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Alzheimer's Disease (AD) is a neurodegenerative disease resulting in progressive cognitive decline. Amyloid plaque deposits consisting specifically of Aβ peptides that have formed fibrils displaying β-pleated sheet conformation are associated with activated microglia and astrocytes, are colocalized with C1q and other complement activation products, and appear at the time of cognitive decline in AD. APP transgenic mouse models of AD, that lack the ability to activate the classical complement pathway display less neuropathology than do the APPQ+/+ mice, consistent with the hypothesis that complement activation and the resultant inflammation may play a role in the pathogenesis of AD. Further investigation of the presence of complement proteins C3 and C4 in the brain of these mice demonstrate that both C3 and C4 deposition increase with age in APPQ+/+ transgenic mice, as expected with the age-dependent increase in fibrillar Aβ deposition. In addition, while C4 is predominantly localized on the plaques and/or associated with oligodendrocytes in APPQ+/+ mice, little C4 is detected in APPQ−/− brains consistent with a lack of classical complement pathway activation due to the absence of C1q in these mice. In contrast, plaque and cell associated C3 immunoreactivity is seen in both animal models and, surprisingly, is higher in APPQ−/− than in APPQ+/+ mice, providing evidence for alternative pathway activation. The unexpected increase in C3 levels in the APPQ−/− mice coincident with decreased neuropathology provides support for the hypothesis that complement can mediate protective events as well as detrimental events in this disease. Finally, induced expression of C3 in a subset of astrocytes suggests the existence of differential activation states of these cells.
Complement proteins of both the classical and alternative pathways (such as C1q, C4, C3, and Factor B) have been colocalized with fibrillar amyloid plaques and cerebral vascular amyloid in the cerebral cortex and hippocampus of AD patients (Strohmeyer et al. 2000;Eikelenboom and Stam 1984;Stoltzner et al. 2000). The C5b-9 membrane attack complex has been found associated with myelin and membranes in AD brain (Webster et al. 1997), demonstrating that in this disorder the entire complement cascade is activated. In vitro, Aβ fibrils (fAβ) activate both the classical complement pathway by directly binding to C1q (Rogers et al. 1992;Jiang et al. 1994) and the alternative pathway via interactions with C3 (Bradt et al. 1998;Watson et al. 1997). Thus, it was hypothesized that in vivo fAβ activates the complement cascade and contributes to local inflammation, particularly by recruiting glia into the area of the plaque, resulting in neurotoxicity and dementia (Tenner 2001;Cooper et al. 2000;Eikelenboom and Veerhuis 1996). This hypothesis was examined and supported in subsequent in vivo studies using a mouse model of AD with a complete deficiency of the complement protein C1q (APPQ−/−) and thus unable to activate the classical complement pathway. While this APP C1q−/− transgenic mouse demonstrated age-dependent amyloid plaque deposition, there was a 50–60% reduction glial activation (GFAP, MAC-1) surrounding the plaques and a similar significant increase in neuronal markers in the CA3 region of the hippocampus (Fonseca et al. 2004). These data suggest that, at ages when the fibrillar plaque pathology is present, C1q contributes a detrimental effect on neuronal integrity, most likely through the activation of the classical complement cascade and the enhancement of inflammation. However, the source of the residual pathology remains unknown. Potential mechanisms include a complement-independent pathway and/or the activation of the alternative pathway of complement by Aβ, a process which would be unaltered by the deficiency of C1q and which would also lead to the generation of the chemotactic factors, C3a and C5a and recruitment of glia to the plaques.
Interestingly, in another murine model the over-expression of an inhibitor of complement C3, Crry, resulted in increased pathology, suggesting that some complement activation fragments (such as C3b, C3a or C5a) may decrease the neuropathology in mouse models of inflammation including those over expressing mutant APP (Wyss-Coray et al. 2002;Mukherjee and Pasinetti 2000) or limit the detrimental responses to neurodegenerative stimuli in other injury models (Van Beek et al. 2003). In addition, recent in vitro studies from this lab demonstrated a neuroprotective effect of C1q on primary neurons in culture in the absence of any other complement components (Pisalyaput and Tenner 2008). Thus, complement components may also be neuroprotective.
To further investigate complement protein expression in our murine models of AD, immunohistochemistry followed by quantitative image analysis and western blot analysis were used to assess the presence and localization of C3 and C4 in the brains of these mice using antibodies that recognize the murine C4 and that differentiate native C3 and C3 cleaved as a result of activation of the complement cascade.
Tg (HuAPP605.K670N-M671L)2576 mice from K. Hsiao-Ashe (Hsiao et al. 1996) were crossed with C1q knockout mice (C1qa−/−) (Botto et al. 1998), and mice with APPQ−/−genotype were generated (Fonseca et al. 2004). Non-transgenic littermates or B6/SJL wild type mice were used as age-matched controls. APPPSQ−/− animals were obtained by crossing Tg2576 APP or PS1 (line6.2 on a SW/B6D2F1/J background from University of South Florida) (Holcomb et al. 1998) with C1q−/−. APPQ+/− or APPQ−/− and/or PSQ−/− mice were intercrossed until APPPSQ+/+ and APPPSQ−/− were generated. (All genotypes were confirmed by PCR.)
Mice at different ages (3, 6, 9, 12, 16 months) were deeply anesthetized with an overdose of pentobarbital (150mg/kg, IP) and then transcardially perfused with cold phosphate-buffered saline (PBS). After dissection, one half of the brain was immediately frozen on dry ice (for Western blots) and the other half fixed overnight with 4% paraformaldehyde in PBS, pH 7.4. Thereafter, fixed tissue was stored in PBS/0.02% Sodium azide (NaN3) at 4°C until use. Fixed brain tissue was sectioned (40 μm) with a vibratome, and coronal sections were collected in PBS (containing 0.02% sodium azide), and stored at 4°C before being stained.
Immunohistochemistry (IHC) was performed on free-floating brain sections. Sections were pretreated with 50% formic acid for 5 min (to enhance subsequent staining of β amyloid) or microwaved (700w) in antigen unmasking solution (Vector Laboratories, Burlingame, CA) (for C3, C4 and CNPase antigens) for 2~5 min. Endogenous peroxidase in tissue was blocked by treating with 3% H2O2 in PBS, 20 min. at room temperature. Nonspecific background staining was blocked by a 2 hour incubation in 2% BSA with 0.3% Triton X-100 (TX). Sections were then incubated with primary antibodies (Table 1) overnight at 4°C, rinsed in PBS with 0.1%TX and incubated with biotinylated secondary antibody (Vector) and streptavidin-horseradish peroxidase (Jackson ImmunoResearch, West Grove, PA) for 1 hour each at room temperature. Finally, the sections were incubated for approximately 2~5 min with diamino-benzidine (DAB) (Vector). Sections were mounted on slides, dehydrated in a series of graded ethanol, cleared with xylene, and then coverslipped with DPX (BHD, Biomedical Specialties, CA). In double-labeling experiments, bound antibodies were detected using Fab′2 FITC-, CY3-, or TRITC-conjugated anti-IgG (Jackson ImmunoResearch, PA). As controls, sections were incubated in parallel without primary antibody or with control IgG of the corresponding species and these sections failed to develop specific staining.
Immunostaining was observed under a Zeiss Axiovert-200 inverted microscope (Carl Zeiss, Thornwood NY) and images acquired with a Zeiss Axiocam high-resolution digital color camera (1300×1030 pixel) using Axiovision 3.1 software. Digital images were analyzed using KS300 analysis program (Zeiss). Percentage of immunostained area (field area of immunostaining/total image area ×100) was determined for all the markers studied by averaging several images per section that cover all or most of the region of study (cortex and hippocampus). Optical sections (z=1μm) of fluorescently labeled specimens were captured using a FLUOVIEW confocal Microscope (Olympus). All experiments were repeated at least twice, with n= 3–6 animals per group per age per marker. All quantitative comparisons were performed on sections processed at the same time.
Tissue samples were prepared as previously indicated (Fonseca et al. 2004). Briefly, fresh frozen half brain (including only cortex and hippocampus) was homogenized in 10 volumes of Tris-buffered saline (TBS, pH 7.4) containing protease inhibitors (0.5 mM phenylmethylsulfonyl fluoride (PMSF), 20 μg/ml aprotinin, leupeptin and pepstatin and 1mM EDTA; all inhibitors obtained from Sigma). Homogenates were briefly sonicated and centrifuged at 15,000 g for 30 min. Pellets were extracted with 2% SDS in TBS with protein inhibitors and centrifuged at 15,000g for 30 min. Protein concentration in the supernatants was determined with BCA protein assay (Pierce, Rockford, IL). Samples (30 μg protein per lane) were run on 10% SDS polyacrylamide gel under reducing conditions (100 mM DTT). Proteins were transferred to PDVF (Amersham Biosciences, Piscataway, NJ) (300 mA for 2 h). Membranes were blocked with 3% dry milk in 0.1% Tween/TBS overnight, then incubated with primary antibodies for 2 h at RT at the dilutions indicated (Table 1). After washing, blots were incubated with the corresponding HRP-labeled secondary antibodies (1:2000 – 1:5000 dilution) for 1 h. Labeling was detected using ECL system (Amersham Biosciences). Blots were stripped following manufacturer's instructions (Amersham) and subsequently labeled with actin antibody (1:10,000 Sigma) following same procedures as above to verify equal loading.
Single ANOVA statistical analysis was used to assess the significance of the differences in plaque area, and anti C3 and anti C4 reactivity among the animal groups (B6/SJL, APPQ+/+ and APPQ−/−). Standard deviation (S.D.) of the mean is indicated by the error bars on the graphs.
As observed in AD brain, C1q immunoreactivity was seen associated with thioflavine-positive Aβ plaques only in the Tg2576 animals (Fonseca et al. 2004) and APP/PS mice models (Matsuoka et al. 2001). To verify and expand these results, brain tissues from APP transgenic mice with (APPQ+/+) and without a functional C1q gene (APPQ−/−) and the nontransgenic control, B6/SJL, were assessed for detectable C1q at 3, 6, 9, 12, and 16 months of age by immunohistochemical analysis. C1q immunoreactivity quantitatively increases with age and amyloid plaque deposition, as shown in Figure 1A for the Tg2576 (APPQ+/+) model. No C1q staining was seen in APPQ−/− animals at any age ((Fonseca et al. 2004) and Figure 1A) nor in the B6/SJL nontransgenic animal (data not shown). Western blot analysis on SDS-extracted brain tissue using a polyclonal anti-mouse C1q confirmed the absence of C1q in the APPQ−/− mice homozygous for the ablated C1q gene (Figure 1B).
Brain sections from mice at 6, 9, 12 and 16 months of age, were then stained with a monoclonal anti-mouse C4 (HBT) that recognizes various forms of C4 α-chain via an epitope in the C4d region of the molecule. (The C4d region contains the thioester which, upon activation of complement and cleavage of C4 by activated C1, can mediate covalent linkage to the activator.) Distinct C4 immunoreactivity was first detected in the APPQ+/+ mice at 12 months, and this reactivity was increased in 16 month old mice, temporally correlating with the appearance of C1q associated with thioflavine-positive plaques (Figure 1A, 2A, 2C). In contrast, at 12 and 16 months little to no C4 immunoreactivity was seen in APPQ−/− mice. Image analysis of the 16 mo animals results in average % field area of 0, 1.2 and 0.15 for B6/SJL (wild type), APPQ+/+ and APPQ−/− respectively (Figure 2C). Results in 16 mo APPPS1Q+/+ vs APPPS1Q−/− mice also show the lack of immunoreactivity for C4 in APPPSQ−/− confirming the lack of classical pathway activation in the C1q−/− mice (Figure 2B).
Western blot analysis was used as an alternative approach to assess C4 levels in extracts from brain tissue of 16 mo old mice. Using both a polyclonal anti-murine C4 antibody and the same monoclonal antibody against C4d used in the immunohistochemical investigations above, uncleaved C4 was detected in the nontransgenic B6/SJL mice, the APPQ+/+ and the APPQ−/− animals (data not shown). However, the 42,000 Mr activation-induced cleavage fragment of C4, C4d, was clearly present at increased levels in the APPQ+/+ brain extracts relative to the nontransgenic and APPC1q−/− mice (Figure 2D and data not shown). These observations are consistent with the requirement for C1q in C1 to induce cleavage of C4 (and thus allow deposition of C4b/d on plaques).
Some C4d immunoreactivity is seen in extracts of brains of 16 mo nontransgenic mice (Figure 2D), data suggesting an amyloid-independent baseline level of this complement fragment since no amyloid deposits are present in the nontransgenic animals (data not shown). In addition, levels of C4d in the APPQ−/− mice were similar to the nontransgenic mice, levels that may be due to amyloid-independent baseline fragment deposition, similar to the non-transgenic mice. C4d staining is not seen in the brain vasculature in any of the animals studied. However, it is also possible that some C4d in the APPQ−/− (that is clustered as seen in Figure 2A) may be the result of activation of the contact system by β-amyloid as previously seen in in vitro systems (Bergamaschini et al. 1999).
C4 reactivity was localized with amyloid plaques and cellular structures surrounding the plaque. To identify the C4 labeled structures, sections were double labeled with antibodies specific for astrocytes, microglia and oligodendrocytes as well as thioflavine to assess plaque associated C4. C4 was not associated specifically with astrocytes (Figure 3A) or microglia (Figure 3B) alone, but was found in thioflavine positive plaque areas (data not shown) containing microglia and surrounded by astrocytes (Figure 3A and B). Confocal microscopy following double labeling for C4 and CPNase, an oligodendrocyte specific marker, demonstrated cell-associated C4 reactivity colocalized with oligodendrocytes. The C4 labeled oligodendrocytes were predominantly found in the APPQ+/+ animals (Figure 4, top panel), but some immunopositive cells are present in sections from APPQ−/− animals (Figure 4, bottom panel). There was no C4 detected in association with oligodendrocytes in age matched wild type (B6/SJL) controls.
We previously reported that while both astrocytic and microglia accumulation and loss of neuronal markers was significantly reduced in APPQ−/− animals, some gliosis and loss of synaptophysin and MAP2 in the CA3 region remained, relative to nontransgenic animals. This observed pathology could be due to either a complement-independent pathway or activation of the alternative pathway of complement by β-amyloid, as reported by Cooper and colleagues in vitro (Bradt et al. 1998). Such alternative pathway activation would be unaltered by the deficiency of C1q. If β-amyloid activation of the alternative pathway was occurring in the APPQ−/− brain, C3 could be covalently linked to the plaques via activation exposed thioester (Bradt et al. 1998). Quantitative image analysis of immunopositive staining with anti-murine C3 showed C3 reactivity in all APP mice starting at 12 mo, but was surprisingly significantly elevated in APPQ−/− relative to APPQ+/+ at 16 mo. Interestingly, this was detected with three distinct anti-C3 monoclonal antibodies (Figure 5A–D), one of which detects full length, native C3 (HBT anti-C3), while anti-C3 monoclonal antibodies 2/16 and 2/11 detects only activated (cleaved) C3 (Mastellos et al. 2004).
Morphologically, the staining of these antibodies differed (Figure 5A, 5C) suggesting native and activated C3 associated with different structures. Confocal microscopy imaging of immunofluorescent double labeling demonstrated that native C3 (HBT, Netherlands) was colocalized with the astrocyte marker GFAP (Figure 6A & 6B). In contrast, anti-C3 monoclonal antibodies to activated C3 (2/11 and 2/16) were associated with thioflavine positive plaques (Figure 7 and data not shown). Finally, using a polyclonal anti-C3 (Cappel), Western blot analysis of brain homogenates confirmed the increase in native C3 (C3 α-chain) in APPQ−/− animals relative to the APPQ+/+ (Figure 5E), and further verified the identification of C3 in the brains of these transgenic animals. Thus, the data accordingly suggest both alternative pathway activation by amyloid plaques and an upregulation of C3 synthesis in astrocytes (consistent with reports of others assessing C3 synthesis in cultured astrocytes in response to injury (Levi-Strauss and Mallat 1987;Rus et al. 1992)). This C3 expression appears to be more robust in the classical complement pathway deficient mouse (APPQ−/−) than in the complement sufficient APP mice.
In the C1q-deficient Tg2576 APP transgenic model of amyloid pathology, the decreased level of inflammatory glial cells and the reduced loss of neuronal integrity in CA3 region of the hippocampus (while levels of both total and fibrillar amyloid deposits remain unchanged) suggested a detrimental role for the complement cascade in this neurodegenerative disease (Fonseca et al. 2004). Here we show that while complement activation by the classical pathway was clearly absent in brain of these Tg2576 C1q−/− animals (Figure 1 and and2),2), fibrillar plaque associated C3b/iC3b, the cleavage product of all three complement activating cascades, was found to be elevated in the classical pathway deficient animals (Figure 5). Since C4 deposition, which could result from either classical or lectin pathway activation, was reduced to baseline levels, this C3 deposition could not be the result of lectin pathway activation. These data are consistent with the activation of the alternative pathway of complement by β-sheet fibrillar amyloid deposits, providing the in vivo correlate of the in vitro Aβ activation of the alternative complement pathway (Bradt et al. 1998;Watson et al. 1997). However, the diminished glial activation and protection of neuronal markers in the C1q-deficent animals indicates that alternative pathway activation does not fully compensate for the lack of classical pathway activation in terms of detrimental consequences. This leads to the question of whether the remaining plaque associated glial activation and/or loss of synaptophysin and MAP2 seen in the C1q−/− Tg2576 mice is due to the activation of the alternative complement pathway and/or to complement-independent events with the activated alternative pathway lacking a detrimental function in this system.
It is important to appreciate that in the absence of C4 deposition (via its thioester), additional "plaque-associated" sites for C3 thioester binding are available and thus the amount of C3 bound to plaques may not quantitatively correlate with the absolute amount of complement activation between these two genotypic models. As a result of this, and given the additional fact that any C3 associated with plaques is long lived due to its covalent nature, deposition of C3 activation fragments may be only loosely correlated with the concentration of C5a, C3a, and/or C5b-9 generated at any given time. Thus, the partial but substantial protection observed in the absence of classical pathway activation (Fonseca et al. 2004) that occurs even when C3 is present on plaques may reflect a difference in the kinetics and/or the extent of complement activation and consequent generation of effector molecules in these models.
While a detrimental role of complement in neurodegeneration has been demonstrated in this and other studies, there is evidence for beneficial effects arising from complement activity which may limit the detrimental responses to neurodegenerative stimuli in certain injury models (Pasinetti et al. 1996;Rus et al. 2005) as reviewed in (Tenner and Pisalyaput 2008). The complement activation products C3a (Van Beek et al. 2001;Boos et al. 2004;Boos et al. 2005) and C5a (Osaka et al. 1999;Mukherjee and Pasinetti 2000;Farkas et al. 2003;van et al. 2003;Sewell et al. 2004;Morgan et al. 2004;Reiman et al. 2005;Woodruff et al. 2006) have been reported to have both protective and detrimental effects in the CNS. Cleavage of C3 in APPQ−/− mice, presumably via alternative pathway activation, and the generation of C3a and C3b may result in neuroprotective activities, thereby contributing to the decreased pathology observed in the APPQ−/− mice in comparison to APP mice. This hypothesis is consistent with the increased pathology observed following inhibition of C3 (Wyss-Coray et al. 2002) by over-expressing Crry, an inhibitor of C3 cleavage and thus also of further downstream complement activation events. These authors suggested a protective role for complement activation, perhaps via the generation of C3b and its opsonizing activity which may contribute to amyloid clearance (Wyss-Coray et al. 2002). If C5a, which is chemotactic for microglia and astrocytes, is generated via the alternative pathway C5 convertase, glia would presumable be recruited into the area of the complement activating fibrillar plaques. However, the influence of C5a in neurodegeneration in AD models is still under debate. Evidence of terminal complement pathway cleavage of C5 and thus generation of C5a and the C5b-9 has not yet been demonstrated in these models. Indeed, the presence of C5a alone in the brain does not necessarily induce or exacerbate inflammation (Reiman et al. 2005). While a direct measure of C5a generation in the brain is problematic (particularly post mortem) as the molecule is short-lived, future investigation of the role of C5a in the progression of disease in these animal models could be approached using C5a receptor antagonists or investigating the effect of a deficiency in either of the C5a receptors (CD88 or the more recently described C5L2).
In another model of neurodegeneration, Fan, et al. demonstrated C1q, C3 and C4 were elevated and localized to areas with fibrillar amyloid deposits in a mouse model of cerebral amyloid angiopathy (Tg-SwDI) (Fan et al. 2007). These results are consistent with the data presented here and with the possibility of a common mechanism of neurotoxicity based on Aβ dependent complement-mediated inflammation and/or neurotoxicity which can result in cognitive loss modeled in each of these systems. This group demonstrated a 2- and 5-fold upregulation of C3 and C1q mRNA, respectively, in the amyloid rich thalamic region of the brains from these transgenics (not in wild type animals). Interestingly, however, in the Fan report, cellular associated C3 immunoreactivity was exclusively localized to microglia (Fan et al. 2007), in contrast to the astrocyte localization in the present study. While it is known that C1q and C3 can be synthesized by neurons, microglia, and astrocytes in the injured brain, the factors involved in the cell and tissue specific regulation of that induced expression are currently an area of active investigation, and ultimately should shed light on the basis for the different apparent cellular sites of synthesis suggested in these studies.
Although C1q plays a central role in the activation of the classical complement cascade, this protein alone has been shown to have multiple effects in disease and homeostasis. For example, it is known that C1q enhances phagocytosis (Botto et al. 1998;Mitchell et al. 1999;Bobak et al. 1987) (and reviewed in (Bohlson et al. 2007)), down regulates the production of proinflammatory molecules in myeloid cells (Fraser et al. 2006;Fraser et al. 2007;Nauta et al. 2004;Yamada et al. 2004), and in vitro has a direct neuroprotective effect on injured neurons (Pisalyaput and Tenner 2008). Neuronal synthesis of C1q has been seen in several injury models (Spielman et al. 2002;Thomas et al. 2000;Fan and Tenner 2005;Rozovsky et al. 1994;Shen et al. 1997) often in the absence of detected induction of other C1 subcomponents C1r and Cls (Veerhuis et al. 1999). These data are consistent with a protective role for C1q in early stages of neuronal injury by mediating the rapid clearance of apoptotic neurons and synaptic debris and/or suppressing the progression of an inflammatory state, hypotheses which are currently under investigation. While clearly more data is needed, if the absence of C1q leads to less modulation (ie higher expression) of proinflammatory gene expression in the brain, the lack of C1q may be the reason that C3 expression in astrocytes is elevated in the APPQ−/− animals.
Upon induction of synthesis of the remaining components of the cascade and the emergence of complement activators (such as fibrillar amyloid plaques in AD (Afagh et al. 1996;Cummings et al. 1996), or amyloid containing drusen in age related macular degeneration (Johnson et al. 2002) or other misfolded or aggregated proteins such as in other dementias (Rostagno et al. 2002)), complement activation could occur and contribute to progression of disease. Indeed, synthesis of most complement factors occurs within the AD brain (Johnson et al. 1992;Shen et al. 1997), and also in "normal" aged brain to a lesser extent (Walker and McGeer 1992). Receptors for complement activation products C5a and C3a are on neurons as well as on microglia and astrocytes [reviewed in (Nataf et al. 1999)], and signature markers (C1q, C4b, C3b/iC3b, C5b-9) indicate that complement activation does occur in the AD brain (Eikelenboom and Stam 1982;Webster et al. 1997;Loeffler et al. 2008) (and data presented here). The consequences of this activation are the generation of C3b, which may facilitate phagocytosis or result in bystander damage due to release of toxic enzymes and oxidative radicals from activated phagocytes ["frustrated phagocytosis"] (Gardiner et al. 1994). C5a is also generated, resulting in recruitment of phagocytic cells to the plaque area and these cells may then be activated by plaque components. Finally, generation of the C5b-9 complex can occur and cause cell lysis if present in high enough concentration or if the expression of the host membrane inhibitor, CD59, is decreased (Yang et al. 2000). However, sublytic C5b-9 has also been shown to be neuroprotective, perhaps via its anti apoptotic effects on oligodendrocytes (Rus et al. 2006). The importance of the balance between activation of complement and the effective regulation of the cascade in neurodegenerative disorders has been most recently evident in the association of specific single nucleotide polymorphisms in complement components C3, C2, Factor B, and Factor H, the latter a complement regulator protein, which together have been shown to contribute >80% of the risk of developing aged related macular degeneration (Hageman et al. 2005;Gold et al. 2006;Maller et al. 2007). Clearly, both the nature of the activators and the local environment also influence development of disease, as these degenerative processes are not seen in all tissues and/or ages.
While the kinetics of all these processes may differ in genetically diverse individuals as well as in the different genetic backgrounds of model mouse strains, the variety of contributing factors may also provide multiple and/or specific targets for regulation of these disease processes both in AD and other neurodegenerative diseases. Given the number of activities as well as regulators of the complement effector system, much more is to be learned of the balance/imbalance that influences health and disease. An recent example of novel functions for these proteins is the interesting data reported by Stevens and colleagues that demonstrates a critical role for C1q and C3 in proper synapse pruning during development but a possible detrimental role in glaucoma (Stevens et al. 2007).
Therapeutic interventions in murine models of Alzheimer's Disease that target inflammation and oxidative stress have proven successful in reducing amyloid plaque burden/pathology as well as the proinflammatory cytokine IL-1β and indicators of oxidative stress (Yao et al. 2004). If complement activation contributes significantly to the inflammation and subsequent loss of cognitive function, then a specific inhibitor of the C1q interaction site on the activator would be valuable as it would block the pathogenic activation but should not affect the systemic protective functions of the complement system. However, if the early complement activation products (C3b, C3a) have beneficial consequences (such as enhanced clearance and promotion of neurogenesis (Rahpeymai et al. 2006)), an inhibitor of the complement system downstream of these events (such as C5a generation or interaction with cellular receptors) or the upregulation of the beneficial activities, would be optimal (Figure 8). Such therapeutic interventions should be particularly beneficial for individuals entering what has been called the "catastrophic" phase of AD, after cognitive dysfunction becomes clinically apparent, the rate of decline appears to accelerate, and neuritic plaques are observable upon autopsy (Cotman et al. 1996). Although multiple potential targets exist for therapeutic intervention in AD, including immunization to prevent accumulation and/or promote clearance of Aβ (Moore and O'Banion 2002;Zhou et al. 2005;Lemere et al. 2003;Selkoe and Schenk 2003) and/or inhibition of oligomeric amyloid formation, multi point interventions will likely be beneficial at different stages of the disease, and thus a cocktail of therapeutic reagents may be more successful in delaying CNS degeneration and the cognitive impairment characteristic of AD.
This work is supported by NIH NS 35144, AG 00538 and NIH Training Grants AG00096-21 (K.P.). The authors also thank Drs. Karen Hsiao-Ashe (University of Minnesota, Minneapolis), Karen Duff (New York University, NY) and Marina Botto (Imperial College, London) for the Tg2576, APPPS1 and C1q−/− mice, respectively, used to construct the AD models lacking the classical pathway (APP Q−/−), Dr. Franz Petry (Mainz, Germany) for the anti-mouse C1q antibody; Dr. John Lambris (University of Pennsylvania, Philadelphia) for his generous gifts of rat anti-mouse C3 antibodies, and Dr. Ron Ogata (Torrey Pines Medical Institute, La Jolla, CA) for polyclonal anti-mouse C4 antibody. We also thank Irma Hernandez, Jennifer Chen, Xiomara Fernandez and Ozkan Yazan for their assistance with immunohistochemistry staining.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Motors Made of Money
Materials used in modern car production are often cheap and synthetic but some manufacturers are using a fibre found in Money
One of the worlds toughest natural fibres called Abaca (or Manilla Hemp) is used commercially in bank notes, fishing lines and various papers but it is now being used in some other less obvious places - inside cars!
Specifically the fibres can help with adding to the strength of the dashboard and other sections of the interior. The Mercedes-Benz A class actually uses Abaca infused polymer in its spare wheel well cover.
This marks the first time that a component containing natural fibres has been used in the exterior of a passenger car and it paves the way for a whole new side to car production.
The Swiss automotive supplier Rieter are behind the components for the A class made with the Filipino fibres. A direct processing procedure for long fibre-reinforced thermoplastics (d-LFT) was refined for the use of natural fibres in order to attain the qualities that an exterior component must possess, including resistance to stone chipping, weather conditions and moisture.
Will it catch on?
Since 2004, DaimlerChrysler have been working on ways to plant and grow Abaca in a sustainable way that also offers some advantages to the commercial process when used as a fibre and this has been progressing steadily. It is now said to bring primary energy savings of more than 60% compared to production with glass fibre.
It does seem as though natural fibres may start to become a much more common component of Mercedes vehicles although there will be many challenges along the way.
Harvesting Abaca
Abaca fibres are only made in the Philippines and are harvested from a plant related to the banana. Check out the videos below to see exactly what Abaca fibres look like and how they are made.
Thanks for reading. Make sure to stay tuned to the Warrantywise blog, Facebook and Twitter for more great content throughout 2015!


