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Aging is associated with shifts in autocrine and paracrine pathways in the cardiac vasculature that may contribute to the risk of cardiovascular disease in older persons. To elucidate the molecular basis of these changes in vivo, phage-display biopanning of 3- and 18-mo-old mouse hearts was performed that identified peptide epitopes with homology to brain-derived neurotrophic factor (BDNF) in old but not young phage pools. Quantification of cardiac phage binding by titration and immunostaining after injection with BDNF-like phage identified a twofold increased density of the BDNF receptor, truncated Trk B, in the aging hearts. Studies focused on the receptor ligand using a rat model of transient myocardial ischemia revealed increases in cardiac BDNF associated with local mononuclear infiltrates in 24- but not 4-mo-old rats. To investigate these changes, both 4- and 24-mo-old rat hearts were treated with intramyocardial injections of BDNF (or PBS control), demonstrating significant inflammatory increases with activated macrophage (ED1+) in BDNF-treated aging hearts compared with aging controls and similarly treated young hearts. Additional studies with permanent coronary occlusion following intramyocardial growth factor pretreatment revealed that BDNF significantly increased the extent of myocardial injury in older rat hearts (BDNF 35 ± 10% vs. PBS 16.2 ± 7.9% left ventricular injury; P < 0.05) without affecting younger hearts (BDNF 15 ± 5.1% vs. PBS 14.5 ± 6.0% left ventricular injury). Overall, these studies suggest that age-associated changes in BDNF-Trk B pathways may predispose the aging heart to increased injury after acute myocardial infarction and potentially contribute to the enhanced severity of cardiovascular disease in older individuals.
- brain-derived neurotrophic factor
- functional proteomics
- Trk B
cardiovascular disease is the leading cause of morbidity and mortality in older individuals (2). Presently, myocardial infarction has a significantly worse prognosis in older persons, with higher mortality and complication rates, than in younger individuals (3, 39, 42), suggesting that senescent changes in the cardiovascular system may predispose older individuals to increased cardiac pathology.
The aging heart has significant changes in vascular function, with diminished angiogenic capacity, endothelial dysfunction, and increased potential for prothrombotic activity (for review see Ref. 49). Previously we described (8) the results of an in vivo phage-display cardiac biopanning study aimed at elucidating the mechanisms governing the dysregulation in PDGF-B-mediated cardioprotection in the aging rodent heart. Specifically, these studies identified an age-associated loss in a subpopulation of TNF receptor 1 microvascular endothelial cells that underlies the impairment in TNF-α-mediated PDGF-B expression, which promotes cardiac angiogenesis and suppresses apoptosis to decrease myocardial injury in rodent models of myocardial infarction (8, 15, 50). Additional research based on these biopanning studies resulted in the identification of an age-related increase in TNF-α-induced reactive oxygen species and lipid peroxidation as a potential mechanism contributing to the dysregulation and loss of the TNF receptor pathways in the older heart (8, 17).
Because of the multifactoral effects of aging on the cardiovascular system, we sought to identify additional cardiac vascular receptor-mediated pathways that may govern the age-related changes in cardiac phenotype and function. Here we report the extension of phage-display studies that identified an increase in the brain-derived neurotrophic factor (BDNF) receptor, Trk B, in the aging rodent heart. Moreover, functional studies revealed that age-associated alterations in cardiac BDNF-mediated pathways can enhance inflammation and increase myocardial injury after myocardial infarction in the aging heart.
Phage-display peptide library in vivo cardiac vascular biopanning.
The age-associated changes in cardiac microvascular surface receptors were probed by in vivo phage-display biopanning with a cyclic peptide pSKAN phagemid library (6 amino acid variable, ∼107 total complexity; Mo Bi Tec) as previously described (8, 17). Young female adult (3 mo old) and aging (18 mo old) C57BL/6 mice (National Institute on Aging Rodent Colony) were anesthetized with Avertin (0.015 ml/g) and injected with phage peptide library phage [1012 colony-forming units (CFU)/200 μl PBS] via their tail veins. Four minutes after injection the mice were killed and the hearts were rapidly explanted. The phage were then recovered with WK6λmutS Escherichia coli. Age-specific phage pools were amplified and titrated for two additional rounds of biopanning enrichment. The phagemid DNAs of the resultant clones (n ≥ 100 3- and 18-mo-old heart pools) were sequenced, and translated motifs were analyzed for homology to known cytokines (FASTA3), as determined by the first homologous mammalian sequence identified with E value <1 as previously described in the identification of the age-associated changes in TNF receptor pathways (8): two clones isolated from the old, but not young, heart pools [ARRGQA (ψO40) and GRRFIR (ψO145)] revealed homology to 1BNDA, peptide sequences BDNF5–9 and BDNF100–106, respectively. In addition, to probe the structural relevance of the ψO40 motif to exposed potential receptor binding domains of BDNF, the region of homology was mapped in a tertiary model and labeled by Cn3D3.0 software as previously described (8).
Individual phage clone in vivo cardiac vascular binding.
To confirm the age-associated differential cardiac binding capacity of the BDNF-like phage, injections with ψO40 phage clone were performed. ψO40 (1012 CFU in 200 μl PBS) was injected into both 3- and 18-mo-old mice as described above (n = 6/group). Titration of the phage incorporated into the hearts was used to quantify the ψO40 binding in the young and older hearts (n = 3 each). The phage clones were recovered from the explanted hearts with WK6λmutS E. coli, which were then titrated by serial dilution to measure CFU.
Protein analysis of cardiac BDNF-Trk B.
To investigate the potential age-related changes in BDNF-Trk B pathways, Western blotting for BDNF and Trk B was performed on protein isolated from 3- and 18-mo-old murine hearts. Briefly, antibodies immunoreactive with murine BDNF (sc-546, Santa Cruz) and the extracellular domain of Trk B (sc-8316, Santa Cruz) were used for Western blots of 10% SDS-PAGE gels with 100 μg of protein samples from 3- and 18-mo-old hearts (n = 3 each). Immunostains of cardiac sections were performed with antibodies to both the extracellular and COOH-terminal truncated domains of Trk B (sc-8316 and sc-8312, Santa Cruz), which were visualized with diaminobenzidine (DAB) and an avidin-biotin complex (ABC) kit (Vector). To study the potential interaction of the ψO40 phage with Trk B, additional hearts (n = 3/group) were harvested after ψO40 biopanning (described above) for sectioning and immunostaining with biotin-labeled monoclonal antibody to phage coat protein pIII (pIII, Mo Bi Tec) visualized with a FITC-streptavidin secondary conjugate and costained with the extracellular Trk B antibody with a Texas red secondary antibody.
Induction of transient cardiac ischemia.
Transient cardiac ischemia (hypoxia) was induced in 4- and 24-mo-old F344 female rats (National Institute on Aging Rodent Colony) as a model of clinical myocardial ischemia (23) to investigate the potential alterations in BDNF pathways. Because of the marked heterogeneity of the coronary anatomy of the murine heart, which requires intramyocardial sutures to ensure ligation of bridging arteries (1, 43), we elected to use the rat cardiac model system, which has a more consistent coronary anatomy for myocardial ischemia and infarction studies (8, 15, 50). Specifically, sets of 4- and 24-mo-old rats were randomized to transient induction of cardiac ischemia and sham operation (n = 5/set). After anesthesia with ketamine (90 mg/kg ip) and xylazine (4 mg/kg ip), a tracheotomy was performed and the animal was intubated and ventilated (Harvard Rodent Ventilator model 683) with room air. A left intercostal thoracotomy was performed at the fourth and fifth intercostal spaces. On identification of the left anterior descending artery (LAD), a 7-0 suture was secured ∼2.0 mm below the level of the tip of the normally positioned left atrium, and four rounds of 10-min ischemia and reperfusion were induced. After the conclusion of the fourth reperfusion the suture was removed, the chest wall was closed, and the animal was removed from the ventilator and placed under a heat lamp to recover. Sham-operated rats received similar treatment but without coronary ligation. Rats were euthanized 24 h after injection, and hearts were excised, fixed, sectioned for immunohistochemical staining with rabbit antibodies directed to BDNF (sc-546, Santa Cruz), and visualized with the ABC-DAB system and costaining with Giemsa. The number of immunopositive cells was quantified in sections at the midpapillary level of each heart, and the number of stained luminal structures in a total of six high-power fields (×40 magnification) per section was analyzed in a blinded fashion as previously described (8, 15).
In vivo response to BDNF in young and old rat hearts.
To probe the functional relationship between changes in BDNF-Trk B pathways and cardiac inflammation, additional sets of 4- and 24-mo old F344 rats (n = 3/set) received intramyocardial injections of BDNF and the extent of changes in cardiac infiltrates was assessed (8, 15). Briefly, the rats were anesthetized and underwent left intercostal thoracotomy, and the LAD was identified. On the basis of previous rat in vivo injection studies with supraphysiological, nontoxic concentrations of BDNF injected into retinal tissue (48) and intact brains (4, 22), 1 μg of recombinant human (rh)BDNF (248-BD, R&D Systems) in 50 μl of PBS or PBS alone was injected through a 30-gauge needle with a 250-μl Hamilton syringe in two injections (25 μl/injection, 2 mm apart) in the mid-left ventricular anterior wall of the rat hearts. The chest wall was then closed, the lungs were inflated, the rat was extubated, and the tracheotomy was closed. The following day the rats were killed, and the hearts were excised, fixed in 4% paraformaldehyde, and embedded in paraffin. Sections were stained with hematoxylin and eosin, immunostained with mouse anti-rat RM1, ED2, and ED1 (Research Diagnostics), and visualized with an ABC kit with DAB. Staining was quantified in the anterior left ventricular wall at the level of the midpapillary muscles from each heart, as previously described (Refs. 8, 15; 10 high-power fields/heart). Two investigators performed quantification independently in a blinded fashion.
Myocardial infarction studies.
