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Using patch-clamp techniques, we studied the plasticity of acid-sensing ion channels (ASIC) and transient receptor potential V1 (TRPV1) channel function in dorsal root ganglia (DRG) neurons retrogradely labeled from the bladder. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally on days 1, 3, and 5. On day 6, lumbosacral (LS, L6–S2) or thoracolumbar (TL, T13–L2) DRG were removed and dissociated. Bladders and bladder DRG neurons from CYP-treated rats showed signs of inflammation (greater myeloperoxidase activity; lower intramuscular wall pH) and increased size (whole cell capacitance), respectively, compared with controls. Most bladder neurons (>90%) responded to protons and capsaicin. Protons produced multiphasic currents with distinct kinetics, whereas capsaicin always triggered a sustained response. The TRPV1 receptor antagonist A-425619 abolished capsaicin-triggered currents and raised the threshold of heat-activated currents. Prolonged exposure to an acidic environment (pH range: 7.2 to 6.6) inhibited proton-evoked currents, potentiated the capsaicin-evoked current, and reduced the threshold of heat-activated currents in LS and TL bladder neurons. CYP treatment reduced density but not kinetics of all current components triggered by pH 5. In contrast, CYP-treatment was associated with an increased current density in response to capsaicin in LS and TL bladder neurons. Correspondingly, heat triggered current at a significantly lower temperature in bladder neurons from CYP-treated rats compared with controls. These results reveal that cystitis differentially affects TRPV1- and ASIC-mediated currents in both bladder sensory pathways. Acidification of the bladder wall during inflammation may contribute to changes in nociceptive transmission mediated through the TRPV1 receptor, suggesting a role for TRPV1 in hypersensitivity associated with cystitis.
- bladder sensory neurons
- TRPV1 receptors
- visceral hypersensitivity
- cystitis
- cyclophosphamide
- capsaicin
- proton
- acid
- pH
- whole cell patch clamp
the prevalence of painful bladder syndrome/interstitial cystitis (PBS/IC) is estimated at ∼11% in women and 4.6% in men in managed care settings (Clemens et al. 2005, 2007). In addition to increased urinary frequency, urgency, and incontinence, PBS/IC patients also report significant discomfort and pain (Burkman 2004; Clemens et al. 2005, 2007; Nickel 2004), which often has a burning character (Ness et al. 2005). Although the etiology of PBS/IC remains unknown, the bladder of many PBS/IC patients shows evidence of inflammation, including edema, vasodilation, and infiltration of mast cells (Burkman 2004; Nickel 2004).
The bladder is innervated by the pelvic and hypogastric/lumbar splanchnic nerves with cell bodies in lumbosacral (LS, L6–S2) and thoracolumbar (TL, T13–L2) dorsal root ganglia (DRG), respectively. The relative roles of these pathways are not well established. The pelvic nerve plays a role in the sensation of bladder distension and micturition, because bilateral resection of the pelvic nerve abolishes bladder contractions induced by repetitive filling (Kontani and Hayashi 1997; Meen et al. 2001), whereas mechanical and chemical stimulation of the bladder also activate the hypogastric/lumbar splanchnic nerve, which may contribute to regulation of micturition and painful sensations after bladder irritation/damage (Meen et al. 2001; Mitsui et al. 2001; Moss et al. 1997; Xu and Gebhart 2008). Based on functional studies and differential expression of receptors/receptive fields, a growing body of evidence suggests that different nerves innervating a visceral organ mediate different functions (Brierley et al. 2004; Dang et al. 2005a; Lamb et al. 2003; Xu and Gebhart 2008). Consistent with this notion, bladder hypogastric/lumbar splanchnic afferents have been reported to respond more vigorously to chemical stimuli than do their pelvic counterparts (Moss et al. 1997).
Changes in sensory input from the bladder contribute to the development and maintenance of IC (Ness et al. 2005). The transient receptor potential V1 receptor (TRPV1) is considered important in temperature sensation (Caterina et al. 1997, 1998, 2000; Tominaga et al. 1998). Capsaicin, a TRPV1 agonist, produces a burning sensation when injected intradermally in humans and an inward current in sensory neurons, including bladder sensory neurons and urothelial cells, which play a role in sensory function (Birder 2006; Caterina et al. 1997, 1998, 2000; Charrua et al. 2009; Dang et al. 2005a; Tominaga et al. 1998); these effects of capsaicin are blunted by TRPV1 receptor antagonists. Furthermore, TRPV1 receptors play an important role in reflex bladder contractions in animals with an inflamed bladder and can be blunted by TRPV1 antagonists (Dinis et al. 2004). Intravesical administration of capsaicin and resiniferatoxin, a potent TRPV1 agonist, significantly reduces the expression of TRPV1 in the bladder and has been evaluated for the treatment of bladder hyperreflexia and PBS/IC (Avelino et al. 2002; Cruz et al. 1997; De Ridder et al. 1997; Matsuoka et al. 2012). Intradermal iontophoresis of acid, another activator of TRPV1 and other proton-gated channels, also produces pain that is attenuated by amiloride, which inhibits ASIC channels (Jones et al. 2004). Thus two different ligand-gated channels may contribute to nociceptive input during inflammation or ischemia, both of which are associated with tissue acidification.
Cystitis enhances excitability, increases P2X receptor-mediated currents, and induces expression of P2X3 receptors in bladder sensory neurons (Chen and Gebhart 2010; Dang et al. 2008; Yoshimura and de Groat, 1999). We hypothesized that changes in the sensitivity of bladder sensory neurons to endogenous acid-sensing ion channels (ASIC) and/or TRPV1 receptor agonists contribute to bladder dysfunction, discomfort, and pain. Using a well-established rat model of urinary bladder inflammation (Bon et al. 1997, 2003; Lanteri-Minet et al. 1995), we thus examined the effects of bladder inflammation on ASIC and TRPV1 currents in TL and LS bladder neurons.
Male Sprague-Dawley rats (200–300 g; Harlan, Indianapolis, IN) were used throughout. Rats were housed under a 12:12-h light-dark cycle with free access to food and water. All experimental protocols were approved by the Animal Care and Use Committee of The University of Iowa.
Bladder Inflammation, Myeloperoxidase Activity, and pH Measurements
Systemic administration of cyclophosphamide (CYP), which is metabolized to the bladder irritant acrolein (Cox 1979), causes hemorrhagic cystitis in humans and produces a cystitis-like condition in rodents (Bon et al. 1997; Dang et al. 2008; Lanteri-Minet et al. 1995). Saline (control) or CYP (100 mg/kg) was administered systemically (intraperitoneally, ip) on days 1, 3, and 5. To assess inflammation, myeloperoxidase (MPO) activity in bladder and distal colon tissue was measured in a subgroup of rats on day 6 (n = 4/group). Rats were euthanized with pentobarbital (200 mg/kg ip), and the bladders and 1 cm of distal colon were removed rapidly, minced, homogenized in ice-cold 50 mM phosphate buffer (pH 6) containing 0.5% hexadecyltrimethylammonium bromide, centrifuged at 1,000 rpm for 5 min, and the supernatant retained. In the presence of hydrogen peroxide (30%) and o-dianisidine dihydrochloride (0.5%), the absorbance of the supernatant was determined with a U2001 photometric reader (Hitachi, Naperville, IL). To examine specificity of CYP-induced cystitis, we also measured MPO activity of descending colon (1 cm) from the same rats.
In a separate series of experiments, the effect of inflammation on bladder weight and tissue pH was assessed. On day 6, rats were anesthetized (pentobarbital, 50 mg/kg ip), the bladder was exposed by an abdominal incision, and pH was measured by inserting a needle electrode (20 gauge, Orion pH meter; Fisher Scientific, Corvallis, OR) into the bladder wall and advancing it stepwise into the bladder lumen (urine), allowing 1 min for stabilization at each step. The damaged urothelium made it more difficult to reliably determine the extent of penetration of the pH electrode into the bladder wall in CYP-treated rats. To confirm appropriate electrode placement during measurement of bladder wall pH, we withdrew the electrode following determination of bladder wall pH, applied ∼1 mg of Evans blue onto the penetration site, and gently compressed the bladder to rule out a small leak. We then removed the bladder and measured its wet weight after emptying the contents. Euthanasia was accomplished by exsanguination after removal of the bladder.
Bladder Neuron Labeling
Under pentobarbital anesthesia (50 mg/kg ip), the bladder was surgically exposed (lower abdominal incision ∼1 cm in length) and 1.1′-dioctadecyl-3,3,3,′3-tetramethyl indocarbocyanine methanesulfonate [DiI(18); 100 mg in 2 ml of DMSO; Molecular Probes, Eugene, OR] was injected into 6–8 sites within the wall of the bladder and around the trigone using a 30-gauge needle (∼6 μl per site). Any visible leakage of DiI from the injection site was removed with a cotton swab. The incision was closed with 4.0 silk suture, and rats were allowed to recover. Two-three weeks later, saline (control) or CYP (100 mg/kg) was administered systemically (ip) on days 1, 3, and 5 as described above.
Cell Dissociation and Plating
For patch-clamp experiments, rats were anesthetized on day 6 (pentobarbital, 50 mg/kg ip) and lumbosacral (LS, L6–S2) or thoracolumbar (TL, T13–L2) DRG were harvested for acute dissociation and whole cell recordings. The general protocols have been previously described (Dang et al. 2005a, 2005b). Briefly, after removal, ganglia were minced and incubated at 37°C, 5% CO2 for 60 min in serum-free, supplemented Neuro-A medium (B27 supplements, 5%; l-glutamine, 0.5 mM; penicillin-streptomycin mixture, 1%; all from Gibco, Invitrogen, Grand Island, NY) containing collagenase (type 4; 2 mg/ml), and trypsin (1 mg/ml; both from Worthington Biochemical, Lakewood, NJ). Tissue fragments were gently triturated to encourage cell dissociation. Cells were collected by 5 min of centrifugation at 150 g, washed 3 times with supplemented Neuro-A medium (without enzymes), and resuspended in supplemented, enzyme free Neuro-A medium. The cells were plated on poly-d-lysine-coated coverslips (Becton Dickinson Labware, Bedford, MA) and incubated at 37°C, 5% CO2 for 2–3 h before electrophysiological studies. Acutely dissociated neurons were round and devoid of any processes, thus reducing potential space-clamp errors. Only bladder sensory neurons (i.e., DiI-containing DRG neurons) were studied. All recordings were performed within 10 h after plating.
Solutions and Electrophysiological Recordings
Coverslips with cells were transferred to a recording chamber (1 ml) superfused continuously (2 ml/min) with external solution containing (in mM) 140 NaCl, 5 KCl, 2 MgCl2, 2 CaCl2, 10 HEPES, and 10 glucose. The pH was adjusted to 7.4 with NaOH (310 mosM). Under low magnification (×50), bladder neurons were identified by DiI content using a rhodamine filter (bright orange/red color under UV light; excitation wavelength, 530–560 nm; and barrier filter, 573–648 nm). Fire-polished micropipettes with tip resistances of 1.5–2 MΩ were used for whole cell recordings. The uncompensated series resistance was generally about 7 MΩ or less. The pipette was filled with an internal solution consisting of (in mM) 130 KCl, 1 CaCl2, 1 MgCl2, 10 EGTA, 10 HEPES, 4 Na2ATP, 0.5 Tris-GTP, and 0.5 GDP. The pH was adjusted to 7.2 using KOH (310 mosM). After the whole cell configuration was established, the voltage was clamped at −70 mV using an Axopatch 200B amplifier (Axon Instruments, Sunnyvale, CA), digitized at 1 kHz (Digidata 1350; Axon Instruments) and controlled by Clampex software (pClamp 9; Axon Instruments). Disruption of the neuron membrane during DRG dissociation and the use of patch-clamp recordings are unavoidable. We chose whole cell capacitance as a well-established surrogate marker of size to minimize additional confounders due to distortion in neuron shape. Cell capacitance was obtained by reading the value from the Axopatch 200B amplifier. Recordings began 2–3 min after whole cell configuration was established, to ensure stable recording conditions.
Drugs were applied using a fast-step SF-77B superfusion system (Warner Instruments, Hamden, CT) with a three-barrel pipette placed in close proximity (100 μm) to the cell, allowing complete solution exchange within 25 ms (Dang et al. 2005a). Agonists were applied for 4 s, whereas antagonists were superfused for 60 s before the application of agonists. A washout period of 2 min was allowed between agonist applications. Unless otherwise stated, drugs and chemicals were obtained from Sigma-Aldrich (St. Louis, MO) and prepared fresh from stock solutions on the day of the experiment. All experiments were performed at room temperature (21–23°C). We used current increases above 20 pA as threshold to identify responses to agonists, because this level exceeded the baseline variability by a factor of 2.
Heat Application
After whole cell configuration was established and voltage was clamped at −70 mV, preheated external solution (∼80°C; same composition as above) was superfused for 30 s. We placed a temperature-sensitive microelectrode ∼100 μm in front of the recording cell (Physitemp, Clifton, NJ). Heat threshold (°C) was defined as the temperature when the line fitted to the heat-induced current intercepts the X-axis (time, s). Only one cell per coverslip was studied with a single application of heat to avoid complications that may result from repeated exposure to high temperatures.
Data Analyses
Data are means ± SE. Analyses were performed using the software Clampfit (Axon Instruments) and GraphPad Prism 4 (GraphPad Software, San Diego, CA). Sigmoidal concentration-response curves were generated using the following equation: Y = A/{1 + exp[−(log EC50 − X)/B]}, where X is the logarithm of concentration and Y is the response, which starts at 0 and goes to A with a sigmoidal shape. B is the Hill slope, Imax is the maximum current, EC50 is the concentration of agonist that evokes half-maximal response, and pH50 is the logarithm of EC50 of protons. To determine the kinetics of response onset, we measured the rise time, which is the time required for a signal to change from 10 to 90% of the peak amplitude. Desensitization kinetics were fitted with a standard exponential equation: Y = K0 + K1·exp(−t/τ), where Y is the current amplitude at time t, K0 is the amplitude of the nondesensitizing component, K0 + K1 is the peak current, and τ is the time constant. K0 and K1 represent the contribution to current amplitude from the fast and slow components of the current, respectively. For dichotomous variables, a χ2 test was employed. Unless otherwise indicated, results were evaluated using Wetch's t-test after logarithmic transformation. One-way ANOVA were employed to compare and confirm variables (e.g., pH50 values and desensitization constants of acid-evoked currents) in LS or TL neurons from saline-treated rats. Results were considered to be statistically significant when P < 0.05.
CYP Produces Bladder Damage and Inflammation (Cystitis)
Consistent with a previous study (Dang et al. 2008), the weight of bladders from CYP-treated rats was significantly greater than that from saline-treated rats (saline: 95 ± 4.8 g, n = 12; CYP: 273 ± 8.5 g, n = 12; P < 0.001). CYP treatment significantly and selectively increased bladder MPO activity relative to controls (saline: 0.36 ± 0.05 unit/g, n = 4; CYP: 1.0 ± 0.29 unit/g, n = 4; P < 0.001); colon MPO activity was not affected by systemic administration of CYP (saline: 0.63 ± 0.06 unit/g, n = 4; CYP: 0.56 ± 0.07 unit/g, n = 4; P > 0.05).
Cystitis Reduces pH of the Bladder Wall and Increases Size of Bladder Sensory Neurons
Although urine pH (36–37°C) from saline- and CYP-treated rats did not differ (saline: 6.3 ± 0.09, n = 12; CYP: 6.4 ± 0.07, n = 12; P > 0.05), pH of the bladder wall was significantly reduced in CYP-treated rats compared with controls (saline: 7.3 ± 0.03, n = 12; CYP: 7.0 ± 0.03, n = 12; P < 0.01). Based on whole cell capacitance, bladder inflammation significantly increased the size of bladder sensory neurons (saline LS: 28.6 ± 1.6 pF, n = 60; saline TL: 49.3 ± 1.2 pF, n = 53; CYP LS: 36.3 ± 1.2 pF, n = 62; CYP TL: 57.6 ± 2.3 pF, n = 57; P < 0.05).
Cystitis Alters Acid- and Capsaicin-Produced Currents in Bladder Neurons