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|Mon - Thu
|noon - 8 pm
|noon - 4 pm
|10 am - 4 pm
Minnetonka Music has moved to a new location to serve you better.
Lots more free parking and the same great products and lessons!
Find us in the Deephaven Court Mall, near Minnetonka Blvd. and Northome Blvd (1 mile west of 101).
Minnetonka Music offers a complete selection of musical instruments, music education, instrument repairs, school instrument programs, sound equipment, music books and instrument accessories. Located in the heart of downtown Deephaven, we take pride in helping musicians and aspiring musicians throughout the western communities of Minneapolis achieve their goals in music.
Excelsior Rock Club
Cooper Alt and Chris Gant's Excelsior Rock Club is coming again to Minnetonka Music in the new year. Kids 8-18, get ready for more intense rock study and all the fun of playing in a REAL ROCK BAND!
Rock Club sessions include:
- 8 Group Rehearsals
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- and a Live Performance at a local music venue (date and location TBD)
Fun is GUARANTEED!
Sessions are on Thursdays, 4:00-6:00pm and 6:00-8:00pm.
To register or for more info, call Minnetonka Music (952) 474-3277 or email Cooper at email@example.com
Open Mic Nights
Local Open Mic Nights offer a great opportunity to showcase your talents!
Excelsior Brewing Company:
2nd and 4th Wednesday of every month, 5:30pm - 10:00pm.
Lake Minnetonka Open Mic Nights at the Southshore Community Center
For more information, visit http://lakeminnetonkaopenmic.org/
Discover 9Tomorrows' CD, 'Gravity In Love'!
'Gravity In Love' is the exciting new release from local Excelsior band, 9Tomorrows. Produced by Dave Kellogg of our affiliate recording studio, who's worked and toured extensively with reggae bands in the Bahamas, this sophisticated, intelligent and energetic mix features an uplifting infusion of modern reggae and songs that range from soulful to danceable.
Look for 'Gravity in Love' at Minnetonka Music and online at itunes.
For more information about 9Tomorrows, visit their website at www.9tomorrowsband.com.
John Rosensteel - 'Savannah's Song'
Enjoy Great Live Music at these Excelsior Venues