To study the potential age-dependent effects of BDNF in a cardiac injury model, a rat myocardial infarction model was used in which the level of coronary ligation was age adjusted to provide similar-size myocardial infarctions in young and old rats, as previously described (8, 15). Sets of 4- and 24-mo-old F344 rats received intramyocardial injections of rhBDNF (1 μg) or PBS (n = 5 each) as described above. The next day the rats were reanesthetized, the heart was exposed, and the LAD was ligated directly below (4 mo old) or 2 mm below (24 mo old; to produce a similar-size myocardial infarction to the younger rats) the left atrial appendage with 8-0 nylon sutures. Pallor and regional wall motion abnormality of the left ventricle confirmed the occlusion. The chest wall was closed, and after recovery the rats were returned to the animal facility for 14 days. At the termination of the experiment the rats were imaged by transesophageal echocardiography as previously described (53) and then killed, and the hearts were explanted. The extent of myocardial infarction measured at the level of the midpapillary heart muscles was scored by Masson's trichrome staining, and the images were analyzed in a blinded fashion with ImageJ 1.22 software (NIH Image) (36, 47). Infarction size with linear approximations to account for area gaps in histology was expressed as a percentage of the total left ventricle myocardial area as previously described (8, 15).
Statistical analysis.
Comparisons of categorical variables were conducted with the binomial distribution test or Fisher's exact test, as appropriate. Those between nonnormally distributed continuous variables employed the Wilcoxon rank-sum test. A P value <0.05 was considered statistically significant.
In vivo cardiac homing of BDNF-like phage to the aging heart.
In vivo cardiac biopanning revealed clones with homologies to BDNF in the older but not younger cardiac-homing phage clones (2/100 vs. 0/101, P < 0.05), including ψO40, which is homologous to the amino-terminal domain of BDNF that mediates high-affinity ligand interactions with Trk B (34) (Fig. 1, A and B). Titering of cardiac eluted phage confirmed the increased cardiac homing in the older murine heart (Fig. 1C), suggesting that BDNF binding sites/receptors may be increased in the aging cardiac microvasculature. Western blots revealed that BDNF levels were comparable in the young and old hearts. Trk B, however, was greater in the aging heart samples. Notably, the isoform of Trk B expressed was the truncated receptor, with a known size of ∼95 kDa (20) (Fig. 1D). The differential expression of Trk B was confirmed by immunostaining of cardiac sections from 3- and 18-mo-old mice (Fig. 1, E and F). Moreover, immunofluorescent staining of the hearts after ψO40 phage clone injection demonstrated that the age-associated increase in the BDNF-like phage colocalized with Trk B in the cardiac microvasculature (Fig. 1G).
Age-associated BDNF-mediated cardiac inflammation.
On the basis of previous reports demonstrating that BDNF is induced in the ischemic (hypoxic) heart (25), a rat model of transient coronary occlusion was used to study potential changes in BDNF patterns in the aging heart. Immunostains revealed a more extensive staining of BDNF in the untreated aging hearts compared with young controls, corresponding to the age-associated increased density of Trk B in the heart. After transient episodes of cardiac ischemia, BDNF staining was also higher in the aging hearts compared with similarly treated young rats or age-matched sham-operated control rats (Fig. 2). Moreover, this age-associated increase in BDNF was associated with a mononuclear infiltrate in the old cardiac myocardium that was not observed in the young hearts (Fig. 3).
To probe the relationship between BDNF and cardiac inflammation, additional rats were treated with intramyocardial injections of BDNF. Histological analysis of these hearts revealed that BDNF did not significantly increase the cardiac mononuclear infiltrate in either the young or the old hearts (Fig. 3). Investigations of the potential age-related differences in the characteristics of these cells by immunostaining for different macrophage surface antigens revealed that the number of cells staining for RM-1, a cell surface antigen found on macrophage in fetal tissue (24, 45), in the cardiac sections was slightly, though not significantly, higher in the young hearts (Fig. 4). In contrast, ED2, a rat homolog of CD163 that is associated with early stages of macrophage activation (29, 41), was significantly greater in both the BDNF- and control-treated aging hearts compared with similarly treated young hearts. Notably, BDNF injections resulted in an increase in ED1, a rat homolog of CD68 (46) that is present on activated/inflammatory macrophages (11, 12), with higher concentrations in the BDNF-treated older hearts.
In vivo BDNF function in myocardial infarction in the aging heart.
To investigate the impact of the age-associated changes in BDNF-mediated pathways in an experimental model of myocardial infarction, additional 4- and 24-mo-old rats were treated with BDNF or PBS control followed by permanent coronary ligation. In the young hearts, intramyocardial injection of BDNF did not alter myocardial infarction size measured 2 wk after acute coronary occlusion compared with PBS controls (Fig. 5, A and B). In the old rats, BDNF was deleterious, with significantly more extensive myocardial injury compared with hearts injected with control vehicle. Moreover, the old hearts treated with BDNF developed a persistent inflammatory infiltration (Fig. 5C) associated with aneurysmal changes in left ventricular wall segments as observed by echocardiography (Fig. 5D), suggesting that the age-associated increase in Trk B and altered BDNF function may contribute to the severity of cardiovascular pathophysiology in the aging heart.
In the present report we describe the age-associated changes in BDNF-TrkB pathways that can result in enhanced pathology in the rodent heart. Specifically, in vivo phage biopanning studies revealed that age-related increases in cardiac microvascular truncated Trk B are associated with shifts in BDNF-mediated inflammatory responses in old hearts. Moreover, delivery of BDNF led to a senescent increase in myocardial injury after acute coronary occlusion, suggesting that the alterations in Trk B pathways in the aging heart may contribute to the more severe cardiac pathology observed in older persons with cardiovascular disease.
Previous studies have revealed the importance of BDNF in the development of the cardiac vasculature, promoting the stabilization of intramyocardial vessels (13). Moreover, although its actions in the adult heart have yet to be fully elucidated, recent clinical studies have shown that BDNF is associated with coronary atherosclerosis and unstable angina (19), and experimental studies have revealed that BDNF may be involved in ischemia-reperfusion cardiac injury (25). These findings, together with the increase in Trk B-positive cells in the senescent cardiac microvasculature, suggest that shifts in BDNF-mediated pathways may predispose the aging heart to increased vascular pathology.
The age-associated increase in Trk B is linked to an age-associated increase in inflammatory pathways and a significant increase in myocardial injury after coronary occlusion. Specifically, immunostains revealed an age-associated increase in ED2 staining, which is similar to the age-related increased number of perivascular ED2+ macrophages reported in rat brain (32). The BDNF-mediated increase in ED1 staining was previously shown to correlate with inflammatory activation and rejection in cardiac transplant studies (26). Moreover, the inverse relationship between ED1 and RM-1 is consistent with patterning of activated macrophages in experimental rat models of pulmonary fibrosis (27). Furthermore, previous studies in the aging rat thymus have reported a link between increased ED1+ macrophages and Trk B (21), suggesting that macrophage activation in the heart may be directly related to the age-associated increase in BDNF-Trk B pathways.
Previous studies have demonstrated an association between BDNF-Trk B signaling and vascular inflammation (14). Specifically, the paracrine actions of truncated Trk B receptor have been suggested to be involved in the perineural response to peripheral inflammation (30). Moreover, the combination of the age-associated alterations in macrophages (33) that may also express Trk B (40) and the potential recruitment of bone marrow-derived Trk B+ cells (28) may act with the age-associated increase in truncated Trk B in the cardiac microvasculature to govern the BDNF-mediated inflammatory induction in the older hearts. Overall, the age-associated changes in BDNF-Trk B pathways may enhance vascular inflammation to increase the severity of cardiovascular pathophysiology in older persons and may provide a functional link to recent clinical studies that have demonstrated the role of inflammation as a cardiovascular risk factor in the geriatric population (9).
Mechanistically, the increase in truncated Trk B and the age-associated increase in immunomodulation may be related to the physiological requirements of the aging cardiac vasculature. Previous studies have demonstrated the importance of inflammatory pathways in the induction of angiogenesis in the heart (31). These findings, in conjunction with the role of age-associated impairment in cardiac angiogenic pathways (8, 16, 50), suggest that the shift in BDNF-Trk B pathways could be a compensatory response to augment angiogenic function in the aging heart. We recently demonstrated (8, 52) that shifts in TNF-α pathways underlie the loss in proangiogenic/antiapoptotic cytokine-mediated function in the older rodent heart. Thus the interrelationship of TNF-α and BDNF in endothelial cells (6) and the antiapoptotic actions of BDNF on Trk B cells (13) may play an important role in maintaining vascular homeostasis in the aging heart. Indeed, the changes in BDNF-Trk B pathways could be related to the age-related increases in TNF-α (7, 10) that can modulate induction of BDNF in monocytes (44).
In light of the multiple and complex interactions that may influence the activity of the BDNF function in the aging heart, we postulate that additional in vivo studies, including investigations with the ψO40 phage peptide, may facilitate the elucidation of the specific molecular and cellular mechanisms that contribute to the proinflammatory predisposition in the aging heart. Indeed, previous studies using peptides encoding sequences of BDNF have revealed both antagonist and partial agonist function in BDNF-Trk B interactions (37, 38), suggesting that similar approaches based on the structure of ψO40 could modulate the function of BDNF pathways. We anticipate that the BDNF phage-based peptides may be useful in probing the specific actions of truncated Trk B, which is known to compete with the full-length receptor (18, 51) but can also signal directly through non-tyrosine kinase signaling cascades (5, 35). These peptides may be useful in assessing the role of Trk B pathways in aging as related to hormonal signaling and other pathways that can modulate the biology of aging in the vasculature. Furthermore, we project that therapeutic approaches to counter the senescent immune activation induced by BDNF may exploit the biophysical interactions of ψO40 with Trk B as a potential means of inhibiting BDNF binding to Trk B in the aging heart.
This work was supported by grants to J. M. Edelberg from the American Federation for Aging Research-Beeson Physician Faculty Scholar in Aging Research and National Institutes of Health Grants AG-20320, AG-20918, and HL-67839.
Article published online before print. See web site for date of publication (http://physiolgenomics.physiology.org).
Address for reprint requests and other correspondence: J. M. Edelberg, Weill Medical College of Cornell Univ., 520 East 70th St., Box 161, New York, NY 10021 (e-mail: jme2002{at}med.cornell.edu)
- Copyright © 2006 the American Physiological Society