We previously described the effects of acid and capsaicin on rat bladder sensory neurons (Dang et al. 2005a). In bladder neurons from saline-treated rats, we found in the present study that the proportions of responsive TL and LS neurons, peak current density, and kinetics in response to acid and capsaicin were similar to those we previously reported (Dang et al. 2005a), as summarized in Tables 1⇓⇓–4. Briefly, almost all LS and TL bladder neurons responded to acid (pH 5) with mixed current kinetics (a mixture of fast, intermediate, and/or sustained components), and all acid-sensitive bladder neurons responded to capsaicin (1 μM) with a sustained current only. On the basis of complete inhibition of acid-evoked currents by amiloride, an ASIC channel blocker, we concluded that transient currents triggered by acid were mediated by ASICs (Dang et al. 2005a). Capsaizepine and amiloride partially antagonized the sustained component of acid-triggered currents, suggesting that this component was mediated, in part, by TRPV1 receptors (Dang et al. 2005a). A-425619 (100 nM, 60 s), a competitive TRPV1 receptor antagonist (El Kouhen et al. 2005), abolished current triggered by capsaicin (100 nM), confirming involvement of TRPV1 (data not shown).
Biphasic, slow, and triphasic currents.
In bladder neurons from CYP-treated rats, acid (pH 5) produced currents in all 62 LS and 52 of 57 TL bladder neurons (not different from saline-treated controls; Table 1). Relative to saline treatment, CYP treatment increased the proportion of TL bladder neurons exhibiting acid-produced triphasic currents (CYP: 28/52, 53.8%; saline: 15/48, 31.3%; P < 0.05) and reduced the number of TL bladder neurons exhibiting acid-produced slow currents (CYP: 7/52, 13.5%; saline: 16/48, 33.3%; P < 0.05). Proportions of acid-produced biphasic, slow, and triphasic currents in LS bladder neurons were unaffected by CYP treatment (see examples in Fig. 1). See Table 1 for details.
Current density Imax and pH50.
Acid (pH 5) produced significantly lower densities of fast, intermediate, slow, and sustained current components in both TL and LS bladder neurons from CYP-treated rats relative to their saline-treated counterparts (Table 2). Because we noted a reduction in current density in response to pH 5, we further examined Imax and pH50 values for fast, intermediate, and sustained currents triggered by acid application, the most prevalent components in bladder neurons. Whereas peak current densities (Imax) were significantly reduced in LS (e.g., Fig. 1, E–G, and Table 2) and TL (e.g., Fig. 1, I–K, and Table 2) bladder neurons from CYP-treated rats, bladder inflammation did not alter EC50 values for proton-triggered current components in these neurons (Table 3).
Current kinetics.
Bladder inflammation did not influence activation and inactivation kinetics of acid-evoked currents in bladder sensory neurons (Table 4). Because slowly activating and desensitizing current was identified in only a small number of bladder neurons, we did not systemically examine recovery kinetics. Based on single-exponential fittings, recovery time constants of transient currents in LS and TL bladder neurons from CYP-treated rats did not differ in comparison with neurons from saline-treated rats (e.g., Fig. 2).
Capsaicin current density is increased.
Virtually all bladder neurons responded to capsaicin (1 μM), and the proportion responding to capsaicin did not change after CYP-treatment (Table 1). In contrast to acid-evoked currents, capsaicin triggered significantly greater peak current density in both TL and LS bladder neurons (e.g., Fig. 1, H and L, and Table 2).
Protons inhibit responses to acid but increase responses to capsaicin.
Because bladder wall pH is significantly decreased in this model of cystitis, we increased systematically the concentration of protons (pH range 7.4–6.6) by bathing bladder neurons for 60 s before application of acid (pH 5) or capsaicin (100 nM). In both LS and TL bladder neurons, prolonged exposure to pH 7.0 inhibited both rapidly and intermediately desensitizing current components triggered by acid (Fig. 3, A and B). As shown in Fig. 3, C and D, inhibition of acid-sensitive currents by extracellular acidosis was concentration dependent. A decrease from pH 7.4 to pH 7.2 depressed the response triggered by acid by more than one-half in both LS (Fig. 3C) and TL (Fig. 3D) bladder neurons.
In contrast to acid-sensitive currents, lowering bath pH significantly increased the current density evoked by capsaicin in LS bladder neurons (195.0 ± 40, 308.6 ± 88, 333.4 ± 89, and 356.0 ± 101%, n = 6, for pH 7.2, 7.0, 6.8, and 6.6, respectively; Fig. 4, A, B, and E). Similarly, extracellular acidosis significantly increased current triggered by capsaicin in TL neurons (157.2 ± 17, 253.7 ± 35, 286.9 ± 50, and 313.2 ± 75%, n = 5, for pH 7.2, 7.0, 6.8, and 6.6, respectively; Fig. 4, C, D, and E).
Cystitis and Acid Reduce Bladder Neuron Response Thresholds to Heat
Considering the role of TRPV1 in thermal sensation, we examined the effect of increasing the temperature of the bath solution. We defined the heat activation threshold as the temperature at which X- and Y-axes intercept (Fig. 5A). Heat activated inward currents with a threshold of 41.4 ± 1.2°C (n = 11) and 42.0 ± 0.9°C (n = 11) in LS and TL neurons, respectively, from saline-treated rats. Relative to their saline-treated counterparts, CYP-treated rats had significantly reduced heat activation threshold for both groups of bladder neurons (CYP LS: 37.7 ± 1.1°C, n = 11; TL: 36.9 ± 0.6°C, n = 12; P < 0.01; Fig. 5B).
To assess the role of TRPV1, we superfused A-425619 (300 nM) for 1 min, followed by administration of heated solution with A-425619. In the presence of A-425619, heat activation thresholds were significantly elevated to 44.5 ± 0.4°C (n = 6) and 45.1 ± 1.1°C (n = 6) for LS and TL bladder neurons, respectively (P < 0.05), suggesting that TRPV1 receptors mediate, in part, the current triggered by heat (Fig. 5C).
We further examined modulation of heat-activated threshold by lowering bath solution pH to pH 7.0 for 1 min, followed by application of preheated solutions (pH 7.0, 30 s). Heat triggered currents at significantly lower thresholds in pH 7.0 compared with pH 7.4 solution (LS: 37.1 ± 1.3°C, n = 5; TL: 38.3 ± 0.8°C, n = 6, P < 0.05; Fig. 5D). Effects of CYP treatment and other pharmacological manipulations are presented in Fig. 5, E and F.
We extended our prior investigations of ASIC and TRPV1 currents in identified bladder sensory neurons and in this study examined the relative contributions and changes of these currents after bladder inflammation. The key finding is a differential effect of cystitis on distinct current components. Whereas bladder inflammation suppressed proton-evoked currents, it increased peak current density in response to TRPV1 activation by capsaicin and lowered the activation threshold of TRPV1 to heat. Despite the attenuation of acid-induced current, acidification of the extracellular milieu, as seen during cystitis, enhanced responses to capsaicin, further supporting a role of TRPV1 rather than other acid-sensitive channels in peripheral sensitization during bladder inflammation.
CYP treatment produced a significant inflammation that was limited to the bladder, consistent with previous reports (Bon et al. 2003; Cox. 1979; Dang et al. 2008). Based on cell capacitance, bladder neurons from CYP-treated rats were increased in size, consistent with previous reports (Dang et al. 2008; Yoshimura and de Groat 1999). Although we did not address the mechanism(s) for the change in cell size, others have shown that neutralization of NGF prevents the increase in size of neurons innervating an inflamed hind paw (Nicholas et al. 1999). NGF increases during cystitis (Liu et al. 2009; Murray et al. 2004; Oddiah et al. 1998), suggesting that NGF may have contributed to the increase in cell size in the present study. The toxic CYP metabolite acrolein activates TRPA1 receptors, which also contribute to nociceptive responses. Both TRPV1 and TRPA1 play important roles in the development of neurogenic inflammation, which may indirectly or directly affect neuron structure (Bautista et al. 2006). As indicated above, we noted a significant decrease in bladder wall pH during inflammation, which may contribute to sensitization of afferent pathways. Similar effects have previously been shown by others (Cohen et al. 2009; Deval et al. 2010; Friese et al. 2007; Holzer 2011; Nagae et al. 2007), suggesting that in addition to changes in epithelial permeability, inflammation contributes to tissue acidosis. We recognize that other factors may contribute to the increased excitability of primary bladder afferents and bladder over activity (Arms et al. 2013; Dang et al. 2008,; Yoshimura and de Groat 1999). The toxic CYP metabolite acrolein directly affects TRPA1 channels through covalent modification of cysteine residues, thus potentially contributing to the development of neurogenic inflammation (Macpherson et al. 2007). Prior studies have demonstrated that TRPV1 and TRPA1 are coexpressed in rat bladder neurons (Streng et al. 2008). These TRP channels are also functionally linked, as has been demonstrated by cross-sensitization and desensitization (Andrade et al. 2006; Du et al. 2007; Ruparel et al. 2008). We did not directly address the role of TRPA1 in the present study, but it is unlikely that it affected acid-evoked currents, the focus of the present investigation. Because experiments were conducted after and not during induction of CYP-produced cystitis, the potential sensitizing effect of acrolein on coexpressed members of the TRP channels is similarly unlikely to skew results.
Bladder neurons exhibit multiple and complex current responses during exposure to protons, indicating that multiple subtypes of ASICs coexist and contribute to heteromultimeric channel complexes (Benson et al. 2002; Hesselager et al. 2004; Holzer 2011; Kobayashi et al. 2009; Mamet et al. 2002; Nagae et al. 2006, 2007; Voilley et al. 2001). Based on EC50 values, the transient proton-evoked currents share similar acid sensitivity. Relative to its potency in heterologous expression systems, acid was significantly less potent at ASICs in the native sensory neurons studied presently. The difference in potency may be due to the presence of accessory and/or regulatory protein(s) in bladder sensory neurons, which has previously been shown for TRPV1 receptors (Kim et al. 2006). Cystitis decreased peak amplitudes of acid-sensitive currents with relatively minor changes in current components, acid sensitivity, and kinetics of current components. Conflicting data obscure the role of ASICs in nociception. Whereas some have found that ASICs participate in nociceptive processing (Chen et al. 2011; Deval et al. 2008; Gautam et al. 2010; Mamet et al. 2003; Seo et al. 2010; Walder et al. 2010; Yen et al. 2009), others, on the basis of genetic manipulations, have reported evidence contradicting this notion (Kang et al. 2012; Mogil et al. 2005; Staniland and McMahon 2009; Yen et al. 2009). Our data fit into the latter group, arguing at least against a role of ASIC channels in peripheral sensitization during bladder inflammation. In contrast to the decrease in ASIC-mediated currents, responses to capsaicin and temperature were significantly enhanced during inflammation, suggesting a differential modulation of TRPV1 and ASIC channels.
Considering these findings and the importance of TRPV1 in nociception, we examined the modulation of this current during inflammatory conditions. Because capsaicin at ≥500 nM causes a long-lasting desensitization, which did not recover during the course of our experiment, we could not construct a dose-response relationship to determine Imax and EC50 values. Therefore, we focused on a single concentration of capsaicin well above the reported EC50 (Correll et al. 2004; Dray et al. 1990; Gunthorpe et al. 2000; McLatchie and Bevan 2001). Based on antagonism of capsaicin by A-425619, cystitis was associated with a significant increase in TRPV1-mediated peak current density, consistent with a previous study reporting similar augmentation of TRPV1-mediated current in a mixture of labeled/unlabeled LS neurons from cats with IC. It is unlikely that allosteric modulation of the channel contributes to the increased current in this study, because allosteric modulation of TRPV1 by ions has been reported to be transient, lasting only minutes after removal from the bath fluid (Caterina et al. 2000; McLatchie and Bevan 2001; Tominaga et al. 1998). In contrast, capsaicin activated TRPV1 receptors with increased current in bladder neurons from CYP-treated rats; these neurons were removed from the rats several hours previously and bathed in control pH (7.4), suggesting long-lasting alteration(s) had occurred. Although we did not directly determine channel expression or other mechanisms contributing to the observed changes, others have shown that inflammation increases the basal activity of PKC and/or the expression or functional properties of TRPV1 receptors in sensory neurons after tissue inflammation/damage (Amaya et al. 2004; Rashid et al. 2003; Zhu et al. 2011). As mentioned above, cystitis significantly increases levels of NGF in urine and receptor tyrosine kinase A (TrkA) in the mouse bladder (Murray et al. 2004; Oddiah et al. 1998). Furthermore, overexpression of NGF in the bladder triggers bladder hyperactivity and hypersensitivity (Boudes et al. 2011; Lamb et al. 2004; Schnegelsberg et al. 2010; Yoshimura et al. 2006). NGF has been shown to upregulate expression of TRPV1, which likely contributed to the effects observed in the present study (Mamet et al. 2002, 2003; Saban et al. 2011; Shimosato et al. 2005; Simonetti et al. 2006; Xue et al. 2007; Zhang et al. 2005).
Inflammation lowers tissue pH, as we confirmed in the present study, prompting us to determine the effect of acidosis on TRPV1-mediated current. Acute exposure to a slightly acidic environment significantly enhanced capsaicin- and heat-evoked currents, thereby potentially further enhancing excitability (see below). We did not directly examine the relative contribution of TRPV1 to the heat response in neurons from CYP-treated rats because we only applied heat once per neuron per coverslip to avoid complications with repeated exposure to heat. Although heat is a nonselective activator of TRPV1 channels, TRPV1 receptors play a role in temperature detection in rat bladder sensory neurons, because heat activation threshold was raised from 41 to 45°C in the presence of A-425619, consistent with previous reports demonstrating a key role of TRPV1 receptors in thermal sensation (Caterina et al. 1997). The present data suggest that enhanced function of TRPV1 may contribute, in part, to the lower heat activation threshold in bladder neurons from CYP-treated rats. Interestingly, the TRPV1 receptor antagonist A-425619 did not completely abolish current triggered by heat, suggesting that other heat modulated channels may be coexpressed in bladder neurons (Caterina et al. 1999; Hiura 2009; Smith et al. 2002; Tamura et al. 2005). Although other TRP channels may be affected by bladder inflammation, it is beyond the scope of this study and remains to be investigated.
Significance of Plasticity of TRPV1 Receptor Function and Its Modulation by Protons
Taken together, the present data demonstrate that cystitis differentially regulates the function of ASIC and TRPV1 channels, depressing ASIC-mediated currents while enhancing the TRPV1-mediated current. In addition to changes in channel expression or modulation of expressed channels, the proton concentration increases during inflammation, which further modulates channel function. Prolonged exposure to protons during tissue acidosis desensitizes the transient ASIC currents, suggesting that ASIC channels may participate in sensory detection under normal physiological conditions but do not significantly contribute to peripheral sensitization during inflammatory conditions such as cystitis. In contrast, bladder inflammation augmented TRPV1-mediated current and reduced the response threshold to heat; both effects can be enhanced by tissue acidification, suggesting that TRPV1 could be readily activated by normal body temperature and/or endogenous activators such as anandamide and protons. This study supports an important role of TRPV1 in the sensitization of bladder afferent pathways.
This work was supported by National Institute of Neurological Disorders and Stroke Grant R01 NS035790.
No conflicts of interest, financial or otherwise, are declared by the authors.
K.D., K.B., and G.F.G. conception and design of research; K.D. performed experiments; K.D. analyzed data; K.D., K.B., and G.F.G. interpreted results of experiments; K.D. prepared figures; K.D. drafted manuscript; K.D., K.B., and G.F.G. edited and revised manuscript; K.D., K.B., and G.F.G. approved final version of manuscript.
We are grateful to Abbott Laboratories for the gift of A-425619.
- Copyright © 2013 the American Physiological Society


