pots developing mold?
Drying Pots developing mold?
Benzine replied to Briana's topic in Studio Operations and Making WorkThere is usually mold on the fresh bags of clay, when I open them up. It grosses my students out, but I simply explain to them, that their hands are probably dirtier, than the clay... The mold on the clay is either white or black. Usually, if it shows up on the wares/ projects, it's only if they sit awhile. The ware boards are worse, since they don't always have a chance to dry out, as they are constantly being used. On those, it's usually a blackish mold. No matter the case, I never worry about it. On the projects, the kiln will take care of the mold, and on the boards, a little soap and water is adequate. The biggest issue is the bacteria that likes to eat the binder in the underglazes. As the saying goes, the smell of those could knock a buzzard off a manure wagon...
Pres liked a post in a topic: Ways To Make Square Forms\Urns
Ways To Make Square Forms\Urns
Benzine replied to nancylee's topic in Studio Operations and Making WorkAfter reading the topic post, your work is the first thing I thought to link to Pres. I remember seeing several "squared" jars on your blog.
Benzine liked a post in a topic: Ways To Make Square Forms\Urns
Beginning wheel throwing projects
Benzine replied to Pres's topic in Studio Operations and Making WorkI've been throwing for fifteen years or so, and I will still leave a bit too much at the base occasionally (Especially with newer forms). Some of it is just getting a feel for what a thick base feels like, and what a thinner base feels like. I also drag my thumb along the base, to create a groove, before beginning some of my pulls. It gives your fingers a path to follow, and has helped me pull more clay, than just a normal pull.
Tyler Miller liked a post in a topic: Source Material on Cobalt and Copper Leaching in glazed wares
Balance as a requirement for being aesthetically appealing
Benzine replied to docweathers's topic in Aesthetic Approaches and PhilosophyI find, that my students are confused by the concept of Balance. They usually simplify it as "Symmetrical= The same on both sides" and "Asymmetrical= Different on each side". It doesn't seem to occur to them that just because Asymmetrical isn't the same on both sides means it lacks "Balance".
I find it interesting that reduction causes iron to flux. Why is this?
Jude liked a post in a topic: Ian Currie Test Tiles Forums?
Min liked a post in a topic: QothW: What studio tool under $100 was your best purchase?
QothW: What studio tool under $100 was your best purchase?
Benzine replied to Pres's topic in Int'l Ceramic Artists Network (ICAN) Operations and BenefitsI really do like the effects that a spray applied layer creates, over top of a glaze. My Dad made a couple really nice pieces, in College, using this method. One is a "Bird Bath" form, with a nice gradient created by the spray. Unfortunately some of his dang kids cracked the ware, when they were younger...
QothW: What studio tool under $100 was your best purchase?
Benzine replied to Pres's topic in Int'l Ceramic Artists Network (ICAN) Operations and BenefitsYeah, I can't comment on that, as I've never tried to sharpen them. The clay body I use, goes pretty easy on the "blade", so sharpness hasn't proven to be an issue yet. I've been watching a lot of "Forged in Fire" lately, so when I do go to sharpen, I'll go all out and heat the blade, then quench it... I'm joking... Or am I...
Callie Beller Diesel liked a post in a topic: QothW: What studio tool under $100 was your best purchase?
QothW: What studio tool under $100 was your best purchase?
Benzine replied to Pres's topic in Int'l Ceramic Artists Network (ICAN) Operations and BenefitsMy Mudtools "Do All Trim Tool". After using loops to trim for years, just love the versatility of the Do All. It's comfortable to use, and it's all I use to trim now... Unless I'm in my classroom, and have to use the loops, because that's all we have there...
So I took one of my demo wheel projects, one that I cut in half with the wire, to show consistent thickness, and used a combination of Magic Water and my saturated slip, to put the two halves back together. The seam is still visible, but that is mostly due to me not worrying about aesthetics as much as performance. After firing, no cracks were visible in the mend, and it held up to the stress of me trying to pull the two halves apart. Is it as strong as the rest of the piece? That I can't say, but it is a pretty good mend! A real test will be with my Art Club's Raku projects. I made a super saturated Raku slip and used the same process to fix some of the breaks on their projects. They came through the Bisque just fine, but we will see how they do with the thermal shock of the actual Raku firing.
Source Material on Cobalt and Copper Leaching in glazed wares
Benzine replied to Tyler Miller's topic in Clay and Glaze ChemistryI have a friend, who used to live in Northern Maine. We would always joke that his phone and internet signals, were bounced off of moose antlers. So if the signal was poor, one of the moose was out of place...
Awesome color. It reminds me of the results/ effects I get with some of my Raku glazes, which is one reason I like it. Is that for functional wares? If it doesn't have an official name, you need to give it one. Based on my experience with the commercial glazes, the names don't always have to make sense. There was color I ordered called "Tabacco Brown", but it was an off white, with small flecks of brown. So it looked more like tabacco spit brown...
Rubber/Silicone Ribs
Benzine replied to RonSa's topic in Studio Operations and Making WorkLike Neil, I still use a wood rib, to compress the bottoms of my forms. I also use a green "Mud Tools" rib, as well as a metal rib for forming. I have honestly never tried using a rib during my pulls. I may need to give it a go sometime.
That tile in the first photo is awesome! What "color" is that?
Benzine liked a post in a topic: Mathematical Definition of "Centered"
Benzine liked a post in a topic: Stenciling designs and carving tips
Stenciling designs and carving tips
Benzine replied to Fredrin's topic in Studio Operations and Making WorkIn order to wrap around, you will have to have wedges cut out, from the top and bottom, to allow for those sections to come together without bunching. Think of the "exploded" version of the Globe: In regards to carving, I was going to recommend an X-ACTO, as I've had success with them. But if that doesn't working, what about a small paring knife? They make specially designed clay cutting/ carving tools for such detailed work, but no sense in buying something if you don't plan on using it regularly.
I'm actually trying new mending methods, as it not only comes up with my High School students, but the Middle School teacher, usually borrows some of my mending slips. So I'm trying to build a better mousetrap, so to speak. The Spooze has been my go to for years. It does a great job. It holds well, sets fast, and can be used right before firing. I just find that the join isn't quite as strong as the surrounding areas. Using Magic Water in conjunction with the Spooze seems to help a bit. But lately I've been using a "Super Saturated" Slip. Just a deflocculated slip, with more clay powder added in. I like it, because, when applied to bone dry clay, it grabs and holds almost instantly. I also use this in conjunction with Magic Water. I am still determining, if the join is any stronger than other methods I've used. Of any of the methods, for fixing wares, I've found the best method, is what I usually tell students, when they bring the damaged project up to me: Me: "What happened?" Student: "I broke my project." Me: "Yeah, I wouldn't have done that, if I were you..."


text:
JESSUP, Md. — TheraPearl on Wednesday named Daniel Baumwald president and Thomas Keeney VP sales.
Baumwald has been with the company since its inception in 2009, coming from Glaceau Vitaminwater/Coca-Cola where he was national account manager. Baumwald will assume management of the TheraPearl team, along with the company's overall direction as it continues to expand.
Keeney will lead TheraPearl's sales team and its retail market expansion. Keeney previously served four years as VP sales and field marketing with Hint, a company that produces and distributes naturally flavored, sugar-free water.
Interested in this topic? Sign up for our weekly Collaborative Care e-newsletter.


