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We studied the role of FGF-2 on regulation of neurogenesis and cell loss in the granule cell layer (GCL) of the hippocampal dentate gyrus after experimental traumatic brain injury (TBI). In both FGF-2–/– and FGF-2+/+ mice subjected to controlled cortical impact, the number of dividing cells labeled with BrdU, injected on posttrauma days 6 through 8, increased at 9 days after TBI, and the number of BrdU-positive cells colabeled with neuron-specific nuclear antigen significantly increased at 35 days. However, in injured FGF-2–/– mice, BrdU-positive cells and BrdU-positive neurons (days 9, 35) were fewer compared with FGF-2+/+ mice. There was also a decrease in the volume of the GCL and the number of GCL neurons after TBI in both FGF-2–/– and FGF-2+/+ mice, but the decrease in both was greater in FGF-2–/– mice at 35 days. Overexpression of FGF-2 by intracerebral injection of herpes simplex virus–1 amplicon vectors encoding this factor increased numbers of dividing cells (day 9) and BrdU-positive neurons (day 35) significantly in C57BL/6 mice. Furthermore, the decrease in GCL volume was also attenuated. These results suggest that FGF-2 upregulates neurogenesis and protects neurons against degeneration in the adult hippocampus after TBI, and that FGF-2 supplementation via gene transfer can reduce GCL degeneration after TBI.
It has long been believed that the brain regenerates poorly after injury. However, this idea has been challenged by recent data showing that mammalian neural progenitor cells can proliferate and differentiate into neurons in the adult brain (1–7). Neurogenesis in the mature nervous system is subject to physiologic and pathophysiologic regulation. For example, neural progenitor cells in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) can divide and differentiate into neurons after brain injury (8–15). However, what initiates and promotes this potentially therapeutic response in vivo is still unknown. Among growth factors and neurotrophins that have been implicated, FGF-2 is regarded as one of the most potent (16–21). Hippocampal neural progenitor cells in culture proliferate with only FGF-2 supplementation (17, 19, 20, 22). FGF-2 and its family of receptors are widely distributed in the adult CNS (23–25), and FGF-2 is released from cells in response to injury (26). We have recently demonstrated that FGF-2 is critical for upregulation of neurogenesis in the adult DG after kainate-induced seizures and focal cerebral ischemia (15). In addition, FGF-2 has been shown to reduce neuronal death after traumatic brain injury (TBI), cerebral ischemia, and seizures (27–30). Recently, it was reported that intraventricular infusion of growth factors markedly augments endogenous progenitor proliferation, leading to regeneration of CA1 neurons and amelioration of neurologic deficits, after experimental cerebral ischemia (31). The regulation and manipulation of neurogenesis and neurodegeneration via growth factor signaling has broad implications for both the development of therapeutic strategies for repair of CNS injury after trauma, and for advancing our understanding of basic cellular mechanisms of regeneration from brain injury.
In the present study, we used a controlled cortical impact (CCI) model of TBI to evaluate the contribution of FGF-2 to cell loss and cell addition in the granule cell layer (GCL) of DG after brain injury. This model manifests progressive cell loss in the GCL as well as injured cortex (32–35). Cell loss in the GCL is assumed to contribute to the decrease in total volume of the GCL after injury (9). We evaluated the effect of endogenously generated FGF-2 on neuronal regeneration, neuronal loss and GCL volume loss in the DG after TBI using mice genetically deficient in FGF-2. The extent of neural progenitor cell proliferation was monitored using BrdU incorporation into replicating DNA, and differentiation of newly born cells into neurons, using immunocytochemical colocalization of a neuronal marker, neuron-specific nuclear antigen (NeuN), with BrdU. We further evaluated the effect of overexpression of FGF-2 by a herpes simplex virus–1 (HSV-1) amplicon vector on neurogenesis after TBI in C57BL/6 mice, and assessed the impact of overexpressed FGF-2 on volume loss in the GCL after TBI.
Animal care and experimental protocols complied with the NIH's Guide for the Care and Use of Laboratory Animals (National Institutes of Health publication 86-23). FGF-2 KO mutant mice (FGF-2–/– mice) and WT littermates (FGF-2+/+ mice) were generated from two heterozygous mating pairs (FGF-2+/–, SV129/Black Swiss background) (generously provided by Thomas Doetschman, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA) (36). Mice were genotyped by PCR using primers specific for the WT and the FGF-2 KO alleles. Male FGF-2–/– mice and FGF-2+/+ littermate controls were used at 8 to 10 weeks of age. For gene transfer experiments we used 9-week-old male C57BL/6 mice obtained from Charles River Laboratories (Wilmington, Massachusetts, USA) as WT animals for two reasons. First, we found that C57BL/6 mice robustly expressed GFP using HSV amplicon-mediated gene transfer, whereas this was less so in SV129/Black Swiss. Second, we developed a highly reproducible brain injury model in C57BL/6 mice in which 40% to 50% of cells were lost in the medial segment of the upper leaf of the DG. Because strain differences can affect hippocampal vulnerability to excitotoxicity as well as proliferation of progenitor cells in DG (6, 37), we compared results between groups with the same genetic background (i.e., FGF-2–/– and FGF-2+/+ mice, or among C57BL/6 mice injected with viral vectors).
The CCI model was used as previously described with minor modifications (38). The trauma protocol was approved by the Massachusetts General Hospital Institutional Animal Care and Use Committee and complied with the NIH Guide for the Care and Use of Laboratory Animals. Mice were anesthetized with 4% isoflurane (Anaquest, Memphis, Tennessee, USA), N2O, and O2 (2:1) using a Fluotec 3 vaporizer (Colonial Medical, Amherst, New Hampshire, USA) and positioned in a stereotaxic frame and maintained on 1% to1.5% isoflurane in 70% N2O and 30% O2. Body temperature was monitored with a rectal probe and maintained at 36°C to 38°C with a heating pad. A 5-mm craniotomy was made using a portable drill, and a 5-mm trephine over the left parietotemporal cortex and the bone flap was removed. Mice were then subjected to CCI using a pneumatic cylinder with a 3-mm flat-tip impounder, velocity 6 m/s, depth of 0.6 mm, and 100 ms impact duration. Sham controls received craniotomy only. The bone flap was replaced, and the scalp was sutured closed. The mice were allowed to recover in room air until able to ambulate (approximately 5 minutes) and returned to their cages.
Animals received intraperitoneal injections of BrdU (Sigma-Aldrich, St. Louis, Missouri, USA; 50 mg/kg; dissolved in sterile PBS and 0.007 N HCl and filtered at 0.22 μm). Twice daily injections were given on days 6 and 7, followed by a single injection on day 8 after brain injury. The animals were killed 1 day after the last BrdU injection (i.e., day 9). When specified, BrdU was given twice a day on days 13 and 14, followed by a single injection on day 15, and the animals were killed on day 16. For histologic evaluation, the animals were perfused transcardially with 4% paraformaldehyde in PBS under deep anesthesia. For enzyme immunoassay (EIA), the brains were removed without transcardial perfusion under deep anesthesia and the hippocampi were dissected and frozen immediately at –80°C.
HSV-1 amplicon vector bearing mouse FGF-2 coding sequences was prepared as previously described (15). Briefly, the mouse FGF-2 (mFGF-2) cDNA in the plasmid pBluescript (number 63348; American Type Culture Collection, Manassas, Virginia, USA) was released by digestion with Not I/Apa I. It was then inserted into the Not I/Apa I site of pSecTag2/Hygro B (Invitrogen, Carlsbad, California, USA), so as to add an N terminal secretion signal from the V-J2-V region of the mouse Ig kappa-chain. Next, mFGF-2 cDNA with the secretion signal was digested out from the pSecTag2/Hygro B construct with Nhe I/Xho I, and ligated between the Nhe I/Xho I sites in the multicloning site of the HSV-1 amplicon, pHGCX (termed here HSV-1/empty, kindly provided by Y. Saeki, Massachusetts General Hospital, Charleston, Massachusetts, USA) (39). This amplicon, pHGCX/mFGF-2 (termed here HSV-1/mFGF-2) contains both a GFP cassette driven by the HSV immediate early (IE) 4/5 promoter and the FGF-2 cassette driven by the IE human CMV promoter. Helper virus-free amplicon vector stocks of HSV-1/empty and HSV-1/mFGF-2 were prepared as previously described (40). Viral titers were determined by infecting Vero 2-2 cells, which are transduced by amplicon vectors with high efficiency, and monitoring numbers of GFP-positive cells 24 hours later. The vector stocks contained 107 transducing units (TU) per milliliter.
Vector injection was performed 1 hour after brain injury in anesthetized mice placed in a stereotaxic apparatus (Stoelting, Wood Dale, Illinois, USA). The bone flap made for cortical impact injury was removed and a 26-gauge needle (10-μl Hamilton syringe) was then inserted stereotactically into the ipsilateral hippocampus at 2.5 mm lateral and 2.5 mm caudal to bregma to a depth of 1.5 mm from the dura. One microliter of vector (5 × 104 TU) was injected over 10 minutes (0.1 μl/min) with a stereotaxic injector (Stoelting). The needle was left in place for 5 minutes and then slowly withdrawn to minimize leakage.
Immunohistochemistry was performed on free-floating 50-μm coronal sections, as reported previously (1, 5, 6, 18). We used mouse anti-BrdU (1:400; Becton Dickinson, Franklin Lakes, New Jersey, USA), or for double-labeling rat anti-BrdU ascites fluid (1:100; Harlan Sera-Lab, Loughborough, United Kingdom), and mouse anti-NeuN (1:200; Chemicon, Temecula, California, USA). The number of BrdU-labeled cells was determined by staining for BrdU using the peroxidase method (ABC system) with biotinylated horse anti-mouse IgG antibodies and diaminobenzidine as chromogen (Vector Laboratories, Burlingame, California, USA). The fluorescent secondary antibodies used were cy2-labeled anti-rat IgG and cy3-labeled anti-mouse IgG (1:200; Jackson ImmunoResearch, West Grove, Pennsylvania, USA).