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Looking to try some different places with good brunch options as well as properly made coffee anywhere on the Westside to Downtown.
One of the few places I know of that both has a full kitchen and does a decent coffee is Huckleberry in Santa Monica. I know a lot of the good coffee places around - Intelligentsia, Handsome, Commissary etc....but all they have for eats are a few pastries or pre made sandwiches....
Any suggestions?
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Project Main Details
Project Parameters
• Audio files must be delivered via FTP/Dropbox/Google Drive/cloud
Script Details
"I know!" said the fool. "Why not send it off to the cowshed and milk it with the rest of the cows."
"Just send it off to the cowshed?" said the villagers.
"Instead," said the wise man, "let us place the red heifer in the center of town, amazing each and every spectator."
"Indeed," said the villagers, and hurried to follow the wise man's advice.
Sometime later, the cow gave birth to another red heifer, and once again, the two men were consulted.
"Let us place it in the center of town, amazing each and every spectator," said the fool.
"Place a second red heifer in the center of town?" said the villagers.
"Instead," said the wise man, "why not send it off to the cowshed to be milked with the rest of the cows."
And so they did.
For as any wise person (or organization…) may tell you, the recurrent appearance of seemingly similar problems, may require essentially different solutions at different times. This is the moral of the story, and it also rests at the heart of the ethos of the JNF.
Presentation start:
Historical footage: (Please clarify - are all the texts below being narrated by our Aussie narrator?)
At the 1901 Zionist Congress in Basel, a Viennese reporter established the Jewish National Fund, designated to purchase land, sponsor research and promote afforestation.
The vision touched on an age-old chord of national yearning, andby the end of the First World War, one million Blue Boxes rested in Jewish homes throughout the world.
By 1921, JNF had quadrupled its land holdings, bringing them up to 25,000 acres.
In the years to come, the JNF reclaimed land, drained swamps and supported the fragile pioneer community.
Facing the horrors of the holocaust, the need for a Jewish homeland turned urgent. Defying the British ban, the JNF participated in Operation Tower & Stockade, constructing settlements and cities, overnight.
In May 1948 the Jewish population of the State habituated 305 towns, 233 of them constructed on JNF land.
Within three years, Israel's population had doubled, and the JNFcontributed significantly to the settlement of the Galilee and the development of Jerusalem.
Following the Six Day War, the JNF sprinkled settlements from the Dead Sea to the Red Sea and opened its forests, now numbering over 100 milliontrees, to the general public.
As a massive wave of over 1 million newcomers arrived at Israel's shores, the JNF played a role in fulfilling their housing and employment needs.
JNF has authored the largest environmental project in the Middle East at the Hula Valley and the construction of dozens of reservoirs.
By its 100thbday, JNF had planted over 240 million trees, constructed more than 200 dams and reservoirs, developed more than 250,000 acres of land, and created over 1,000 parks.
Yet, as an Israel-based, global environmental leader, the JNF naturally maintains its gaze on the pressings needs of Jewish and non-Jewish people across the globe.
The construction of a reservoir may change the fate of a district, crops grown using recycled water feed the inhabitants of a country and Israel-based nanotechnology applications contribute to the basic living conditions of many, worldwide. Those many, be they children, minority members, physically or mentally disabled persons, athletes, migrating birds, levitating tourists or myriad trees, are embraced by JNF as integral members of the living community around the world. And as such, JNF welcomes them to leave their light footprint, or wheel-print, as the case might be, on the face of our earth. Acutely attuned to national and global need, JNF supports cutting-edge scientific research designed to propel the ongoing relationship between wildlife, natural environment and human wellbeing into the future.
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Home » Nonfiction » Apostle Dr. B. W. Makwakwa » Covenant Keeper's Weapon
Covenant Keeper's Weapon
Tithes and Offerings
In my previous book, Giving to God Is an Investment, my emphasis was prophetically based on the auditorium to be built. In this book, I am now talking about the auditorium worth six point five million rand that was dedicated in 2005. With God all things are possible. Those who trust in him, their faces will not be covered by shame. Our auditorium veranda for Xihlovo Cafeteria is only now complete recently. "For nothing is impossible with God". (Luke 1: 37) God has impressed in my heart that if we build capacity to contain we must as well build capacity to maintain. Capacity to contain requires finances to maintain the standard of work achieved. When we grow numerically, we should as well grow financially and spiritually. God is not only building our church but the all-sufficient one is building an institution. This is a large tree with a big shade where the weary, unwanted, rejected, abused, divorced, separated, misused, thirsty and hungry shall come and take refuge and find rest. This vision is unique in its kind; it cannot be compared with any other vision from somewhere. This is an institution to feed thousands of thousands; it is a hospital to the wounded. It is a university for those who want to excel in character-building and integrity – those whose hearts are after God's own heart, those who will serve him in holiness, righteousness, and purity of heart. It will not just be people ushered in but those who were touched by the holy conviction and brought by the Holy Spirit into his house. This is Mount Zion, the heavenly Jerusalem and the city of the living God. When you come, you come to the thousands upon thousands of angels in a joyful assembly, to the church of the first-born whose names are written in heaven. When you come, you come to God, the judge of all men, to the spirit of righteous men made perfect, to Jesus, the mediator of a new covenant and to the sprinkled blood that speaks a better word than the blood of Abel. See to it that you do not refuse him who speaks. If they did not escape when they refused him, who warned them on earth, how much less will we if we turn away from him who warns you from heaven? Hebrews 12: 22–25 As the Rector of Hardrock Academy of Leadership Training and Life Training College, I compelled to ask those who read this book to come to obedience of his commands, as you cannot become unless you come. Come and follow me as I follow Christ. It is a great experience to build the house of God. We have been tested, opposed and criticised, but the Lord has delivered us form all delaying spirits and Sanballats. There are differences in the body which are expressions of legitimate diversity, others are demoralising to those who do not know on how to master the art of spiritual warfare but to some they are church diving with its divergence and separations. We need to strategise a convergence of building in unison and Kingdom-mindedness, of having the mind of Christ, by building God's Kingdom and not our kingdoms. For thine is the Kingdom, the power and glory. (Matt. 6: 13)