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- Please select a date to see the proper prices!
- Meal can be requested on the spot
Best offer
81.56 € / person / night, no meal
Description of the accommodation:
Rooms, services Discover the beauties of China and check out the opportunities provided by Millennium Harbour View Xiamen! The hotel is welcoming all guests in Xiamen with 352 comfortable rooms to stay in. Since the hotel has an own restaurant, you may also try fine local meals on the spot. Parking possibility is available nearby for guests arriving by car. You may also enjoy relaxing wellness services on the spot, <a/an> hairdresser's parlour will also be available to you. Car rental service and organized city tours will help you discover the most important attractions. Fans of actively spent leisure time will also have the chance to play bowling nearby. Should you want to do sports while you are on travel, you may also take the services offered by the gym. Upon preliminary notice airport transfer can be requested. The café and the bar have excellent atmosphere for a relaxed evening talk or a personal meeting. Your valuables may be the safely secured in the safe. Wireless Internet connection (WiFi) is available at the hotel, ensuring that you can stay up-to-date during your holiday. The exact equipment and the exact list of available services of Millennium Harbour View Xiamen can be read on the information sheet below.
Payment In order to finalize the reservation you may be required to provide credit card guarantee or advance payment by credit card, depending on the chosen room, date and price.
Arrival, opening hours The earliest time for arrival and check-in is 14:00, the latest time for departure and check-out is 12:00. The personnel of the hotel can speak in Chinese - China and English with you.
Millennium Harbour View Xiamen rooms Rooms
- Please select a date to see the proper prices!
Accommodation services
Free WiFi in shared places
Relaxation: Fitness, Bowling
Organized sightseeing nearby, Car rental nearby
- Wellness section, relaxation
- Finnish sauna
- Hairdresser's parlour
- Pool (Outdoor - seasonally open)
Default services: Bar, Cafe, Elevator, Safe deposit box
Airport transfer
Own restaurant
Bathrobe, Hairdryer, Desk in the room, Mini-bar, Tea/coffee-maker