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Water Taxi in a River of Vampire Fish
New York City flooded following decades of climate change and earthquakes. And after his father died, Jackson Lowry rowed a small taxi-boat to help his friends and neighbors. But now a mysterious realtor sets in motion a cryptic plot laced with the nefarious Circuit and a wealthy investor who pits Jackson against his better judgment.
This novelette also contains two bonus short stories. In the special feature "Five Paintings," two art critics battle over the value of a rich collector's paintings. In "Five Sketches of an Everyday Infinity" the journalist Leopold reveals the secrets of the infinite to his new companion, the artificial intelligence named Synthoid Etteri.
All three tales in the book come from the futuristic Infinite Things world, affected by global climate change, artificial intelligence, and a growing new economy focused on green technologies.
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Filled with Humans and Synthoids, the Moon's colonies suffer strange accidents and deadly crimes. In "The Escape Artist Who Saved the Moon" Arcman wants a new job. But first he must escape puzzling time-loops. In "Lila of Regolith City," Synthoid Lila's street-urchin ways serve her well until a murder reveals new secrets. Both novelettes come from the futuristic Infinite Things world, affected by global climate change, artificial intelligence, and a growing new economy focused on green technologies.
Future Build
A dozen futuristic tales: a brilliant artist rages through a time-travelling magic mirror; young Sasha navigates the complex morality of genetically engineered foods called planimals; an android bodyguard loses his boss's head; and a contractor struggles to repair his virus-infected 3-d house printer.
Bring yourself on a voyage into the heart of the twenty-first century. Biotechnology, quantum physics, artificial intelligence, self-driving cars, robotics and many other trends of the future weave throughout these stories.
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Biomimic Generations
Superhuman biomimic Sera Fisher wants to atone for her wrongdoing. But she's hounded on all sides by the Void, an innovative warmaker who's destroyed most of civilization, and by a new tribe of post-humans called the LinkUp. Sera can flee or fight. If she runs, her friends Alice, the Poet and her cat Buster will perish. If she fights, she can never atone for her mistakes. Sera's time has come. Her enemies won't make her choices any easier.
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Legendary inventors Irwin Caest and Marty Mullany made their millions in neurogaming with their immersive space-faring game StarFold. But now they just can't get a break.
Even with the help of Z, Ishtar, and Onsoong, their newest invention, named Thomas, suffers crippling anxiety attacks. If they can't help him, Starfold will fail.
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There's a reason why the Gold Coast is the fun and adventure capital of Australia - it's because there is so much to see and do! With so many Gold Coast attractions to choose from, you'll be spoiled for choice these school holidays. Top of the list of things to do on the Gold Coast has to be the thrill-a-minute theme parks that are easily accessible by car, bus or train.
10:00 am – 5:00 pm
Dreamworld is Australia's largest theme park with over 40 rides and attractions – including five roller coasters. If you love thrills and spills, make sure you check out the Tail Spin, Buzz Saw, Giant Drop and Tower of Terror – guaranteed to leave your heart in your mouth!
If heart thumping rides aren't your thing, there are a bunch of milder options. There are tiger, dingo and crocodile attractions, ABC Kids World and the DreamWorks Experience with all the little ones favourite movies. With all the family in tow, Dreamworld is just the ticket.
Part of the Dreamworld complex, Whitewater World is one of the newer Gold Coast attractions and the splashiest fun you'll have on your holiday! The older kids will love Surf School and if you have young children, Wiggle Bay is a haven where you can relax and enjoy some quality time.
For the serious water slider, the Triple Vortex, the Wedgie and the Green Room shouldn't be missed, and for some major family fun, make sure you take a splash on the Super Tubes Hydro Coaster, Temple of Huey and Little Rippers waterslides.
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9:30 am – 5:00 pm
A world of fun awaits you at Movie World where you'll enjoy action-packed shows, thrilling rides and a range of kid's activities.
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Getting to the Theme Parks
Dreamworld, WhiteWater World, Movie World and Wet'n'Wild are conveniently located in close proximity to each other just off the Pacific motorway (M1) at Coomera – 17kms (20 minutes) north of Surfers Paradise and 48kms (40 minutes) south of Brisbane.
It's an easy drive along the Pacific Motorway and all theme parks are serviced by both bus and rail from the Gold Coast and Brisbane. For more information or to plan your journey, visit translink.com.au or Con-x-ion on 1300 266 946.
9:30 am – 5:30 pm
Sea World is more than just a theme park – it's a marine mammal park and an oceanarium as well. So you get three times the entertainment, education and action packed school holiday activities!
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Getting to Sea World
Sea World is located on Sea World Drive at the Gold Coast's Main Beach and is just a 15 - 20 minute drive north from Surfers Paradise and Broadbeach, and 45 minutes south of Brisbane. Sea World is serviced by bus from the Gold Coast and rail/bus from Brisbane. For more information or to plan your journey, visit translink.com.au or Con-x-ion on 1300 266 946.
If it happens to be rainy during your holiday on the Gold Coast and the theme parks simply aren't an option, you'll need to be prepared with activities to make the most of a rainy day!