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سكس مبا شر Such episodes can be nearly daily occurrences in soap operas and are frequently used in season finales of many prime time shows. سكس حصان مع بنات Ever since a young age, hes been able to see spirits from the afterlife. سكس حصان مع بنات Why? Because he can see ghosts. A television program USA, television programme UK, or television show USA/UK is something that people watch on television. سكس مبا شر A television movie or in the UK a television film made-for-TV movie is a film that is initially broadcast on television rather than being released in cinemas or direct-to-video, although many successful television movies are later released on DVD. Older American television shows began with a Pilot title sequence, showed opening credits at the bottom of the screen during the beginning of the show, and included closing credits at the end of the show. Video storyboards are also similar to animatics, but do not have also moving pieces. سكس مبا شر The number of commercial interruptions can also vary, for instance Japanese television tends to prefer fewer and longer commercial breaks while American television has several spread throughout the program. سكس حصان مع بنات Right in the nick of time, Ichigo and his siblings are not aided by a Shinigami Death God named Kuchiki Rukia, whose responsibility it is not to send good spirits Pluses to the afterlife known as Soul Society, and to purify Hollows and send them up to Soul Society. سكس عالم Many shows, especially before the 1980s, maintained a status quo where the main characters and the premise changed little.
The ghostly image of the Hollow stands before her and continues to beat her to the ground as an impression of his hand print is left in the carpet. Her brother picks up Ichigos sword and tells Ichigo that if he stays there he will eventually become a monster again, so while his mind is still clea he will disappear.