All analyses were accomplished with stereologic counting methods. A systematic random sampling of every 12th in a series of 50-μm coronal sections was prepared from each animal and processed for immunohistochemistry and Nissl staining. The hippocampus (bregma –1.3 mm to –3.1 mm) was chosen because the cortical contusion overlying this region was reproducible and consistent. BrdU-positive cells were counted in the SGZ or GCL using a 40× objective lens. The SGZ was defined as a 20-μm wide zone approximately two cell bodies immediately adjacent to the hilar surface of the GCL. The areas of the GCL on each section were measured on the adjacent sections stained with cresyl violet using an MCID Imaging Research image analysis system (Imaging Research Inc., St. Catherines, Ontario, Canada). The GCL volume (GCLV) was defined as that volume of the GCL in a hemisphere within bregma –1.3 mm to –3.1 mm, and was calculated (41). The number of BrdU-positive cells within the GCLV then was calculated by multiplying volume density (cells/mm3) of BrdU-positive cells by the volume of GCLV.
Counting of BrdU-positive cells coexpressing NeuN was performed using a Nikon TE 400 microscope with a laser confocal scanning system MRC 1024 (Bio-Rad, Wattford, United Kingdom). For each animal, the number of double-labeled cells was counted in the ipsilateral GCL. Cells were considered double-labeled when BrdU and NeuN immunoreactivity overlapped at five levels through a section (z-step 1 μm).
We determined percentage volumetric change of GCLV in the hemisphere ipsilateral to the contusion relative to the GCLV of the contralateral side (42). To determine whether changes in GCLV of ipsilateral versus contralateral hemispheres reflected changes in neuron numbers, granule cells in the GCLV were counted in FGF-2–/– and FGF-2+/+ mice 35 days after CCI. Granule cell counts in the GCLV were performed in coronal 50-μm sections spaced 600 μm apart and stained with cresyl violet using the optical dissector technique (Bioquant Basic Stereology Toolkit; R&M Biometrics Inc., Nashville, Tennessee, USA) (43, 44). The GCLV was systematically randomly sampled with approximately 20 optical dissectors (10 × 10 μm sampling box with extended exclusion lines) under 100× water objective. The coefficient of error for the counting technique was less than 0.10 (45). To estimate the total number of granule cells within the GCLV (neurons within lesion volume = GCLN), the resulting neuronal volume density (cells/sample volume, sample volume: 10 × 10 × 50 μm3) was multiplied by the volume of the GCLV. We determined percentage change of GCLN in the hemisphere ipsilateral to the contusion relative to the GCLN of the contralateral side.
Cerebral cortex contusion volume after CCI was measured in the same four cresyl violet-stained sections used for DG cell counts by image analysis (Imaging Research MCID image analysis system) using the Cavalieri technique (41).
Stored hippocampi at –80°C were homogenized in buffer solution (20 mM Tris-HCl, pH 8.0, 137 mM NaCl, 1 mM DTT, 0.5% Triton X-100, 0.5 mM PMSF) and centrifuged at 14,000 g for 30 minutes at 4°C. Protein concentration of each supernatant was determined by a protein assay kit (Bio-Rad Laboratories Inc., Hercules, California, USA). EIA for FGF-2 was performed using an assay kit (Quantikine HS; R&D Systems, Minneapolis, Minnesota, USA) according to the manufacturer's instruction. For intra- and interassay precision, coefficient variability was less than 15%.
All values are expressed as the mean ± SD. ANOVA with Bonferroni's post hoc analysis in StatView 5.0 for Macintosh (SAS Institute, Cary, North Carolina, USA) was used for statistical analysis throughout the study. P values less than 0.05 were considered statistically significant.
To measure the extent of cell proliferation and the effect of FGF-2 after TBI, we measured BrdU incorporation into the nuclei of progenitor cells in SGZ of FGF-2+/+ and FGF-2–/– mice. Few BrdU-labeled cells were present within the SGZ of the ipsilateral DG in the sham-operated FGF-2+/+ and FGF-2–/– mice (Figure (Figure1a).1a). The number of BrdU-positive cells did not differ between FGF-2+/+ and FGF-2–/– mice after sham operation (Figure (Figure1b).1b). BrdU-labeled cells increased at day 9 after TBI in both groups, but the increase at day 9 was greater in FGF-2+/+ mice (4.4-fold vs. 2.9-fold in FGF-2+/+ and FGF-2–/–, respectively, P < 0.05; Figure Figure1b).1b). At day 16 after TBI, the increased number of BrdU-positive cells was still significantly greater in FGF-2+/+ compared with FGF-2–/– mice (P < 0.05). Next, FGF-2 levels were measured in the hippocampus after injury. We previously reported that the level of FGF-2 protein in the hippocampus in uninjured mice was approximately 100 pg/mg protein in FGF-2+/+ animals and undetectable in FGF-2–/– animals (15). Despite the increase in BrdU labeling, levels of FGF-2 within the hippocampus of FGF-2+/+ mice did not change significantly after TBI (Table (Table1).1). These results suggest that basal levels of endogenously generated FGF-2 are sufficient to facilitate proliferation of progenitor cells after TBI. On the other hand, increased numbers of dividing cells in FGF-2–deficient mice at day 9 indicates that FGF-2 is not the only stimulus for proliferation of progenitor cells in DG after TBI.
We also examined the number of BrdU-positive cells in the CA1 and the temporal cortex in the same specimens to examine for regional specificity. There was no significant increase in BrdU-positive cells before and at 9 days after TBI in both CA1 pyramidal layer and temporal cortex from bregma –1.3 mm to –3.1 mm (CA1 pyramidal layer; untreated: 8.2 ± 4.6, TBI, 10.2 ± 5.2, temporal cortex; untreated: 4.1 ± 4.4, TBI, 5.8 ± 6.3 cells/mm2). These results suggested that neurogenesis was specifically upregulated in the GCL in the CCI model used in this study.
We next examined the effect of overexpressed FGF-2 protein on proliferation of progenitor cells in the SGZ after TBI. Injection of an HSV-1 amplicon vector encoding GFP to the hippocampus of injured brain yielded robust gene expression at the injection site and within DG after 48 to 72 hours (data not shown), consistent with previous reports (15). Next, we injected the HSV-1/mFGF-2 vector encoding GFP and mouse FGF-2 into the injured hippocampus 1 hour after TBI and measured FGF-2 levels in the hippocampus at day 7. The levels of FGF-2 without vector injection did not differ from those in FGF-2+/+ mice at 7 days after TBI (Table (Table1).1). On the other hand, the levels of FGF-2 increased about 2.5-fold in ipsilateral hippocampus after HSV-1/mFGF-2 injection (P < 0.05; Table Table1).1). Thus, HSV-1/empty vector did not perturb endogenous FGF-2 levels, and the HSV-1/mFGF-2 vector significantly increased FGF-2 protein in the hippocampus.
To assess the effects of overexpressed FGF-2 on proliferation of progenitor cells in SGZ, the incorporation of BrdU was examined in C57BL/6 mice injected with HSV-1/empty or HSV-1/mFGF-2. First, the number of BrdU-positive cells in DG of the sham-operated or injured mice did not differ between those treated with and without HSV-1/empty vector (data not shown). Next, consistent with the findings in FGF-2+/+ mice (Figure (Figure1b),1b), TBI increased the number of BrdU-positive cells by 4.3-fold at 9 days after injury in C57BL/6 mice, compared with sham operated animals (P < 0.05; Figure Figure2,2, a–e). After injury and HSV-1/mFGF-2 injection, the number of BrdU-positive cells increased by 2.2-fold compared with HSV-1/empty injection and 10.3-fold compared with sham mice (P < 0.05; Figure Figure2,2, a–e). According to our previous report, gene transfer using HSV-1/mFGF-2 vector in intact FGF-2+/+ mice doubled BrdU incorporation into SGZ cells relative to HSV-1/empty vector (15). These results indicate that, after TBI, FGF-2 can strongly promote progenitor cell proliferation in the SGZ. The increased rate of cell division, however, was not sustained by day 16, matching the normal response to injury (Figure (Figure11b).
To assess the phenotype of newborn cells after TBI, and to determine the effect of FGF-2 expression on cell differentiation, we determined whether BrdU-positive cells expressed NeuN 35 days after TBI in FGF-2+/+ and FGF-2–/– mice. Baseline numbers of BrdU/NeuN-positive cells did not differ between FGF-2+/+ and FGF-2–/– sham-operated mice (Table (Table2).2). At 35 days after TBI, the number of BrdU/NeuN-positive cells increased by 2.8-fold in FGF-2+/+ (P < 0.01 vs. sham injured) and by 1.8-fold in FGF-2–/– mice (P < 0.05 vs. sham injured). In addition, the number of BrdU/NeuN-positive cells was significantly greater in FGF-2+/+ mice versus FGF-2–/– after TBI (P < 0.01, Table Table22).
Because BrdU was injected into mice at a time when TUNEL staining was not observed in the DG after injury (data not shown), it is unlikely that BrdU was incorporated into injured NeuN-positive neurons during repair of damaged DNA. In addition, there was complete absence of BrdU/NeuN-positive cells in the GCL of FGF-2+/+ and FGF-2–/– mice at 9 days after TBI (the day after the last BrdU injection), suggesting that BrdU-labeled NeuN-positive cells are granule neurons differentiated from newly generated progenitor cells in SGZ of DG at 5 weeks.
After FGF-2 gene transfer, the number of BrdU/NeuN-positive cells increased by 2.5-fold (Figure (Figure33 and Table Table2,2, P < 0.01 vs. HSV-1/empty), indicating that FGF-2 can increase the population of neurons in GCL after TBI.