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There is long-standing constitutional protection of the right to marry that applies to same-sex couples.
By the time you read this, the Massachusetts Supreme Court may have decided whether or not the Constitution protects a right to gay marriage. Regardless of what the court decides, it will hardly settle what has become one of our most hotly contested constitutional debates. Evan Gerstmann's new book, Same-Sex Marriage and the Constitution, won't settle it either; but it is a clear and fair-minded guide to the strengths and weaknesses of the leading constitutional arguments for and against gay marriage.Jeffrey Rosen


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On August 14, I was prescribed 10mg of citalopram. I began taking it that day. I took it for roughly a week then went off of it on my own for 3 days due to awful side effects. My anxiety increased by 100x, didn't sleep, didn't eat for 4 days, increases pulse and constant heart palpitations. I felt absolutely awful. I returned to the medication at 5mg for a few days then returned to the doctor. I went back to the doctor on August 28 and the changed my medication to sertraline 12.5 for 4 days then 25mg from then on. Today is my 6th day of Sertraline. I feel a significant improvement but I still have shakes, chills, and occasionally feel my heart beat out of control. I have also been prescribed .25mg clorazepam for panic attacks. I take it every night at bed just to help me sleep. I have had fewer panic attacks and am generally happier but still wonder when full effect of medication will happen. I also would like to know if skipping three days made the entire process start all over again, or the change of medication made the process start all over again. Any and all conversation is welcome and appreciated. I want to know I'm not alone. I also occasionally get cold chills on the left side of my body and find that sometimes it will tingle. Not go numb but just tingle. I also have a stiff upper back and I have just assumed this is from all of the tension I have held for so long. Just looking for similar experiences.
Celexa to Zoloft, how long until side effects go away?
- Asked
- 3 Sep 2015 by MCScott88
- Active
- 3 Sep 2015
- Topics
- celexa, zoloft, depression, anxiety, panic disorder, generalized anxiety disorder, citalopram, side effect, anxiety and stress, prescription
Responses (1)
It is going to take upwards of a month or so for the full effects of the Zoloft and you may still need an increase in dosage since you are taking a low dose. Some of what you are experiencing is side effects which will subside in the first couple of weeks. Heightened anxiety in the beginning is not unusual, but the clonazepam should help with this.
Do you think skipping 3 days then starting again caused the cycle of side effects to restart?
When you change medications it is like starting over again.
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This chicken and white bean soup is delicious, filling, and comforting. Imagine coming home from work to a nice big pot of soup. No need to worry about making your dinner in a hurry, just warm up a bowl of this Hearty Chicken and White Bean Soup and enjoy.
Soup is probably the easiest low glycemic meal you can make. It can be eaten for lunch and dinner and is very easy to make.
Last fall, I wrote a post about How to Make a Perfect Low Glycemic Soup where I shared all my secrets on cooking a hearty healthy soup. If you follow the simple rules I shared in that post, you will become a real pro at cooking soup.
I usually cook a pot of soup once or twice per week. I always cook a big batch so that we have enough leftovers to last us a few days. You can also freeze it in glass containers to use later.
Another great way to get more variety in your diet is to partner with a healthy eating buddy and exchange dishes you prepare at home. This is how it works: you and your buddy cook different dishes in big batches and then exchange half of the prepared food. This way you only cook once but get twice the variety. This works really well with soups – you only cook one kind of soup (for example, this chicken and white bean soup) but get to eat 2 different kinds of soup. How fun is that?
This buddy system works really well for people who have similar taste and nutrition preferences. However, it's not a good fit for people with allergies.
So, as we are getting closer to the weekend, why not to try this chicken and white bean soup?
- 2 Tbsp olive oil
- 1 onion, chopped
- 1 medium carrot, grated
- 1 zucchini, chopped
- 1 red bell pepper, julienned
- 1 yellow bell pepper, julienned
- 1 L/ 4 cups chicken stock
- 1 can (796 ml/28 oz) diced tomatoes
- 4 skinless boneless chicken thighs, cooked and cut into small pieces, See notes
- 1 can white kidney beans
- 1/2 Tbsp red paprika
- 1/2 Tbsp garlic powder
- 1/2 tsp cayenne pepper
- salt to taste
- 2 cups frozen green peas
- In a large pot, heat the olive oil over medium heat. Add the onion and cook, stirring occasionally until the onion is translucent for about 2 to 4 minutes. Add the carrot and cook until the vegetables start to caramelize, for about 4 more minutes.
- Add the zucchini and red and yellow bell pepper. Stir and saute the vegetables until they start to soften for about 2 to 3 minutes.
- Add the chicken stock, diced tomatoes, chicken, beans, red paprika, garlic powder, cayenne pepper and salt. Bring to a boil. Cover and cook for 8 more minutes.
- Add the green peas. Bring to a simmer and cook for 1 more minute.


text:
They forgot how the Internet worked for a moment.
Warning: This article contains Game of Thrones spoilers.
Game of Thrones co-creators David Benioff and D.B. Weiss are really sorry about Sunday's episode—but definitely not for reason you think.
Death is nothing new on the show, which has seen at least one character meet the darkness in every episode this season. But Hodor's ultimate sacrifice and the reveal of what "Hodor" means—which occurred in the same sequence as Summer, the Three-Eyed Raven, and the Children of the Forest's deaths—is by far the most profound series of deaths for fans in quite some time, and the reaction to it has been comparable to Ned Stark's beheading and the Red Wedding.
Benioff and Weiss didn't appear on Jimmy Kimmel Live to apologize for killing fan-favorite Hodor at the end of "The Door" because, well, they've killed loads of main characters—hundreds, by their estimate—and they've received a lot of money and prestigious awards for it. They just sort of forgot that the Internet would meme the hell out of it, and now nobody can get onto an elevator or walk into a building without somebody getting emotional at hearing "Hold the door."
"So, so sorry," Weiss said before they offered an impractical but effective solution to the problem. "People are the worst."
Pure, uncut internet. Straight to your inbox.


text:
GraphicRiver 3D Linear Model of the Children s Slides 4148852
Category: Stock Vector | Comment: ( 0 )
GraphicRiver 3D Linear Model of the Children s Slides 4148852
Stock Vector \ Objects \ Buildings
Linear \ Line \ Layer \ Illustration \ Industry \ Perspective \ Project
Stock Vector - 3D Linear Model of the Children s Slides 4148852 by ultrapro @ GraphicRiver
Stock Vector \ Objects \ Buildings
Graphics Files Included: Vector EPS, AI Illustrator; Layered: No; Minimum Adobe CS Version: CS5.
3D model of the children's slides. linear model
Barbed Wire Pattern Vector; Old Soviet Scales Drawing Ink Style; Vector Greeting Card with Congratulations; 3D Linear Model of the Children's Slides; Church of the Intercession on the Nerl; Seamless Vector Texture of Branches; Seamless Vector Texture of the Branches.
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text:
Brit Shaker Aamer may get £1million after Guantanamo hell
THE last British resident held at Guantanamo Bay could now be in line for a £1million payout.
Shaker Aamer is set to sue the Government after he was released on Friday from the military facility in Cuba after 13 years. It is understood the father of four, who is now in hospital, has already been reunited with his wife Zin.
He is due to meet his children this weekend, including youngest son Faris, who was born on the same day Mr Aamer arrived at Guantanamo. Mr Aamer, 46, is said to have a number of medical conditions including posttraumatic stress disorder.
He is now expected to take legal action against the Government over its alleged complicity in his mistreatment. A source said: "Proceedings were initiated some years ago on his behalf that could not be followed until his return to the UK.
"Without their devotion to justice I would not be here in Britain now"Shaker Aamer
"They will now, undoubtedly, be progressed."
Mr Aamer said he was seized by bounty hunters while working for a charity in Afghanistan in 2001. After returning to the UK, he paid tribute to those who fought for his release, saying: "Without their devotion to justice I would not be here in Britain now."


text:
Urethane ceiling domes enhance interiors with rich texture and traditional appeal. Many of our urethane ceiling domes include classic decorative details, ranging from floral motifs to crisp moulding. Whether you seek something subtle or ornate, we have a urethane ceiling dome for you. Each ceiling dome is factory primed and ready for your paint or faux finish. Each dome is manufactured out of a high density urethane foam, which is great for durability, but is also lighter than other materials to make installation a snap. Enhance your room with a beautiful ceiling dome focal piece.
California residents: see Proposition 65 information
- Modeled after original historical patterns and designs
- Solid urethane for maximum durability and detail
- Lightweight for quick and easy installation
- Factory primed and ready for paint or faux finish
- Can be cut, drilled, glued or screwed
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- 63-5/8 in. od x 59-1/2 in. id 13-3/8 in. d artisan ceiling dome with light ring (62 in. Dia x 13-3/8 in. d rough opening)


text:
British mobile phone giant Vodafone has announced the sale of its 3.2 percent stake in China Mobile for around 4.3 billion pounds (6.6 billion dollars, 5.2 billion euros).
The sale, announced late Tuesday, is the first in what is expected to be a series of sell-offs of Vodafone's minority holdings as it seeks to focus on core markets in a bid to improve its share price.
Around 70 percent of the net proceeds of the China Mobile sale, after tax and transaction costs, will be returned to shareholders through a share buyback, said Vodafone. The remainder will be used to reduce the group's debt.
Vodafone, the world's biggest mobile operator by revenue, initially bought a 2.18 percent stake in China Mobile in 2000 and increased its holding to 3.2 percent in 2002.
The group insisted that despite the sell-off it would continue cooperating with China Mobile.
Vodafone chief executive Vittorio Colao said in a statement that the sale "combines our stated portfolio strategy with ongoing cooperation with China's leading telecommunications company".
Colao has previously stressed to investors that the moblie phone group is determined to reshape its portfolio of assets and focus on core markets in Europe, Asia and India.
He told Vodafone's annual general meeting in July that the company was not aiming to "manage minorities", as he headed off a shareholder rebellion over the slow progress of sell-offs.
-- Dow Jones Newswires contributed to this report --


text:
Norfolk New Homes Directory
The Norfolk New Homes Directory is one of the most useful real estate sites on the Internet for finding new homes for sale in Norfolk. New Homes Directory .com is the easiest place for home searchers to find new homes and new condos as well as the most efficient means for new home builder to get results promoting their new home communities in Norfolk.
Norfolk New Home Communities Site Map
- Heritage Park by Caruana Homes Inc.
- Rivercrest by Crestline Homes