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SEE THESE GIRLS STRIP ALL THE WAY: http://goo.gl/DWhdL
This year, when we were thinking about what to get you, we decided to keep things simple: a twist on the traditional Christmas carol. You all know the carol The 12 Days Of Christmas, right? Well, we've replaced "days" with "girls". Simple. You won't get a better present this year! Just choose your girl and click to watch them strip...
Subscribe for loads more girl videos: http://bit.ly/pAt2Km
See more girls and gags at: http://www.zootoday.com/
Start from this video: http://www.youtube.com/watch?v=G8WnHvYRApE
Like ZOO Magazine on Facebook: http://www.facebook.com/ZOOMagazine
Follow ZOO Magazine on Twitter: http://twitter.com/#!/zoo_uk


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Maybe Accepting Guests
- Last login 11 months ago
Join Couchsurfing to see Denes's full profile. It's free!
About Me
I love to travel and meet new people, try and get to know as much of this small world as I can.
Simplicity is my guide. :)
Why I'm on Couchsurfing
I have not had a lot so far, I've only met 2 beautiful people from here.
travelling, scuba diving, photography, cycling, movies and music from 60`s and 70`s, philosophy
- photography
- movies
- traveling
- music
- cycling
- scuba diving
- tourism
Music, Movies, and Books
Movies: Hair, Mediterraneo, Il postino, In the mood for love, Cinema Paradiso, Barbershop, Casino, The English man who went up a hill but came down a mountain
Music: Queen, world music, gipsy instrumental music, Arabic, Italian music
Books: Red and black, Parfume, Crime and punishment, 1984, Brave new world, Into the wild
One Amazing Thing I've Done
A couple of years ago I cycled across Canada from Vancouver all the way to Halifax on my own so I had the chance to taste the biggest freedom I`d ever had before. Since then I`ve been addicted to it. :)
Countries I've Visited
Austria, Canada, Egypt, Germany, Italy, Russian Federation, Ukraine, United States
Countries I've Lived In
Canada, Egypt, Hungary, United States


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Lord And Taylor
July 21, 2010 by staff
Lord And Taylor, Customers enter Lord & Taylor Garden City on Saturday were treated to a fashion show of couture and cosmetics introduced next fall of the main designers of the industry.
Before the models on the catwalk, the audience enjoyed the breakfast provided by Sarabeth gourmet restaurant, located on the second floor of the store. Customers also received a bag full of complimentary cosmetic samples of different companies.
The show began with the comments of José Ricaurte, vice president and general manager of Lord & Taylor Garden City. After each model, a name was drawn from a box for a chance to win a basket full of cosmetics from different designers. Allison Becker, personal fashion adviser for Lord & Taylor Garden City, served as master of ceremonies and costumes described in each model.
Models had a makeover of one of the cosmetic companies, including Bobbi Brown, Lancome, Dior, Laura Mercier, NARS, Borghese, Clinique, Chanel, Elizabeth Arden, Shiseido and Estee Lauder. They were also adorned with clothes and accessories from leading designers in the industry. As the models walked the runway, make-up called the cosmetic products used.
After the fashion show, every line of cosmetics offer special events. Customers may have taken professional photographs, receive mini-facial and makeup courtesy and take samples of new cosmetic products.
Lord & Taylor Store today for all the latest fall trends seen in the show. Contact your personal fashion consultant Allison Becker at 516-742-700, ext. 420 or by e-mail to firstname.lastname@example.com.
Please feel free to send if you have any questions regarding this post , you can contact on
Disclaimer: The views expressed on this site are that of the authors and not necessarily that of U.S.S.POST.


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Search Engine Marketing, Website Design and Printing Management Company in Vancouver, BC.


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Sub-standard equipment built into the planes coupled with the decision to eliminate flight demos for those aircraft are raising serious concerns over the Air Force's strategy, according to industry sources.
One glaring deficiency in the Air Force's blueprint for the light air support aircraft was the design of the ejection seat, sources say.
Program planners did not take into account the smaller stature of some pilots in the Afghan army, as well as Air Force trainers assigned to advise Afghan aircrews.
The ejection seat, when deployed, could result in serious injury or death of those smaller U.S. or Afghan pilots, sources say.
Another cause for concern is that the Air Force has waived its need for comprehensive flight demonstrations for the Afghan air support planes. That requirement was part of the initial slate of capabilities requested by service officials for the Afghan fleet.
News of these shortfalls comes as the Air Force attempts to salvage a deal to sell a number of these aircraft to the Afghan military.
In April, the Air Force announced plans to amend its proposal for the planes, delaying planned deliveries of the aircraft to Kabul by 15 months.
The Air Force said its amended proposals request will be released on April 30, allowing the companies to rebid, and the Air Force expects to choose a recipient in early 2013.
Under that new time line, the plans won't reach Afghan soil until late 2013, according to service estimates.
The Air Force had initially awarded the contract for 20 light attack aircraft for the Afghan army to Sierra Nevada and its partner, Brazilian company Embraer, after disqualifying a proposal by Kansas-based aircraft manufacturer Hawker Beechcraft.
But after Hawker Beechcraft sued in the U.S. Court of Federal Claims, the Air Force launched an investigation and canceled the award to Embraer and Sierra Nevada in February, citing problems with its internal documentation.
On Thursday, Hawker Beechcraft filed for bankruptcy protection after reaching an agreement with its lenders that will eliminate $2.5 billion in debt.
The aviation company filed for Chapter 11 in New York as part of a restructuring deal to transfer ownership of the company to its creditors.
However, some on Capitol Hill are still rallying to the company's side, demanding answers to the ongoing issues with the Afghan aircraft program.
Rep. Tim GriffinTim GriffinFlynn discloses lobbying that may have helped Turkey Tea Party class reassesses record Huckabee's daughter to run '16 campaign MORE (R-Ark.), a member of the House Armed Services Committee, pressed the air service to provide information to his office on the ejection seats. More than 480 Hawker Beechcraft employees work in Arkansas.
In a letter to Air Force Secretary Michael Donley in early April, Griffin requested information on how the service was planning to address the ejection seat issue.
The issue has created some unwanted tension between Brazil and the United States. Brazilian President Dilma Rousseff discussed the issue with President Obama during a state visit to Washington in April.
Hawker Beechcraft supporters claim a deal of this size should be carried out by an American-based defense firm, not one headquartered in South America.
Embraer President and CEO Frederico Curado told reporters in Washington back in April that the foreign allegations were disingenuous, since Embraer and Sierra Nevada planned to build the planes in Florida.


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Very nice end unit. Excellent condition! New paint, fireplace, full basement. Beautiful Pool, Rec Room and Tennis.
Listing information
- Year Built: 1984
- Status: Sold on 9/22/2016
- Parking Type Description: Off Street 2 cars
- Association Fee: $205
- Property ID: 103941625
- Beds: 2
- Total Rooms: 5
- New Construction: No
- County: Albany
- Style: Condominium
- Baths: 2 (Full: 1 3/4: 0 1/2: 1 Other: 0)
- Fireplaces: 1
- Total Square Footage: 1,400 ($107.07 per sq. foot)
- School District: Albany
Age Description Estimated
Amenities Ceramic Tile, Country Kitchen, Wood Floors
Appliances Dishwasher, Disposal, Microwave, Other, Range W Oven, Refrigerator, See Remarks, Some All Negotiable, Washer Dryer
Attic Full, Walk Up
Basement Full
Condition Excellent
Cooling Type Central Air
Exterior Brick
Exterior Features Patio
Heat Fuel Natural Gas
Heat System Hot Air
HOA Includes Exterior Maintenance, Insurance, Lawn Care, Recreation Facilities, Snow Removal, Trash Removal
Homeowner's Association Yes
Interior Features Cable Hook Up, High Speed Internet Acc, Paddle Fan
Living Rm Fireplace Type Fire Place Wood
Lot Description Level
Master Bedroom Second Floor
Other Possession - Tba, Tax Id Section - 40.12, Tax Identification Block - 2, Tax Identification Lot - 4
Roof Asphalt Shingle
Sewer Public
Total Taxes Description Estimated
Water Public
Dining Room Main Level
Kitchen Main Level
Living Room Main Level
Bedroom 2nd Level
Listed by Lawrence Walker of Coldwell Banker Prime Properties 518-439-9600


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USE: Use PRE-WASH in a hand held atomizer. Spray liberally onto soiled areas. Do NOT wet material prior to spraying PRE-WASH. Leave for about 1 minute. Rub if necessary. Launder items in the usual manner.
First Aid:
Eyes: If splashed in eyes, flush with water for 15min. Seek medical advice.Skin: Wash affected area with soap and water.Inhalation: If mists are inhaled, remove patient to fresh air. Seek medical advice.Swallowed: Do NOT induce vomiting. Give milk or water to dilute. Seek medical advice.
Download PRE WASH Stain Remover MSDS
© 2017 Cleaners Supermarket Pty Ltd. All Rights Reserved


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Jack Nicholson and Paul Rudd have been going to work each day this week in Center City, as they star as father and son in the untitled James L. Brooks comedy that just started shooting here.
This week's work is out of sight in the Widener Building, but nearby office workers know where to look.
The cast and crew will be here into the fall, and another casting call has been announced:
They're looking for "foreign diplomats": men and women, all ethnicities, ages 35-60, who own their own national dress (i.e. saris, kufi caps, kaffiyehs, thawbs, turbans, etc.) SAG and non-union actors will be considered. Heery Casting asks applicants to email a .jpg photo of yourself wearing this national costume to firstname.lastname@example.com. Include your phone number.
(Post corrected.)