text:
Locksmith in Cedar Park TX by Austin Premier Locksmith
Austin Premier Locksmith is a full locksmith service providing commercial, automotive, residential, and motorcycle services to homes and businesses in the Austin metro area with a large variety of security systems and excellent customer satisfaction. Austin Premier Locksmith is committed to providing our customers with prompt and reliable service. From lost car keys to transponder programming, key duplication to bump proof locks we have a solution for everything. 24 hours Emergency lockout services, and lost key replacement services. From replacing a key cylinder to installing commercial security doors, Locksmith in Cedar Park provides a wide range of services and 100% Guarantee Bonded Licensed & Insured.
Here at Austin Premier Locksmith we provide emergency locksmith service around the clock for you because we understand the importance of your security needs. Whether you require a locksmith for your vehicle, a locksmith for your home or a commercial locksmith we will always have the right solution for you, every time.
Austin Premier Locksmith is a name that you can trust! Cedar Park TX Locksmith services all types of locksmith needs. For your entire locksmith problem call (512)981-5046 and our representatives will be assisting you with your needs.
Locksmith Cedar Park TX., Locksmith in Cedar Park TX, Cedar Park TX locksmith service, locksmith service in Cedar Park TX


text:
Qinhuangdao Mingyu T.D. glass co.,ltd
float glass, clear float glass, clear louver glass, bronze float glass, louver glass, Manufacturer and Supplier - China
clear nashiji pattern glass (234)
clear nashiji glass
color: clear
thickness: 4mm, 5mm, 6mm,ect
pattern: nashiji
Clear Nashiji Patterned Glass
Size:1220 x 1830mm, 1500 x 2000mm, 1524 x 2134mm, 1830 x 2440mm etc.
Patterns: Aqualite, Bamboo, Beehive, Nashiji, Chinchilla, Crystal, Diamond, Flora, Karatachi, Masterlite, Millennium, Mistlite, Morgon, Moru, Rain and Wanji etc.
Clear Nashiji Patterned Glass:
As a kind of decorative translucent flat glass with embossed patterns on one or both surfaces, patterned glass can fully allow the light to pass through and on the other hand, can limit or prevent clear view effectively. That is, it is both light transmittance and opaque. They are mainly used on windows, indoor compartment, bathroom and so on.
1. Rich and colorful pattern designs provide unique decorative results: obscure and quiet, or sparkling and lively, or serious and elegant, or bold and generous...
2. Tangible stereoscopic patterns will never fade.
3. Patterned glass can be cut, ground, drilled, tempered, laminated and printed, etc.
4. The perspectives can be divided into transparent, nearly transparent, nearly invisible and completely invisible.
Best wishes
We can produce as your demands.Any interest pls feel free to contact us.
We will do our best to support your business!


text:
XTERRA EX2 Off-Road Triathlon/Duathlon
Saturday, June 21, 2014
Schaeffer Farms Trail System - Germantown, MD
The eighth annual 12 Hours of Cranky Monkey Mountain Bike Relay Race challenges solo racers and teams of 2 or 3 to complete as many 10-mile laps as possible in a 12 hour period, from 8am-8pm. In addition, we will once again bring back the 3 hour solo option. This is perfect for those not able to commit the time or training to compete in the full race.
Schaeffer Farms Trail System will be home to the 12 Hours of Cranky Monkey Mountain Bike Relay Race. With its awesome trails, convenient location, huge transition/pit areas, and the ability to camp on-site before and after the event, Schaeffer is the perfect venue to support this 12 hour mountain bike relay race. It's going to be an excellent weekend of mountain biking action!
The 12 Hrs of Cranky Monkey has been wildly popular since its inception and will undoubledly attract similar large numbers and talent in 2014.
Self-selected classes include:
3 Hr - Solo Classes: Female, Beginner Male, Male Open, Clydesdale (200+ lbs)
12 Hr - Solo Classes: Solo Female, Solo Male, Solo Male Masters 35+, Solo Male Masters 45+, and Solo Single-speed
12 Hr - 2/Team Classes: Duo Co-Ed, Duo Female, Duo Male, and Duo Male Masters 80+ (combined team age).
12 Hr - 3/Team Classes: Co-Ed, Female, Male, and Male Masters 120+ (combined team age).
Thank you for visiting EX2 Adventures.
Since the year 2000, EX2 Adventures has produced quality
outdoor adventure experiences for the greater Washington DC metropolitan community. We encourage you to browse our site and join us at our events. Whether as a competitor, volunteer, or sponsor you are sure to have an excellent experience!
Web Design by: Will Ramos - All Content Copyright © 2016-2017 EX2 Adventures - All Rights Reserved.
EX2 Adventures - 4450 Rivanna Lane MB #3719 - Fairfax, VA 22030-4441 - Contact Us


text:
LONDON-L ArchivesArchiver > LONDON > 1998-01 > 0884135507
From: <>
Subject: Telegraph co
Date: Tue, 6 Jan 1998 18:11:47 -0700 (MST)
My g gfather John Roseblade lived in North Woolwich in the 1880's. I've
been told that he worked laying the first telegraph cable to France.
Don't know if there's any truth to this but would like to know if I can
get records of a telegraph company from that time.
Any help would be appreciated.
Thanks in advance
Madeline in cold and snowy Edmonton, Canada
Perpetually in search of family tree:
This thread:
|Telegraph co by <>


text:
Washington firm may aid in solving county's medical health dilemma
By MEGAN COOPER
Mt. Pleasant News
Hillcrest Life Services of Washington may join with Henry County in order to provide mental health services to those in need.
Sarah Berndt, administrator for Central Point of Coordination (CPC), said, "As of right now, we have to send people to Fairfield for services. We don't have the right resources here in town and some of these people aren't making those appointments." This is in reference to people who have court-appointed commitments to receive mental health care.
Berndt presented a solution to the board during Tuesday's Board of Supervisors meeting. She said, "We have been trying to get Hillcrest Life Services to expand into Henry and Louisa County. I have a contract now, and we can make that happen."
All Hillcrest Life Services will need in order to expand into Henry County would be locating a space to set up shop and start-up money. "We have money to give them the start-up money. We can use our emergency services fund, since we don't have that service, and they can come to our office and we can share the space with them. They need three rooms and reception space. We will have to do some moving around, but we have the room," Berndt said.
Berndt went on to say, "They would want to put a privacy glass window up, but they would pay for that. We would need to put a half-door in, and we would be responsible for that, but that can't cost much. They (Hillcrest) are willing to pay a reasonable rent." With Hillcrest a part of the county, those in need would have services available to them that they didn't have before and more court appointed commitments would be made.
"Hillcrest would give us three days a week for therapy and one day for doctor time. We can route all court made appointments to one spot. We have it so we can make all court appointments to Hillcrest. It makes everything easier," Berndt expressed to the board.
She then informed the board that, "It's a requirement for the county to have this service available. I'm asking you to embrace this idea. I advocate strongly that we do this."
Berndt then presented a rough copy of the contract that has been developed to the board. Greg Moeller, board member, looked over the contract and then Gary See, chairman of the board, suggested a visit to the CPC office on Tuesday in order to make a more sound decision about how Hillcrest would fit into the space. It was agreed upon, and the board will visit CPC Tuesday, at 10 a.m.
After the CPC discussion, See discussed his meeting with the Mt. Pleasant Area Development Commission. "Our commitment for the market research might go down. Winfield has expressed interest in the research, New London we know is on board, but we still don't know about Wayland. There has been good interest by those involved and I think it will hold value for them," See said.
He told the board that, "I think that even if Wayland does, or doesn't, we will still probably do the whole county." Final plans for the actual start date of this research have not been made as of now.
Moeller finished the meeting with a brief synopsis of his meeting with Healthy Henry County Communities, and he said, "the Transformation Grant money has been spent. HHCC bought new bike racks for Salem and even bought new flashing stop signs to put up. The committee also brainstormed ideas for new members and discussed how to get current members more active."
HHCC will meet again on Tuesday Oct. 1, from 1-2:30 in the lower-level meeting room at the ISU Extension office.
The board's next meeting is Tuesday at 9 a.m.