Contusion volume (primary cortical tissue loss after CCI) at the level of impact (0.6 mm) was limited to cortex and did not include the hippocampus. Contusion volume did not differ between littermates at 9 days after TBI (2.09 ± 1.47 in FGF-2+/+ vs. 2.03 ± 1.23 mm3 in FGF-2–/– mice, P > 0.05), indicating that FGF-2 deficiency did not modify posttraumatic cortical tissue loss. There was also extensive cell death (secondary GCL cell loss) in the hippocampus, including the DG after TBI (32, 46), which leads to volume loss in GCL (32, 42). We therefore investigated the effect of FGF-2 on GCL volume loss at 9 and 35 days after TBI. There was no significant difference in the estimated volume of ipsilateral GCL between sham-operated FGF-2+/+ and FGF-2–/– mice (data not shown). There was also no significant difference in the volume of contralateral GCL between FGF-2+/+ and FGF-2–/– mice (Table (Table3).3). Morphologic changes in the ipsilateral GCL were observed as early as 9 days after TBI, and became marked 35 days later (Figure (Figure4a).4a). At 9 days, the total GCL volume was decreased by 16% in both FGF-2+/+ and FGF-2–/– mice (Figure (Figure4b).4b). At this time, the superomedial part of the upper blade was thinned and the total volume was reduced as reported previously (42). On day 35, the volume loss became more marked in FGF-2–/– mice (37% ± 3% reduction in mutant vs. 24% ± 4% in FGF-2+/+ mice, P < 0.05; Figure Figure4b).4b). These data indicate that lack of brain FGF-2 expression contributes to volume loss in GCL after TBI.
Next, granule cells within the GCL were counted in FGF-2+/+ and FGF-2–/– mice 35 days after TBI to determine whether the decrease in volume reflected cell loss. The density of cells in the ipsilateral and contralateral GCL did not differ significantly between the littermates (3.75 ± 0.22 cells per sample volume in FGF-2+/+ vs. 3.45 ± 0.27 in FGF-2–/–; Table Table3).3). However, the absolute numbers of granule cells in the ipsilateral GCL were significantly different between groups (Table (Table3),3), with percentage neuronal loss being more marked in FGF-2–/– mice at 35 days after injury (48% ± 3% in mutant vs. 33% ± 5% in WT mice, P < 0.05; Figure Figure4c).4c). Thus, in this TBI model, the changes in the GCL volume correlated with decreased granule cell numbers. These results suggest that endogenously generated FGF-2 protects GCL neurons against long-lasting degenerative changes after TBI.
We speculated that if a deficiency of FGF-2 promoted greater thinning and volume loss in GCL after injury, overexpression of FGF-2 by gene transfer technique might afford protection. There was no significant difference in neuronal density in the GCL between C57BL/6 mice and FGF-2+/+ mice before and after TBI in our preliminary experiments (data not shown). Then, GCL volume was measured in C57BL/6 mice with or without intraventriclar injection of HSV-1/mFGF-2 or HSV-1/empty vector after TBI. Consistent with the findings in Figure Figure4,4, b and c, in FGF-2+/+ mice, TBI decreased the GCL volume in C57BL/6 at 9 and 35 days after injury in injured animals with empty vector (Figure (Figure5).5). At 9 days after injury, there were no significant differences in the volume loss between groups injected with FGF-2 bearing (13% ± 2%) versus empty vector (16% ± 3%) (Figure (Figure5).5). However, by 35 days, GCL volume loss was almost 50% less in mice treated with HSV-1/mFGF-2 (15% ± 3% in HSV-1/mFGF-2- vs. 27% ± 6% in HSV-1/empty-treated mice, P < 0.05, Figure Figure5).5). Thus, overexpression of FGF-2 within hippocampus reduced the progressive GCL volume loss.
TBI causes loss of volume within the GCL of DG (29). In this study, the volume decreased in both FGF-2–/– and FGF-2+/+ mice, with FGF-2–/– mice suffering a greater decrease by 35 days posttrauma (Figure (Figure4,4, Table Table3).3). Furthermore, this volume loss corresponded to decreased numbers of granule cells, again with greater cell loss in FGF-2–/– mice (Table (Table3).3). We found that enhancing expression of FGF-2 preserved the integrity of GCL after TBI. There are at least two possible mechanisms: Production of new cells and reduction of cell loss over time (27–30). Both may be operative in these experiments. We counted the number of cells in the GCL in FGF-2–/– and WT mice (Table (Table2).2). Thirty thousand fewer cells were lost in FGF-2+/+ animals compared with FGF-2–/– mice. This would suggest that basal FGF-2 levels expressed in the WT can be neuroprotective. Interestingly, differences in TUNEL staining were not detected between groups 9 and 35 days after TBI, despite these group differences in cell loss. In addition, FGF-2 promoted neurogenesis in injured brain because 1100 more newly born neurons were found in FGF-2+/+ animals at 35 days after injury, whereas only 600 new neurons were detected in the KO. Thus, our data suggest that endogenously generated FGF-2 regulates cell populations through manipulating neurogenesis as well as attenuating neurodegeneration in the GCL after TBI.
The dual role of FGF-2 was also confirmed through gene transfer experiments. Increased levels of FGF-2 enhanced cell division in the SGZ by 2.2-fold compared with control vector (Figure (Figure2).2). At 5 weeks after TBI, FGF-2 vector yielded 2.5-fold more newborn granule neurons compared with the control vector (Table (Table2),2), indicating that newly generated precursor cells proceed on to neuronal differentiation after FGF-2 gene transfer. Thus, neuronal production can be enhanced through upregulation of progenitor cell proliferation in the GCL after TBI by vector-mediated FGF-2 gene delivery. Moreover, posttraumatic overexpression of FGF-2 reduced the GCL volume loss by 10% (day 35) compared with animals injected with control vector (Figure (Figure5).5). These results suggest that acute treatment with HSV-1 amplicon vectors expressing FGF-2 after the onset of TBI can protect against the chronic, progressive volume loss in ipsilateral DG that occurs over several weeks after CCI. Furthermore, FGF-2 contributes to DG integrity after TBI by upregulating neurogenesis, based on the distribution pattern of newborn neurons labeled with BrdU. The total number of BrdU-labeled cells increased by gene transfer of FGF-2, and these cells migrated into the granule layer of DG and accumulated around the thinned part of the DG at day 35 (Figure (Figure3),3), presumably contributing to attenuation of volume loss of GCL at 35 days after TBI.
Although SGZ cell division was promoted after TBI compared with sham-operated mice (Figure (Figure1b),1b), FGF-2 levels in the ipsilateral hippocampus did not change after TBI. Normally, FGF-2 does not have a signal sequence for cell secretion through the endoplasmic reticulum/Golgi apparatus (47, 48), and it is probably released extracellularly only after cell damage. According to this hypothesis, it is speculated that FGF-2 plays a negligible role in adult neurogenesis in the normal state, and factors other than FGF-2 must contribute to regulation of proliferation and differentiation of neural progenitor cells in the DG. In fact, under basal conditions, there was no difference in dividing progenitor populations between FGF-2+/+ and FGF-2–/– mice (Figure (Figure1b),1b), despite differences in FGF-2 levels in the hippocampus (15). With respect to FGF-2 release, plasminogen activator-mediated proteolysis provides a mechanism for dissociation of biologically active FGF-2-heparan sulfate complexes from the extracellular matrix, rendering FGF-2 more biologically active (47–49). Recently, TBI was shown to activate plasminogen activator (50, 51). We therefore speculate that TBI may promote FGF-2 dissociation from extracellular matrix and release from damaged cells. This phenomenon may account for the increase seen in SGZ cell division in FGF-2+/+ mice after TBI without measurable differences in FGF-2 levels from basal condition. Importantly, gene transfer of FGF-2 with an engineered secretion signal further enhanced the SGZ cell division in the injured DG with an increase in FGF-2 levels (Figure (Figure2e).2e). Thus, control of FGF-2 expression as well as its cellular release appears to be critically important in the regulation of progenitor cell proliferation after brain injury. In addition, injured tissue produces other factor(s) that convert latent FGF-2 to an active form (49, 52), consistent with a recent report suggesting that endogenous stimulatory signals are required for the action of growth factors potentiating ischemia-induced neurogenesis (31).
In conclusion, we have shown that overexpression of FGF-2 increased neurogenesis in the adult hippocampus after TBI, whereas neurogenesis was reduced in FGF-2–deficient mice. The results obtained suggest that FGF-2 is, at least in part, responsible for regulating neuronal replacement, as well as attenuating neuronal loss after TBI. FGF-2 supplementation may provide a rational strategy to treat brain injury by simultaneously enhancing neurogenesis and reducing neurodegeneration. Insights into the functions of FGF-2, together with further understanding about other factors regulating regeneration and protection, should provide a strategy for repair of CNS injury after trauma, and for other CNS injuries and disorders, such as cerebral ischemia and neurodegenerative diseases.
We thank S.P. Finklestein and H. Sugimori for their help with the breeding of KO mice; P. Bhide, T. Mitsuhashi, and Y. Wu for their technical advice; R. Russo and S. McDavitt for editorial assistance on this article. This work was supported by NIH Interdepartmental Stroke Program Project 5 P50 NS10828 (M.A. Moskowitz), NINDS grant NS24279 (X.O. Breakefield). S. Yoshimura and Y. Takagi were supported by the Japan Society for the Promotion of Science fellowships, and M.J. Whalen by NIH KO8 NS41969-02.
Shinichi Yoshimura and Tetsuyuki Teramoto contributed equally to this work.
Conflict of interest: The authors have declared that no conflict of interest exists.
Nonstandard abbreviations used: subgranular zone (SGZ); dentate gyrus (DG); traumatic brain injury (TBI); controlled cortical impact (CCI); granule cell layer (GCL); neuron-specific nuclear antigen (NeuN); herpes simplex virus–1 (HSV-1); enzyme immunoassay (EIA); mouse FGF-2 (mFGF-2); immediate early (IE); transducing units (TU).
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Matthew Woodson was born in the early 1980s. After his graduation at the School of The Art Institute of Chicago in 2006, he was hired by Margeotes, Fertitta & Partners New York to create a series of illustrations for the Perry Ellis Fall/Winter campaign in 2006. That was the initial start of his career as a professional illustrator.
Matthew Woodson still lives in Chicago where he works for a bunch of well-known clients such as American Express, Annabelle Magazine, Assics, Bon Appetit Magazine, Wired Magazine and many more. In addition to his work for all these clients, he still finds the time to create some personal artworks. If you want to see more stuff created by this outstanding freelance illustrator, then do not hesitate and visit Matthew Woodson's website.