text:
The Yutu rover of the Chinese lunar mission has found a new type of rock on the moon, says a study published in Nature Communications, on Tuesday.
If we set aside the orbiters that were forced to crash land, the Yutu is the first explorer that has landed on the moon since the 1970s and is poking around an area that was reshaped on account of volcanic activity in what is reckoned as a relatively recent activity. At just under 3 billion years old, these slightly-less-ancient flows have rock unlike the samples brought home by previous missions.
It is believed that some 4.5 billion years ago, the moon formed as a consequence of a planet, Mars-sized planet having collided with the young Earth at that time about 4.5 million years ago, creating a hot mass of molten rock. Some 500 million years later, building heat arising from decayed radioactive elements inside the moon ought to have given rise to the melting in the mantle causing volcanic eruptions.
Till now, the basalts that have been sampled from the moon had all been with very high or very low titanium content. Upon examining the young rocks, it was found that the basalts had high levels of iron and intermediate level of titanium. This observation gains importance since the composition and order of mineral in the basalt can only reveal the source of magma that helped in the formation.
Bradley L. Jolliff, from the Washington University, stated that "The variable titanium distribution on the lunar surface suggests that the Moon's interior was not homogenized". Jolliff had also collaborated with the Chinese researchers for analyzing the data from the rover. He added further that "We're still trying to figure out exactly how this happened. Possibly there were big impacts during the magma ocean stage that disrupted the mantle's formation."
The results of the present research are expected to reveal the unexpected diversity of the moon and encourage scientists to study the surface from the orbiters.
Jolliff added that the 'ground truth' for remote sensing in the form of a well-characterized sample from a strategic location, is now available. Since similar signals are coming from orbits in other places, it has now become known that those other regions could also have similar basalts.


text:
Cost-Benefit Analysis in Developing Countries: What's Different?
There are both similarities and differences between conducting cost-benefit analysis in developed and developing countries . While the fundamental principles and theory underlying cost-benefit analysis maybe the same , the methodologies and the estimation techniques that are most appropriate in each context may substantially differ . The incompleteness and deficiencies of the labour , goods, and financial markets in developing economies may render revealed preference approaches to valuation unsuitable and inferior to stated preference models . But yet , even stated preference models are difficult to operationalize in developing countries where the literacy rates may not be too encouraging to allow for complete understanding of such valuation methods . It is largely because of the latter's complexity that the paper here suggests the newer method of adapting to the damage schedules approach to yield meaningful and more straightforward valuation of non-market goods and services . Understanding the differences in applying cost-benefit analysis to developed and developing countries will go a long way to helping policy makers make informed decisions.
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|Date of creation:
|May 2012
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Web page: http://egc.sss.ntu.edu.sg/
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References listed on IDEAS
Please report citation or reference errors to , or , if you are the registered author of the cited work, log in to your RePEc Author Service profile, click on "citations" and make appropriate adjustments.:
- Jack L. Knetsch & J. A. Sinden, 1984. "Willingness to Pay and Compensation Demanded: Experimental Evidence of an Unexpected Disparity in Measures of Value," The Quarterly Journal of Economics, Oxford University Press, vol. 99(3), pages 507-521.
- Kahneman, Daniel & Ritov, Ilana & Schkade, David A, 1999. "Economic Preferences or Attitude Expressions?: An Analysis of Dollar Responses to Public Issues," Journal of Risk and Uncertainty, Springer, vol. 19(1-3), pages 203-235, December.
- Kahneman, Daniel & Knetsch, Jack L., 1992. "Valuing public goods: The purchase of moral satisfaction," Journal of Environmental Economics and Management, Elsevier, vol. 22(1), pages 57-70, January.
- H. Semih Yildirim & George Philippatos, 2007. "Efficiency of Banks: Recent Evidence from the Transition Economies of Europe, 1993-2000," The European Journal of Finance, Taylor & Francis Journals, vol. 13(2), pages 123-143.
- Dinwiddy,Caroline L. & Teal,Francis J., 1996.
"Principles of Cost-Benefit Analysis for Developing Countries,"
Cambridge Books,
Cambridge University Press, number 9780521473583, October.
- Dinwiddy,Caroline L. & Teal,Francis J., 1996. "Principles of Cost-Benefit Analysis for Developing Countries," Cambridge Books, Cambridge University Press, number 9780521479165, October.
- Beal, Diana J., 1995. "A Travel Cost Analysis of the Value of Carnarvon Gorge National Park for Recreational Use," Review of Marketing and Agricultural Economics, Australian Agricultural and Resource Economics Society, vol. 63(02), August. Full references (including those not matched with items on IDEAS)
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text:
Monarch GlidePath PLus ~
All of Our Pollinator numbers have dwindled, including the all important Bee and the Monarch Butterfly.
It has become Urgent to Save Our Pollinators and Ultimately to Help Save Ourselves.
What can we all do to help?
It really is quite simple.
Plant a butterfly / pollinating garden, to include pesticide free milkweed & This Helps Save All Our Pollinators, including the Monarch and All of Our Earth!
Restore Habitats. Plant Native. Use Less Water.
Be Pesticide and Lawn Free. : )


text:
According to The Bank of England as reported by Breitbart:
Britain's central bank, the Bank of England, has stated that the high level of immigration that Britain is currently experiencing does in fact lead to lower wages, with those hurt most by the policy being on the semi-skilled or unskilled end of the country's workforce: almost 1 in 4 Britons.
The predatory left continues to pretend to be advocates of the downtrodden while, simultaneously, advocating the displacement of Western culture through mass immigration.
Please report typos...
More racist hate crime reports at AbateTheHate.com [click here]
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Image credit: Reuters via Breitbart ####
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text:
NEW YORK – Mel Brooks (search) will shoot the film version of his hit Broadway musical "The Producers" (search) at a new movie studio in the Brooklyn Navy Yard.
Brooks, a Brooklyn native, said new financial incentives and his love of New York helped persuade him to shoot at the recently opened Steiner Studios.
Mayor Michael Bloomberg and Gov. George Pataki (search) credited new state and local tax credit programs with attracting Brooks' film to New York.
Brooks had another reason.
"The bagels, just the bagels alone," he said. "You go to Toronto, they're mushy."
"The Producers: The Movie Musical" will star Nathan Lane (search), Matthew Broderick (search), Nicole Kidman (search) and Will Ferrell (search). The $45 million production will begin shooting in late February, Brooks said Tuesday at a press conference at Steiner Studios.
Lane and Broderick will repeat their roles as the rapscallion producer Max Bialystock and his nebbish accomplice Leopold Bloom. Brooks is producing the new film, to be directed by Susan Stroman, who directed and choreographed the stage show.
The stage musical was based on the original 1968 movie by Brooks starring Zero Mostel and Gene Wilder as two producers who set out to swindle investors by creating a musical flop. Brooks wrote the original film, which became a Broadway success in 2001 and won a record 12 Tonys.
Steiner Studios is the centerpiece of the city's efforts to revitalize the Navy Yard, a World War II shipbuilding hub that had lapsed into disrepair. Another five films are expected to be shot there soon, a Steiner official said, although they have yet to be publicly announced.


text:
Here the Unique and luxury RoofTop Terrace Design with Amazing View on Penthouse Apartment in Moscow. roof terrace which not only features magnificent views of surrounding rooftops but also provides a comfortable place to relaxation. an terrace floor to admire the view with breakfast. The apartment consists of a combination of contrasting shades of white, beige and dark. Furniture and other decorations are done in a minimalist style. living room is separated from the kitchen wall with a small artificial feature that saves space, but offers little 'privacy for those areas. Areas such as a bedroom and bathroom are separated more firmly to make them comfortable. check out the apartment picture with roof terrace design to view the Moscow city here:
Reference via


text: You've been waiting for the streets to be completed and the building to begin...well, the wait is over! Active building in Phase 2 of Town Creek has commenced and we have already sold one of the three houses we started! If you have been thinking about building in Town Creek, contact us soon as these homes and lots will go fast!!