text:
My Nonprofit Reviews
Review for Mitziut, Chicago, IL, USA
Mitziut is an incredibly topical, necessary, of the moment movement to promote a real relationship with community and Judaism. Like many people with young children, I was looking for a place where I 'fit' and where I could pass on my love for my religion to my son and husband. Mitziut holds a monthly Sabbath celebration for families and children and it has given our family and child an authentic experience with his religion and has been a real community builder for us. I SO APPRECIATE MITZIUT IN MY LIFE!!!
More Feedback
If I had to make changes to this organization, I would...
Encourage members to contribute more time/energy to their community
What I've enjoyed the most about my experience with this nonprofit is...
being with soulful people who care about their religion and each other
The kinds of staff and volunteers that I met were...
really into having ongoing learning/artmaking/Jewish learning/community building going on.
Ways to make it better...
I become more committed and invested in the organization!
In my opinion, the biggest challenges facing this organization are...
life! peoples busy lives often preclude full involvement in their religious communities.
How frequently have you been involved with the organization?
About every month
When was your last experience with this nonprofit?


text: On 2008-09-17, Jonathan Cast <jonathanccast at fastmail.fm> wrote: >> In my mind pooling vs new-creation is only relevant to process vs >> thread in the performance aspects. > > Say what? This discussion is entirely about performance --- does > CPython actually have the ability to scale concurrent programs to > multiple processors? The only reason you would ever want to do that is > for performance. I entered the discussion as which model is a workaround for the other -- someone said processes were a workaround for the lack of good threading in e.g. standard CPython. I replied that most languages thread support can be seen as a workaround for the poor performance of communicating processes. (creation in particular is usually cited, but that cost can often be reduced by process pools, context switching costs, alas, is harder.) > Kernel threads /are/ expensive. Which is why all the cool kids use > user-space threads. Often muxed on top of kernel threads, because user-threads can't use multiple CPUs at once. >> The central aspect in my mind is a default share-everything, or >> default share-nothing. > > I really don't think you understand Concurrent Haskell, then. (Or > Concurrent ML, or stackless Python, or libthread, or any other CSP-based > set-up). Or Erlang, Occam, or heck, even jcsp. Because I'm coming at this from a slightly different perspective and place a different emphasis on things you think I don't understand? No, trust me, I do understand them[1], and think CSP and actor models (the differences in nondeterminism is a minor detail that doesn't much matter here) are extremely nice ways of implementing parallel systems. These are, in fact, process models. They are implemented on top of thread models, but that's a performance hack. And while putting this model on top restores much of the programming sanity, in languages with mutable variables and references that can be passed, you still need a fair bit of discipline to keep that sanity. There, the implementation detail of thread, rather than process allows and even encourages shortcuts that violate the process model. In languages that are immutable, taking advantage of the shared memory space really can gain efficiency without any noticeably downside. [1] I used to work for a company designing and modeling CSP-based hardware designs. In my spare time I started writing a compiler from our HDL to Concurrent Haskell, but abandoned it when I left for grad school. -- Aaron Denney -><-


text:
Shaping the future of health and social care
Mark Raeburn, managing director of Capita One, explores the key issues raised when local authority leaders came together to discuss health and social care integration.
ARE local authorities entering a new era of a more joined-up health and social care service for the nation? With the New Year off to a flying start, this might be a good time to reflect on what integration will look like at a local level.
What challenges need to be overcome to support health and social care in working together more closely in the community? Can technology play a part in shaping a more efficient and effective service in the years ahead?
These were some of the questions that came up for debate at a roundtable event recently hosted by the Association of Directors of Adult Social Services (ADASS) in partnership with Capita One. The event brought together seven directors of adult social care to discuss the challenges ahead and reflect on the work already taking place to design and deliver a more integrated model of health and social care.
Building bridges
One priority is to lay down the foundations for strong working relationships between the services, according to John Powell, director of adult social services at the London Borough of Redbridge.
"We've intentionally gone into GP practices, starting dialogues in the localities and working together," he said.
"GPs, district nurses and social workers are all working together, bumping into one another. What we're now trying to do is build on the existing relationships we have."
Relationship building is central to success and a recent survey* suggested that addressing the issues around this is a key focus for local authorities. When asked, 65 per cent of local authority leaders indicated that the greatest challenge of delivering a more integrated service was the cultural shift for the people involved, compared with 35 per cent who stated that bringing systems together was the greatest challenge.
As Powell highlighted: "Where integration and joint working is successful, it is because of longstanding arrangements with relationships between people in the various organisations."
Play to your strengths
However, in aspiring to a more joined-up working environment, some local authorities emphasise the need to preserve the distinct identity of the two sectors and are examining how this might help to ensure that people receive the best possible treatment and care in their communities.
Liz Bruce, director of adult social services for the London Tri-borough councils, suggested that the values and expertise of the different services must be taken into account in an integrated future.
"We should be clear about our ask and our offer in social care. The strengths and skills that you have if you mix up health and social care are tremendous if we get it right. Health is really good at other things that we in social care shouldn't take the lead in," she explained.
"By defining the roles and responsibilities of health and social care, citizens and their communities will get the best of both worlds from their services. This shouldn't be a land grab, it should be a partnership."
Providing the platform
There is a growing desire among local authority leaders to explore how technology might enable the shift towards a more people-centred approach to health and social care integration too.
David Pearson, director of adult social services at Nottinghamshire County Council, emphasised that the role of technology in supporting and managing service users' needs could be significant. But he underlined that "no matter how systems are brought together, it is important that, for social workers and health professionals, it feels as if it is one integrated system rather than multiple systems".
Local authorities are on the cusp of a new era in the delivery of health and social care. By building stronger connections - both cultural and technological - between those who support the most vulnerable in our communities, it is possible to shape a future in which people get the support they need to live more independent lives, for longer.
To read the full local authority interviews, please visit: www.capita-one.co.uk/ADASS/LGE
* The survey was carried out by Capita One at the National Adult and Children's Services Conference in November 2016.and 72 local authority senior leaders responded.