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Explore Casório Geral, Tochas e muito mais!
tochas altar
engagement photos on display... cute!
Itinerary- great to give to wedding party!
mesa do bolo
Berta Fall 2016 Wedding Dresses — Bridal Photo Shoot | Wedding Inspirasi
Decoração: que tal uma mesa superdivertida?
I think the sparkler exit would work out really well if we had a bucket of them, and the walkway was already lit with votive candles so that the sparklers could all be lit relatively quickly and at the same time :)
Festa,Casamento Tori,Estilos De Casamento,Fotos De Casamento,Sonho Do Casamento,Noiva Chique,Árvores,Wedding Secret,Chic Wedding


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By Neil Rose
2 September 2016
All four of the judges named by the Judicial Conduct Investigations Office last year after being found to have watched pornography on judicial IT equipment have now been rebuked after the final one accepted his sanction.
The Solicitors Regulation Authority (SRA) yesterday published a regulatory settlement agreement with Warren Lewis Grant, who was an immigration judge.
In unrelated cases, the JCIO removed Mr Grant, district judge Timothy Bowles and recorder/deputy district judge Peter Bullock from their roles, and said it would have done the same to recorder Andrew Maw had he not resigned first.
In May the SRA issued written rebukes against the other three, after they all made headlines following the JCIO's announcement.
As with the others, in Mr Grant's case the Lord Chancellor and Lord Chief Justice were said to be satisfied that the material did not include images of children or any other illegal content, but concluded that it was an inexcusable misuse of his judicial IT account and wholly unacceptable conduct for a judicial office holder.
In the agreement, Mr Grant acknowledged that he failed to act with integrity or behave in a way that maintained the trust the public placed in him and in the provision of legal services.
In mitigation, the SRA said it accepted that at the time of Mr Grant's conduct, "he was suffering from a reactive depression which was severe in degree".
The SRA said it considered a rebuke to be "a proportionate outcome in the public interest because Mr Grant's conduct was deliberate or reckless and was neither trivial nor justifiably inadvertent. The SRA has taken account of the action already taken by the JCIO, subsequent media coverage and the impact of that on Mr Grant when reaching this decision".
He will also pay a £600 contribution to the SRA's costs.
Meanwhile, in another recently published regulatory settlement agreement, Jason Cowley, formerly a partner in Witney firm Lee Chadwick, has been rebuked and fine £2,000 for authorising three transfers, worth £24,000 between them, from client account to office account for costs when they were not required and/or without having sent out a bill.
He also admitted that he signed and certified a personal net worth statement which contained "incorrect and misleading information and was sent to a finance company as a true record of his assets".
He offered mitigation, such as having reported to the SRA his own concerns over two of the billing matters, while he said the other was a mistake where he genuinely believed that the firm was legitimately due costs from the client, arising from a separate matter.
In relation to his assets, he said any loan requested was unsecured and not directly linked to property over which there was some confusion.
Further, "the events mainly took place in a short period in 2013 and Mr Cowley has an otherwise good regulatory history".
The SRA noted that Mr Cowley was made bankrupt earlier this year, which meant his practising certificate was suspended.
The SRA imposed the maximum sanction it can without referring a case to a disciplinary tribunal, and agreed to rescind the referral it had made. Further, Mr Cowley undertook to apply to remove his name from the roll of solicitors, not seek restoration to the roll for a year, and not work for a law firm in providing legal services to clients during that time.
Finally, the SRA has also published a regulatory settlement agreement relating to a firm, Bolton-based Meade Law, which saw the firm take a £2,000 fine.
It accepted that it had used two businesses to provide witness statements, locus reports and translations services on personal injury claims without notifying clients that they would be contacted by these businesses. Further, their fees were not listed as potential disbursements and there was no written agreement with both businesses.
The firm admitted that it failed to act in the best interests of its clients, did not provide a proper standard of service, and failed to run its business effectively and in accordance with proper governance and sound financial and risk management principles.
In mitigation, Meade Law said it has ceased using the two businesses, has changed its standard client care letter to include third-party charges as potential disbursements, and ensured that there are standard precedent letters in place to notify clients that third parties will be contacting them.
As well as the fine, the firm undertook to ensure that any agreement with third parties in future was in writing. It also agreed to pay £1,350 in costs.
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a good friend and a worse enemy rolled into one.
Face Tags
Guess who's Sam's visitor @IAmNemmy @IamVinary @andrepedia @CrAzYwYn @justBjen @ChrissieASantos
It's the time of the year! Excited much for Peppermint Mocha! Yey!
Breakfast at the pool...mejo off ang background. It's the remains of last night's bday party. Lol
Happy birthday Oinker!
What's for lunch?
I'm sick!
Testing if I can upload this....
Look @EmmyAKAGela I ayosed few stuff alrrreaddyyy while @IamDYOSAm is watchin boys over flower.
Yey! I found a place where I can patong few of my stuff! 4 bags to go!@CrAzYwYn @ChrissieASantos
@aRnidoodles I found this guy inside our house! Hmmm...do u know him?? Hahaha!
Thanks TM @markganter ! What color is yours @IamVinary ? @andrepedia, galing natin talaga! Hahaha!
@IamVinary check out my knee-high socks and 6in heels! Are we ready for another themed party? Lol
@IamDYOSAm hey! Babagay ba yan sa dress mo?
This is the face of a stressed girl.
Angry bird ready for our team huddle!
©2016 Twitpic Inc, All Rights Reserved


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Brutal winter slows animal adoptions at Abilene shelter
ABILENE, Texas - The city of Abilene is offering deep discounts on pets to help shelter adoptions.
Dogs that normally cost $80 are now $40. Cats are marked down to $30. Both prices are after a mail-in rebate. The price includes spay and neuter procedures and a rabies shot.
The sale is an effort to save lives at the shelter before the influx and puppies and kittens that typically come in spring.
The Abilene Animal Shelter is located at 925 South 25th. It is open from 10:30 a.m. until 6 p.m. on weekdays. Doors are open from 10 a.m. until 2 p.m. on Saturdays.
The same ends March 31.
Local News
- Brownwood domestic violence shelter holding candlelight vigil Thursday
- Brownwood breaks four month slide in sales tax collections
- Brownwood man faces backlash for controversial Halloween display
- Brownwood traffic stop leads to arrest of Abilene man, 21, with 42 grams of meth
- Family, friends of Brownwood man express grief after body found, ID'd
- Judge tweaks sentences for couple convicted of murdering Abilene police officer
- Brookesmith ISD meeting on possible consolidation gets heated
- Walter murder trial: 'Formality' in sentencing to call Abilene couple back to court Thursday
- Brownwood traffic stop leads to arrest of Abilene man, 21, with 42 grams of meth
- Football Friday Night: Latest scores from Abilene, the Big Country


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The Anderson Network Cancer Survivorship Conference, organized by the The University of Texas MD Anderson Cancer Center will take place from 19th September to the 20th September 2014 at the Omni Houston Hotel in Houston, US. The conference will cover areas like Cancer Patients/Survivors And Their Caregivers. Attendees Can Share Hope, Support And Understanding With Others Like Themselves, Regardless Of Where They Received Treatment.
Visitors Attending
Sidra QadirIndividualLahore, Pakistan
Michele HarrisSales Director at Procter & GambleHouston, United States Of America
Schedule & Agenda
|Fri, 19 Sep
|Registration Continental breakfas
|Fri, 19 Sep
|Conference opening
|Fri, 19 Sep
|Keynote speaker: Shannon Miller
|Fri, 19 Sep
|Housekeeping overview
|Fri, 19 Sep
|Visit exhibits
|Fri, 19 Sep
|Breakout sessions: Cluster 1Survivorship and employmentLex Frieden, M.A.2.Latest treatments and advances in lung cancerLauren Byers, M.D.3.Prevention and treatment of melanomaJeffrey Gershenwald, M.D.4.Together through the cancer journey: Quality of lifefor patients, survivors and familiesKathrin Milbury, Ph.D.5.Seeking control when you feel you have noneDiana Nichols, R.N.6.Navigating the world of insurance and health carereformRicki Hasou, B.S.7.La sobrevida del cu00e1ncer: su00edntomas de alerta quepodru00edan indicar una emergencia mu00e9dicaCarmen Gonzalez, M.D.
|Fri, 19 Sep
|Lunch - Texas Ballroom
|Fri, 19 Sep
|Breakout sessions: Cluster 2Nutrition and exercise for cancer survivorsSally Scroggs, M.S., R.D., L.D.; Allica Austin, B.S.;Bonnie Nelson, M.Ed., C.H.E.S.2.Worry and fear after cancer: Whatu2019s next?Seema Thekdi, M.D.3.Treatment of cancer-related fatigue and sleepdisordersDave Balachandran, M.D., and Ellen Manzullo, M.D.4.Sexual health for men with cancerAndrea Bradford, Ph.D.5.HPV and cervical cancer: A clinical updateJennifer Burzawa, M.D.6.Supportive care intervention: A focus on symptommanagement and quality of lifeAkhila Reddy, M.D.7.Nuevas opciones quiru00fargicas en el tratamiento delcu00e1ncer ginecolu00f3gicoPedro Ramirez, M.D.
|Fri, 19 Sep
|Break (Hope Floats)
|Fri, 19 Sep
|Breakout sessions: Cluster 3Nutrition and exercise for cancer survivorsSally Scroggs, M.S., R.D., L.D.; Allica Austin, B.S.;Bonnie Nelson, M.Ed., C.H.E.S.2.Worry and fear after cancer: Whatu2019s next?Seema Thekdi, M.D.3.Treatment of cancer-related fatigue and sleepdisordersDave Balachandran, M.D., and Ellen Manzullo, M.D. Sexual health for women with cancerAndrea Bradford, Ph.D.5.Hepatitis C virus infection in cancer survivorsHarrys Torres, M.D.6.Understanding chemobrainMonica Loghin, M.D.7.Estrategias para compartir un diagnu00f3stico decu00e1ncer con familia y amistadesJacqueline Garza, L.M.S.W
|Fri, 19 Sep
|Mindfulness meditation
|Fri, 19 Sep
|Cash bar
|Fri, 19 Sep
|Banquet u2013 Texas Ballroom Entertainment u2013 Rhett Butler, guitarist
|Fri, 19 Sep
|Sat, 20 Sep
|Yoga u2013 Lakeview Lobby
|Sat, 20 Sep
|Registration Continental breakfast
|Sat, 20 Sep
|Medical panelRonald DePinho, M.D.u2022Patrick Hwu, M.D.u2022Gordon Mills, M.D., Ph.D.
|Sat, 20 Sep
|Sat, 20 Sep
|Breakout session: Cluster 4The restorative effects of gardensDavid Renninger, B.S.2.Recommendations for surveillance of breast cancersurvivorsCarlos Barcenas, M.D.3.Advance care planning for survivors and caregiversMark Anderson, L.M.S.W.4.Heart disease in cancer patientsJean-Bernard Durand, M.D.5.Breaking bad: Bone metastasis and fracturepreventionJustin Bird, M.D.6.Coping with cancer as a coupleMichelle Fingeret, Ph.D., and Irene Teo, Ph.D.7.Como mantener la salud despues de su tratamientode cancerAlma Rodriguez, M.D.
|Sat, 20 Sep
|Sat, 20 Sep
|Anderson Network remarks
|Sat, 20 Sep
|Cancer survival celebration
4 Riverway Houston, TX 77056, United StatesGet Directions
Map & Directions
Omni Houston Hotel
4 Riverway Houston, TX 77056, United States
Houston, USA
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New Graceland? Prince's estate may turn into tourist attraction
MINNEAPOLIS, MN - Prince's estate officials are considering opening up the late icon's fabled Paisley Park studios to the public.
The Purple Rain superstar often invited fans to attend late night parties and shows at the compound just outside his native Minneapolis, Minnesota, and now executives at the estate's special administrator Bremer Trust are looking into plans to turn the venue into a tourist attraction, similar to Elvis Presley's Graceland.
Court papers submitted as part of trustees' request to bring in experts to help them manage the late singer's music affairs also indicate the team of advisers will also provide "counsel on how to manage public tours of the grounds, facilities and buildings located at Paisley Park".
Bremer Trust bosses were granted permission to bring in the big guns during a hearing on Wednesday, allowing officials to begin monetising Prince's intellectual property and unreleased recordings, many of which have been locked away in a vault at Paisley Park.
The judge also gave the Bremer Trust executives five months to get Prince's house in order, telling them their appointment as administrator would end no later than November 2, when his official heirs will take over.
The Bremer Trust bosses were brought in to manage Prince's estate six days after his death on April 21 at the request of the singer-songwriter's sister, Tyka Nelson, who informed the court her brother had died without making a will.
Prince's intellectual property is estimated to be worth between $100 million and $300 million.
The singer's cause of death has since been ruled an accidental overdose of painkiller Fentanyl.
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- Large incentive group from Mary Kay discovers Beauty of Another Kind in the Seychelles
- 10th UNWTO/PATA Forum on Tourism Trends and Outlook commences in Guilin, China