text:
I think so before the 5k on Sunday. I know it's only a 5k but I look forward to any small challenge. My plan today was to take it fairly easy by only running 2 miles at about a 11 minute pace.
Mile 1 - 9:55
Mile 2 - 9:32
That's all I'm saying. Is there another sub 10 minute mile in the tank? I guess we'll see on Sunday!
Stay tuned!
Subscribe to: Post Comments (Atom)


text:
tanning salons in Caldwell, ID
Scizrs Hair Nail & Tanning Salon514 N 14th Ave, Caldwell, ID map
Electric Sun Tanning Salon5216 Cleveland Blvd Ste D, Caldwell, ID map
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text:
|12 Jan 2011
HDD Too Many Bad Sectors. What Should I Do?
Recently my hard drive on my desktop CPU has been screwing up lately. As of thirty minutes ago, it now tells me that I must run another disk check for the third time in a week because there are corrupt files. But when I run disk check, it says there's problems and I have to use system restore to get to a previous point so it can run it. But then I can't run system restore because my HDD has too many bad sectors and must be fixed before using any restore points.
I've had it with this thing and I want to just wipe, reformat, and reinstall windows. Tried to use Western Digital's software to wipe it clean but it tells me that I can't wipe my Windows drive.
What can I do??? Thanks.
|My System Specs
|12 Jan 2011
If you decide to re-install Windows, during installation you will get the opportunity to format the drive and re-partion it again. That will start you off with a clean drive.
|My System Specs
|12 Jan 2011
Oh, so just do a clean install of windows 7 and that will clear the drive???
|My System Specs
|12 Jan 2011
Thats correct, but you must choose to format the drive.
I highly recommend you refer to this tutorial which will guide you through the clean install. Sections 6,7 and 8 of the tutorial show the screens and actions needed to format your drive.
Clean Install Windows 7
Of course, be sure to back up any data that you do not want to lose during the format and installation.
|My System Specs
|12 Jan 2011
Some reading maybe, before any further actions...:
| How to fix bad sectors Repair Software
More Discuss:
Kill disk:
Active@ Kill Disk Hard Drive Eraser. Low Level Format.
Buy another Hard drive and reinstall your Windows 7 and go through Activation Process:
Activate Windows 7 Online
Activate Windows 7 by Phone
|My System Specs
|12 Jan 2011
Windows 7 Home Premium 64 bit
My advice is backup your important data and buy a new hdd as it sounds like yours is about to crash.
|My System Specs
|12 Jan 2011
Windows7 Pro 64bit SP-1; Windows XP Pro 32bit
I would do a bug check.
Download and run free Malwarebytes. Malwarebytes
Download, install, use the update tab and then run a full scan.
Anything it finds when prompted delete.
When it is done running a log file will pop up on Notepad. Save to desktop.
Then up load with next post to be checked. Screenshots and Files - Upload and Post in Seven Forums
Good first check before new install or buying a new hard drive.
|My System Specs
|12 Jan 2011
Windows 7 x64
I would buy a new hard drive. Install Win 7 on the new drive. Then copy all your data from the old drive to the new drive.
|My System Specs
|13 Jan 2011
I think you guys may be right.
My computer now won't even boot to windows. It gives me an error every time saying a "required device is inaccessible". Start Up repair says it can't fix what's going on. When I try to run a clean install of Windows 7, once it gets to the "Expanding Files" part, it throws me an error saying it's missing required files and setup must cancel. (Which is strange because I just did a repair install from this disk about 4 days ago) And If I try to revert back to a system restore point, my cpu says there are none.
I'm so pissed right now. This HDD only lasted 9 months
|My System Specs
|13 Jan 2011
I think you guys may be right.
My computer now won't even boot to windows. It gives me an error every time saying a "required device is inaccessible". Start Up repair says it can't fix what's going on. When I try to run a clean install of Windows 7, once it gets to the "Expanding Files" part, it throws me an error saying it's missing required files and setup must cancel. (Which is strange because I just did a repair install from this disk about 4 days ago) And If I try to revert back to a system restore point, my cpu says there are none.
I'm so pissed right now. This HDD only lasted 9 months
Be sure here in the SevenForums you'll find all the help you might need to reinstall your windows 7.
|My System Specs
|Thread Tools
|Similar help and support threads
MBR with bad sectors
Hi all, i have read a lot of posts regarding fixing the MBR. I dont have a bootable CD.. my laptop, gigabyte Q1500m, only boots in safe mode, after pressing F8. the normal boot takes me to a windows 'reparing error' screen, and after sometime it says that this error cannot be fixed. if...
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Packard Bell machine with original HD - ancient beast. Owner is unemployed like me, so can't afford a new HD or machine. Windows CHKDSK shows 52KB in bad sectors (my usual response - get a new HD) Ran SeaTools For DOS - it found the expected 13 bad sectors and offered to repair them, so I...
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Hello all, I have been reading posts here ever since I got my Windows 7. Today, I have had to sign up because I have a problem with my OS/HDD. Some days back, I got a "Windows detected a hard disk problem". So I scheduled a check disk. It moved some files, and my is back to normal (not slow...
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Hello, I have a 1 Tb Hitachi HDD as seen in the picture. I was wondering how can i remap the bad sectors into a new partition and then hide it. I've been said that it doesn't have much to live anymore.:( Thank you.
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Bad Sectors
I had always thought of bad sectors as being physical damage, and therefore cause for an RMA, but I found some old forum threads on the subject, one of which said this: My computer has had more than it's share of forced restarts, due to freezes where the only alternative was to use the reset...
|Performance & Maintenance
Bad HDD sectors
I have bad sectors on my WD HDD 350GB? What causes this? I install my windws 7 from a Disc image using powerISO and it worked great with no prbolems on my HDD. Later on i had to replace my mobo! so i decided to reinstalled windows again only this time with the same image but on a DVD as a boot...
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St. Louis's Forgotten Sit-In Story
Long before four male African American college students held their February 1, 1960, sit-in at the Woolworth's lunch counter in downtown Greensboro, North Carolina, St. Louisans were using the tactic to push for a change in their city's segregated dining establishments.
"Female members of the Citizens Civil Rights Committee were the true movers and shakers behind the lunch counter sit-ins."—T. D. McNeal
St. Louis's history of peaceful sit-in protests began in the middle of World War II, a time when blacks had grown tired of being asked to defend democracy and civil rights abroad without being afforded equal rights back home.
Five women—some white, some black, and all members of the newly created Citizens Civil Rights Committee (CCRC)—made history on May 15, 1944, by holding St. Louis's first organized lunch counter sit-in. It began that evening when the women seated themselves at the downtown Stix, Baer & Fuller lunch counter and remained there until it closed. During that time the African American women in the group, including CCRC leader Pearl Maddox, were never served.
CCRC held similar interracial sit-ins weekly at Stix and the other two downtown department stores, Famous-Barr and Scruggs-Vandervoort-Barney, throughout May, June, and July. A public statement released by the group in 1944 noted that although no white customers had abandoned their meals or refused to enter the establishments because blacks were present, the managers' had claimed their white customers would never be comfortable dining with blacks.
Because the managers clearly required further convincing, a group of 40 black women and 15 white women visited the three lunch counters on July 8, 1944. Carrying signs that read "A Nazi's bullet knows no prejudice" and "Fox holes are democratic, are you?" the women sat down together and waited to be served. Although all three lunch counters closed for the day instead of feeding the CCRC women, the large-scale sit-in was a success in that it attracted attention. Thousands of handbills were distributed outside the stores, and the white-owned St. Louis Post-Dispatch finally printed a story about the group's efforts.
CCRC's sit-in campaign ended the following year without achieving true desegregation in the city's dining establishments. It did, however, inspire another group that identified strongly with the principles of nonviolent direct action.
"The whole idea of CORE from the beginning was to win over to our way of thinking people who were initially opposed to what we were trying to accomplish."—Irv Dagen
The interracial Committee of Racial Equality (CORE) formed out of a small discussion group in 1947 and set its sights on desegregating St. Louis's restaurants, with full procedures in place for doing so. CORE members would contact various owners and managers and ask them to weigh the benefits of desegregating their businesses. These polite conversations might happen multiple times before a dining establishment agreed to desegregate—if it ever did. Those that didn't, particularly Stix, Baer & Fuller, received a more public message.
CORE began its direct-action campaign at Stix in 1948 by contacting the store's leaders. When that proved futile, members began distributing leaflets titled "All We Ask Is Fair Play" and "The Grand Leader—in Everything but Democracy" to explain how Stix was treating African Americans and encourage customers to let the store's managers know that this was wrong. After months of passing out informational flyers, CORE members headed inside.
In early 1949 two white CORE members sat down at the Stix lunch counter and ordered food. After it arrived, they were joined by four black CORE members. The six individuals then proceeded to eat together. The white CORE members ordered dessert, which they were also planning to share, before Stix staff placed Closed signs on the counter.
Smaller sit-ins followed with similar results, but the CORE members had discovered something that they believed should appease Stix's management. In an April 12, 1949, letter, CORE members noted that "white customers continued to sit at the counter and eat, even sitting in seats next to the Negroes." Stix remained silent, so CORE kicked its efforts into high gear, launching weekly Saturday sit-ins with anywhere from 20 to 30 members taking up some of the 97 available seats. The book Victory without Violence describes one especially large Stix sit-in.
One Saturday, fifty-seven CORE people sat at the first-floor counter all day. Demonstrators remained quietly from 10 a.m. to 4:30 p.m. on Saturday, and from 4:30 to 8 p.m. Monday. At first, they sat next to one another. Later, they changed strategy to occupy every other seat. White customers would sit between them and be served. CORE members placed small signs on the counter before them: "We are Being Refused Service," along with explanatory leaflets.
The sit-ins at Stix's downtown location lasted for 18 months before CORE decided to focus its efforts elsewhere. Despite the store's stubborn policy (it didn't desegregate its lunch counter until 1952), CORE member Charles Oldham recalled that progress was made in the hearts of the employees.
We sat there for eighteen months and we became friendly with the waitresses who wouldn't serve us and with the security people. They would talk to us and discuss family and so on. I remember, after we left, we came back a year or two later, and they greeted us very happily.
Not all sit-ins were group affairs. In 1953, Irene Williams, a CORE member and Saint Louis University student, conducted a solitary sit-in at the Woolworth's near campus, a block off of Route 66. Williams entered the Woolworth's every Wednesday at noon and settled into her management-assigned seat near the end of the lunch counter—right by a pot where hot soup spilled regularly and a sharpener where large knives were honed before being slid back down the counter. She shared some of her story in Victory without Violence.
Most of the women behind the counter were . . . unflinchingly mean-spirited toward me. . . . Yet there was one gentle soul who frequently shoved a bowl of soup toward me and smiled benignly. I made an effort to eat it but had a hard time because I think it was soup that someone else had returned.
After about two months one of the women behind the counter asked me if I wanted to order anything. I said no for two reasons: one was that I never had expected to have the opportunity to order and the other was that I was so sure I would not that I didn't even take my purse inside but left it in the car.
After that, I was always given the opportunity to order and I always did so. The manager then informed me that I could sit wherever I wanted. . . . Near the end of the semester he met me at the door and said the sit-in was no longer necessary because he was opening the entire store to everyone. I think he even smiled. I know I did, broadly.
A particularly compelling aspect of the St. Louis lunch counter sit-ins is the overall lack of violence. Unlike restaurant sit-ins in the Deep South, where racist laws abounded and protesters were beaten and arrested, the St. Louis sit-ins were met largely with either heartfelt support or the willful denial of change. As CORE member Bonnie Rosen recalled:
We were not verbally or physically abused; we were simply shunned. Waitresses gave us a wide birth, pretending not to see us; and people at other tables avoided looking at us. . . . We were shaking up the status quo, and they didn't know how to behave. So they pretended we were not there. But we did not go away.
—Jen Tebbe, Editor