text:
Sat 7th Jul at 7:00pm
The Importance Of Being Earnest
@ Hartland Abbey, Bideford
Featuring: Miracle Theatre Company
This event has been and gone!
Catch the next one:
Check out the info below for future tour dates, and track them to receive alerts when they tour near you
The Importance Of Being Earnest: Miracle Theatre Company
This summer Miracle is performing 'the funniest play ever written', 'The Importance of Being Earnest' by Oscar Wilde.
Set in 1912 with the Titanic sinking, mass production just beginning on the Morris Oxford and the Turkey Trot causing outrage across the dance floors of polite society, this tale of the strange contents of a handbag found at Victoria station cries out for the sort of surreal treatment that has become Miracle's hallmark…expect a hilarious high energy performance!
Audiences of all ages enjoy the full 'open air theatre experience', by bringing along well stocked hampers, cushions and blankets. Bring whatever you need for a cosy evening. Warm woollies, blankets waterproofs and insect spray! Performances will go ahead in all weather conditions!
There will be some refreshments and drink available.
Miracle Theatre Company
Miracle Theatre Company is one of the South West's leading touring companies. Miracle produce work which is varied, engaging and enjoyable which builds instant rapport with audiences of all ages. With a reputation for exciting new writing & popular adaptations of classical works, Miracle tours to open air venues during the summer months - performing rain or shine!
Miracle Theatre Company tour dates
Track this event
- Event has been added to your calendar
- Any important updates will be sent to your email address
- Add to your personal Ents24 calendar
- Sync with iCal, Outlook and others
- Receive important updates
Venue Facts
Venue: Hartland Abbey
Website: hartlandabbey.com
Email: ...
Enquiries: 01237441264


text:
Click the Bolt!
Help! A cute little alien just crash-landed on an unknown planet in a solar system far, far away. Use your physics and problem-solving skills to find more fuel for his trashed flying saucer. This free game will take you through 50 puzzling levels on 10 different planets.The helpless alien's fate is in your hands: only you have the power to bolt and unbolt wooden planks that push him to all the yummy fuel sources. Grab all 3 treats each level and our quirky extraterrestrial friend can go home. Collect all of a planet's stars to warp to the next one.Is your logic and coordination good enough for some outerspace physics? Try to pass all the levels and reach Planet 10!Key Features:- Stunning retina graphics- Game Center leaderboards and achievements- 10 planets and 50 levels!- Innovative cross between physics and puzzle gameplay mechanicsWe like getting comments. Rate and review us, and stay tuned for more games...Like us on Facebook: [https://www.facebook.com/a10com]Happy gaming!


text:
A massive recall of popular infant cold medicines has parents cleaning out their bathroom cabinets and scrambling for old-fashioned remedies as cold and flu season approaches.
Because of fears that the products may be misused and possibly lead to fatal overdoses, leading drug makers Thursday voluntarily removed 14 over-the-counter medications from the market. The medicines include top-selling products sold under the brand names Tylenol, Triaminic, Robitussin, Little Colds, Pediacare and Dimetapp.
The recall does not affect cold and cough medicines intended for children 2 years and older, or single-ingredient fever reducers or pain medications for infants.
Parents are advised not to use recalled medicines they may have at home for children younger than 2 years old. Whether refunds will be granted differs by manufacturer and drugstore.
Drug makers say infant cold medications are safe when taken as directed, but concerns are mounting about overdoses and accidental ingestion of the drugs.
The recall comes a week before a U.S. Food and Drug Administration meeting to review the safety and effectiveness of pediatric cold medications. At themeeting, the federal agency may strengthen warnings about the medications' risks for children and require new package labeling, as some health advocates have urged.
At least 1,500 children under age 2 required emergency room care in 2004 and 2005 after taking non-prescription cough and cold medicines, health officials reported. Another review conducted for the FDA documented 54 deaths involving decongestants and 69 involving antihistamines from 1969 to 2006.
"These medicines are — and always have been — safe at the recommended doses," said Linda Suydam, president of the Consumer Healthcare Products Association, which announced the recall. "These voluntary actions are being taken out of an abundance of caution."
Many pediatricians already urge parents not to give cough and cold medications to their young children, saying they simply don't work that well.
"This should not be viewed as some tragic day for parents with sick kids, because these medications didn't do much to begin with," Dr. Peter Contini, a San Jose pediatrician, said Thursday.
At Children's Hospital Oakland, pediatricians have long recommended against giving over-the-counter cold medicine to young children.
"In general, we try not to give cold medicine to children under 2," Dr. Kelley Meade said, "because a cold is going to last seven to 10 days anyway, and there could be side effects."
Instead, she and other pediatricians at Children's recommend giving children fluids, keeping their noses clear and perhaps using a humidifier.
For infants and toddlers, Meade recommends parents use a nose suction bulb, which the hospital gives to parents, to clear the nose and then perhaps nose drops made of slightly warm tap water or a saline solution.
"A recipe for saline drops is half of a teaspoon of table salt in one cup of water" which can be dropped into the nose with a nose dropper, she said.
In August, the federal government advised parents not to give any cold and cough medications to children under 2 unless specifically directed to do so by a doctor.
Yet the drugs remain popular, Contini said, because parents want to ease their children's misery.
Laura Ino is one San Jose parent who plans to keep using cold medications for her son, who turns 2 next week. As a manager of pharmaceutical clinical trials, Ino is confident the medicines are safe when used as directed, but she acknowledged that parents could overdose their children if they are not careful. She said she keeps close tabs on her child's weight to ensure the proper dose and calls the doctor with any questions.
"I totally believe in them," Ino said of the medications. "I don't believe your kids should suffer."
In contrast, Sarah Granger of Menlo Park spent Thursday clearing her 21-month-old daughter's cold medications out of the medicine cabinet. This week, she has been giving her daughter two of the recalled medications for a cold.
"Accidents happen, so I think it's smart they're recalling these medications until they can figure out how to dispense them more safely," said Granger, who writes for the Silicon Valley Moms Blog. Her daughter was feeling better Thursday, she said, "but I'll be anxiously awaiting replacement options."
Those options, pediatricians say, include old-school remedies: infant or children's Tylenol or Motrin to reduce body aches and fever, a humidifier, rest and plenty of fluids, Contini said.
Using a nasal saline spray and a suction device for little noses also can relieve congestion, said Dr. Chris Halaburka, another San Jose pediatrician. Getting a flu shot, which is recommended for children from 6 months to 5 years old, also can reduce the severity of flu and other respiratory infections, she said.
Her challenge, she said, is helping parents understand what to do to make their children more comfortable — and how to cope with the fact that they might be miserable for a few days.
"It's normal for children up to age 4 to have up to 14 colds a year," Halaburka said. "That's how we build our immune system."
Staff writer Barbara Grady and MediaNews wire services contributed to this report. Contact Barbara Feder Ostrov at firstname.lastname@example.com or 408-920-5064.
If you're interested
For more information, visit the U.S. Food and Drug Administration's Web site at http://www.fda.gov.
The 14 recalled medications, and alternative treatment
Consumer Healthcare Products AssociationDimetapp: Decongestant Infant Drops, Decongestant Plus Cough Infant Drops
Little Colds: Decongestant Plus Cough, Multi-Symptom Cold Formula
Pediacare: Infant Drops Decongestant, Infant Drops Decongestant & Cough, Infant Dropper Decongestant, Infant Dropper Long-Acting Cough, Infant Dropper Decongestant & Cough, Infant Cough DM Drops
Triaminic: Infant & Toddler Thin Strips Decongestant, Infant & Toddler Thin Strips Decongestant Plus Cough
Tylenol: Concentrated Infants' Drops Plus Cold, Concentrated Infants' Drops Plus Cold & Cough
A humidifier to help relieve congestion
Bed rest
Nasal saline spray
Infant or children's doses of acetaminophen or ibuprofen to reduce fever and relieve pain
Offering plenty of fluids and healthy foods
Consumer Healthcare Products Association, MediaNews reporting.