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Amon Amarth
Available immediately, Swedish heavy metal titans Amon Amarth - in partnership with Swedish video game developer and publisher Ride and Crash Games AB - has unleashed a new Amon Amarth mobile video game!Read More
Dimebag Darrell
Time for another sneak peek in advance of this Friday's release! Today, Revolver presents an additional exclusive trailer for 'Dimevision Vol 2: Roll With It Or Get Rolled Over', giving fans an insider's look at the upcoming video.Read More
Mother Feather
Currently finishing work on their sophomore album with Grammy-nominated producer Joshua Valleau, Mother Feather has launched a new lyric video for the track 'Egyptology.'Read More
Fates Warning
On January 12th, Metal Blade Records will re-issue two of Fates Warning's fan-favorite albums, 'Perfect Symmetry' (1989) and 'Parallels' (1991), as part of the label's 'Originals series'.Read More
Cannibal Corpse
Cannibal Corpse recently released their new album, 'Red Before Black', via Metal Blade Records; for their efforts, the band has now entered the international charts!Read More
New Releases
Upcoming Releases
Latest News
Hamferð reveals details for new album, 'Támsins likam'
- November 15th, 2017 – Releases lyric video for first single,...Read More
Good Tiger releases new video, "Grip Shoes", online
- November 15th, 2017 – Today, rock quintet Good Tiger is thrilled to...Read More
Cattle Decapitation launches guitar play-through for "Circo Inhumanitas"
- November 8th, 2017 – After recently releasing a bass play-through for...Read More
New video trailer revealed from Dimebag Darrell's 'Dimevision Vol. 2: Roll With It Or Get Rolled Over' DVD/CD
- November 7th, 2017 – Everyone loves sneak peeks! Today, Guitar World...Read More
Mother Feather launches lyric video for "Trampoline" – track set to be aired during 'Shameless' season premiere this weekend!
- November 4th, 2017 – Photo credit: Austin Phelps Currently finishing...Read More
Cannibal Corpse streams new album, 'Red Before Black', via Noisey.Vice.com
- November 3rd, 2017 – Kicks off USA tour today Cannibal Corpse has...Read More
Second exclusive video clip revealed from Dimebag Darrell's 'Dimevision Vol. 2: Roll With It Or Get Rolled Over' DVD/CD
- November 3rd, 2017 – Metal Blade Records recently announced the...Read More
Cannibal Corpse streams new single, "Scavenger Consuming Death", online
- November 2nd, 2017 – Tomorrow (November 3rd), Cannibal Corpse will...Read More


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MOVIE SYNOPSIS [ General Audiences ] Starred by Aida Chotkaraeva, this film directed by Samat Erkinbekov and Mamakeev Nurlan was premiered in TV or cinema in 2014. The film "Bravo!" had an original production of Kyrgyzstan. You can watch Bravo! online on TV cable or theaters with original audio in Kyrgyz at different dates. This film premiered in theaters in 2014.
Rating: 5 by 10 users./
Runtime: 100 minutes
Aida Chotkaraeva, Kubanych Kurmanbekov and Nurlan Nasip.
100-minute film (full movie) directed by Samat Erkinbekov and Mamakeev Nurlan.
The original audio of Bravo! has dialogues in or Kyrgyz, it was produced in Kyrgyzstan.
It premiered in cinemas or television in 2014.
Screenplay written by Ermek Talaibekov, Samat Erkinbekov, Kubanych Kurmanbekov and Rustom Askerov.
Nurbek Mambetisaev.
Nurlan Mamakeev and Eldiyar Kenensarov.
This film was produced and / or financed by KG Club Production.
Composed by Azamat Takyrbashov.
KG Club Production.
Without commercial breaks, the full movie Bravo! has a duration of 100 minutes; the official trailer can be watched in streaming on the Internet. You can watch this full movie free in English or Kyrgyz in movie TV channels, renting the DVD or with VoD services (Video On Demand player, Hulu) and PPV (Pay Per View, Netflix).
See the page of this full movie, Bravo! in FULLTV Movies.


text:
The Simple Guide to Mobile Learning and Modern Learner Engagement
Bitesize, Portable, Untethered Learning.
With the rise of rapid eLearning and Open Source LMS, it's apparent that technology drives forward thinking. Mobile Learning has opened up a whole new world of informal learning, putting it right in the hands of your clients and employees.
Find out:
- Who's using mobile learning
- If mobile learning can work for you
- How to implement a corporate m-learning program at your organization
Download our Mobile Learning guide now!


text:
❀ ヅ
♥Blessed Are The Animals♥
My memorials give me somewhere to bring my grief, and to express my wish to honor those who have gone.
I no longer live near any of 'my' cemeteries and Find a Grave is a place where I can come and be just a grieving mother or daughter, and others always understand me. My heart will always have a Rhysa shaped hole in it, which nothing can ever fill.
If you have lost someone precious to you, I ask God's courage and comfort for you, this is my prayer.
♥ `*•.¸ ♥ `*•.¸ ♥ `*•.¸ ♥
ღThank Youღ from my heart to each dear soul who has visited and left flowers and kind thoughts for my daughter,
Rhysa D Overton (Sep & Feb) -
my mother Thelma Norean Sides Benton (Dec & May) and others in my family.
♥ `*•.¸ ♥ `*•.¸ ♥
i thank you God for most this amazing day: for the leaping greenly spirits of trees and a blue true dream of sky; and for everything which is natural which is infinite which is yes
- e e cummings
♥"It's not about how you look, it's about how you see."♥
"Forgotten? No, we never do forget:
We let the years go; wash them clean with tears,
Leave them to bleach out in the open day,
Or lock them careful by, like dead friends' clothes,
Till we shall dare unfold them with less pain,—
But we forget not, never can forget."
― Dinah Maria Mulock Craik
I need to say that even tho permitted by FaG rules to claim priority rights to the memorial, when you have burial location info not on the memorial the kinder thing would be to inform the owner of the grave location. Chances are it means a lot to the owner. I have had many memorials taken from me without a word of notice because I could not find out the cemetery. We each are in need of a kind gesture to get us thru the day and I will happily do the same for you.
The Beautiful Angel of a Beautiful Angel ~
Valencia Michelle Ramirez (Oct & Aug), and her wee, precious Granddaughter, Asia (May & May)
Their Mother's Joy ~ Mariesa Jean Weber (Aug & Oct), and sister Gina Marie Weber (Mar & Aug)
Born an Angel ~ River Logan Hall (Feb & Feb), and his beautiful Grama Jeannie (Sep & Aug)
Precious Little One ~ Wesley James Tatum (Aug & Aug)
*The only pix of Wesley that anyone, even his Mum, is permitted to use on his page are tokens with his pic. Please feel free to use and re-use them.
Sister and Brother ~
Baby Charlotte (Jan & Mar)
Baby Joshua (Aug & Oct)
♥ .•**•. ♥. •**•. ♥ .•**•. ♥
Are you a friend or relative of someone listed in my memorials?
Many of my memorials are related in some way to me, but many are not. All my memorials, however, are made with very great personal respect and the most loving intentions, the goal ALWAYS being to honor the memory of some dear person.
I will consider every request for transfer.
If you'd like me to remove or modify a memorial I have made for your family member I will happily do so.
If you should wish a photo removed that I have added, please just leave me a note and it will be promptly and cheerfully (✿◠‿◠) deleted.
***☺ If I can help with aged or damaged photo(s) of yours, anything I can do is freely offered. Just post it on any memorial of yours and tell me where to find it. I download a copy and the original is of course untouched.
"Earth's fairest flowers grow not on sunny plain,
But where some vast upheaval rent in twain
The smiling land . . . .
After the whirlwinds devastating blast, after the molten fire and ashen pall, God's still small voice breathes healing over all.
From riven rocks and fern-clad chasms deep, flow living waters as from hearts that weep.
There in the afterglow soft dews distill and angels tend God's plants when night falls still,
Angels passing by that way
Will gather lilies at the break of day."
"Just living is not enough" said the butterfly fairy, "one must have sunshine, freedom and a little flower."
-Hans Christian Anderson-
My husband and I are rattie and ferret people and have for years adopted from the local rescues and shelters.
The ones we bring home are otherwise not likely to be adopted due to age and/or medical issues.
We give and get tons and tons of love :). Ferrets are soft and cuddly and affectionate and just awesome, playful little love bugs.
Over the years there have been 43 ferrets (plus others...dogs, cats, ratties, mousies, birdies, fishies, gerbils and degus) in our family circle, each one a beautiful little spirit.
Our lives have been and are enriched beyond all measure by the presence of our fuzzies.
Each furbaby brings something unique and special to our family, and we are so thankful for the privilege. You will find our rainbow babies listed in My Faerie Garden virtual cemetery.
I am a long time vegan, and all God's creatures are near to my heart.
*A wonderful quote shared with me by PURPLE~LADY, it's so True:
"Love is more than words, it is demonstrated thru actions. Love is manifested in the day-to-day occurrences of small kindnesses & spoken words. Love is lending a patient ear and taking time to care." ~Anonymous~
LOVE is a four-legged word...
- 504 Memorials Added
- 437 Memorials Managed
- 1 Memorial per Week
- 1,061Photos Added
- 4Photo Requests
- 19Volunteer Photos Taken
- 54,351 Flowers Added
- 4Virtual Cemeteries
- 33 Fame Ratings
- 227 Sponsorships
466 Memorials
44 Memorials
194 Memorials