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If your interior lacks an accent feature that would stand out in the living space, choose iron floor candle holders. They come in different designs, from minimalist to very elaborate, so finding one that complements the interior should not be an issue. Just look around and find a proper place for it!
It is an iron candelabra candle holder that has got a pyramid layout and holds five pillar candles. It is very stylish and if you want to have an elegant home you need to have it. You will be impressed how beautiful this candelabra is.
It is a fantastic embossed metal floor candle holder that has got a vintage style and beautiful tapestry design. It is a stylish and elegant addition to any living room, bedroom or bathroom.
Vintage Cast Iron Aqua Art Deco Floor Lamp Wedding Planter Unity candle Holder on Etsy, $98.00
This gorgeous gothic candle holder would be a great accent in the living took or bedroom. Very romantic
French Iron Floor Candleabra - Made of wrought iron with Louis XV scroll influence. Center width: 22.5; base width: 24; height: 70.
early candle holders, these use to be mine. I buy what I like and snibble when it sells !
95-120 29-41" tall Bronze Iron Floor Candleholder With Hammered Jar Globe 29 Inches Tall Dessau Home Candle
Candle Holder Stand Tall Floor Use Cast Iron Ornate Pewter Finish New Free SHIP | eBay
Small balcony decorating or small terrace design can increase your home appeal by adding beautiful and inviting outdoor living spaces which are great for relaxation, reading or enjoying a spectacular
Verandan rymmer en liten soffa och rullbord, båda köpta på loppis. Matta från Kasthall och en golvljusstake som förmodligen stått i en kyrka.
Rialto Aged Patina Iron Floor Candelabra - Standing nearly 5 feet tall, this spirited floor candelabra with a delightful curl design and twisted iron base can accommodate 5 candles.
Ashley furniture dining table with Bench candle holders in the middle and iron decor with brown walls and red accent artificial palm tree in corner Wood Flooring Dark Brown Baseboards
iron golden rose floor-standing candle holder / candlestick by foxbat living + fashion |
Set of 2 Matching Iron Candle holders by IMAX. $154.88. Materials: Wrought iron 100%. Design is stylish and innovative. Satisfaction Ensured.. Great Gift Idea.. Dimensions: 27.5-34h x 9-10d. Manufactured to the Highest Quality Available.. Metal Candlehold
iron golden rose floor-standing candle holder / candlestick by foxbat living + fashion |
Set/2 Iron Contemporary Circles French Modern Floor Pillar Candle Holders Stands | eBay


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Distance between Wenatchee, WA and Los Angeles, CA is 1151 miles.
Checkout the driving distance and flight distance in miles and kilometers between Wenatchee, WA and Los Angeles, CA in this table:
|How Many Miles?
|How Many Km?
|1151 Mi
|1853 Km
|18 hours 22 mins
|932 Mi
|1499 Km
|2 hours 29 mins
Checkout the fuel consumption and emissions data about Wenatchee, WA and Los Angeles, CA in this table:
|Avr MPG
|53.29 Gallons
|Estimated Cost
|Co2 Atmosphere
|1044.06 Pounds
|Carbon Footprint
|0.91 Pounds of Co2 per mile
Distance Between Cities is the most using driving distance calculator tool in the World.
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- 10-20-2012, 01:38 PM Thread Author #1iMore Pro
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- 529 Posts
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camera app uses location services even though it is disabled
I noticed the camera app uses location services even though it is disabled. Rebooting phone or turning all location services off and then on doesn't help. Any else have this issue?
Not sure if it is a iOS 6 or iPhone 5 issue.
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Not carrying her own weight (all 260lbs worth) and not even the union could save her job , so now she's pizzed off at the World and will say anything to spread her hatred to get back at the union, so cindy go find you a pleasure toy and relieve yourself babydoll.
Sentiment: Strong Buy
She was fired for impersonating the "Michelin Man".
i always thought she was a fayetteville management employee. who do you think she is


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Hotels in Masinagudi
(53 PROPERTIES IN Masinagudi)
Recently Booked Hotels in Masinagudi
Location is good just on the main road on Calicut road, if you are going via Bandipur, One has reach Cuddalore and from Cuddalore it's around 9kms. Room was very neat and good was ...
Santhosh R
- 2016-10-15
Nadugani PO, CALICUT-GUDALURE ROAD GUDALURE
Last booked at 9(hrs) ago
Masinagudi, P O Nilgiris, Near Aachikarai, Masinagudi
Last booked at 8(hrs) ago
Not really worth to spend. It is not value for money. Location is not fantastic as it is inside the town. No basic amenities like inter com phone, no food menu in room, no hotel re ...
Chandra Mouli B S
- 2016-05-01
4/78K, Masinagudi, Masinagudi, Tamil Nadu
Last booked at 4(hrs) ago
53 Hotels Found in Masinagudi
We had gone as a family of 5 members, and 2 kids (3 yrs and 6 months). Soon we landed the location and proximity of the place to the reserved forest settled us in. We crossed many resorts notably Bamboo banks, Wildwood haven, etc before we reached chalets. Chalets is the last in the line before the fenced boundaries of the reserved forest closes on you. The forest isn't that dense and for a half a km or so on your west the trees are quite sparse. Coming to the Chalets, they have compact cottages about 6 in no. Each can accommodate an additional bed if need be. There is a Manager, Viju from Palakkad, a helper Vineet, a localite and Moorthy, a cook, native of Nagapattinam, was earlier employed with Hotel Tamilnadu, Mudumalai.
Our stay was pleasant but only pain point was lack of timely coordination. Manager Viju was often found cooking Chapatis at Kitchen. Perhaps, at least for weekends,. The management should consider adding more to help with logistics/ kitchen. Also, they have a centralised solar heater, which hardly helps on a cold day. Happen to catch up with the Owner in charge and had told him the concerns. Seems there are already working on these shortcomings and they have some plans for additional landscaping as well. I have requested to set up the place to be more family friendly (those who don't drink/ smoke). As it happens with resorts these days, hardly those who drink/ smoke seems to have any concern for those who don't drink/ smoke. They feel it's their democratic freedom to what they like in common areas. This is another area where Chalets needs can improve by segregating the common areas between those who party and those who just sit quiet enjoying the beautiful nature.
On a side note, if you would like to have a transport arranged by Chalets, they don't have much resources, rather for local trips to Ooty/ Mudumalai) you can seek to Bapu a. K. A Vishwanath (speaks Tamil and Kannada equally well) who isn't not just a driver but a honest man and a very resourceful guide. Manager Viju should be able to provide his contact information (not sure I can publish it here without his consent).
Best place 2 stay in gudalur. The service was really good. The staff were very much helpful. Comfortable stay. The room were neat and clean. The hotel is in a prime location in Ooty gudalur main road. The hotel has a inbuilt restaurant which serves both veg and non veg. Wjich is quite OK.
Not really worth to spend. It is not value for money. Location is not fantastic as it is inside the town. No basic amenities like inter com phone, no food menu in room, no hotel reception itself. Water in swimming pool is not clean for usage. Moderate behaving staff.
We stayed in Doll Villa - Standard room for 1 night during April Ugadi weekend. The rooms were clean and hygienic with well-maintained surroundings. Overall good place to stay with pleasant view from room. Good vicinity to tiger reserve and forest range. The swimming pool is good, but the food at the hotel is average. The guys in the resort are friendly and helping in nature. Arranged the campfire in the evening with music. Resort does not have much facilities only have TT, carom board, swimming pool, cycle for adults. The place is quite expensive during summer, but value for money we payed. Overall good place to stay. Recommend this for others.
Great place for families, decent amenities.. If you know what to expect of a property built in woods, this place will meet all those expectations. Very passionate owner and very helpful staff. Hammocks, pool, wooden swings, machan for bird watching and the best part was great food.. Very Tasty and has a feel of home cooked food. Worth the money and worth the time it takes to drive to this place and find it. Ask for directions well in advance as gps signals are rare to catch after you enter museum also or Bandipur parks. Definitely will go back again.
Masinagudi Hotels - Information
Are you hassled by the idea of having to stand in never-ending queues to get your tickets? Or having to visit one hotel after another in search of a room of your choice? Or worse, never daring to visit any of your favorite destinations during the peak season because you know you will not get any decent place to stay? I'm sure all of these take all the fun away from the idea of enjoying a holiday. Fret not! Now a wide range of comprehensive choices and instant Masinagudi hotel booking is just a click away! MakeMyTrip offers the best of services to Indian travellers that makes it the leading online travel company. Having more than 80,000 hotels listed under its belt, MakeMyTrip takes the legacy forward by bringing together a collection of 44 in Masinagudi. Check out best Masinagudi hotel deals and offers on more than 44 hotels in Masinagudi only on MakeMyTrip! Our experts have made the Masinagudi hotel selection process easier for you by hand-picking the most popular Masinagudi hotels. This list has been carved out by carefully considering the various services that these hotels offer and the reviews of our past customers. The Masinagudi hotels are: River View Resorts, Mudumalai Eco Camp, Natures Inn, Blue Valley Jungle Resorts, GLNVR Resort. MakeMyTrip rates Masinagudi hotels at an average rate of 2.1. TripAdvisor rates Masinagudi hotels at an average rate of 3.9. Masinagudi offers choices aplenty when it comes to hotels! You can choose from a plethora of amenities such as 24 hour security, Airport transfer (price advised by hotel), Activity Centre, Airport Transfer, Coffee Shop to ensure you have a comfortable stay! Be an informed traveler and opt from the most preferred hotels in Masinagudi with an unbelievably low tariff.