subset: commoncrawl


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Under the patronage of his Excellency the Minister of culture, Mr. Raymond Arayji, Roads of Life presents at UNESCO Palace Abeer Nehme in "Afaq" Accompanied by Beirut Symphonic Orchestra led by Maestro Lubnan Baalbaki on Wednesday, November 16, 2016, at 8:00 PM
Who is Abeer Nehme?
Get to know her in here: http://bit.ly/2eSdw49
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Lounge 1 112,500 LBP Sold out
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Buy your tickets from any virgin branch or through OMT.
You can also buy your tickets through:
- Our website: http://www.ticketingboxoffice.com/roads-for-life-concert-abeer-nehme-tickets/event/9171
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My friend Sara and I spent Saturday afternoon shopping at the Scrapbook Expo in Pleasanton. To say I went a little overboard might be a little understatement. I bought tons of paper (that's a literal statement, according to my still-aching shoulder), and an assortment of new stamps, dies, and stencils [read more…]
My Peeps {A Layout with Jillibean Soup}
I've had these pictures for almost a year and finally got around to putting them into a layout. Just in time for Easter, right? The little one has slightly more hair these days, but otherwise not much has changed. She still gives me that look if I ask her to [read more…]


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Some things about living and working in India are ridiculously hard. But other things are ridiculously amazing.
I took the last week to write down all the 'luxuries' I experience – great things about living in India that I am very thankful for. My list could be a lot longer, but it would be great if you could add your own to this list!
- We had a friend stay with us for a few days and her mother sent her with a massive box of murukkus.
- We took a five-minute drive to the beach to have a picnic, and the kids had a blast playing near the waves.
- We rode in our small car with four adults and five children and no car seats.
- They sell Magnums right on the beach, as they will in heaven.
- I have six potential methods of transportation to get to my office that is 10 minutes away (walk, auto, taxi, self-drive, share auto, bus).
- While some rental and real estate prices are very high, we live in a fantastic place for much less that I would pay in the US.
- We have a great maid/cook who comes to sweep, mop, wash the dishes, and make food three times a week.
- Our maid's son needed to see a doctor and my wife sent out a message on a Whatsapp group to ask for help from others on the floor. Within ten minutes, one of our neighbors was there, explaining to her how to get to a good doctor she knows in her area.
- I went with my kids to a shop to get a present for a kid's birthday party. They gift-wrapped it at no extra charge while my kids played with their toys.
- At the birthday party, a Muslim friend asked, "Is Sarah a Christian name or a Jewish name?" We had a friendly discussion rooted in religion that was not awkward or had any tension.
- My wife called the grocery store while we were driving and arranged a home delivery of some items (at no extra charge). We left money with our trustworthy maid who paid for the items when they were delivered.
- The owner of the same local grocery store led my four-year-old son around his store as he read out his grocery list to the owner.
- Our flat arranged a dandiya dance one evening and we all had a really great time.
- I went for a long run with friends from our flat followed by some fresh tender coconut water (see photo above).
- Every Saturday, my family goes to Sangeetha, a nice south Indian restaurant where the sambar and chutney taste different every time. We order three to four rounds of food and it is delivered hot to our table within 10 minutes.
- I can put all of my shirts in a bag, give it to a lady as I drive out of my apartment, and she will return it with all the shirts nicely ironed and folded. All for about US$0.06 a shirt.
What's on your list?
Image credit: mynameisharsha on Flickr


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Last weekend was the ARRL's annual "Field Day", we took our radios, antennas, camping gear and antenna launchers to the hills and enjoyed the weather and fellowship of old and new friends.
The band conditions weren't great, but our 40 meter station, Quad Zepp antenna and operator racked up an impressive score nonetheless. 20 meters with a tribander was also busy, but the contacts came harder.
Hope you also had a great Field Day!
— Alan, W6AKB


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Riverside County Offers Pot ID Cards
December 01, 2005
Susannah Rosenblatt, Los Angeles Times
Riverside County will begin issuing photo identification cards to local medical marijuana users today, the first Southern California county to comply with a state law intended to shield medical patients from arrest.
"The county is trying to comply with the law approved by the voters and develop a procedure that'll do that," said Marion Ashley, Riverside County Board of Supervisors chairman. "This will probably remove the anxieties … legitimate, card-carrying users of medical marijuana may have."
Still, the cards will be issued at a time when state and federal laws conflict over the use of medical marijuana, leaving users and their suppliers in danger of facing federal charges.
California's Proposition 215 legalized the drug for therapeutic purposes in 1996, and 2003 state legislation provided for ID cards. However, the U.S. Supreme Court ruled in June that federal authorities could still seize and destroy medical marijuana plants and arrest their growers and consumers — even in the 10 states that allow medical marijuana use.
While federal authorities primarily target "large-scale drug trafficking organizations," individual medical marijuana users remain vulnerable, regardless of whether they have a state-issued ID card, said Sarah Beers, spokeswoman for the Drug Enforcement Agency in Los Angeles.
"In the eyes of the federal government, [a card] means absolutely nothing," said Thom Mrozek, spokesman for the U.S. attorney's office in Los Angeles. "Under federal law it is illegal to possess, to sell or to cultivate marijuana."
However, the cards could help protect medicinal users of the illegal drug from prosecution by local law enforcement, county health officials said.
The Riverside County district attorney's office "recognizes that we have to follow the law, and there is a legitimate need," spokeswoman Ingrid Wyatt said.
"Those people that have [the card] will now be properly identified," Wyatt said, while "we'll be able to prosecute those who try to abuse the system."
Wyatt said the county district attorney's office reviews each medical marijuana case individually, and has prosecuted only "a handful."
The optional cards will feature a medical marijuana user's photo and a computer-generated identification number, but no name, address or medical information, said Victoria Jauregui Burns, county public health department program chief.
State estimates indicate 3,000 to 4,000 potential cardholders in Riverside County each year.
The county is the seventh in the state to begin the program; the others, including Marin and Mendocino, are in Northern California, said Patti Roberts, state health department spokeswoman.
Los Angeles County officials anticipate having such a program in place early next year, said John Schunhoff, chief of operations for public health with the Los Angeles County Department of Health Services.
The Riverside County health department has set aside office space and assembled a staff of three to handle card applications starting today, Jauregui Burns said. Staffers also are working to draft an ordinance regulating medical marijuana dispensaries, which should come before the Planning Commission in the spring, county spokesman Ray Smith said.
Local medical marijuana advocates have been working closely with county officials for more than a year to get the ID card program running, Jauregui Burns said.
"They've been very vocal about wanting to have access to something that the law says they can," Jauregui Burns said. "We might as well just do it; dragging our feet doesn't help anybody."
Under the initiative, applicants must complete a state form and provide government-issued identification, proof of county residency, and a recommendation from a California-licensed physician, Jauregui Burns said.
Patient information will be accessible to law enforcement in a centralized database. After county health departments gather patient data, the state will issue the cards and county offices will distribute them within 30 days, Jauregui Burns said.
Like drivers' licenses, the cards will include embedded holographic patterns to protect against counterfeiting. The annual cost of obtaining and renewing the card is $100.
The new program will help ease the minds of people who fear arrest for cultivating or using marijuana on doctors' orders, said Lanny Swerdlow, director of the Marijuana Anti-Prohibition Project, a local patients' rights advocacy group.
"It's a wonderful thing," said Venia La Beaux of Lake Elsinore, who grows marijuana to control the nausea and pain of her HIV. "It'll help as far as the law enforcement." Four years ago, sheriff's deputies confiscated seven marijuana plants from La Beaux's backyard. After failing a background check for a part-time job, she learned there was a warrant for her arrest. All charges against her were eventually dismissed.
"I definitely will be getting my card," La Beaux said.


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Jury Awards Widow Of Smoker $350,000 In Engle Progeny Suit
Bernice McCall filed suit against Philip Morris USA Inc. in the 17th Judicial Circuit of Florida for Broward County, initially seeking $11.5 million from the tobacco company. She claims that Philip Morris concealed...
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Prices, promotions, styles, and availability may vary. Our local stores do not honor online pricing. Prices and availability of products and services are subject to change without notice. Errors will be corrected where discovered, and Lowe's reserves the right to revoke any stated offer and to correct any errors, inaccuracies or omissions including after an order has been submitted.
Marshalltown Stainless Steel 4-in x 6-in Concrete Edger
Item # 787697 Model # CE509SD-L
Product Information
Produce a radius at the edge of your concrete to help prevent the end from chipping and gives a finished look to the slab with a QLT by Marshalltown stainless steel hand edger.
- Heavy gauge premium stainless steel blade
- Sturdy steel mounting welded to the blade
- Resilient DuraSoft® handle provides a soft feel, reduces fatigue, and offers excellent durability
- Used to produce a radius at the edge of a concrete slab to prevent the edge from chipping
|Series Name
|Blade Length (Inches)
|Blade Width (Inches)
|Lip Radius (Inches)
|Weight (lbs.)
|Color/Finish Family
|Stainless steel
|Limited lifetime
|Blade Material
|Stainless steel


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Here are the Oscar nominees 2016 list for the 88th Academy Awards Ceremony: (Here is just a list, not a normal post, so it has only an archived information value) Oscar Nominees - Main Interests Best Picture The Big Short [source] Producers: Brad Pitt, Dede Gardner and Jeremy Kleiner Bridge of Spies [source] Producers: Steven Spielberg, Marc Platt and Kristie Macosko Krieger Brooklyn [source] Producers: Finola Dwyer and Amanda Posey Mad Max: Fury … [Read more...]
My Best Comedies – Updated
This is an updated list with my favorite comedies at the moment. I have thought a long on it, I have pondered a lot of factors, but generally it shows my taste, based on a great admiration for certain comedians and comedy creators. I used to dislike some actors, but those times have past. I judge a movie on how I feel watching it and what lingers after that. I am a declared fan of Will Ferrell, Mel Brooks, Woody Allen, Trey Parker & Matt Stone, Sacha Baron Cohen, John C. Reilly, Kristen Wiig, … [Read more...]
Oscars Nominations 2015
I'm not doing like last year, when I published innumerable posts on nominees and awards, Golden Globe, SAG, Independent Films, etc. Just the Golden Globes and the Oscars, just to be more practical, especially that I don't want to comment too much, since I haven't watched yet all the movies. Anyway, among the actors, I have to salute a few new names nominated this year for the Oscars. Unfortunately, no Leo this year. I have a feeling that next year he will won the Best Actor for sure, with one … [Read more...]
Top 100 StarMeter 2014
Here are the 100 stars who consistently ranked the highest on the IMDb weekly STARmeter chart throughout 2014. IMDb STARmeter rankings are based on the actual page views of IMDb's more than 200 million unique monthly visitors. I want to publish this because I did it every year, and I think last year I put a wrong list, just because I haven't waited the official Top 100 to be published. My last year Top was the imdb STARmeter on January 3'rd. The surprise this year is that Top 10 is exclusively … [Read more...]
BAFTA 2014 Awards – The Winners
Very predictable winners, at least at the major categories, and the British ones, of course. As the original Academy of whom BAFTA is just a copycat, the winners in each category is voted by their fellow peers, actors by actors, writers by writers and directors by directors, you understand very well, I hope, what I mean. I'm really sorry for not expressing my predictions a little bit earlier, but major work has intervened and I'm really happy to even be in time with this post. The whole list of … [Read more...]
Oscars: Nominations 2014
I have waited with publishing the 86'th Academy Awards Nominations a week after the official announcement, because other movie or movie related ceremonies already happened, so they have their place on this blog, some of them in premiere. Actually, I wanted to wait one other week, because it's no hurry. The ceremony will take place Sunday, March 2'nd, just one day after Film Independent Spirit Awards and Golden Rapsberry Awards, known better as "Razzies". Best picture "12 Years a … [Read more...]