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Part 3 of a three-part investigation into potentially romantic hotels on the Flowered Coast of Normandy, featuring the Grand Hotel in Cabourg, Les Manoirs de Tourgéville near Deauville, the Royal and Normandy Barriere Hotels in Deauville, several less luxurious hotels in the area and recommendable restaurants.
The Royal and The Normandy in Deauville and Others Hotels and Restaurants on the Coast
The 5-star Hotel Normandy Barriere in Deauville has for some time now been the star of the Flowered Coast, a choice destination for both leisure and meeting travelers who heed the call of luxury in this well-to-do resort and meeting town.
The Normandy Barriere is so well known that despite having set out to test its romantic potential when I'd left Paris two days earlier I ended up on in its sister 5-star, the Royal Barriere, at the opposite side of the Barriere casino. The equally stellar Hotel du Golf Barriere is by the course a few miles inland.
If that sounds like a Barrieres for one town that's because the Lucien Barriere Group, 60% of which is held by the Desseigne-Barriere family, is inextricable associated with leisure and wealth in Deauville. So is French President Nicolas Sarkozy, a personal friend of its CEO Dominique Desseigne. I note that not because a foreign traveler's sense of romance need be affected by French politics but rather because two days before my arrival a tripartite summit meeting brought together at the Royal President Sarkozy, German Chancellor Merkel and Russian President Dmitry Medvedev, and an assortment of sharp-shooters among the 1200-strong security force in the area. (All three of Deauville's Barriere hotels were reserved for participants of the G8 meeting here in May 2011.)
On the way to my room a hotel employee showed me the suite where French president and his wife had Carla stayed. I sat on the bed to test the mattress. The room had a living room, which mine didn't, but mine actually had a better view, without helicopters hovering above the beach or warships just off the coast.
The Normandy was built in 1912 in what is called Anglo-Normandy style, interpreted here to mean that it's a massive feel-good manor pea of green half-timbers beneath a steep slate roof. There are 290 rooms facing in all directions, including 28 suites and apartments. Its main entrance is from the town side.
The Royal is more attractive when seen from the beach side. Built a year after its big sister, it's dressed primarily of stone with winks to the region in the form of inlaid brick and red stripes of paint. The Royal resembles a luxury coastal hotel in New England rather than Old England. Open March through November, it has 252 rooms including 30 suites.
The Barriere style as expressed at the Royal is a classic traditional French grand hotel style, a flowing plush of red carpets with round motifs, thick drapes, heavy furniture and damp blue and reds tones. More recently renovated rooms, however, have straightened some of the lines, Directory-style, though colors remain hearty. Despite the thoroughly modern amenities, the Barriere style as interpreted by decorator Jacques Garcia at the Royal and the Normandy has an intentionally old-fashion air to it. Most rooms are quite spaciousness.
Unlike the Grand Hotel in Cabourg, the channel is not at your feet here since the Royal and the Normandy are several hundred yards back from the beach and low tide withdraws water's edge even further.
There is a sea view from the 4th to the 7th floors on the north side of the hotels, but a swimming pool, a conference center, tennis courts, pavilion and/or restaurants fill the lower part of one's gaze. I don't think of the view as romantic so much as longing, but perhaps there's a similarity there. My view:
On the opposite site the upper floors of the Royal also offer appealing views to the small-town feel of the residential quarters of Deauville.
Deauville's American Film Festival draws stars and novas to town in September. The walk of fame is along the boardwalk, with famous names of the screen noted by the changing booths. The view colored umbrellas on a long and wide stretch of beach sand is shorthand for Deauville. But the water on the English Channel is cold and the clouds move in fast. No American in his or her right mind would come to Deauville for a lie on the beach, attractive as it may be, though the British would.
So it isn't the view of the beach that would make or break Deauville or either of these hotels as a romantic destination.
The Royal has spa facilities and a small pool, a gastronomic restaurant (see other restaurant suggestions below), lobby chairs to sink into, a grand ballroom as breakfast room, and willing service. A seawater therapy center and an Olympic size pool are across the street. The casino is next door and on its opposite side you can get a change of luxury hotel scenery at the bar of the Normandy.
There's a general sense of well-being in the well-heeled heart of Deauville. There are golf courses in the area and, more significantly, a thoroughbred race track. (Cabourg has a racetrack especially know for trotters.) This part of Normandy is horse country, and Deauville is especially known for its thoroughbred trade and races. It's a sister city to Lexington, Kentucky and to Kildare, Ireland. The most romantic stroll on the beach of Deauville may well be on horseback.
So many ways in which to fill a two or three leisurely day and a resort-casual nights, even when the Norman sky turns gray.
The Royal is a fine place. I would like to have gotten to know her better. But, alas, a single night was all I had. Still it was enough to understand what my friend is looking for in her 5-star Deauville dream: to be spoiled.
Royal Barrière Deauville, Boulevard Cornuché, 14800 Deauville. Tel. 02 31 14 39 59. Rates vary significantly depending on season and length of stay. Check website High season rack rate typically 480-1535€, with sea views beginning at 605€.
Deauville Tourist Office, in the center of town by Town Hall, place de la Mairie. 02 31 14 40 00.
Restaurant L'Essentiel. 29/31 rue Mirabeau, 14800 Deauville. Tel. 02 31 87 22 11. To contrast with the old-fashion grandeur of the Royal, I went to what I came to think of a lounge bistro, a brightly lit space of clean lines, dark wood chairs and grey walls. There's also a large patio-courtyard space outside. The 50€ tasting menu was excellent, a delicious discovery, and unParisian in that compared with the capital it was reasonably priced for such a feast. L'Essentiel serves French-Asian fusion, each part recognizable, making it both inventive and traditional, a wise mix of savors without gimmickry. I'm not a big fan of music in restaurants (the amiable director of Manoirs de Tourgéville had called me "old school" when I suggested that the music in the hotel's restaurant was excessively musical), but I didn't mind the discreet lounge music here. Owners and chefs Charles Thuillant and his Korean wife Mi-Ra work hand in hand in the kitchen, except when she has a baby in hand. Dishes are served on slate or on Franco-Asian simplified porcelain, tableware appears appropriate rather than gadgety. Accommodating service.
Restaurant Le Spinnaker is a fine fish restaurant on the same street. 52 rue Mirabeau, 14800 Deauville. Tel. 02 31 88 24 40.
If looking to create a chic and easy picnic, you'll find excellent prepared foods in the center of town at the deli/caterer Breton Deauville, Place Morny.
Notable hotels in other categories in Deauville
La Villa Joséphine (3-star), 23 rue des Villas, Deauville. 02 31 14 18 00. I haven't stayed at this 3-star but a most reliable source tells me of the charms and refinement of this late-19th-century villa operated since 2005 by Joséphine Petit and located a few block from the center of town. Room rates are 118-348€ (excluding breakfast), discounted pricing possible.
Hotel de l'Espérance (2-star), 32 rue Victor Hugo, 14800 Deauville. Tel. 02 31 88 26 88. In the center of town though calmly situated, this clean, contemporary,10-room, budget-friendly, client-friendly hotel may have three less stars than the Normandy or the Royal and fewer knick-knacks than the Villa Joséphine, but it makes for a private or intimate escape, alone or with a lover. Patrick Bartert, owner along with his wife Murielle, is a former chef who willingly offers his view of the culinary offerings of Deauville and the surrounding area and explains his appreciation for the culinary traditions of Auguste Escoffier (1864-1935). Room rate 100-150€ in high season, 67-99€ in low season.
Between Deauville and Cabourg
Villers sur Mer
L'Outre-Mer (3-star), 1 rue du Marechal Leclerc, 14640 Villers sur Mer. Tel. 02 31 87 04 64. Full of charm and color, exuding playful flamboyance and a feminine touch, the Outre Mer is a friendly and joyful 14-room hotel on a coastal town between Cabourg and Deauville. Half of the rooms have a partial sea view, some with balcony. Romantic, yes, but with its moderate price and the beach across the street it's also worth considering for family travel or for a writerly pause. Room rates 98-185€ excluding breakfast. Even when your budget sends you to more stellar hotels the tea room here offers a cheery stop (with pastry) while exploring the coast.
Lunch at La Digue de Villers, a fish and seafood restaurant overlooking the beach from avenue de la République in the town of Villers sur Mer. Open daily.
La Villa des Bains (3-star), 31 rue des Bains, 14510 Houlgate. Tel. 02 31 24 80 40. The absence of a grand hotel in Houlgate means that it's typically ignored while driving between Cabourg and Deauville, but meander along the slopes a few hundred yards back from the coast and you'll find an astounding array of top-of-the-line mansions built in the late 19th and early 20th centuries. Meanwhile, in the commercial heart of town and two blocks from the be
To return to Dreams of Romance on Normandy's Flowered Coast, Part 1: Cabourg, click here.
To return to Dreams of Romance on Normandy's Flowered Coast, Part 2: Les Manoirs de Tourgéville, click here.
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UPDATE: MetroLink trains have resumed operation between the Maplewood-Manchester and Richmond Heights stations. It says trains are now operating on schedule and passengers are no longer being transported via shuttle between those stations.
A suspicious package has halted MetroLink trains near in central St.Louis according to St. Louis police.
Shortly before 8 p.m. Saturday, a suspicious package was located near the Brentwood MetroLink station off Hanley Road. Officials said a cylinder wrapped in aluminum with a fuse-like material sticking out was found on the east side of the train tracks.
St. Louis County Police Department became the lead agency in the investigation late Saturday evening. The Arson and Explosive Unit were called in to assist the case.
Metro closed the Brentwood station, and temporarily ceased train operation between the Maplewood-Manchester and Richmond Heights stations. MetroLink Station Shuttles are transporting passengers by bus between the Maplewood-Manchester, Brentwood and Richmond Heights stations.
Passengers should expect delays of up to 60 minutes while officials inspect the package.
As more information becomes available, this story will be updated.


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Can anyone recommend great days out in the North West of England?(12 Posts)
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So I saw a ad on Nintendolife for the game, here is the site http://passport.game321.com/api/lp/g_monster2.php
Sp00ky scary skeleton back to play games and dew other fine things indead!
The Graveyard (Backloggery) l Youtube Channel I eShop Gurus l Super Smash Bros. 4 Brawler Card I Mario Kart 8 Player Card l My Super Mario Maker levels!
3DS Friend Code: 5198-2878-6360 | Nintendo Network ID: Undead_terror | Twitter: Undead_terror


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NEW YORK --- The back-to-school season got off to a strong start as discounts and high temperatures in July drove shoppers to air-conditioned malls. But merchants worry that momentum won't continue through the remainder of the second-biggest shopping period of the year as the weather gets cold and the deals dry up.
Despite a flow of bad economic news that kept consumer confidence shaky, a number of retailers reported July revenue on Thursday that beat Wall Street estimates, including discounter Target, department store Macy's, and luxury chain Saks. The International Council of Shopping Centers' preliminary tally of retailers' revenue at stores open at least a year -- a key indicator of a merchant's health -- was up 4.6 percent, a slower pace than June's 6.9 percent gain but in line with forecasts.
While the numbers offer encouraging signs for the start to the back-to-school shopping period, which runs roughly from mid-July through September, there are concerns that shoppers will stick to the habits of the Great Recession by focusing on necessities and waiting for sales. That could be a big problem for retailers, which are raising prices in order to offset rising fuel, labor and other production costs.
"Early going, July looks like it's shaping up to be a solid month despite all the economic headwinds," said Ken Perkins, the president of RetailMetrics LLC., a research firm. "But the concern is whether shoppers will buy back-to-school items at full price."
The back-to-school season is important for retailers because it accounts for 16.1 percent of annual retailers' revenue, according to the International Council of Shopping Centers.
It's also an opportunity for retailers to gain insight into consumers' shopping habits heading into the biggest shopping season of the year, which starts on the day after Thanksgiving.
Retailers will get a better sense of how consumers are spending during the back-to-school season in August when the bulk of the purchases is done. But so far, analysts and retail trade groups are sticking to their forecasts for the season, ranging from unchanged to up 3 percent compared with a year ago. The National Retail Federation expects families to spend $603.63 on back-to-school items, from clothing to supplies, down slightly from last year's $606.40.
"Overall, July sales reports were decent, but the worry is when you look further out over the next three to six months," said Michael P. Niemira, the chief economist at the ICSC. "The growing economic uncertainty may take its toll on future spending."