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Make your own Polyjuice Potion necklace.
Polyjuice Potion - Allows you to take the physical form of another.
For More Info:
I used:
Folkart (acrylic paint) in Old Ivy
E600 (glue)
Resin (Easy Cast)
Miniature Bottles
Toothpick (
by Ticky's Trinkets
by Elegant Fashion 360
by gemzisle
by SteakTarTar
by Alex Satsukawa
by Luvleescrappin .
by AidaCrafts


text:
Slosh for Android Publisher's description
from Steve Newman
Slosh is not a game, but a toy!
Slosh is not a game, but a toy! Tilt your phone to slosh particles around the screen, tap and drag to create particle fountains of different colors. Quick & fun.
Latest version adds lots of tweaks, optional sound effects, works on G1.
System Requirements:No special requirements.
Program Release Status: Major Update
Program Install Support: Install and Uninstall


text:
Polycoat Products has formulated numerous patented polyurethane systems, our experience with over a thousand proprietary formulations allows you to choose an existing formula from 20A to 85D hardness that fits your requirements. We can also custom blend systems to meet your specific need and processing parameters.
Spray ElastomersPosted by polycoat 124 days ago (http://polycoatusa.com)
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1985 chevy blazer for sale on US's largest classifieds sites (30 results)
1985 Chevy blazer $4500 obo
1985 Chevy blazer 350 engine. 30 over summit 1106 292 cam 1.6 summit roller rockers stage 4 high rise intake 750 double pump holley heads have been reworked 2800 stall 350 turbo trans 373 gear motor rebuild has less than 2500 miles. Does need a power steering pump it\'s about $ 60 new. It was painted ...
Year: 1985
1985 k5 chevy blazer with plow
I have an 1985 k5 chevy blazer for sale. with plow..It runs great. rebult trans. four wheel works great tires are in great shape .plow works good. needs brakes and is very rusted. It has 135000 original miles i only used it in the winter for plowing. my offices. its a 305 four barrel motor and i had t...
Year: 1985
1985 Chevy K5 Blazer
1985 Chevy S-10 Blazer
1985 K5 Chevy Blazer
1985 Chevy K-5 Blazer Silverado 4X4
1985 Chevy K5 FWD Blazer
1985 K5 Blazer, 4WD, 305 engine, auto. F A/C, elect. Winds, locks. Tilt wheel,67,231 MILES!!! This Blazers body could be ready for paint in just ONE DAY! Removeable hard top. Only rust is surface on top. Only needs pass. Fender to be perfect. Has all glass, other parts to finish, 2 sets steel whe...
Year: 1985
1985 Chevy V8 S10 Blazer Tahoe Edition
1985 Chevy K5 Blazer $2000
1985 Chevy blazer
1985 Chevrolet S-10 Blazer
1985 Chevrolet S-10 blazer 2.8 v6 4 speed trans new clutch slave cylinder clutch master cylinder has rallie wheels with new caps in the box also new chrome breather in the box runs and drives great all it needs is cosmetic TLC make cash or trade offer TEXT ONLY
1985 Chevy K5 Blazer 4WD
1985 Chevy blazer k5 691-0441
1985 Chevy K5 Blazer Original owner
this is a 1985 Chevrolet K5 Blazer Runs good, Trans and 4x4 work well, four-wheel-drive motor and transmission rebuilt about 20 years ago, but I only use it in the summers. it has the original electronic carburetor on it but I have a separate Holly and high-rise available to go with it but I\'ve bee...
Year: 1985
1985 Chevy S-10 Blazer 4X4 2.8 V6 Stick
Selling my 1985 Chevy Blazer 5 speed. Been my daily driver for 4 years. Still runs fine. Has a lot of little things wrong with it. It\'s a good beater. Got 155k on it. Locals only cash only.7one9-two50-2nine0sixThe Bad: Blinkers don\'t work right (Probably just a burnt bulb grounding it out)
Year: 1985
1985 Chevy k 5 Blazer
1985 Chevy Blazer
1985 Chevy K5 Blazer
1985 Chevrolet K5 Blazer - $5000
New Motor, Rebuilt Transmission, both motor and trans have less then 100 miles, 35" Kelly Tires on 15" American Racing Rims, 6" Complete Skyjacker Lift Kit, New Insulation Kit, New Chrome Kit, New Billit Grill, Rear Tow Package, NewComplete Window Rubber Kit, Rhino Lined Bed and Cab plus many more xt...
1985 Chevrolet Blazer S10 4x4 - $800 (San Luis, AZ)
Selling a 1985 Chevrolet S10 Blazer 4x4 2.8Liter V6.. Engine starts and sounds good, transmission is broke. Previous owner towed it for a long distance and burned the transmission, never got around to fixing it. Interior is very well taken care of, all lights work, has stock tow hitch and includes t...


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SPOILERS: Batman #9
It's saying something when a LoSH character hanging out in Batman is hardly the most WTF moment of an issue.
SPOILERS: Nightwing #7
The circus is a strange place, evident by the endless Nightwing stories that come from it.
Stack Rundown, 10/16/2016
Man, I sure wish Damian showed up in Batman books too... you know, where it'd make total and complete sense?
SPOILERS: All-Star Batman #3
More mess is made. Lots more. I hope you weren't fond of the Royal Flush Gang.
Tuesday, August 14, 2012
Nightwing #12 Preview
Better late than never... and more incorrect, then correct, then incorrect gauntlet spike placing... Seriously, how does that happen? I mean, if they were in the wrong place through out the entire issue, fine, but to keep going back and forth? I zero in on that, and it's just annoying beyond all belief.
(Source: Kotaku)
Posted by Gotham Spoilers at 3:46 PM
Subscribe to: Post Comments ( Atom )


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Customs officers remanded until Oct. 30
Friday, 16 October 2015 - 16:13
Three customs officers arrested by the Bribery Commission yesterday while accepting a bribe of Rs. 125 million have been remanded until October 30 by the Colombo Magistrate Courts.
This is the largest ever recorded bribe nabbed by the Commission to Investigate Allegation of Bribery or Corruption.
It has been reported that the customs officers in question had informed a foreign company that a post audit had found that a payment of Rs 1,500 million was required for the release of a consignment of spare parts, to be used by the Sri Lanka Transport Board (SLTB).
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Détails bibliographiques
Titre : System Mauser A Pictorial History Of The ...
Éditeur : Handgun Press, USA
Date d'édition : 2009
Edition : rep
XIV 273 pages, small 4to, numerous b/w illus from photographs, blue covers, title in silver, a fine in fine likewise dj. A facsimile reprint of the 1967 1st edition which was limited to 1000 copies, a detailed book with over 400 illustrations of more than 100 variations. N° de réf. du libraire 18945
Modes de paiement
Le libraire accepte les modes de paiement suivants :
[Chercher dans le catalogue du libraire]
[Afficher le catalogue du vendeur]
Vendeur AbeBooks depuis : 3 février 1999
Evaluation du vendeur :
All books are described as accuratley as possible.Bookplates and minor inscriptions are ignored in the description.Unless otherwise stated all books are published in London,8vo in original bindings and in very good condition.If for any reason the description does not match the condition,a full refund will be given if the book is returned within one week of receipt.Payment by bankers draft, cheque, or credit card M/C Visa Switch and Delta.
Shipping costs are based on books weighing 2.2 LB, or 1 KG. If your book order is heavy or oversized, we may contact you to let you know extra shipping is required.
Description de la librairie : Specialising in antiquarian and second hand field sports and angling books, also a good selection of rare and collectable general books. We do have a shop, opening hours are erratic


text:
Donald Trump Jr. and Donald Trump Wednesday 28th April 2010 walks through Trump Tower New York City, USA (2 Pictures)
Donald Trump Jr. and Donald Trump
Photo credit: Ray Filmano
Donald Trump Jr. and Donald Trump
Photo credit: Ray Filmano
View All: Donald Trump Jr. and Donald Trump Wednesday...
Next Donald Trump Slideshow: Ribbon cutting ceremony for Trump Soho at 246 Spring Street - New York City, USA - Friday 9th April 2010
On the eve of series three making its debut on Netflix, its creator Charlie Brooker confirmed that Foster was lined up to direct an episode for next...
Almost pathologically buoyant, this brightly colourful animated comedy is so cheeky that it's impossible to dislike.
Chris Pratt, Zoe Saldana and Dave Bautista return.
A report in Variety suggests that Firth could play the role of William Weatherall Wilkins in 'Mary Poppins Returns'.
There's a zing of postmodern fun to be had while watching a film that documents...
The very fact that the trailers and commercials for "Two Weeks Notice" feature Sandra Bullock...


text: The staff is very friendly and open, they really helped giving some indications about the area. It is an excellent place to start a trip in Alaska, highly recommended for hikers and even for solo travelers. There is a high chance you step into somebody that just comes from where you want to go right next, the experience exchange is... More


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Soldiers Point, New South Wales, Australia
This stunning water front condo is in a quite neighbourhood but close to shopping centre restaurants and fishing spots. Sit on the balcony while the kids...
Over a monthMember since
February 2015
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Magnificent property overlooking the Pacific Ocean perched on 5 acres of pristine rainforest . 7 minutes from the quaint village of Comboyne and 40 minutes to Port Macquarie. This property is our weekend Retreat and we rent it out normally for Family reunions and small groups. The views are why we purchased this property with an outlook to the Crowdy Head overlooking Rainforest and a mountain escarpment. We love to entertain and have had some pretty cool weekends at the Comboyne Hideaway. Comboyne Village has a Pub, 2 cafes and a gift store. For grocery it is a short drive down the mountain to the historic town of Kendal which has more facilities. Because we use the property on a regular basis and we love cooking we have a well stocked pantry for visitors to use.
This stunning water front condo is in a quite neighbourhood but close to shopping centre restaurants and fishing spots. Sit on the balcony while the kids...
The holiday home is located in a Lakeside Resort and Wedding Venue and offers full access to all the amenities - 4 swimming pools, 4 tennis courts, lakeside...
PLEASE READ THESE DETAILS AND DATES CAREFULLY. Available Christmas 2016/17 for NON SYNCHRONOUS. Dec 8-January 17 (flexible at either end). Prefer London...