text:
Golden Yin Yang
Updated May 08, 2006 by vikram sheorey
Comment #1 Monday, May 8, 2006 3:04 PM
To be honest and not just tell you what you want to hear..LoL
I liked your first one much better..this one seems kinda "rough around the edges" compared to the other...
ALL of mine are like that too,LoL..just the way it is when your learning.
One hint about the "Preview" make a *copy* to upload as the screenshot..if you take it out of the folder then there is no preview in LS's preview window when your looking through your logons..
I see you figured out the "Marquee" thing, awesome!
Im not familiar with the proggie your using so I cant begin to offer any help with it, im surprised the "Marqee" suggestion worked, I assumed you were using Photoshop...The techniques vary from program to program...
I love oriental themes so I'll definitely be keeping a watch for more!
Take care and thanks for sharing!
Comment #2 Monday, May 8, 2006 3:16 PM
|One hint about the "Preview" make a *copy* to upload as the screenshot..
I know, made a big mistake with that, the preview with the LS application is nothing like the real thing!! I will sort that out as soon as possible.
|I see you figured out the "Marquee" thing, awesome!
To be quite honest I'm still trying to figure out what the "Marquee thing" is - just a happy coincidence.
As for the software I was using it's good old MSPaint!! Probably why it might look a bit rough.
Anyway thanks very much for your input, it's comments like this that really help.
Forgot to ask, how do you update a skin? Just upload it again?
Comment #3 Monday, May 8, 2006 4:17 PM
|Forgot to ask, how do you update a skin? Just upload it again?
YuP..Just be sure to click the *Update* button next to the logon, then re-upload your updated version the same as you did the original, it will have to pass through moderation once more, sometimes the second time through goes fast though, but I have had it take much longer as well..
Please login to comment and/or vote for this skin.
Welcome Guest! Please take the time to register with us.
There are many great features available to you once you register, including:
- Richer content, access to many features that are disabled for guests like commenting on the forums and downloading files.
- Access to a great community, with a massive database of many, many areas of interest.
- Access to contests & subscription offers like exclusive emails.
- It's simple, and FREE!


text:
Refresh, detangle and condition in a instant! Tame bedhead or freshen up squished and frizzed up curls. Apply right on top, or underneath other Blended Cutie products. Aloe water sooths tender scalps and moisturizes thirsty curls. Beantree provides slip and shine for easy styling. Leaves curls feeling satiny soft and smooth.
Is this product right for me?
Find your hair type »
Aqua, Guar Hydroxypropyl Trimonium Chloride, Vegetable Glycerin, Propanediol, Sodium stearoyl glutamate,Oryza sativa (Rice) bran oil, , Vanilla Planifolia , Parfum, Rosmarinus Officinalis, Silk powder, Aloe Barbadensis, Methylheptyl Isostearate, Sodium Decylglucosides Hydroxypropyl Sulfonate Patent, Preservative (Phenoxyethanol and Caprylyl Glycol and Sorbic Acid), Xanthan Gum


text:
JACKSONVILLE -- Pilot Corp. of America is the mystery company that Jacksonville and state leaders have been wooing with financial incentives to relocate its corporate headquarters to Jacksonville.
The Jacksonville Economic Development Commission is scheduled Thursday to vote on supporting the state's decision to provide $127,900 for roadwork at the site where Pilot Corp. intends to build an office building for its 66-employee headquarters.
The roadwork assistance would be on top of $264,000 in financial incentives previously approved by the state and City Hall for Pilot Corp. The state would pay 80 percent of that amount, and the city would foot the bill for the rest.
The plant employs 200 people.
© 2017. All Rights Reserved. Contact Us


text:
Email This Page to a Friend
This page has been sent to the email address you provided.
(Cart Empty)
This Closet Mirror Door Track is made from heavy extruded aluminum and fits on a variety of door systems, including Contractors Wardrobe. Unless cutting directions are provided, we will cut all items ordered to 8 ft length. Shipping charges quoted in your shopping cart are for items cut to 8 ft or less. Please leave detailed cutting instructions, including lengths and quantities, in the comments box at the checkout.
Return Policy |
Shipping Policy |
Terms of Use / Privacy Policy |


text:
Most GOP govs shun Romney
Expand Messages
- http://www.politico.com/news/stories/0208/8274.html
Most GOP govs shun Romney
By: Charles Mahtesian
Feb 2, 2008 08:51 AM EST
As chairman of the Republican Governors Association in
2006, Mitt Romney crisscrossed the country to elect
GOP governors and broke the groups fundraising record
by hauling in $20 million.
Yet just two of the 16 governors he worked to elect
then are supporting his presidential bid.
In fact, just three of the nations 22 Republican
governors have endorsed him.
There are plenty of reasons that might explain the
former Massachusetts governors surprisingly weak
support among his former colleagues. But one of them
stands out: He appears to have inadvertently alienated
a good many of his fellow governors as RGA chairman.
Right or wrong, the general impression was that he
spent way too much time on himself and building his
presidential organization, said a top Republican
strategist who has worked closely with the RGA in
recent years. I dont think anyone ever questioned
Romneys commitment to the organization or the work he
put in. They questioned his goals or his motives. Was
it to elect Republican governors, or to tee up his
presidential campaign?
A campaign manager for an unsuccessful 2006 Republican
gubernatorial campaign echoed the sentiments. We
definitely got the vibe from the staff that our state
was never a national player when it came to the
strategy that the RGA was putting together, he said.
Everything they were telling me was about Michigan.
They were dumping everything into Michigan.
For Romney, his inability to win over the governors he
worked closest with has proven costly. On the eve of
Tuesdays crucial primary in Florida, Gov. Charlie
Crist announced his support for John McCain despite
the fact that Romney, as chairman of the RGA, had
greenlighted a $1 million check to Crists campaign in
McCain won Florida by 36 percent to 31 percent over
Romney. And the exit polls found that 42 percent of
the voters said the popular governors endorsement was
very important or somewhat important.
On Thursday, two more big-state governors who were on
the 2006 ballot, Arnold Schwarzenegger of California
and Rick Perry of Texas, lined up behind McCain.
Schwarzeneggers decision came just days before
California Republicans vote in this Tuesdays primary.
Perry switched to McCain after his first endorsed
candidate, Rudy Giuliani, ended his campaign.
Altogether, six of the 16 Republican governors elected
or reelected in 2006 are backing McCain. South
Dakotas Michael Rounds is supporting Mike Huckabee.
Nebraskas David Heineman and Rhode Islands Donald
Carcieri are behind Romney. But the rest of the class
is sitting it out, having declined to endorse anyone.
One reason, said a Republican consultant familiar with
the thinking behind some of the governors decisions,
is that Romney rubbed some governors the wrong way
during his tenure at the RGA.
Everything seemed to have strings attached to it,
the consultant said. If they were going to make a
donation, they wanted a quid pro quo like an
endorsement or a donor list or a volunteer program.
Theres no interest like self-interest in politics. So
when [governors] think their political lives are in a
do-or-die situation, thats not the time to offer help
with strings attached.
Phil Musser, a Romney supporter who served as his RGA
executive director, says Romneys dearth of
gubernatorial support is less revealing than it
appears. With his peer governors, he is very popular
and well-liked, Musser said. There wasnt much
grousing from anyone.
Instead, Musser points to a variety of factors that
might have led some governors to sit out the
presidential primaries the volatility of the GOP
field, the reluctance of newly elected governors to
take sides and deference to Huckabee, who was familiar
to many of them as the former chairman of the
nonpartisan National Governors Association.
The fact that very few new Republican governors were
elected in 2006 due to the gale-force Democratic
winds, Musser said, also accounts for the low number
of Romney supporters.
Part of it is the widespread, scattered nature of the
field, part of it is that no one wants hurt feelings,
and part of it is decisions made about self-interest,
said Musser, now a Republican consultant.
Still, with just three governors behind him the
little-known Heineman and Carcieri, and Missouris
Matt Blunt, who recently announced he would not seek a
second term Romneys base of support stands in stark
contrast to the impressive roster assembled in 2000 by
then-Texas Gov. George W. Bush, who had 24 governors
backing him.
And Romneys thin list of gubernatorial supporters
pales when compared with some of the heavyweights
aligned with McCain, including Minnesotas Tim
Pawlenty, who was elected to a second term in 2006 and
is frequently mentioned as a vice presidential
prospect, and Indianas Mitch Daniels, who served a
stint as President Bushs budget director.
McCain also has the backing of Utahs Jon Huntsman
Jr., who represents a heavily Mormon state where
Romney is exceptionally popular.
Beginning in 2005, McCain, who has spent his entire
political career in Congress, made a concerted effort
to line up gubernatorial support in anticipation of
his 2008 run. He met with nearly every incumbent
Republican governor, and campaigned and raised money
for them and for other Republicans running for
governor in 2006.
We were always asking what we could do for them
which, compared to what was going on at the RGA with
Mitt Romney running for president, was a welcome
relief, said John Weaver, a former McCain strategist.
If they had a need, we were there to fill it.
Campaigns, like football games, are often won by what
happens in practice.
Your message has been successfully submitted and would be delivered to recipients shortly.