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According to the latest forecasts, automakers are expected to regain momentum this month after sluggish performances in March, with the industry making up the lost momentum triggered by the harsh winter end.
New market forecasts coming from J.D. Power and LMC Automotive put the consumer demand at its highest rate in a decade this April, thanks to the warm – spring weather – spreading across the continental US. Now the overall new sales of new cars, trucks and SUVs are expected to reach 1,463,700 units – up 5 percent from the same month last year and the best level for April since 2005. The seasonally adjusted annual rate of sales, or SAAR, is forecasted at 16.6 million autos based on the first four months. "The industry continues to outperform prior-year levels with respect to retail sales and transaction prices," comments John Humphrey, senior vice president of the global automotive practice at J.D. Power. According to the analyst, the average new-vehicle transaction price in April for now has surged to $30,680, with the record set last year ($29,948) ready to be broken.
The J.D. Power Power Information Network (PIN) sets the benchmark for a new consumer spending record for the month thanks to the strong sales and high transaction prices – predictions call for a total of $36.2 billion to be spent on new light vehicles. Meanwhile, LMC Automotive is forecasting a total market for the year of 17 million units, with retail sales reaching 13.9 million autos this year. April sales would reach a total of 1,179,000 vehicles in the firm's opinion.


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I wasn't sure how to spend my weekend yesterday and my daughter craved for this, her request come in time, else, I probably would try a new recipe.
I baked this cake many times but my daughter isn't tired of it because it's so yummy!! It's her favorite.
In fact, I like it as well but taking into consideration of the high calorie and my waist line, I have to scarify my sweet tooth and put all these aside. How sad!
I reposted the recipe here for your easy reference. Enjoy Baking !!
- Preheat oven at 175*C for 15 mins.
- Prepare a 10" round pan or 9" square, grease base and line with baking paper.
Egg Yolk Mixture
- 6 egg yolks (large)
- 90g sugar
- 1tbsp water
- 20g milk
- 1tbsp (15g) melted butter
- 150g top flour or cake flour
- 1 tsp Rum
- ½ tsp vanilla essence
Egg White Mixture:
- 6 egg whites (large)
- 90g sugar
- ½ tsp cream of tartar
Egg White Mixture:
- 6 egg whites (large)
- 90g sugar
- ½ tsp cream of tartar
Filling and Topping:
- 250g Philadephia cream cheese
- 70g butter
- 20g sugar
- 2 tsp lemon juice
- 60g toasted almond flake
1. Whisk egg yolk and sugar at high speed until light and thick (abt 4 mins).
2. Stir in water and milk and then melted butter. Mix well.
3. Change to low speed and stir in flour. Add vanilla essence and Rum to combine.
4. In another mixing bowl, beat egg whites and then add in sugar and tartar. Beat till stiff (abt 3 mins).
5. Fold egg white mixture (step 4) into step 3 using spatula. Mix well (don't overmix).
6. Bake at 175*C for 30-35 mins. Remove from oven and rest to cool.
7. Cream cheese, sugar and butter together until light and creamy. Add in lemon juice and blend well.
8. Slice cake horizontally into 3 layers. Spread 1/3 of the cream cheese over the bottom (1st layer) of cake.
9. Repeat the same for 2nd and 3rd (top) layer of cake and cover the top with almond flakes.
10. Leave the 4 slides clean and chill in fridge for 1-2 hours before serving.


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Implement user_valid_point in usrtm_valpt.c.
If custom addressing is used, this function must translate the string form of the address to its corresponding domain and offset. If the address is invalid or the address is out of the range, the point should be returned as invalid.
Regardless of addressing mode, if the device has configurable memory, this function should determine whether the point address is a valid one. One method for accomplishing this is to attempt to read the data value from the configured location in the device's memory. A second method is to read the memory configuration from the device and use this information to determine if the address is valid.
Implementation checklist.


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text:
In the neighborhood with no shortage of starry eateries from Monsieur Benjamin to Petit Crenn, Nightbird is an even worthier addition offering former-Manresa alum in a bouqtiue eatery with accompanying mixology bar. The facade blends into the Gough thoroughfare, leading to a series of small parlor rooms with timber floors, smooth plaster walls and very-compact tables. An eat-at counter compliments the additional Linden Room, a separate mixology cocktail bar that sure to be a hipster hideaway for decades to come.
The Food
Chef Kim Alter debuts her first solo project with a rotating, prix-fixe menu of seasonal ingredients married in dishes like clarified tomato soup with oyster borage and seaweed, farm fresh corn, lobster with chanterelles and truffles, and rabbit with peaches and squash.
Last Word
Chef Kim Alter debuts her first SF dining room with mixology bar and rotating prix-fixe menus.