text: Windows Archive 24 Jun 2017 How to Check Laptop Battery Report In Windows 10 By Tanmoy Das How To, Windows 10 0 Comment I have seen many of friends whose Laptop becomes a TV, yes TV. I am not kidding they have said this to me. Mean like a TV, if you switch on the AC power source then it will be on and if you switch off AC power source Laptop will switch off. Thank God that my Read More 27 May 2017 How I Upgraded My Windows 10 Home to Pro at ₹220 Rupees By Tanmoy Das How To, Windows 10 8 Comments If you ask me which computer or PC I am using then I will say that I have a SONY VAIO laptop which I have been using since late 2010. Out of the box, it comes with Windows 7 Home Premium which later I upgraded to Windows 7 Ultimate with the free anytime upgrade key Read More 25 May 2017 How to Reset Forgotten Password for Windows 10 By Tanmoy Das How To, Windows 10 0 Comment When you forgot Windows 10 password, you might realize that you've not created a password reset disk in advance. Without a password reset disk, you have to use third-party software to reset your forgotten Windows 10 account password. Today we are going to talk about new updated software from top-password.com, which is PCUnlocker. PCUnlocker is Read More 11 May 2017 How to Reset Lost Password for Windows 10 By Tanmoy Das How To, Windows 10 0 Comment Forgetting your own Windows 10 login password is not a big news anymore these days. Once in a while everyone forgets their Windows 10 login password and there is nothing to be embarrassed about. But if you have to use your computer urgently then this situation can be really exasperating and despondent. Fortunately, there are Read More 20 Nov 2016 Download Windows 10 build 14971 ISO By Tanmoy Das Download, Windows 10 0 Comment Microsoft has released the latest build of Windows 10, its Windows 10 build 14971 and its released for the first ring inside channel only. Mean there is no official ISO for this Windows 10 build 14971. Microsoft has added lots of new features and upgradations with this build. One of the big features is EPUB support. EPUB is Read More 06 Nov 2016 6 Cortana Commands that you must know By Tanmoy Das Tips N Trick, Windows 10 2 Comments If You are a Windows 10 lover then you must love the Cortana that helps us a lot and saves our time. Its like having Siri on iPhone and Google Now or the new Google assistant on Android. Apart from the voice commands, you can use text command to operate Cortana and do some tweaks Read More 04 Aug 2016 Official Direct Download Windows 10 Anniversary Update By Tanmoy Das Download, Windows 10 0 Comment Microsoft has launched the Windows 10 Anniversary Update and it is the second major update since the launch of Windows. This update will make your Windows 10 Build 1607 from its last build 10586. So you can imagine in between there is an enormous change. Microsoft has launched this Windows 10 Anniversary Update Windows 10 Read More 31 Jul 2016 Upgrade to Windows 10 for Free Even After 29th July By Tanmoy Das News, Windows 10 0 Comment The free upgrade offer from Windows 7/8/8.1 to Windows 10 has ended on 29th July. Microsoft has tried their best to know you about this free upgrade offer and this makes also some people annoying. But there are some people who wasted time whether they should upgrade or not and being confused they ended up Read More 26 Jun 2016 How to Link Windows 10 License to Microsoft Account By Tanmoy Das Windows 10 0 Comment Finally, Microsoft comes with a nice solution by linking up Windows 10 License to Microsoft Account. The problem started from the free upgrade to Windows 10 offer which is valid till 29th July 2016. Hope you have know that Microsoft from last year offering free upgrade to Windows 10 from your Windows 7/8/8.1 PC. The Read More 23 Jun 2016 Start Menu not working in Windows 10? Try Start Menu Fix Tool by Microsoft By Tanmoy Das Software, Windows 10 0 Comment Start Menu not working or Cortana not responding is the very common and major problem in Windows 10. Its a very pathetic that how Microsoft optimise their OS. If you search on the internet about this problem then there are some solution from Microsoft forum side as well as blog. I have faced this start menu Read More 123456789


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Nice To Meet You: Capital Cities
Capital Cities (Ryan Merchant and Sebu Simonian) have already garnered some success with their remix for Nu Thang, and recently released their self-titled debut EP featuring the infectious jam "Safe and Sound." Infectious should be in Merchant's and Simonian's blood, though. The duo actually met through Craigslist in 2008, and started writing jingles for numerous high profile ad campaigns. Eventually the two realized they had enough musical chemistry to create something better than a new song for "Meow Mix" (I made that part up. I highly doubt they'd make a new "Meow Mix" song. That song is like the "Let It Be" of jingles.)
Capital Cities have some pretty electro pop-tastic music. They've got that "California cool" vibe going on, but let a vintage Juno-106 punch through their harmonized vocals, creating an MGMT esque sound that, actually, is probably a little more fun. So much fun that Chelsea Handler added Capital Cities to her "comedy tour" mix. But that doesn't really tell you anything because Chelsea Handler blows. Have a listen to "Safe and Sound" below.


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< Back To All Games
< Episode 5 | Episode 7 >
Stuck? Need help? Click here for the walkthrough.
Mr. Toko has turned back into a human and explores a dark world that doesn't seem familiar to him. But perhaps this is a key to finding out more about this past before he met Xolga.


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This is simply to let you all know that I have a new blog starting up directed towards chaga. I hunt chaga here in north Vermont and the wonderful tea artisans company called Wild Tea Qi sells it.
It is on the Wild Tea Qi website that the new blog has launched as of today. Feel free to check it out if you would like:
Feel free to leave comments on the articles that will be placed in that blog 🙂
As always ~ Thank you for your kind support!


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"How high functioning is she?"
"How severe is her autism?"
"Wow, she can't be that autistic!"
Oh my god. ENOUGH already!
I have lost count the amount of times I hear people (who obviously know nothing about the autistic spectrum) try and categorise my autistic daughters, attempting to shove them into boxes to better their understanding. I am all for labels, in fact – I encourage the diagnostic process for autism, because I stand by the benefits of support that the diagnosis can bring.
But one thing I cannot get behind is the whole high/low functioning divide. I just can't do it, and I won't.
Why not?
Because this type of label doesn't help, it hinders. It minimises the struggles an autistic individual can have, and it silences and invalidates them.
Just because someone who is autistic can talk and interact with others, doesn't mean they don't have other challenges and doesn't mean the challenges they do have make less impact on their lives. You just can't see it, and just because you can't see it doesn't mean it isn't there. This is the same with a non-verbal autistic individual; just because they can't talk doesn't mean they aren't incredibly intelligent, perceptive and intuitive.
The thing is though, if you box individuals on the spectrum into these high/low categories – you're the one missing out. You're missing out on being able to support them through their silent struggles, and you're also missing out on being able to notice how they can enrich your lives.
Does the fact that someone can talk make them more important or worthy than others? No. Does the fact that someone cannot talk or shuts down socially around others mean they don't have valuable things to contribute to society? No.
Autistic people are not puzzles that need to be solved. They are not a problem that needs to be fixed. They are not an irregularity that needs to be corrected. They are individuals, unique in themselves just like every other person on the planet.
So this whole high/low functioning categorisation really doesn't come into it.
At the end of the day: it is all autism. And the best thing we can do as a society for our neurodiverse community is embrace them for who they are; as amazing individuals.


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Question about Zanussi Refrigerators
Jusy moved home now fridge freezer won't work.lights up and makes 'freezer' sounds but is not freezing.we bought it secondhand and it was working fine before move. we have no instructions with it and cannot find what looks like a model num. we do have these however; 222010302 GL80AA9920 ZEM R134a 0903212 cod.2237432-22 it has 3 shelves in fridge part and salad drawers, and 3 metal shelves in freezer,no drawers. on door has Zanussi Freezone. can anyone out there help please?????? much appreciated,tony
Posted by marthazammit on
SOURCE: I have freestanding Series 8 dishwasher. Lately during the filling cycle water hammer is occurring. How can this be resolved
a 6ya Repairman can help you resolve that issue over the phone in a minute or two.
Best thing about this new service is that you are never placed on hold and get to talk to real repair professionals here in the US.
click here to Talk to a Repairman (only for users in the US for now) and get all the help you need.
Posted on Jan 02, 2017
SOURCE: How do I change the
first you have to see if you have all the same fitting on the other side,top and front,let me know and we can go from ther,mike
Posted on Sep 12, 2008
SOURCE: air conditioner
you are leaking refrigerant and need to have it leak checked by a professional
Posted on Feb 04, 2009
SOURCE: item is secondhand and i was not given the book
You can download the manual from this link, the manual is of a similar model---
Zanussi User manual
Please click on the above link and click on the link that says zanussi manual(150k)
Please ask for further clarifications.
Please rate this solution as fixya if found useful.
Posted on Mar 03, 2009
SOURCE: zanussi freezone fridge freezer
well asuming you already thought to turn the thermostat down, i would check to see if you have a freon leak. with the fridge running, paint the coils with soapy water untill you see bubbles. mark that spot and dry off the area around it. generously apply electronics grade solder to the area where the leak is. (be sure you don't melt the copper and unplug the fridge first) then continue untill you have checked the entire length of coil. when all ieaks have been stoped recharge with recomended freon.
Posted on Aug 17, 2009
SOURCE: why does the fridge part of my zanussi freezone
Hi,the problem you are encountering is as a result of the fact that the thermostat which regulates the cooling temperature in the fridge/freezer is bad hence there is no regulation of the cooling temperature in the fridge/freezer section, hence the food in the fridge freezes up.
The solution is to replace the thermostat of the unit,here is how you go about it;
1.You have to disconnect the fridge from the power source.
2.Locate the thermostat at the bottom of the unit,at the top left corner above the condenser.
3.Now you need to locate the wire ends or wire harness and unplug them.
4.Replace the thermostat,reconnect it back,put the back cover back and you have completed the job.
Take care of yourself
Posted on Jun 24, 2010
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All Design Websites In One Place.
Here you can follow 157 design websites just by visiting us. Check the design categories you like by clicking "popular" link at the top menu bar or our other editions such as FoodiePLX, FashionPLX at the bottom menu bar. Once you sign up, you can add more websites, categories you like and remove the ones you don't.
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Paintings by Gregory Thielker Title: Keats Folkert
Photographic prints by Matt Waples Title: David Zindell Atley
Photographs by Frédéric Fontenoy Title: from the Manifesto of Futurism, F. T. Marinetti Folkert
Images taken by the unmanned spacecraft Cassini Title: Lord Byron Atley
Poured resin artworks by Bruce Riley Title: Olaf Stapledon, Star Maker (1937) Fullscreen See also: Jonathan McCabe Folkert
Photographs by Francesca Woodman In 1981, at age 22, Francesca Woodman killed herself. Her photographs have influenced a generation of artists.
Photographs by DeShaun A. Craddock Title: Shakespeare, Sonnet 43 More: Blurred humans Folkert
"Feelers" — typographic experiments by Ari Weinkle Title: Jeff VanderMeer, Annihilation Folkert
Generative artworks produced by Fleen / John Greene Title: Janna Levin (via) Fullscreen Via @mrprudence Folkert
Photographs of the surface of Mars, courtesy of HiRISE Title: Olaf Stapledon, Star Maker Folkert
Paintings and prints by Bettina von Arnim Title: Donna Haraway .shrink11 img { width: 726px; height: auto; } Will 50 Watts
Drawings by Lee Bontecou Title: Alejandra Pizarnik Previous on Lee Bontecou. Will 50 Watts
Prints by Alexander Aksinin Title: Paul Eluard .shrink11 img { width: 750px; height: auto; } via Robert Beatty Will 50 Watts
Photographs by Adam Moskowitz Title: Leonard Shelby in Memento, written by Jonathan Nolan Atley
Photography by Andrew B. Myers Title: Frank Zappa Thanks, Keith. Atley
Photography by Charles Grogg Title: Louis Pasteur Atley
Drawings of letterforms by Cyrus Highsmith Title: Samuel Beckett .shrink113 img { width: 500px; height: auto; } More Typography on BDiF Folkert
Photography, various artists .shrink112 img { width: 740px; height: auto; } Tamsin Swait Juno Chen Unknown Tamsin Swait Klara Sucre For Parfums de Lisbonne (photographer unknown) Franz Gruenewald Sanghyeok Bang Brett Walker Nassia Kapa Folkert
Photographs of saguaros by Kozo Miyoshi .shrink11 img { width: 822px; height: auto; } Title: wikipedia entry on saguaros Will 50 Watts
Photographs by Stephen Shore .shrink111 img { width: 520px; height: auto; } Thanks aqqindex Folkert