text:
On Online Labeling with Polynomially Many Labels
In the online labeling problem with parameters n and m the authors are presented with a sequence of n keys from a totally ordered universe U and must assign each arriving key a label from the label set {1, 2,...,m} so that the order of labels (strictly) respects the ordering on U. As new keys arrive it may be necessary to change the labels of some items; such changes may be done at any time at unit cost for each change. The goal is to minimize the total cost.
Provided by: Charles University Topic: Big Data Date Added: Oct 2012 Format: PDF


text:
Get a free shipping quote.
Brownie has very smooth gaits,very calm and sweet. Really wants to please. Doing great in the saddle, she needs a forever family!! Check us out on Face Book too!! We have lots of gaited horses that need homes.
We are a small volunteer based rescue (501c3) that specializes in GAITED breeds and donkeys. We have alot of horses looking for their forever homes, check us out on FaceBook too!!
Avoid Scams and Fraud - Potential areas of fraud: wire transfer, moneygrams, money orders, cashier checks, shipping, escrow, "transaction protection", "guarantee". Check out the Buyer Safety section for more info.


text:
Oppositions View: Mowbray Boro (h)
Boro left St Andrew's with nothing as two goals from Marlon King and a long range strike from Wade Elliott cancelled out Grant Leadbitter and Scott McDonald's efforts and won them their fourth home league win of the season.
It was a disappointment for Mowbray who could have seen his club go level on points at the top of the league with Cardiff.
He told Sky Sports: 'We came to win tonight and tried to be positive. We got our noses in front twice and it's tough to take when you're in front feeling reasonably comfortable.
'I think the nature of the goals were obviously disappointing for us. I don't think they had to work too hard for any of their goals and that's the most disappointing thing for us.
'I haven't seen the penalty again but I've told (Andre Bikey) you can't hang a leg out in the box, you have to defend properly, stay on your feet and push people from goal.'


text:
Thousands ride to promote road harmony
Thousands of cyclists have ridden south from Adelaide to McLaren Vale to promote safe road use between cyclists and motorists.
The Southern Expressway was closed to cars during the ride for the Amy Gillett Foundation.
The late cyclist was killed while road training in Germany in 2005.
Foundation chief executive Tracey Gaudry says about 9,000 cyclists per year end up in hospital in Australia.
"With 1.94 million people around Australia riding their bike regularly - that is riding their bike three times a week or more - we've got a lot of work to do to bring about and to ensure we have a harmonious relationship between bike riders and all other road users," she said.
Topics: community-and-society, charities, safety, lifestyle-and-leisure, mclaren-vale-5171, adelaide-5000, sa
First posted


text:
Donald Spengler delivers packages for a living, but he delivers smiles for fun.
The 55-year-old mailman has been purchasing loads and loads of stuffed animals, children's books, toys, board games and puzzles and donating them to children at hospitals all around the Western suburbs for the last six years.
"It gives me a good feeling," said Spengler. "But to be honest, I have gotten a little carried away."
So far he estimates he's doled out about 21,000 stuffed animals, all paid out of pocket, always buys brand new merchandise. It's a quiet – and expensive – passion that no one can quite figure out.
"To all the kids here at Alexian Brother's hospital he's Santa Claus," said Patsy Buckberg, an official with the suburban hospital's pediatric wing.
"I remember when I first met him: He rolled the big cart into my office and asked I would be interested in working with him," she said.
At first Buckberg was skeptical, but after she heard that he wasn't asking for anything in return and he didn't even care deliver them personally she relented, and she's happy she did.
"Because of Don every single child that comes into this hospital leaves with some sort of toy or game or something," she said.
It all started in 2004:
"I was in a hospital visiting one of my friends and I noticed in the ER they had children that were crying and I overheard one of the nurses saying I wish we had something that could calm down the kids," Spengler said.
"So I went to the local Hallmark and bought a little stuffed clown and asked the parents if I could give it to the kid. When I bent down to hand it to him he just snatched it out of my hand, and just like that the tears stopped and he started smiling."
The event brought so much satisfaction to Spengler that he decided to donate toys on a regular basis.
"A few months into it I used to go into a store and just buy them out of stuffed animals," he said. "Now I go straight to the distributor."
It's gotten to the point where Spengler had to take out a second mortgage on his house to fund his charitable crusade. Right now he has 50 large plastic tubs that are filled with stuffed animals sitting in his garage, and more are coming to his friend Jack Garvin, who owns a carpet and frame company along Spengler's route.
Garvin lets Spengler use his warehouse to receive deliveries (he's also the one who encouraged Spengler to talk to the media.)
"It's not unusual for the UPS guy to roll up and deliver 10 or 20 CASES of stuffed animals, which we receive," Garvin says. "Don is a heck of a guy."
"I'd have to get a calculator out to figure it precisely," he says.
What started as a simple gift has ballooned into a multi-hospital operation. Last year Spengler hit 12 hospitals in one day.
"I'm not sure why he does it," Buckberg says. "I always assumed he had some event in his childhood that made him want to do it."
Spengler says that's not the case.
"I'm just one guy, I have no family and the only thing I really do is go to baseball games – not pro, Kane County Cougars," he says. "This is just something I like to do."