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It was my last full day in Victoria. We decided to celebrate it by staying in a beautiful Victorian Bed and Breakfast called the Humboldt House. As we waited for our room I got to look around the eye catching waiting area. Antiques were spread out all around and the furniture looked like it belonged in a historical romance
novel. I imagine Jane Austen would be very comfortable here. When we got the key to our bedroom, we saw that the door was labeled "the Mikado". We stepped inside and our breath was swept away. Comely, Comfy and reminiscent of the Japanese culture, this room was worthy of its name. Here another lovely bottle of champagne was accompanied with chocolate truffles. My companion and I didn't wait to enjoy them.
Chocolate and champagne is wonderful but we still needed to eat. Luckily, we found a marvelous place that was just a couple of blocks away, The Old Spaghetti Factory. A classic Italian restaurant that originated in beautiful BC (Vancouver to be precise). If you want something yummy go for the crisp green salad with spaghetti and mushroom sauce. Delicious! My companion strongly recommends the same thing for all you meatatrians except add on the Meatballs. Don't forget to enjoy the bread with the whipped garlic butter. That stuff is dynamite.
So after a big meal like that, I am ready for my next adventure. The very famous Victoria's Own Ghostly Walks. Creepy, entertaining and informative, this walk is a writer's dream. You will get all kinds of inspiration from the stories. My two favorite stories were of a man named Joe Newana (I hope I spelled that right) who was from Hawaii and
a very dangerous man. If you want this ghost to leave you alone, you have to tell him a joke and make him laugh. I guess I said something funny that night because I sure didn't see him. The other awesome story is the tale of the Humboldt/ Douglas Street vortex. At this intersection, people have disappeared without a trace. The most famous case was of a whole city bus disappearing into thin air with many people in it. How crazy is that?
My group and I managed to avoid any supernatural bad luck but I will never forget the stories. The ghost walk is a unique way to learn about Victoria's rich, albeit freaky, history and get some good exercise (or exorcise). Either way, it is good for everybody and the fresh air is good for the soul. It certainly helped me sleep that night, not that I needed help at the contented, serene Humboldt House. The next morning, I


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A new car called Barnard is being finished up in South Africa (Perana Z-One by Zagato is also from South Africa) just outside Bloemfontein. The name may not get one all excited but it will certainly match the performance of some of the finest brands in Europe.
The Barnard was conceived, designed and produced in South Africa and comes with an acceleration rate of 0-100km/h in under four seconds and moves on to attain a maximum speed of more than 300km/h.
There are also plans to make a variant that will bump top speed to 400km/h, but performance is not attained in a straight line. The mind behind the car belongs to Chris Barnard, who has a true passion for endurance racing and always envision making a race car the Le Mans style.
As such the Barnard does not come with power steering, vacuum-assisted or anti-lock brakes, traction control and power windows.
It comes, however, with a monocoque chassis made from advanced steels and a body built almost entirely out of composite materials. Assisting performance is a number of aero enhancements with a flat undertray, rear air diffuser, and remarkable cutouts in the wheel arches at the front.
The arrangement of the chassis has been designed to look like that of the original Porsche 962 and its powerplant option, a twin-turbocharged V8, also comes from Porsche. Considerable modified inside and out, the Porsche powerplant is rated at about 617hp (460kW) but that figure can still be bumped appreciably prior to production.
The Barnard, unlike other well-know and established brands, can be built to suit the customer's specifications based on the powertrain. The car was built to go with most overhead camshaft V8s made by the luxury brands of Europe. The work on the Barnard is still ongoing, bit delivers should be here by the middle of this year and expected pricing will be around $110,000.


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Published on : Saturday, November 5, 2016
Khaled al-Anany, Egypt's Antiquities Minister declared that there is a decrease in the price of the Luxor Pass, which gives access to ancient monuments in the city and the surrounding area.
Anany was speaking at the 5th Global Summit on City Tourism in Luxor. He said that the board of the Supreme Council of Antiquities (SCA) permitted the price reduction at its last meeting on Sunday. This decision is for attracting tourists to Egypt and for funding the ministry's work for renovating tombs and museums.
Anany's announcement was combined with opening of the tombs of Seti I and Nefertari to visitors. Luxor is currently hosting the Global Summit organized by the UNWTO for boosting and improving its tourism globally. Mostafa Amin, secretary general of the Supreme Council of Antiquities, said the first type of Luxor Pass had been lessened from US$270 to $200. This pass helps visiting all the archaeological sites, including those of Seti I and Nefertari. The second permit price has also been lessened from $110 to $100.
Tags: Antiquities Ministry, Egypt


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I mean The Sacred Valley and Machu Picchu are amazing, and the idea of leaving the Incan ruins for a city that have Spanish buildings, namely cathedrals, built on top of the Incan ruins sounded like such a turnoff. I honestly felt like I didn't care to learn the history of how Spain conquered one of the greatest civilizations, and that I'd feel really sad seeing modified ruins.
And oh boy did we fall in love with Cusco!
Even with the tourist traps and the fact that most people stopped to ask me to take their picture, I still love Cusco. Jacob couldn't resist taking at least one picture of me offering my services. I guess a DSLR around your neck lets people know you're likely capable.
We loved touring the Cathedral of Santo Domingo. It's definitely worth the price, and if you don't have a local who knows all the happenings, be sure to get a tour guide.
As much as I hated the idea of Incan ruins being converted to modern buildings, when I saw it in practice I was in awe, so beautiful!
My other favorite thing was the fact that every single building has a cool door. They are either beat up and what most Americans pay big money for in the shabby chic scene, or completely ornate and elaborate. I started taking pictures of us just in front of the doors.
We also got excited to find the famous 12 point stone in the historic part of town.
Seriously, one day of touring three Cathedrals, walking through town, and talking to the locals, and Cusco had a big piece of my heart.
Beyond Dinner and a Movie
Grab Our 5 Ways to Keep Your Love Alive and Make Date Night Fun


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Mud Glorious Mud / directed by Steve Asquith, David Mitton ; produced by Britt Allcroft ; written by Jonathan Trueman ... [and others].
Available copies
- 1 of 1 copy available at Evergreen Indiana.
Current holds
0 current holds with 1 total copy.
|Call Number / Copy Notes
|Shelving Location
|Due Date
|Garrett PL - Garrett
|JDVD THO (Text)
|Juvenile DVD
Record details
- Physical Description: 1 videodisc (40 min.) : sound, color ; 4 3/4 in.
- Publisher: Troy, MI : Anchor Bay Entertainment, 2008.
Content descriptions
|General Note:
| Based on the books by Rev. W. Awdry.
Features: sing alongs, character gallery, activity sheet, sneek peeks.
|Formatted Contents Note:
| Edward the really useful engine -- Thomas and the avalanche -- Missing freight cars -- Mud glorious mud -- A friend in need -- Edward, Trevor and the really useful party.
|Participant or Performer Note:
| Narrators: Alec Baldwin, George Carlin, Michael Brandon.
|Date/Time and Place of an Event Note:
| Originally broadcast on television 1991-2007.
|Summary, etc.:
| On the magical island of Sodor, Thomas and his cohort work together when they confront bad weather.
|Target Audience Note:
| TV rating: Not rated.
|System Details Note:
| DVD, Dolby digital stereo.
|Terms Governing Use and Reproduction Note:
| For private home use only.
|Language Note:
| Closed-captioned.
Search for related items by subject
|Awdry, W. > Television adaptations.
Thomas, the Tank Engine (Fictitious character) > Juvenile films.
Railroad trains > Juvenile films.
Thomas, the Tank Engine (Fictitious character) > Drama.
Railroad trains > Drama.
|Children's television programs.
Animated television programs.
Television adaptations.
Video recordings for the hearing impaired.
Fiction television programs.
Fiction television programs.


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Visit our sister site, BirdSong Nature Shop, for great prices on thousands of backyard birding items:
|A ruby horsechestnut
G. Lumis
|The leaves of ruby horsechestnut
G. Lumis
|The fruit and leaves of a ruby horsechestnut
G. Lumis
Scientific Name: Aesculus X carnea
Hardiness Zones: 3 to 7
Height: 35 ft
Spread: 35 ft
Form: rounded
Type: deciduous tree
Annual Growth Rate: less than 12 inches
Flowers: Red
A small, rounded tree with red flowers in the spring. It may not be as susceptible to foliage problems as A. hippocastanum. The compound leaves are dark green, but their size gives the tree a coarse texture.
'Briotti' (Ruby Horsechestnut) - A hybrid tree that bears clusters of bright red flowers and has heat resistant dark, green foliage.
'Fort McNair' - Flowers pink with a yellow throat.
'O'Neill's Red' - Red flowers.
Text courtesy Michigan State University Extension


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Adobe has launched a platform called Advertiser Cloud that will allow its customers to manage and buy its digital and TV ads, the company announced Tuesday.
The launch follows Adobe's $540 million acquisition of video ad tech company TubeMogul, which closed in December.
The Adobe Advertising Cloud includes three components: Search, TubeMogul's demand-side platform, and what Adobe calls "dynamic creative optimization," which lets marketers change and test what their ads look like, depending on their performance.
The Advertiser Cloud will also integrate with other existing products that marketers use, such as Adobe Analytics.
Speaking to Business Insider, Brett Wilson, the former TubeMogul CEO and current vice president and general manager of advertising at Adobe, said: "Adobe, traditionally, has been known for having a marketing cloud that primarily helped advertisers measure interactions with their audience and data. Advertisers usually have totally separate media execution software. Adobe is the first marketing cloud to have a fully executable advertising layer, riding the gap between martech and ad tech."
Adobe's closest competitors — Salesforce and Oracle — have long been seen as potential strategic buyers of ad tech companies as they look to grow out the services they can offer their marketing customers. However, while both of Adobe's rivals have made major acquisitions in the marketing tech and data space, they have yet to provide marketers demand-side platform software that allows them to buy ads. Some observers within the ad tech industry think Adobe's acquisition of TubeMogul could spur Salesforce and Oracle into reactively buying more companies in the ad tech sector.
Wilson said a big problem for marketers right now is "leaky integrations" between analytics software and media execution software, which results in lost time trying to pair the two.
Consolidation saves time,…