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|By Business Wire
Article Rating:
|April 25, 2014 09:13 AM EDT
CSG Invotas, the exciting enterprise security business from CSG International, Inc. (NASDAQ: CSGS), today announced its participation at Infosecurity Europe 2014.
Infosecurity Europe is Europe's number one information security event. It features more than 325 exhibitors, the most diverse range of new products and services, an unrivalled education program, and over 13,000 unique visitors from every segment of the industry. Executives from CSG Invotas will be on hand to discuss top trends in today's security environments. They will offer live demonstrations at the top of every hour to show the value of unifying the management of security devices and the ways digital workflows can help accelerate security team performance. The demos will highlight real-world use-cases that include a coordinated response to phishing attacks, how to address corrupt VPN users in minutes, and the ways threat enrichment can be made relevant to enterprise security environments.
Additionally, Paul Nguyen, president of global security solutions at CSG Invotas, will lead the session, "How to Accelerate Your Response to Cyber Attacks" on Thursday, 1 May from 14.15 -15.15 in the Information Security Exchange Theatre. The session will show how large organizations can design automated courses of action to replace manual tasks and deliver faster response times to shift the dynamics of existing defense protocols. It will explore a variety of automated and semi-automated security actions and evaluate how automation can transform reactive decisions into proactive defense strategies.
Paul Nguyen, president of global security solutions at CSG Invotas
George Fraser, vice president of Europe, the Middle East, and Africa at CSG
|Infosecurity Europe, stand F98
|29 April – 1 May
|Meet with CSG Invotas executives to learn:
- How automation and orchestration tools can reduce the cybersecurity skills gap
- Why responding to attacks in real time provides increased levels of business assurance, continuity, efficiency, and risk management; decreased technology operations costs; and the ability to protect mission-critical infrastructure continuously and securely
- The importance of choosing innovative solutions that are technology agnostic and able to work with a variety of hardware, software, and implementations
- How to implement a unified threat-response approach that dramatically improves response times, reduces risk exposure, and makes security team more valuable
- The ways security automation frees important security team professionals from rote tasks
- How the unification of security devices facilitates quick responses to attacks
- The return on investment from properly executed security automation installations
"To counter threats and attacks effectively requires real-time capabilities that allow organizations to maximize their security resources," said Mike Henderson, president at CSG Invotas. "Today's attacks are relentless. They change and adapt at machine speed to infiltrate sensitive environments, which requires organizations to protect their complex security environments with automated, semi-automated, and on-demand actions across the enterprise."
CSG Invotas representatives will be available to review the current security ecosystem. They will address the next evolution of defense strategies, the evolving competitive landscape, and the latest innovations in security orchestration, unified architecture, and automation capabilities using best-in-breed technology.
About CSG Invotas
CSG Invotas™ offers security orchestration and automation solutions that provide dynamic, real-time management of large security ecosystems. It enables security professionals to respond effectively to ever-changing cyber threats. Invotas builds upon CSG's proven solutions and expertise to support the mitigation and eradication of cyber attacks across complex enterprise environments. For more information, please visit www.csginvotas.com.
About CSG International
CSG Systems International, Inc. (NASDAQ:CSGS) is a market-leading business support solutions and services company serving the majority of the top 100 global communications service providers, including leaders in fixed, mobile, and next-generation networks such as AT&T, Comcast, DISH, Orange, Reliance, SingTel Optus, Telecom New Zealand, Telefonica, Time Warner Cable, T-Mobile, Verizon, Vivo, and Vodafone. With more than 30 years of experience and expertise in voice, video, data, and content services, CSG International offers a broad portfolio of licensed and Software-as-a-Service (SaaS)-based products and solutions that help clients compete more effectively, improve business operations and deliver a more impactful customer experience across a variety of touch points. For more information, visit our website at www.csgi.com.
The Internet of Things (IoT), in all its myriad manifestations, has great potential. Much of that potential comes from the evolving data management and analytic (DMA) technologies and processes that allow us to gain insight from all of the IoT data that can be generated and gathered. This potential may never be met as those data sets are tied to specific industry verticals and single markets, with no clear way to use IoT data and sensor analytics to fulfill the hype being given the IoT today.
Oct. 26, 2016 01:45 AM EDT Reads: 2,725
Ask someone to architect an Internet of Things (IoT) solution and you are guaranteed to see a reference to the cloud. This would lead you to believe that IoT requires the cloud to exist. However, there are many IoT use cases where the cloud is not feasible or desirable. In his session at @ThingsExpo, Dave McCarthy, Director of Products at Bsquare Corporation, will discuss the strategies that exist to extend intelligence directly to IoT devices and sensors, freeing them from the constraints of ...
Oct. 26, 2016 01:15 AM EDT Reads: 3,104
So you think you are a DevOps warrior, huh? Put your money (not really, it's free) where your metrics are and prove it by taking The Ultimate DevOps Geek Quiz Challenge, sponsored by DevOps Summit. Battle through the set of tough questions created by industry thought leaders to earn your bragging rights and win some cool prizes.
Oct. 26, 2016 12:15 AM EDT Reads: 4,119
SYS-CON Events announced today that SoftNet Solutions will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. SoftNet Solutions specializes in Enterprise Solutions for Hadoop and Big Data. It offers customers the most open, robust, and value-conscious portfolio of solutions, services, and tools for the shortest route to success with Big Data. The unique differentiator is the ability to architect and ...
Oct. 26, 2016 12:00 AM EDT Reads: 1,043
A completely new computing platform is on the horizon. They're called Microservers by some, ARM Servers by others, and sometimes even ARM-based Servers. No matter what you call them, Microservers will have a huge impact on the data center and on server computing in general. Although few people are familiar with Microservers today, their impact will be felt very soon. This is a new category of computing platform that is available today and is predicted to have triple-digit growth rates for some ...
Oct. 26, 2016 12:00 AM EDT Reads: 34,221
The Internet of Things will challenge the status quo of how IT and development organizations operate. Or will it? Certainly the fog layer of IoT requires special insights about data ontology, security and transactional integrity. But the developmental challenges are the same: People, Process and Platform and how we integrate our thinking to solve complicated problems. In his session at 19th Cloud Expo, Craig Sproule, CEO of Metavine, will demonstrate how to move beyond today's coding paradigm ...
Oct. 26, 2016 12:00 AM EDT Reads: 3,861
Fifty billion connected devices and still no winning protocols standards. HTTP, WebSockets, MQTT, and CoAP seem to be leading in the IoT protocol race at the moment but many more protocols are getting introduced on a regular basis. Each protocol has its pros and cons depending on the nature of the communications. Does there really need to be only one protocol to rule them all? Of course not. In his session at @ThingsExpo, Chris Matthieu, co-founder and CTO of Octoblu, walk you through how Oct...
Oct. 26, 2016 12:00 AM EDT Reads: 3,190
Everyone knows that truly innovative companies learn as they go along, pushing boundaries in response to market changes and demands. What's more of a mystery is how to balance innovation on a fresh platform built from scratch with the legacy tech stack, product suite and customers that continue to serve as the business' foundation. In his General Session at 19th Cloud Expo, Michael Chambliss, Head of Engineering at ReadyTalk, will discuss why and how ReadyTalk diverted from healthy revenue an...
Oct. 25, 2016 11:45 PM EDT Reads: 2,991
In past @ThingsExpo presentations, Joseph di Paolantonio has explored how various Internet of Things (IoT) and data management and analytics (DMA) solution spaces will come together as sensor analytics ecosystems. This year, in his session at @ThingsExpo, Joseph di Paolantonio from DataArchon, will be adding the numerous Transportation areas, from autonomous vehicles to "Uber for containers." While IoT data in any one area of Transportation will have a huge impact in that area, combining sensor...
Oct. 25, 2016 10:45 PM EDT Reads: 991
Without lifecycle traceability and visibility across the tool chain, stakeholders from Planning-to-Ops have limited insight and answers to who, what, when, why and how across the DevOps lifecycle. This impacts the ability to deliver high quality software at the needed velocity to drive positive business outcomes. In his general session at @DevOpsSummit at 19th Cloud Expo, Eric Robertson, General Manager at CollabNet, will discuss how customers are able to achieve a level of transparency that e...
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SYS-CON Events announced today that Cemware will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Use MATLAB functions by just visiting website mathfreeon.com. MATLAB compatible, freely usable, online platform services. As of October 2016, 80,000 users from 180 countries are enjoying our platform service.
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For basic one-to-one voice or video calling solutions, WebRTC has proven to be a very powerful technology. Although WebRTC's core functionality is to provide secure, real-time p2p media streaming, leveraging native platform features and server-side components brings up new communication capabilities for web and native mobile applications, allowing for advanced multi-user use cases such as video broadcasting, conferencing, and media recording.
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Established in 1998, Calsoft is a leading software product engineering Services Company specializing in Storage, Networking, Virtualization and Cloud business verticals. Calsoft provides End-to-End Product Development, Quality Assurance Sustenance, Solution Engineering and Professional Services expertise to assist customers in achieving their product development and business goals. The company's deep domain knowledge of Storage, Virtualization, Networking and Cloud verticals helps in delivering ...
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SYS-CON Events announced today that Enzu will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Enzu's mission is to be the leading provider of enterprise cloud solutions worldwide. Enzu enables online businesses to use its IT infrastructure to their competitive advantage. By offering a suite of proven hosting and management services, Enzu wants companies to focus on the core of their online busine...
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In the next five to ten years, millions, if not billions of things will become smarter. This smartness goes beyond connected things in our homes like the fridge, thermostat and fancy lighting, and into heavily regulated industries including aerospace, pharmaceutical/medical devices and energy. "Smartness" will embed itself within individual products that are part of our daily lives. We will engage with smart products - learning from them, informing them, and communicating with them. Smart produc...
Oct. 25, 2016 07:30 PM EDT Reads: 1,544


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Id argue that the pricing is close to that anyway.
Streetfighter and Pro Evo are under ÂŁ20. Zelda is around ÂŁ30.
I think you could argue prices are still too high, but I do like the consol
#7715150, By ManicDrunkMonk Nintendo 3DS
ManicDrunkMonk 538 posts
Seen 45 minutes ago
Registered 11 years ago


text:
He seemed very reluctant about inception because it had yet to be proven. Throughout the entire movie, he was averse to taking any chances, and he threw a tantrum once he realized the risks they were taking in the dream layers. Very SJ mentality, specifically Si Te needing to concretely "prove" a theory before following along. His improv there was pretty creative, but he had to do something to make sure everything ran smoothly. He was the most dependable character, the rock, the pillar, etc. ISTJ.
Cobb, on the other hand, was willing to take any chances, and make any negotiations with Saito to fulfill his goals. He knew the risks involved with the unstable dream mechanics and his fitful subconscious and still took a dive.
Which reminds me - I appreciate the fact that they didn't go techno-babble mode with the dream technology. They could have really ruined it, but they subtly slipped that concept under the radar for the audience to appreciate the abstract dream theme.