text:
Research Topics
D Tagu
Affiliation: Institut National de la Recherche Agronomique
Country: France
Detail Information
- Genetic analysis of phenotypic variation for ectomycorrhiza formation in an interspecific F1 poplar full-sib familyD Tagu
UMR INRA UHP 1136 IaM Interactions Arbres Micro Organismes, INRA, 54280, Champenoux, France
Mycorrhiza 15:87-91. 2005....
- Annotated expressed sequence tags for studies of the regulation of reproductive modes in aphidsD Tagu
INRA Rennes, UMR INRA Agrocampus BiO3P, BP 35327, Le Rheu F 35653, Cedex, France
Insect Biochem Mol Biol 34:809-22. 2004..Fifteen genes involved in developmental and differentiation events were identified by similarity to known genes. Some of these may be useful candidates for markers of the early steps of sexual differentiation...
- Transcriptomic and proteomic analyses of seasonal photoperiodism in the pea aphidG Le Trionnaire
INRA, UMR 1099 BiO3P, Rennes, France
BMC Genomics 10:456. 2009..To understand the molecular basis of the switch in the reproductive mode, transcriptomic and proteomic approaches were used to detect significantly regulated transcripts and polypeptides in the heads of the pea aphid Acyrthosiphon pisum...
- Seasonal photoperiodism regulates the expression of cuticular and signalling protein genes in the pea aphidG Le Trionnaire
INRA, Agrocampus Rennes, UMR 1099 BiO3P Biology of Organisms and Populations Applied to Plant Protection, F 35653 Le Rheu, France
Insect Biochem Mol Biol 37:1094-102. 2007..This suggests that photoperiodic changes could affect cuticle structure and cell to cell communication in the head of aphids in relation with the switch of reproductive modes...
- Hydrophobins in ectomycorrhizas: heterologous transcription of the Pisolithus HydPt-1 gene in yeast and Hebeloma cylindrosporumD Tagu
UMR INRA UHP 1136 Interactions Arbres Micro organisimes, INRA Nancy, Champenoux, France
Eur J Histochem 46:23-9. 2002..cylindrosporum. Heterologous transcript accumulation did not alter the phenotype of either species. The lack of altered phenotype resulted from the absence of HYDPt-1 polypeptide accumulation in transformed strains...
- AphidBase: a centralized bioinformatic resource for annotation of the pea aphid genomeF Legeai
INRA UMR, Le Rheu, France
Insect Mol Biol 19:5-12. 2010..AphidBase strongly supported community cooperation and coordination in the curation of gene models during community annotation of the pea aphid genome. AphidBase can be accessed at http://www.aphidbase.com...
- Cloning and expression analysis of a new hydrophobin cDNA from the ectomycorrhizal basidiomycete PisolithusS Duplessis
UMR INRA UHP 1136, Interactions Arbres Microorganisms IaM, Centre de Nancy, France
Curr Genet 39:335-9. 2001..This suggests that other factors act as regulators of hydrophobin gene expression in ectomycorrhizae...
- Sex versus parthenogenesis: a transcriptomic approach of photoperiod response in the model aphid Acyrthosiphon pisum (Hemiptera: Aphididae)T Cortes
Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de Valencia, Apartado de Correos 22085, 46071, Valencia, Spain
Gene 408:146-56. 2008..Implications for current studies on gene regulation of the dichotomy sex vs. parthenogenesis in aphids are discussed...
- T-DNA transfer from Agrobacterium tumefaciens to the ectomycorrhizal fungus Pisolithus microcarpusA G Pardo
Programa de Investigación en Interacciones Biológicas, Universidad Nacional de Quilmes, Roque Saenz Pena 180, B1876BXD Bernal, Provincia de Buenos Aires, Argentina
Rev Argent Microbiol 37:69-72. 2005..Transformation resulted in phleomycin resistant clones which were confirmed by PCR to contain the resistance cassette. A. tumefaciens-mediated gene transfer would allow the development of RNA interference technology in P. microcarpus...


text:
#26 ET-Cup - ETTv and 2nd Matchweek! (23848 Views)
written by SPU9 on 07.05.07 17:57
Since NxM and Skydeh are busy with the Worldcup I decided to help a bit by writing a roundup about the first Matchweek of the #26th ET-Cup.
We passed the first Matchweek as nearly all the matches have been played.
If you go through the results you`ll see no unexpected results since none of the underdogs won their matches during the first week.
1st Matchweek results:
Group Alpha:
dtekt eSports vs. immortal 4:0
Meridian vs. aero 4:0
Group Beta:
vicious and evil vs. oceans6 4:0
dvotion vs. team effect 0:4 (defwin)
Group Charlie:
Spreading Death vs. A-Link 4:0
Vfight! vs. Suicide League 4:0
Group Delta:
team-violence vs. 7lives! 4:0
polar esports vs. adapted 4:0
Group Echo:
a.ToOn vs. deAth wAtch 4:0
Group Foxtrot:
[flag=eu] Northern Darkness vs. [flag=eu] xSporting 4:0
Group Golf:
[flag=ee] overload-gaming vs. [flag=be] BoozZe 4:0
[flag=pl] Beyond the Grave vs. [flag=pl] Phobos-Gaming 4:0
Group Hotel:
[flag=il] eSrael.org vs. [flag=il] Devil-inside 4:0
[flag=nl] sereNity-gaming vs. [flag=fi] Xtreme 4:0
So it is on [flag=eu] Phantasmagoria`s (ex Sleepers) shoulders to provide us a surprising win against 6 man mixteam of "known players" playing under the name of [flag=it] eC4 during the first matchweek.
If eC4 are playing as they have been playing so far, I cant see Phantas winning this one.
Match: [flag=eu] Phantasmagoria vs. [flag=it] eC4
Maps: Frostbite and Bremen_b1
Date/Time: Tuesday, 21.00Cet
ETTv: GamesTV.org
Therefore as spectators we would need to wait for the 2nd Matchweek to see an underdog winning against a big name.
Additionally the teams are allowed to change up to 2 players of their ET-Cup Lineup by messaging SPU9 @ #ET-Cup till tonight 22.00 CET - be fast, changes will only be considered if you message in time!
Now I wish all participants good luck and lots of fun
(thx to [flag=fi] decem for fixing the post ;p)
IRC: #ET-Cup
nice :)
I like the railgun picture @ banner!