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Emerson Network Power, a business of Emerson (NYSE:EMR) and the global leader in enabling Business-Critical Continuity, announced the Innovation Partnership Program for its Embedded Computing business. The new program, comprised of a broad range of collaborative software vendors, suppliers and integrators, expands Emerson Network Power's portfolio of solutions in multiple embedded computing markets.
Within the program, participating companies work with Emerson to meet customers' application-specific needs by transforming leading-edge embedded technologies into globally available business solutions. Partner products are tested for compatibility and interoperability with Emerson's hardware and software products. With a diverse array of partners spanning a broad range of technologies and applications, the Innovation Partnership Program ensures that customers will receive comprehensive, application-specific solutions with guaranteed interoperability from a single source.
Partners are invited by Emerson to the program and participate at one of three program levels based on a wide range of factors including technology, ecosystem contribution and business objectives. The program levels are Strategic Partner, Integrated Solution Partner and Emerson Compatible Partner.
Emerson Network Power's Strategic Partners include: Cavium Networks, EMC Corporation, Freescale Semiconductor, Hybricon Corporation, Intel® Corporation, Interphase Corporation, MontaVista Software, Inc., and Wind River Systems, Inc.
Integrated Solution Partners include 6WIND, IP Infusion and Red Hat, Inc. Emerson Compatible Partners include Astute Networks, GoAhead Software, SANBlaze Technology, Inc, SURF Communication Solutions, Tail-f Systems and VirtualLogix.
"The broad range of technologies and applications that our partners bring to the table enhances our product portfolio and gives us access to untapped markets," said Jorge Magalhaes, vice president of marketing for the Embedded Computing business of Emerson Network Power. "Working with our partners to deliver innovative solutions directly to the street ensures product interoperability, enables us to meet emerging customer needs and strengthens the embedded computing ecosystem."
About Emerson Network Power
Emerson Network Power, a business of Emerson (NYSE:EMR), is the global leader in enabling Business-Critical ContinuityTM from grid to chip for telecommunication networks, data centers, health care and industrial facilities. Emerson Network Power provides innovative solutions and expertise in areas including AC and DC power and precision cooling systems, embedded computing and power, integrated racks and enclosures, power switching and controls, monitoring, and connectivity. All solutions are supported globally by local Emerson Network Power service technicians.
About Emerson
Emerson (NYSE: EMR), based in St. Louis, Missouri, USA, is a global leader in bringing technology and engineering together to provide innovative solutions to customers through its network power, process management, industrial automation, climate technologies, and appliance and tools businesses. Sales in fiscal 2008 were $24.8 billion. For more information, visit www.Emerson.com.
Business-Critical Continuity, Emerson Network Power and the Emerson Network Power logo are trademarks and service marks of Emerson Electric Co. AdvancedTCA, ATCA and CompactPCI are registered trademarks, and MicroTCA is a trademark of the PCI Industrial Computer Manufacturers Group (PICMG). Intel® is a trademark or registered trademark of Intel Corporation or its subsidiaries in the United States and other countries.


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#LoveAudio? Are you a student pursuing a degree in Audio Arts & Acoustics? Experience in your field is key. Whether you have set your career goals, or you are still exploring your options, this event is for you. Panelists will share what it took for them to succeed, and how you can make a name for yourself in the industry.
The panel will cover:
• Employability of an Audio Professional
• Establishing your brand and owning your own studio
• Building clientele as a freelancer
• Juggling part-time and freelance work
• The importance of an internship
• How to excel as a session, live, or sound engineer or music producer
• Handling a myriad of projects in music, TV, film, voiceover, and live sound
Confirmed panelists so far include*:
Matt Edgar is the Founder and President of Audio Integration Services (AIS), in Chicago. The company was founded in 2007 and quickly grew from a home office, to a full installation shop. By 2008, AIS began doing installs nationally and internationally, and became the North American distributor for Void Acoustics. AIS has positioned itself for not only their design capability, but their unparalleled event production, by using the latest technology to design elegant sonic and visual solutions for event productions or install.
Johnny Gaskill is Production Director for Special Events Management in Chicago. If there's a live music act at a Special Events Management produced street fest, you can bet Johnny is involved. From overseeing staging/sound systems to working closely with performers, bands and their management months ahead of their event appearances, he's tireless. Johnny makes sure everything runs smoothly for nearly 250 acts at 50-plus events each year.
Michael Kolar has been working in the recording/music industry since 1994. Having over 20 years experience, Michael is fluent in rap, rock, gospel, and R&B music. With a combined total of over 20 million plays on SoundCloud of Michael's mixes, local and national artists seek him out for a competitive sound. As former Vice President of the Engineering & Recording Society, Michael's technical expertise matches his creativity and love of music. He has worked with a bevy of artists from Chance the Rapper to Zayn Malik.
Colin Sipos is a Chicago-based commercial music composer/Senior Audio Engineer with Earhole Studios in Chicago. Additionally, he is an independent record producer. A musician from age 11, he nurtured his talent exploring the poles of music in school ensembles, garage bands, and riffing through his parents' record collection. Fast forward, passion bloomed into profession.
Joe Tessone is the president of Mystery Street Recording Company and its lead audio engineer. He is a graduate of Columbia College with a degree in Audio Design and Production. His specialties include recording, mixing, and mastering, as well as analog audio preservation and in-ear monitor consulting.
*Panelists are subject to change with availability.
School of Media Arts, Audio Arts and Acoustics, Students, Career Center, School of Fine and Performing Arts, Music
Tom Joyce
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About Margaret Thatcher
Margaret Thatcher changed the way people saw women in politics. When she grew up she became Great Britain's first female prime minister. Not only that, she was prime minister for longer than anyone else in the twentieth century. Eleven years! She was a member of Britain's Conservative Party and won three elections in a row. Margaret was not afraid to speak her mind, and not everyone liked her way of thinking. One journalist even called her the "Iron Lady." The nickname stuck, but that didn't affect Margaret. She stayed true to herself and is remembered as one of the most important politicians in Great Britain's history.
Margaret's Childhood
Margaret was born in 1925 in the small town of Grantham, England. Her parents, Alfred and Beatrice, ran a grocery store. Margaret lived above the store with her parents and older sister, Muriel. Margaret and Muriel both attended a local public school in town and sometimes worked at the grocery.
Her parents were Methodists and often helped neighborhood charities. Margaret's father was also the mayor of the town. She liked listening to him talk about what was happening in the world. This made her get interested in politics.
For fun, Margaret would go to the cinema, which was a new thing back then. She loved movies! She also enjoyed listening to the radio.
Science or Politics?
Margaret went to Oxford University where she studied chemistry. As a student, she became more interested in politics. Although Margaret loved chemistry, she decided to follow in her father's footsteps and become a politician.
She never forgot chemistry though. She often said that she was more proud to be the first prime minister with a science degree than to be the first female prime minister.
Margaret's Political Life
Margaret ran for the parliamentary seat in Dartford when she was just in her twenties. (Parliament is responsible for making British law.) She lost, twice. Then she returned to school to get her law degree.
Although Margaret lost the election, she never lost her ability to get people to listen to her and she spoke easily to people. In 1959, Margaret finally won a seat in the House of Commons. From there she rose up to become the first woman to lead the Conservative Party in 1975. And then, in 1979, she became the prime minster of Great Britain.
Being Prime Minister
As prime minister, Margaret changed many things in England. By the end of the 1980s the British economy was much stronger and more people had jobs. Margaret was considered responsible for the country's prosperity and stability.
Being a Woman in Politics
Although Margaret Thatcher became popular as prime minister, she was often criticized because she was a woman in politics. She was once asked by Parliament if she found it hard to balance career and the duties as a mother. She often did not like being asked to explain her work and family circumstances.
Later in life, Margaret wrote two best-selling memoirs while touring the world as a speaker. In 2011, a movie based on her life called The Iron Lady came out. It starred Meryl Streep who plays Margaret.


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The charming boutique shops, cafes and restaurants along The Kingsway on Bloor are even more beautiful when decorated with the twinkling lights and festive decorations of the holiday season. This residential area, located in Toronto's west end, just west of the historic Old Mill Inn and Spa, features all the winter activities you desire – without the hassle and congestion of being downtown. It's an excellent perfect place to take a leisurely stroll, stop for warm mug of hot chocolate, or maybe enjoy dinner with friends after some holiday shopping.
Looking for something a little more active? You won't have to go far. Toronto's west end is the perfect location for starting off your winter fun! Lace up your skates and head over to Colonel Sam Smith Park, Toronto's first outdoor skating trail. The outdoor trail is 250 metres long and offers a nice change of pace from the usual counter-clockwise skating routine, and a picturesque view of the lake. If you have little ones with you, or newbie skaters, there is even an open area providing a spot for those just learning.
If slopes are more your style but getting out of the city isn't in the cards, the Centennial Park Skiing and Snowboard Centre should fulfill your adrenaline needs! The park is a favourite ski and snowboard destination among Etobicoke residents and certainly closer than Whistler!
How about some food to fuel all these activities? Enjoy dishes like rigatoni with smoked chicken and bacon, leaks and asiago cream or maple mustard seared salmon with white wine thyme sauce at Grappa Restaurant or a classic "Steak & Frites" at Merlot Restaurant. Other restaurants such as Santa Monica Trattoria and ViBo are all wonderful options, too.
If you prefer to do your own cooking and creating, be sure to visit the year-round Montgomery's Inn Farmers Market. The market is held every Wednesday from 2pm to 6pm. During the winter months, the market runs indoors with a great selection of organic fruits and vegetables, fresh bread, fine cheeses and wine. Local farmers and food artisans bring ethically raised meat and honey as well. It's a great place to find the perfect ingredients for a delicious and comforting soup or stew to banish the chill of a winter's day.
And since it is the start of the holiday season, we thought we'd share a tip on one place to find a ton of great ideas and decorations! Just a short drive north, Plant World creates its annual Christmas Shop, with stunning displays and scenes set up throughout their warehouse. With an array of wreathes, ornaments, candles, ribbon and more, it's hard to imagine you'll need to visit anywhere else for all your holiday decorations.
From skates to skis, fine dining to homemade cooking, the BlOORVISTA neighbourhood is the perfect spot for all of your winter fun.