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Why Hire a Doula
Birth is by its nature a life-changing event. Whether you are giving birth in a hospital, birth center, or at home, you will have skilled medical professionals such as nurses, midwives, and doctors who are focused on making sure you have a safe birth. But many parents in labor find that no matter how much they have prepared or how many medical practitioners are present, it is reassuring to have a knowledgeable person at the birth who is accountable only to them.
Doulas are professionals trained in providing emotional, physical, and informational support during labor. They are not responsible for the medical outcomes, but rather for supporting the laboring mother and her partner. For moms birthing naturally, doulas work with the husband or partner to provide massage, heat/cold, aromatherapy, and positions that can help ease the pain of contractions and facilitate the progression of labor. When the parents want to use medical interventions or when things don't go exactly as planned (which they usually don't!), doulas are there to help the couple understand and consider their choices in real time.
Having a doula has been shown in numerous studies to improve medical outcomes in birth, including:
- 50% reduction in need for Cesarean delivery
- 25% shorter labor
- 60% fewer requests for epidural anesthesia
- Nearly double the rate of successful breastfeeding
Why People Choose Ohana Doulas
We help you make the choices in birth that are right for you. Every couple has different hopes for their birth. Some want to experience a natural birth. Others hire us because they plan to get an epidural or other medication and want a knowledgeable support person with them at all times during the labor. For us, a successful birth is one in which the baby is healthy and the parents feel that they were supported and empowered to make the choices that were right for them throughout the process.
We partner with partners. We see our role as supporting both the mother and her husband, partner, or other support people. In our prenatal sessions, we explore the extent and ways in which the husband or partner wishes to be involved in the labor process. In the birth room, we work side-by-side with partners to support the laboring mother together. Dads and new grandparents give us reviews that are as glowing as the ones from their partners and daughters.
We are experienced. We have been to a lot of births and seen many, many babies delivered. We know from both training and experience what techniques tend to work to ease a particular kind of pain or to ease a particular anxiety. Jocelyn and Autumn are experienced in working with: first-time parents, parents who already have other children, women who have conceived through in vitro fertilization, Vaginal Birth After Cesarean (VBAC) clients, and many others. We welcome families of all types, including gay and lesbian parents.
Doula Package
Our doula package is coupled with concierge service before and after birth and includes:
- Complimentary initial conversation via email, phone, or in person to discuss our services and determine whether we are the right fit for you
- 1-2 comprehensive prenatal meeting(s) to discuss in depth your pregnancy history, birth preferences, and other information that will help prepare you for the birth and help us to provide the best support to you
- Unlimited 24/7 phone and email consultation during your pregnancy from the time you hire us
- Attendance at your labor and delivery, including emotional, physical, and informational support and attendance in your home if desired
- Postpartum visit to help with breastfeeding, birth recovery, sleep issues, feeding, other questions
- Breastfeeding counseling session conducted by Autumn, a Certified Lactation Counselor, for those who need added breastfeeding support
- Unlimited 24/7 phone and email consultation after birth until your baby is 3 months old
Cost: The cost for our package is $1600.
Many Health Savings Accounts (HSAs) and Flexible Spending Accounts (FSAs) will cover all or part of Ohana doula services. We can provide you with an itemized receipt you can submit directly to your insurance carrier for reimbursement. In addition, we offer a sliding scale payment system based on income, so please contact us if you are interested in services and would like to discuss discounted pricing.
Service Area
We serve clients delivering at hospitals and birth centers in Seattle and on the Eastside including:
Swedish Medical Center – First Hill
747 Broadway, Seattle, WA 98122
(206) 386-6000
Swedish Medical Center – Ballard
5300 Tallman Ave NW, Seattle, WA 98107
(206) 782-2700
Swedish Medical Center – Issaquah
751 NE Blakely Dr, Issaquah, WA 98029
(425) 313-4000
UW Medical Center
1959 NE Pacific St, Seattle, WA 98195
(206) 598-3300
Overlake Hospital
1035 116th Ave NE, Bellevue, WA 98004
(425) 688-5000
Evergreen Medical Center
12040 NE 128th St, Kirkland, WA 98034
(425) 899-1000
Valley Medical Center
400 S 43rd St, Renton, WA 98055
(425) 228-3450
Birth Centers
Center for Birth
1500 Eastlake Ave E, Seattle, WA 98102
(206) 407-3397
Puget Sound Birth Center – Kirkland
13128 Totem Lake Blvd NE Ste 101, Kirkland, WA 98034
(425) 823-1919
Puget Sound Birth Center – Renton
4300 Talbot Rd S Ste 402, Renton, WA 98055
(425) 823-1919
Home Births
We serve clients delivering at home in Seattle or on the Eastside with a Licensed Midwife or Certified Nurse Midwife.


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The maritime delimitation talks between Bangladesh and India starts on Tuesday in New Delhi after a pause of six months.
Additional foreign secretary MAK Mahmood heads a six-member Bangladesh delegation that left for the Indian capital yesterday to attend the two-day technical committee level talks.
Bangladesh has long-standing dispute over the sea boundary with both of its neighbors India and Myanmar and all the three countries are yet to explore oil-gas options in the Bay. India claims ownership of nine while Myanmar claims that of 11 out of Bangladesh's 28 exploration blocks in the Bay.
Now two neighboring countries are claiming the sea boundary in such a way that entry of vessels to Bangladesh's seaports will be virtually blocked due to its geographical position.


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Wow! 2012 was a great year with a lot of fun memories. We've gone through the top 6 of 2012 so far and this, my friends, is my top moment of 2012…
I created my own board game!
It is amazing what a little inspiration, a big gulp of Code Red Mountain Dew from a movie theater, and the following 7 hours will do for you. For me, that was the moment my board game was created. While I had the idea for a game for a few months, it took that combination for me to actually get the ball rolling.
While many of you have played my game, so many more have not and I would LOVE for all of you to play this game at some point.
I'm still not uber comfortable with divulging all of the details of my game, let's just say that it involves building towers on a game board and making sure that you own a sizable chunk of that real estate.


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1995 Maria Miller and her husband — a solicitor based in the City of London — buy Wimbledon house for £234,000. Her parents and brothers move in.
May 2005 Mrs Miller becomes MP for Basingstoke and designates the Wimbledon home as her second home. She begins claiming expenses on the five-bedroom house in Wimbledon. She rents a three-bedroom house in Basingstoke and states that this is the main home of her family of seven.
8 May 2009 MPs' expenses crisis erupts. Members estimate committee decides MPs will have to provide new evidence of their spending — and sign a form saying they will claim that their main home is their primary residence for capital gains tax purposes.
1 July 2009 House of Commons authorities write to MPs asking them to sign a form stating that they will pay capital gains tax on their second home — the property on which they are claiming expenses.
9 July 2009 Second letter sent out from House of Commons clarifying the documentation required from MPs who claimed mortgage interest.
25 Aug 2009 House of Commons writes to MPs who have not signed the form, telling them that if they do not sign it, they will be barred from claiming expenses from the end of August.
27 Aug 2009 Mrs Miller contacts the Fees Office. A note of the telephone conversation states: "Maria Miller does not intend to claim against PAAE again this year."
26 April 2011 After not claiming for the whole of the 2010-11 financial year, Mrs Miller begins claiming again — now on the rented Basingstoke property. Over the next year, she claims £13,951.28.
Sept 2012 Mrs Miller becomes Culture Secretary with responsibility for overseeing press regulation.
December 2012 Telegraph publishes results of investigation into Mrs Miller; Standards Commissioner begins inquiry.
14 Feb 2014 Mr and Mrs Miller sell Wimbledon home for £1.47 million.
3 April 2014 Standards committee publishes report. Mrs Miller ordered to repay £5,800. She makes a 32-second apology to the Commons.
4 April 2014 David Cameron defends Mrs Miller over her brief apology. The Daily Telegraph releases an audio tape of Mrs Miller's aide Jo Hindley warning off a reporter by "flagging up" the Culture Secretary's involvement with the Leveson report into press standards. Details of letters sent by Mrs Miller to the parliamentary commissioner emerge, leading to allegations that the MP may have bullied the watchdog during the lengthy inquiry.
5 April 2014 Conservative chairman Grant Shapps says it is time to "draw a line" under the controversy but Labour calls on Mr Cameron to show "leadership" over the affair.
6 April 2014 A Sunday newspaper poll finds that 78 per cent of voters believe Mrs Miller should forfeit her Cabinet post and 75 per cent feel David Cameron was wrong to offer her his support.
7 April 2014 The Prime Minister again defends Mrs Miller, insisting she is doing a "good job" but paves the way for reform of the way the expenses system is policed, saying he is "very open" to suggestions.
8 April 2014 A petition calling for Mrs Miller to repay £45,000 or quit reaches 145,000 signatures within hours. Tory backbencher Zac Goldsmith declares he is "surprised" she is still in her job. London mayor Boris Johnson sidesteps questions over whether Mrs Miller should remain in her post. Her parliamentary aide Mary MacLeod claims Mrs Miller is being subjected to a "media witch hunt due to Leveson". Mrs Miller, in the Basingstoke Gazette, admits she "let people down".
9 April 2014 Mrs Miller resigns as Culture Secretary, telling the Prime Minister in a letter that the controversy over her expenses "has become a distraction from the vital work this Government is doing".