text:
That title is a mouthful and that's a lot of lemon, but it was a big week.
We all want life to be wonderful, birthdays to be special, and dessert to be the exclamation point on top of it all. At least, that's what I want. Nevertheless, sometimes the timing is off. Way off. Things don't turn out as we hoped.
Not bad, but the expected highlights were not there. We are left disappointed.
What happened took a departure far from the way we thought things would be. Been there, done that, more than I care to count.
Did I build it up too much?
Did I expect something I shouldn't have?
Should I stop expecting anything, so I avoid this feeling of … disappointment.
I had a birthday last week, not a biggie, one I refer to as a "peak" birthday, just past the uphill climb and right before the downhill slide on Decade Mountain. Forty-five to be exact. I have no problem with age and growing older, I have earned every grey hair and
fine line, the goal is to savor each day and celebrate.
Two challenges: Limoncello Tiramisu and my husband being out of town on a business trip.
I had been planning the tiramisu for more than six months, collecting recipes for ladyfingers, candied lemon peel, and lemon ice cream to go with it. Admittedly, I am a lemonhead, though chocolate is a close second. So the stage was set, the lemon ice cream and the ladyfingers were made two days in advance (yes, I made the ladyfingers from scratch, it was my birthday after all), then the tiramisu and candied Meyer lemon peels were prepared the day before. The much anticipated birthday dessert was done.
Except it wasn't, because the mascarpone cream broke, which meant the entire thing was an expensive, time-consuming failure. Although, the girls didn't complain about the extra ladyfingers.
Matt was gone all week at a conference and super busy. I knew he would be gone on my birthday, which was a bummer, but he failed to even acknowledge it, thinking he was good until we would celebrate upon his return (the next day). Um, no. This led to a snarky email from me and a conversation I did not want to have on my birthday. 🙁
Yes, even after 24 years of marriage, we (both of us) still make mistakes and have to deal with being disappointed by each other.
So where do you go from here?
After tasting the tiramisu (5-6 times) in disbelief, dump it into the trash and start over. Ugh.
Lemon Pudding Cakes, anyone? This had been a close second in my lemon birthday dream.
Send the snarky email to a friend in an attempt to garner sympathy, but only one you are sure will not talk ill of your hubby and will expect the best from you. She agreed he was wrong, but still held me accountable for my response. Everyone needs a friend who will encourage them to put down the shovel.
Cry, if you feel like it. This kind of disappointment doesn't bring a lot of tears, but even one or two can turn into anger or resentment if not released to roll down your face. Tears are not a sign of weakness, they simply testify to what we are feeling.
Forgive. Grace is like water for a garden, apply liberally, there are seeds just under the dirt.
Put flowers in some water and let your daughters and friend take you to dinner. During dinner, glance around the table at the rich blessings in your life, letting the unpleasant events of the day roll away with the emptied plates.
Savor the Lemon Pudding Cakes with Lemon-Lovers Ice Cream and Candied Lemon Peels. (Save the Rice Crispy Treats your thoughtful friend brought over for snacking later~thank you, Pati).
Re-read the cards and Face Book well wishes from friends and family just before your head hits the pillow, let it highlight everything.
Always expect the best—from your dessert and the ones you love—even though you risk being disappointed.Print
Lemon-Lovers Ice Cream
Tangy, creamy, lemony dessert perfect for the most discriminating lemon lover.
- Yield: 1 1/2 quarts
- Category: Dessert, Ice Cream
- 1 1/4 cups whole milk
- 4 whole egg yolks
- 2 tablespoons lemon zest — finely minced
- 1/2 cup fresh lemon juice — strained
- 3/4 cup honey
- 1 teaspoon vanilla extract
- 1/2 teaspoon lemon extract — optional
- 1 1/4 cups heavy cream
- pinch salt
- In a saucepan, whisk egg yolks and milk until combined. While continuing to stir, heat over medium heat until just before simmering. Remove from heat and strain through a fine mesh strainer into a bowl. Cover with plastic wrap, pressing wrap on the surface of the custard. Place in the coldest part of the refrigerator for 2-3 hours, or until well chilled.
- In another bowl, mix the lemon zest, juice, honey, and extracts with a whisk until well blended. Refrigerate until ready to use.
- Once all the ingredients are well chilled, combine lemon syrup, custard, heavy cream, and salt in a mixing bowl or large measuring cup with a pour spout.
- Mix in an ice cream maker according to manufacturer's directions; most take between 20-30 minutes.
- Serve immediately for soft serve ice cream or freeze in an air tight container for 2 hours for a firmer consistency.
Shared on the following Blog Hops:
Mom Trends Friday Food
Real Food Whole Health Fresh Bites Friday
Real Food Forager Fat Tuesday
Hearth & Soul Hop


text:
Clear Creek clinches playoff spot with win over Alvin
Updated 11:31 pm, Friday, October 21, 2011
ALVIN — Clear Creek clinched a District 24-5A playoff spot with a 26-14 victory over Alvin at Alvin Memorial Stadium on Friday night.
"That was our objective coming in," Clear Creek coach Darrell Warden said. "We felt like, 'Win, we're in,' and here we are."
Each time the Yellowjackets (4-4, 2-3) challenged the Wildcats' lead, Alvin (5-3, 4-1) pulled away.
With Clear Creek's 20-14 lead in danger, a sack by the Wildcats' John Smith halted Alvin and brought up a 4th-and-14 with 7:33 left in the fourth quarter.
On the subsequent possession, the Wildcats used a 60-yard screen pass to Colby Davis and a 15-yard touchdown grab by Deon Lewis to finally put the Yellowjackets away.
Trending High School Sports Video
- Cy Fair's Eric Hallett - The Houston Chronicle's Editors Choice Athlete of the WeekTexanLive
- Texan Live Top 10 Plays of the week - Week 12 Houston High School FootballTexanLive
- Jackson Jones Cy Woods QB - Chron Athlete of the weekTexanLive
- Chron's boys player of the week: Jackson Jones, Cypress Woodschron
"This game is about momentum — it doesn't matter who you're playing," Warden said. "If you catch a little momentum here and there, all of a sudden it starts rolling and hopefully it'll snowball your direction.
"If you're not careful, it can snowball the other direction. I think we captured the momentum and kept it on our side most of the time."
Senior quarterback Austin Smith powered Clear Creek's offense, completing 68 percent of his passes for 334 yards and three touchdowns.
Alvin's pass rush pressured Smith, but he hung tough in the pocket.
"I don't mind getting hit as I throw, it's kind of fun," Austin Smith said. "It was tough. They had a good defense. We just found holes and we executed."
The Yellowjackets' two-headed rushing attack of John McDowell and Corey Jackson could not keep up with Smith and the Wildcats.
McDowell ran for 72 yards on 12 carries, and Jackson gained 109 yards on 22 attempts, but the Wildcats kept both out of the end zone.
"Coming into the game, we felt like we had to stop John McDowell," Warden said. "He's gotten outside on everybody and gone the distance on quite a few teams."
The Yellowjackets quarterback tandem of Josh Ceyanes-Erwin and Aaron Jackson could not offset the damage being done by their Clear Creek counterpart. The Yellowjackets were frequently put in bad spots as Ceyanes-Erwin fumbled four snaps.


text:
The summer of 2012 was big for Preston Memorial Hospital as it established land and a certificate of need for its brand new hospital, but perhaps the summer of 2013 is better.
Tuesday, the hospital announced its partnership with Mon Health Systems, securing the final piece of the puzzle.
"Preston Memorial Hospital is going to become the newest addition of the Mon Health System, and join Mon General Hospital as one of two premier hospitals in our growing healthcare organization," said Glenn Adrian, the Chairman of Mon Health System Board of Directors.
Tuesday's announcement helps secure $38.5 million Preston Memorial needs for its new hospital.
Preston County Commission President Craig Jennings calls the announcement the biggest he's seen during his tenure on commission.
"The biggest question in peoples' minds here in Preston County was, 'are we going to be able to afford this?'" Jennings said. "I think now they will rest at ease knowing we have a partner now that will help us bankroll this and I think it's just positive from here on out."
Preston Memorial Hospital will become the fifth leg of Mon Health Systems, joining Mon General, Mon EMS, Mon Healthcare and the Village at Heritage Point.
In 2007, Preston Memorial began preparing to build a new facility. The more 83,500 square foot hospital will have 25 private rooms and provide new and expanded service.
"Healthcare, as I said is every changing it's so competitive and it's very difficult as a small rural community hospital," said Preston Memorial President Melissa Lockwood. "We always say we're not competing with a Mon General or a Ruby Memorial Hospital, but on some fronts you do from time-to-time. This will secure that financial future. "
"We have to get people cared for closer home," said Mon General President Darryl Duncan. "We know they'll be more compliant with our health care, the costs will be lower, we know they'll have better access. If you can bring high quality services to a local community, it works out on a lot of different levels."
The new hospital will be located on land near Preston High School. The ground breaking ceremony is expected to come later in September. The hospital is scheduled to open in the spring of 2015.
Clarksburg Studio
Can't Find Something?
All content © Copyright 2000 - 2015 WorldNow and WBOY Television. All Rights Reserved. For more information on this site, please read our Privacy Policy and Terms of Service.