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Tour through Albanian natural beauty and history
Booking code SHCU72
7 Days € 499
Travel dates:2017-05-20 to 2017-05-26 Reservation
Travel dates:2017-10-09 to 2017-10-15 Reservation
Tirana - the vibrant capital and visits to its main attractions
Durrës and its Roman amphitheater
Apollonia - the city founded in 588 BC, and visit of the archaeological site
Llogara National Park
Drive along the Ionian Coast of Albania and visit of many characteristic villages along it
The city of Saranda, located on a natural shelf facing the island of Corfu
Visit of Butrinti - the most important archeological site of Albania, an UNESCO World Heritage
Visit of Berati and Gjirokastra - UNESCO World Heritage
Selected traditional restaurants "A la Carte" during the entire journey and many culinary highlights.
Day 1: Tirana, the vibrant capital.
After arrival at noon, transfer from Mother Teresa airport to the hotel in downtown Tirana.
Founded in 1614, Tirana became the capital of Albania in 1920 and is the main cultural and industrial centre of Albania.
In the afternoon, a tour of the city is planned along with a visit to the Ethem Bey Mosque, Skanderbeg monument, clock tower. Then we take the cable car to Dajti mountain, part of Dajti National Park, covered with dense beech forests. From the cable car terminal (1050 m) theres a magnificent view over Tirana, Durrës and the whole central-west Albania up to the Adriatic sea. Here we will have dinner at a traditional restaurant "A la carte" and then return to Tirana.(-/-/D)
Day 2: Durrës, Apollonia and Vlora.
After breakfast at the hotel drive to Durrës. We will have time for a short visit to the city and its Roman amphitheater and a drink in one of the bars by the sea promenade.
Durrës was founded in 627 BC by Greek colonists from Corinth and Corfu. They named it "Epidamnos" with the surrounding area called Epidamnia. The city was one of the starting points of the Via Egnatia, connecting the Adriatic Sea with Byzantium.
The amphitheatre of Durrës is one of the greatest monuments of antiquity in Albania and was built in the first decades of the 2nd century, probably during the reign of the Roman Emperor Hadrian.
The journey continues in the direction of Apollonia. The city was originally founded in 588 BC as a Corinthian colony and was named after the god Apollo. It is today situated near the modern town of Fier and offers the visitor a unique insight into the immense importance this region once held. It is estimated that the city had about 60,000 inhabitants, a record for ancient times. As a trade centre, the city started to decline in the 4thCentury following a large earthquake which altered the course of the Vjosa river and Apollonias famous harbor silted up.
Drive towards the coastal city of Vlora. Dinner and accommodation are planned at a hotel with a special location by the sea, in Radhimë, near Vlora. Here you will be able to enjoy not only the view, but also the delicious cuisine.Vlora is situated in the southwestern part of Albania, exactly where the two seas meet: the most southern part of Adriatic Sea and northern part of Ionian Sea. Vlora, through Otranto channel, is the nearest point of Albania to the Italian coast.(B/L/D)
Day 3: Ionian coast and Saranda.
Drive to Llogara National Park. With an area of 1020 ha, Llogara is covered with everlasting greenery. In the inner part of its forests there are beautiful lawns, countless natural resources and diversified animal and bird species. An amazing part of this geo-park is the balcony" in Llogara pass, at the height of 1050m, where the Ionian Sea can be seen.
After a short coffee break, the tour along the Ionian coast begins.
The Albanian Ionian Coast runs from Vlora to Saranda, in the south, opposite to Corfu. The coastline is famous for its small bays, pebbly beaches and crystal clear waters. The Riviera is one of Albanias natural beauties and certainly one of the most picturesque places in the whole Mediterranean. As the road winds down from the pass of Llogara, the vista opens up to reveal the stunning delta of Palasa and its white pebbled beach. This is one of the largest and probably the most spectacular pristine beach of the entire Albanian coast.
We will stop for a short visit of the village of Dhërmi and its churches. The old village is set into the mountain and is one of the oldest and most characteristic villages on the Ionian Coast, with its stone, mountain houses and historical monuments. The earliest signs of settlement date back to the 1st century B.C.. There were no less than 30 churches in the village. The village as a whole comes together to create an aesthetically harmonious architectural jewel, offering amazing views of the Ionian Sea.
Our next stop is planned in Jali beach, where we will have lunch.
Drive to Himara and short walk uphill to the old traditional village and the castle on the top of a hill overlooking the bay. It had been built as a fortress for the Epirus tribe of Chaonians and is an important part of the long history of the Himara people to be safe and independent. At the foot of the castle, wonderful beach of Livadhi stretches along the coast and nearby the Cave of Kardini, where Homers epics Journeys of Ullyses/Odissey in the Country of the Himariots" were inspired.
The next stop is planned at the bay of Porto Palermo, surrounded by mountain slopes and agave plants.Apart from the natural beauty, it was also one of the most important military bases during the cold war. From the road you can see the tunnels where Albanian military submarines were moored. During the communist years, it was forbidden to walk or even to be in this area without permission. Just in the middle of the bay lies the castle of Ali Pasha Tepelena, which we are going to visit.
The journey continues in the direction of Saranda, located on a natural shelf facing the island of Corfu. Dinner is planned at a restaurant in Lëkursi castle, built by Sultan Suleiman during his military campaign against Corfu. It lies on a hill overlooking the bay.(B/L/D)
Day 4: Butrinti and Gjirokastra.
Drive to Butrint and visit of the most important archeological site of Albania, an UNESCO World Heritage. Butrinti is known since the 7th century B.C. as the most important city of Epirus. Its building is linked to the presence of the Trojan prince Aeneas. The day continues with the drive to the old Roman town of Hadrianopolis, and then, on the way to Gjirokastra, we will enjoy the spectacular secluded scenery of the Blue Eye spring and park.
The tour continues towards Gjirokastra, another UNESCO World Heritage Site. It is an outstanding example of an Ottoman merchant town and one of the few still surviving in the Balkans. We will visit the castle, the ethnographic museum and the artisan centre. Dinner in a traditional restaurant.(B/L/D)
Day 5: Berati.
After breakfast drive to Berati. It is a 2407 years old city that forms a wonderful combination of eastern and western cultures and traditions. The city's life began as an Illyrian settlement. Later, in the 3rd century B.C., it was turned into a castle city known as Antipatrea. During feudalism churches with precious frescos and icons were built inside the castle. Today, the castle is made unique by the fact that people continue to live inside of it. Short walk uphills to the castle of Berati and visit of the churches. Dinner and accommodation are planned in a beautiful and comfortable hotel, surrounded by unspoiled nature.(B/L/D)
Day 6: Tirana
Drive to Tirana. A visit of the Mosaic of Tirana (the oldest surviving remains in Tirana, built almost 2 millennia ago) and the National Historical Museum. In Tirana some free time is planned and then dinner in a traditional restaurant accompanied by traditional music. After dinner, you can have a drink in one of the nice bars in "Blloku" quarter, the most animated quarter of the capital and enjoy the night life of Tirana.(B/L/D)
Day 7: Transfer to the airport according to the scheduled flight.(B/-/-)
Additional information
If you are coming in a prearranged group, you can decide the date of this tour yourself.
This journey starts around noon on the arrival day. If you arrive in Tirana in the evening of this day, it is impossible to participate in activities scheduled for day one. All saved expenses will be reimbursed.
The journey begins immediately after landing at the airport in Tirana where reception is scheduled. If you enter Albania through other border checkpoints and via other routes, we can pick you up against additional charge, enabling your participation in the travel. If this is the case, you should carefully fill in the appropriate field of the reservation form
If you wish to travel to Albania a few days earlier or extend your tour by a few days, we are at your disposal to further organize your travel according to your wishes. All related services and costs are not included in the tour price and as such will be additionally calculated. For this purpose you should carefully fill in the field "Comments" in the booking form and explain in detail all your desires through an e mail sent to us.
Number of the participants: 15 people
The full board price includes:
Transfer from and to the airport
All trips according to the program schedule.
Entries and visits listed in the program.
6 nights hotel accommodation in a double/twin room with shower or bathtub and toilet.
5 x full board.
Dinner on the arrival day and breakfast on departure day.
Coffee and water during all meals and coffee breaks.
Selected restaurants "A la carte" during the entire journey.
Accompaniment by an English-speaking guide during the entire journey.
The price does not include
Any type of insurance.
Beverages (except water and coffee) in hotels, restaurants and bars.
Equipment list
Sneakers for traveling and sightseeing
Drinking bottle/ Thermos Flask


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Christmas tree lights spark fire in Broadmoor
A Christmas tree burst into flames and caused $30,000 in damage when its lights sparked a house fire in the living room of a Carolyn Sue Drive home, according to the Baton Rouge Fire Department.
A child in the home plugged in the lights to the tree at 1235 Carolyn Sue Drive, and moments later another child saw something sparking about 5 p.m. Monday, said Mark Miles, a BRFD spokesman.
As the tree caught fire, a baby-sitter rushed the children out of the house, and firefighters arrived soon afterward to find the tree in flames, Miles said. They contained the fire to the living room within 10 minutes, but the house sustained heavy smoke damage, as well as some water damage, Miles said.
Wife booked in stabbing of husband
Sheriff's deputies arrested a Baton Rouge woman accused of attempted murder after deputies say she stabbed her husband Monday night as their 13-year-old son looked on.
Stephanie Robertson was fighting with her husband at their Villere Drive home when she went to the kitchen, pulled out a knife and told her husband she would stab him, according to a report.
The two then struggled for the knife, and Robertson stabbed him in the upper chest, causing him to fall to the floor, the report says. The report did not specify the man's condition at the hospital but did say he was conscious while being placed in the ambulance.
Robertson, 39, 7020 Villere Drive, was booked into Parish Prison early Tuesday on counts of attempted second-degree murder and domestic abuse battery.
Authorities book five on suspicion of DWI
Authorities arrested at least five people suspected of driving while intoxicated in East Baton Rouge Parish and booked them into Parish Prison between 2:30 p.m. Sunday and 2:30 p.m. Monday, booking records show.
Those booked and the counts against them:
John Adams, 48, 1137 Michael St., Marrero, first-offense DWI and careless operation.
Luan Bui, 40, 11371 Glenda Drive, Baton Rouge, first-offense DWI, one-way street violation and reckless operation.
Holly Ehrlich, 39, 19132 Bellerive Court, Baton Rouge, first-offense DWI and domestic abuse battery.
Kevin Harrison, 36, 1900 Blount Road, Baton Rouge, first-offense DWI, improper lane use, driver's license suspended or revoked and flight from an officer.
Hau Mai, 29, 1652 Nie Parkway, New Orleans, first-offense DWI, possession of alcohol in vehicle, possession of marijuana and failure to signal.
To talk to a crime reporter at The Advocate, call (225) 388-0369.


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The Hillier Manual of Trees and Shrubs
A reference manual for beginners and experienced gardeners, which was first published in 1972. It contains descriptions of trees and shrubs with information as to colour, size and habit. There are sections on nomenclature and classification, planting, pruning and garden planning, an illustrated glossary and notes on horticultural awards.
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