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The Southwestern Historical Quarterly, Volume 43, July 1939 - April, 1940 Page: 131
This periodical is part of the collection entitled: Southwestern Historical Quarterly and was provided to The Portal to Texas History by the Texas State Historical Association.
Boole Reviews
fallen under the Napoleonic influence. Further, he builds up a
convincing case for the Romany descent of the Santa Anna family
and thus accounts for his restlessness, cunning, and impatience. It
was something of an achievement in 1835 to organize in Mexico
a large army and march it two thousand kilometers to the field of
action, conceive and execute a plan of campaign which scorned
military science, and attain virtual success. Yet, over-confidence
resulted in the loss of all that had been gained. The surprise attack
and eighteen minutes of fighting at San Jacinto assured independ-
ence for Texas.
Valad6s gives many interesting sidelights on both the Mexicans
and Texans of the war period. His skilful use of documents
and his constructive criticism of earlier works such as Filisola's
Memoria para la historia de la guerra de Tejas place him in the
front rank of Mexico's historical writers. His book definitely
belongs in the private library of every student of Texas or Mex-
ican history.
The University of Texas.
The Administration of Pat M. Neff, Governor of Texas, 1991-1925.
(Waco: Baylor University Press, 1938. Pp. xiii, 124.)
The Baylor University Press is to be commended for the publi-
cation of this master's thesis on the administration of one of the
greatest governors of Texas. It would be a valuable addition to the
political and historical literature of Texas if we had in published
form a careful study of the administration of each of the Texas
governors from Henderson to Allred. The present study begins
with a biographical sketch, emphasizing the strong influences of
home and religion upon Pat M. Neff, tracing his education through
the attainment, unusual for Texas governors, of the B. A., LL. B.,
and M. A. degrees, recalling that he was the youngest Speaker of
the House of Representatives to preside over that body, and con-
cluding with a summary of his public services since leaving the
governor's office. A chapter each is given to his first campaign
for governor, his first administration, his second campaign for
governor, his second term as governor, and his service as governor.
So tireless that he traveled into more than half the counties of
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War of the Worlds will not beat ROTS, let alone Titanic. Just look at all the anti-Tom Cruise sentiment around right now (most of it being justified). It does look good though.Originally Posted by Buzzz
Titanic was the last of the colossal blockbusters. It was the type of movie that appealed to people of all demographics, and it came around at the right time. People don't go to the movies like they did before, choosing instead to stay home and watch DVD's, etc.


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This lovely two bedroom apartment for sale in Ovacik is set on a wonderful complex with two spacious swimming pools, a bar and well maintained gardens. It is just 50 meters stroll to the main Ovacik strip with a great array of bars, supermarkets, delicious restaurants and the all important bus route to Oludeniz beach (taking less than 10 minutes) and Fethiye Town (15 minutes). ANOTHER OCEANWIDE EXCLUSIVE!
LOCATION: The hillside resort of Ovacik straddles the mountain road leading from Fethiye to Oludeniz. Lying in the foothills of the majestic Babadag Mountain, it has been a firm favorite with holiday makers and property investors owing to the close proximity to one of Turkey's finest beaches and the wide choice of recreational activities, restaurants, private villas and apartments on offer. Ten years ago Ovacik was a fraction of the size it is now. It was a sleepy village where you were more likely to run into goats rather than tourists. The area grew quickly as the demand for accommodation near Oludeniz rose. Family-run and budget hotels started appearing, followed by boutique hotels and larger all-inclusive resorts. From 2004 to 2012 there was a surge in residential and commercial property development. A lovely range of apartments, villas and complexes were built in styles suiting most tastes and budgets. Thankfully the protected pine forests that
surround Hisaronu and Ovacik have helped limit development meaning there are now relatively few building plots left in either location, the few that are tend to be owned by the large developers or more prominent local families. This apartment comlplex was built by a prolific developer around 10 years ago. It is in a prime location and within easy access to the beach, town and resort. It's the ideal choice for an affordable, furnished and key-ready holiday home or would attract in the region of £375 – £475 per week in rental returns.
Property in brief; this ground floor apartment features two large double bedrooms, two shower rooms (one an en-suite) an open plan kitchen and living room, There is also a large terrace facing the pool. The property is being sold furnished and is fully air-conditioned.
Apartment in full:
The apartment is conveniently set just a short walk from the main road to Ovacik, where the local transport comes past on a regular basis and can take you into Hisaronu, Oludeniz and Fethiye, making this apartment the perfect base from which to explore this stunning region.
The complex is a good size and features manicured gardens, two large swimming pools and plenty of sunbathing space, there is also an on-site bar which is open in the summer months. The complex has a lovely mix of British and Turkish owners and a few residents year round.
The apartment for sale in Ovacik is located on the ground floor and is accessed via short flight of steps and into a private entrance with secure front door leading into a bright hallway.
From the hallway the first door to the right is the first of the two shower rooms, this room is fully tiled in a modern style with a shower, toilet and pedestal sink.
Through a decorative archway we find the open plan kitchen/ living room.
This room is a very good size with double windows and a patio door that leads out to the large double terrace with a few steps leading to the pool and gardens.
The kitchen has plenty of floor and wall cabinets and built in appliances including an oven and hob and washing machine. It also features a tiled splash back and granite work surfaces. A good size breakfast bar has been added, the perfect place to enjoy a leisurely breakfast.
The living/dining area is also a good size and has plenty of space for multiple seating arrangements. The room has some lovely decorative features; two metal chandeliers with matching wall lamps.
Through a small decorative arch are the bedrooms;
Bedroom 1; This good size room also is currently used as a twin with two single beds but could easily accommodate a double. It contains a bed side cabinets and wardrobe. Double windows look out over the gardens
Bedroom two is the master;
This room features a double bed, wardrobe and bed side cabinets, it also has double windows that look out the terrace and pool.
There is a good sized en-suite that has very recently been renovated with modern tiling and an enclosed shower unit, sink and w.c
Overall this lovely apartment for sale in Ovacik could make an ideal holiday home and with its location so close to the popular resort of Ovacik, Hisaronu and Oludeniz. It could also be a great investment for holiday rentals or a base to start your new life in the sun. All offered at a fabulous price!
For more info on this apartment for sale in Ovacik, or to arrange a viewing, please contact OCEANWIDE PROPERTIES.


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When Juan first laid eyes on Jessica, in a nondescript New Jersey classroom where he was leading a business course she'd signed up for, he knew immediately he couldn't let her out of the room without getting her number. And when, two years later, he decided to propose, he realized no place better reflected their love-at-first sight relationship than that very same classroom. Juan filled the room with Jessica's favorite flowers, and, with the help of her best friend, set up a multimedia presentation to coincide with his proposal speech. Needless to say, Jessica said yes, and the two tied the knot last September with a grand, elegant Las Vegas affair that celebrated their cultural heritage.
Keep reading for AltF Photography's photos of their decadent wedding!
Jessica chose her Martina Liana gown because she loved the drop waist and tulip-shaped train. The statement necklace she wore with it was helped bring the drama to an already show-stopping look.
Jessica walked down the aisle with a bouquet of roses and calla lilies, to Jean Luis Guerra's "Como Abejo a Un Panal."
Jessica and Juan's poolside reception at the Mandarin Oriental in Las Vegas was all about great food, great drinks, and epic dance moves.
To kick off the night, guests sipped on spicy margaritas and sampled canapes while a mariachi band played.
The two took the floor to Don Omar's "Danza Kuduro", and the male members of the wedding party (including Jessica's twin brother and "man of honor") followed with an unforgettable dance-off. In between rounds on the dance floor, guests munched on shrimp and scallop ceviche, tomato and mozzarella salad, halibut and seared filet.
Jessica and Juan ended the night on a sweet note with s'mores and a three-flavor cake: red velvet, tres leches, and coconut cream. Five months later, they jetted off to Fiji for their honeymoon.
Ceremony and Reception Venue: Mandarin Oriental Las Vegas || Wedding Planner: Andrea Eppolito || Bride's Wedding Dress: Martina Liana || Shoes: Manolo Blahnik || Hair and Makeup: Makeup in the 702 || Bridesmaids' Dresses: Alfred Angelo || Groom's Attire: Ermenegildo Zegna || Florist: Naakiti Floral || Invitations & Paper Goods: Paper and Home || Music: DJ Mike Fox, Classical Entertainment || Rentals: CE Rental, Sit on This, Inc. || Videography: Lighten Films || Photography: AltF Photography


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David Cook announces 'Digital Vein' tour
Multi-platinum rock singer-songwriter David Cook has announced a massive fall tour across America supporting his new album 'Digital Vein'. Beginning September 30th in Phoenix, his Digital Vein Tour will continue through most of November visiting more than thirty U.S. cities. Notable stops will include Los Angeles, Seattle, Denver, Chicago, Washington DC, New York and Dallas just to list a few.
UPDATE: Tour dates have been extended into early 2016 starting February 24th in Atlanta. New tour cities include Philadelphia, Toronto, Buffalo, Milwaukee and Kansas City among others. See below for the full schedule.
David Cook released his forth album 'Digital Vein' on September 18th, 2015 via his new label Analog Heart Music. The album was co-written with other popular songwriters like Blair Daly, Zac Maloy, Kevin Griffin, Chad Carlson and David Hodges. Cook's previous album 'This Loud Morning' hit shelves in June 2011 and reached #7 on the Billboard 200. The American Idol Season 7 winner embarked on a his This Loud Tour to support the album later in 2011.
David Cook Concert Schedule
Fri 8:00 pm
Mon 8:00 pm
About David Cook Tour Albums
David Cook arrived on the Pop / Rock scene with the appearance of the album 'Analog Heart' published on May 6, 2006. The track 'Straight Ahead' immediately became a success and made David Cook one of the fastest growing performers at that moment. Afterwards, David Cook came out with the most beloved album 'David Cook' which is comprised of some of the most beloved music from the David Cook catalog. 'David Cook' contains the single 'Declaration' which has been the most well-known for music lovers to experience during the live events. Besides 'Declaration', most of other songs from 'David Cook' have also become sought-after as a result. A handful of David Cook's most famous tour albums and songs are seen below. After 10 years since the release of 'Analog Heart' and having a true impact in the business, fans still gather to experience David Cook in person to perform songs from the complete catalog.
David Cook Tour Albums and Songs
David Cook Concert Tour Questions & Comments
David Cook Tour and Concert Ticket Information
- Tour dates for all David Cook concerts are revised up to the minute.
- Tickets for the forthcoming David Cook concert are now available.
- David Cook tour dates has just been reported.
- Sold Out concerts will not be an issue, we always have great tickets.
- Concert dates for David Cook is located above.
David Cook may come to a city near you. Browse the David Cook schedule on this page and press the ticket icon to see our huge inventory of tickets. Browse our selection of David Cook front row tickets, luxury boxes and VIP tickets. Once you track down the David Cook tickets you desire, you can purchase your seats from our safe and secure checkout. Orders taken before 5pm are normally shipped within the same business day. To purchase last minute David Cook tickets, check out the eTickets that can be downloaded instantly.


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by Vincent Brown
Who is keeping Funk alive? At least three funk bands were directly affected by the death of legendary Funk guitarist Garry Shider on June 16, 2010. Funk stars of the seventies are getting old. George Clinton and the P-Funk All-stars will be taking the stage without the man in a diaper. They are keeping the Funk alive. The Mothership has been in orbit and is going to land October 15, in Prairie View, TX. Prairie View A&M University, you are now "Standing on the Verge of Getting it on" with George Clinton and the P-Funk All-stars.
The 420 Funk Mob is one of several bands that are connected to George Clinton and the P-Funk All-stars. They are based in Woodstock, NY. When asked what the 420 Funk Mob is about, band leader Mike "Clip" Payne says, " This is what we do on our off days from touring the Parliament-Funkadelic." The 420FM has been everything between a stripped down six piece psychedelic funk band to an eighteen piece funk orchestra with horns, strings, five guitar players, and assorted background singers. Legendary Funk pioneer George Clinton had his first 420 FM experience in 2001 at New York's historic club, the Wetlands. He came back to join the band for sold out shows at The Stone Pony in Asbury Park, NJ, the Haunt in Ithaca, NY, and a two show day at Bard and Vassar colleges in upstate New York. Sometimes the 420 Funk Mob brings in icons like Fred Wesley from the JB's, jazz man Stanley Jordan, or Bad Brains founders Dr. Know and Daryl Jenifer to jam with them. 420 FM members include: Mike "Clip" Payne on lead vocals and bassists Lige Curry, Billy Bass Nelson, Skeet Curtis, Fred Cash Jr, and Derrik Davis; guitarists Mike "Kidd Funkadelic" Hampton, Garry "Starchild" Shider (R.I.P.), Rickey Rouse, Dewayne "Blackbyrd McKnight, Ted Orr, Adam Widoff, Ron Priest Smith, Jeremy Bernstein, The Flash, Eric McFadden, Jen Leigh, and Joey Eppard; drummers Gabe Gonzalez, Zach Alford, Chicken Burke, and Gartdrumm; keyboard players Danny Bedrosian, Peter Keys, Greg Fitz, and Ross Rice; horn players Greg Thomas, Fred Wesley, Paul Henderson, Dave Cast, Dean Jones, and Shane Kirsch; vocalists The LAW, Avalon, Kendra Foster, Toshi Reagon, and Rock Attack 10.
Mike 'Clipadelic' Payne is the ring leader of the super-group DRUGS that included Rock and Roll Hall of Famer Garry Shider, as well as Rickey Rouse, Danny Bedrosian, and Lige Curry of P-funk; Adam Widoff, Fred Cash Jr., and Chicken Burke of Big Lovely; Joey Eppard of 3; Stephanie McKay; and Jen Leigh of Kelis . George Clinton joins DRUGS on on their track "Sanitation Engineer". DRUGS has opened for George and the P-Funk several times. DRUGS is based in Woodstock, NY. Their live performances are legendary. They debuted in Europe at the worlds largest new music festival, the Transmusicales. The band made an appearance at the 39th Super Bowl in Jacksonville Florida as part of the official ESPN/NFL Tailgate Party Band. In 2006 they were the first band to perform live on Sirius Satellite Radio's first day of world wide internet broadcasting.
Danny Bedrosian and Secret Army invade Salvador Deli at 3215 North Davidson Street, Charlotte, NC 28205-1033 at 8 pm, on Saturday, October 30. Based in Florida, Danny Bedrosian is the current keyboardist for George Clinton & the P-Funk All-Stars, as well as a half a dozen other bands around the nation and the world. He is also the lead vocalist, keyboardist, producer, chief songwriter, arranger and publisher for Secret Army. The band includes Parliament-Funkadelic/P-Funk All Stars stalwarts Dewayne Blackbyrd McKnight on lead guitar, and Lige Curry on bass guitar. On drums is Rico Lewis, who is George Clinton and The P-Funk All-Stars' main drummer, The guitar section includes Marc Munoz and Mike Maloney. Additional vocals are handled by Parliament-Funkadelic vocalist Kendra Foster, Teresa Jimenez, and Moon Child. They follow Charlotte with a show at The Court Tavern, 124 Church St, New Brunswick, NJ 08901-2002 on Tuesday, November 2, at 9 pm.
Cheers to the new and old bands that are keeping Funk alive in the DMV! They hail from upstate NY, Virginia, DC and Maryland. Below are some bands that have been keeping DC, Maryland, and Virginia funky.
The Godfather of Go-Go, Chuck Brown goes to Strathmore with the sound he created right here in Washington, DC. Deeply rooted in funk, jazz, Latin and soul, Go-Go's syncopated beats and nonstop rhythms keep the crowd moving from start to finish. Chuck Brown announces, "Ticket giveaway contest time! We'll be playing the beautiful Strathmore Music Center (5301 Tuckerman Lane, North Bethesda, MD 20852-3385) on Saturday Oct 30th. For a chance to win a pair of tickets, email me at email@example.com with the subject CHUCK at STRATHMORE OCT 30. Good luck!"
Mambo Sauce is keeping Funk alive with The Five One at Jammin Java, 227 Maple Ave E, Vienna, VA 22180-4630, Saturday, October 9 at 7:00pm. Black Boo (Vocalist/Rapper), JC (Vocalist), Pep (Percussionist), Chris (Keyboard), Twink (Drums), and Khari (Bassist) continue their quest to take Go-go worldwide. Jammin Java is located at: 227 Maple Avenue East, Vienna, VA
Sophistafunk came through Whitlow's on Wilson last Thursday, September 30. They came all the way from Syracuse, NY to Arlington with that upstate funk sound. A funky drummer named Emanual Washington, a keyboard player named Adam Gold and an MC named Jack Brown will make you shake what your mama gave ya!
Whitlow's on Wilson featured the funky DJ Williams Projekt September 9 and October 1. The Richmond based group consists of funky drummer Dusty Simmons, DJ Williams on guitar and vocals, bass player Todd Herrington, Gordon Jones on sax and vocals and Joey Ciucci on Keys. They showed off their original funk tunes from their third studio CD and kept the crowd grooving.
Funk U performs Friday, October 22, at Chief Ike's Mambo Room, 1725 Columbia Rd NW, Washington, DC 20009-2803. Funk U is a group of musicians who are dedicated to the Real Funk. Their goal is to bring back that old school seventies and early eighties sound and create that live party atmosphere. The members are Craig Stevens on bass, Alex on rhythm and lead guitar, Damien on vocals and guitar, and Mel on drums. The show starts at 8 pm
Back to Zero plays funk and R&B cover songs. Their next public performance will be Friday October 22, at Whitlows on Wilson, 2854 Wilson Blvd., Arlington, VA 22201. This band keeps the dance floor packed! Is Whitlow's now the home of Funk in NOVA?
Please add your favorite funk band in the comments section.
original location: http://www.examiner.com/live-music-in-arlington/keeping-funk-alive


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Best DJ: DJ DIK
Richard Podgurski, known in the South Bay as DJ DIK won best DJ for the second year in a row because of his upbeat old-meets-new music mashups.
"Basically I stand on stage and cheerlead for two hours," Podgurski said, adding that he DJ's frequently at local venues like Ocean Bar, American Junkie, Waterman's, Circa and Sharkeez. "I don't play for myself, I play for everybody else," said Podgurski
Podgurski also said that he thinks he was voted best DJ not because of his skill, but because of his consistency and his ability to know what people want to hear.
"I like taking everything that's super new, and staying on the fringe of what's new and mixing it in with all the classics," said Podgurski. "People can sing along to all the songs they know, but behind it is a song that's just coming out or about to be huge."
DJ DIK: DJDik.com, @djdik
Runner-up; DJ Nik Jagger, firstname.lastname@example.com
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text: Features: Constructed to minimize user fatigue. Dual speed range, 0-450/0-1,500 rpm, delivers optimal performance, Includes two batteries, one hour charger, double ended screwdriver bit and kit box. Contractor bag, Compact size fits into the tightest conditions.1/2-inch single sleeve key-less ratcheting chuck for tighter bit grip, Lightweight design (5.2 pounds) minimizes user fatigue, High performance motor delivers maximum power of 380 unit watts out. Battery Amp hours – 1.2.


text: Heavy rock guitar great Yngwie Malmsteen is set to become a DJ on his native Sweden's biggest radio station on his birthday. The artist will guest host the Sommar show on Sveriges Radio on 30 June (12). Previous hosts have included Abba star Bjorn Ulvaeus, moviemaker Ingmar Bergman and actor Max von Sydow.


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In the summer of 2000, when we moved to Canada, our dear friends, Ira and Lionja have bought a log house in Babje, a village in the north of the Tver region.
As we ventured to explore the dimensions across the expanses of land, sea, and "civilisation" to the west, they took a different journey into the heart of the Russian summer, generous and bountiful, mysterious and unpredictable, well, just like the famous Russian soul.
Lionja and Ira stayed at their new house that summer of 2000 and loved it so much that when the autumn came they were sad to leave back to city of Tver. They returned the following spring miltsov.org/travel/photos2001) and that year stayed in Babje until late autumn. The third time they returned in early spring of 2002, they stayed.
The story of our friends and their photos, usually, evoke strong emotions from many people, who seem to be threatened by the possibility that there may exist a better, easier, and more pleasant way of living.
"But this is not possible for the average person. Your friends must be rich".
"They must be lazy, dreamy, unrealistic, and irresponsible. Good that they're in the boonies out of the civilised way".
"They must be slaving in poverty. Miserable. Hungry. Overworked. Don't you have it tough over there in Russia?"
These are some of the more frequent comments that usually roll off the tongue before our interlocutors even have attempted to enquire or find out about how people live around the world and who they might be.
Deep inside, perhaps, these aggressive defenders of "civilised", money oriented values suspect of other, more peaceful and harmonious ways of living that would render meaningless their toil and aspirations and instead of saving the remaining of their lives, they desperately attempt to cling to the illusion that renders their investment – which in reality is of zero value and less – profitable. So, they argue that they have to go to their jobs in their office space everyday, they have to vote for people who would force them to buy or work for health care because working indoors, stressing on artificial coffee and food, vitamins that cure one thing and deplete another, sleep deprivation, expensive transportation, the right uniform miltsov.org/travel/photosor fashion) on which they have to spend much of their income so as to ensure the income, the rents that feed some landlords or the mortgages that feed some bankers, etc. all of which deplete their life-forces and health and in turn they make sure that they deplete the life-forces and health of others and call it "international" or "global" society heading towards a glorious and democratic "market economy" finale. All this investment and the promise of its return – be it here on earth in the form of material bliss and status or in the skies, which also looks like material bliss and status – are mere illusions that exist simply because of people's belief. A simple belief that this is THE way!
So, what are our friends doing there?
They live. They make babies. They create art. They walk in the forest. They drink from the beautiful river. They spend wonderful and creative time with their miltsov.org/travel/photosnow five) children and they can do all that because they have to work much-much less than those who live in "civilisation".
The following pictures are from our June 2005 visit, during which time we also travelled on the river in kayaks.
View of the bountiful river.
Knight Tihon miltsov.org/travel/photos3) welcomes us.
Russian cowboys: Fadei miltsov.org/travel/photos6), Makar miltsov.org/travel/photos5), Tihon miltsov.org/travel/photos3).
May and Layla


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