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15 reviews | 3.7 out of 5
I eagerly awaited this game. I bought it at Wal-Mart on the release day. Brought it home, and boy was it real. I couldn't do a thing with the car. I crashed, wrecked, and couldn't finish a race at first. That night was very disappointing. I tried again at 7 this morning. By 1pm I was winning races at the Rookie level. By 5pm I was winning races with no computer assistance. I'm not ready to deal with tires and fuel, yet. I should be ready in another day or two. I found it hard with the wheel. I like the controller and nunchuck. Following the grooves on the tracks is recommended. I haven't been able to consistantly do that after 10 hours of play. Driving in traffic is hard. Short Courses are rediculous. Road courses are impossible. I recommend playing an entire season on Rookie before moving on. You've got to practice before you race on most of the courses, or you will wreck a lot or restart your races over and over. Very good game. Very realistic. I recommend for all NASCAR fans!
I play this game every day it gets me exited and it gets your adrenalin pumping you feel like your in the race awesome game
Once you start playing it you will not put the controller down. I keep playing it every single minute of the day that I have free. It will not disappoint you.
Gift for my husband. It took him a while to get used to the steering, but he really likes to play it.
Graphics are not as good as I thought it would be. Fun game to play.
Bought for Father's Day gift and enjoyed by all!!
Son and hubby loves it !!!!!!!!!!!!!!
Very disapointed no where nesr what advertised
I expected a game that would be able to play with the wii wheel being that it was set up for the wii.
I am not happy, but will keep it for my grandchildren to play. I just as it is a nascar game it's something i'd like, but that ship has sailed.
Do not...I REPEAT DO NOT buy this game! Total disappointment. you cannot control the car. they did a good job on the graphics and other stuff. Game would be great if you could successfully play it
Don't bother with this game. If you want a fun Nascar game for the Wii, get yourself Nascar 2005 by EA Sports and some Wavebird Gamecube controllers. This game is so poor even my teenage kids won't want to play it. Can't believe that I wasted my money on this. SO VERY DISAPPOINTING! Nascar should be ashamed of this product!
After getting used to not over compensating turns this game keeps my grandson on the edge of his seat. It's fast paced and various levels that have a mixture of easy to harder. Well worth buying this game.
If you are a teen, this may work for you but for little kids about 6 or 7 it does not work. extremely complicated hard to control.


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Up 113,903 this week
Renato Baldini (1921–1995)
Renato Baldini was born on December 18, 1921 in Rome, Lazio, Italy. He is known for his work on Girl with a Suitcase (1961), Winnetou: The Red Gentleman (1964) and Four Ways Out (1951). He died on July 5, 1995 in Rome. See full bio »
Born:in Rome, Lazio, Italy
Died:(age 73) in Rome, Lazio, Italy

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Note: Power supply is not in the package, if you need one, you can order this power adapter (SKU code: PJ0015.)
1. 96 High-quality 850nm IR LED 2. 10mm LED diameter, high power 3. 100M night vision distance 4. Power AC110-220V, DC12V or AC 24V (optional)
5. Beam Angle: 15deg
Gross Dimension: 17.5cm(W) X 12.5cm(L) X 11.5cm(H) Work Temperature: 0 C to +40 C Weight: about 1000g Power supply: DC 12V or AC 24V or AC100-240V
Posted by S****n on 17th May 2011
quick and got what was described,thanks
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Posted by L*****e on 16th Sep 2010
the quality is OK, good for night view camera


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Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors
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- Bonde, AK., Tischler, V., Kumar, S. et al. BMC Cancer (2012) 12: 35. doi:10.1186/1471-2407-12-35
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Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells.
We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC).
Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade.
Data presented here identify a novel role for macrophages in EMT-promoted tumor progression. The observation that TAMs cluster with intra-epithelial fibroblastoid cells suggests that the role of macrophages in tumor-EMT extends beyond the invasive front. As macrophage infiltration and pronounced EMT tumor phenotype correlate with increased grade in NSCLC patients, we propose that TAMs also promote tumor progression by inducing EMT locally in tumors.
KeywordsTumor-associated macrophages (TAMs) Macrophage depletion Clodronate liposomes Tumor progression Tumor invasion Epithelial-mesenchymal transition (EMT) TGF-β
The malignant potential of solid tumors highly depends on adjacent stromal cells such as cancer associated fibroblasts (CAFs), mesenchymal stem cells (MSCs) and immune cells [1, 2, 3, 4]. Macrophages belong to the latter, and their migration from the stroma into tumors correlates inversely with patient survival in many cancers, among others breast, lung and thyroid carcinoma as well as Hodgkin's lymphoma [5, 6, 7, 8, 9]. These correlations have largely been related to the macrophage secretome which involves factors that stimulate tumor cell proliferation and survival, angiogenesis and release of proteases essential for extracellular matrix (ECM) remodeling [10, 11, 12]. Vice versa, several paracrine signaling loops have been identified through which macrophages orchestrate invasion of tumor epithelia into its own newly formed desmoplastic stroma [13, 14, 15, 16, 17, 18].
An important step in tumor progression is the acquisition of invasive properties by tumor cells. EMT is a well characterized mechanism, through which epithelial cells trans-differentiate and acquire an invasive mesenchymal phenotype [19, 20]. EMT has recently been recognized for its involvement in disease progression and the mechanisms have been linked to metastasis and to the generation of cancer stem cell-like cells [21, 22, 23, 24, 25]. Concordantly, we have previously identified strong correlations between EMT-associated marker expression in non-small cell lung cancer (NSCLC) patients and various clinico-pathologic parameters of tumor progression, such as size and decreased survival [26].
As EMT represents a crucial step in disease progression it is of importance to identify and characterize the mechanisms regulating this process. Whereas it is well established that the stroma hosts cytokines, growth factors and enzymes that can induce EMT, the sources of these factors remain to be fully indentified [27, 28, 29, 30, 31, 32, 33, 34, 35, 36]. CAFs, MSCs and Th2 polarized CD4+/CD8+ T-lymphocytes have all been shown to contribute to EMT at the tumor-stroma interface [37, 38, 39, 40, 41]. Pro inflammatory macrophages (classically activated or M1) have likewise been shown to induce EMT at the invasive front mainly through TNF-α mediated stabilization of Snail, a key mediator and marker of EMT [21, 42]. Interestingly, M1 TAM induced EMT in tumor cells located at the invasive front correlates with metastatic disease in a murine breast cancer model which underscores the importance of both EMT and macrophages in disease progression [21].
In this study we asked if TAMs regulate EMT in intratumoral epithelial cells, as well at the invasive front. We used clodronate-liposomes (clodrolip) to deplete TAMs in F9-teratocarinomas. In combination with established in vitro culture techniques we identified alternatively activated M2 macrophages as potent regulators of EMT in F9-tumor cells as well as in the murine epithelial mammary gland cell line, NMuMG. In a candidate screen, we identified macrophage-derived TGF-β and consecutive activation of the β-catenin pathway as mechanisms of action. An important aspect of this study was to evaluate the clinical relevance of TAM-induced EMT in disease progression. This was addressed in a NSCLC tissue microarray cohort, which confirmed a significant correlation between intratumoral macrophage density, EMT markers, intraepithelial TGF-β levels and tumor grade. The data presented here identify intratumoral macrophages as potent regulators of intraepithelial EMT, adding another level to the importance of macrophages in EMT and disease progression.
Antibodies and reagents
Primary antibodies: Anti-rat-E-cadherin, anti-rabbit-β-actin, anti-mouse-vimentin, anti-rabbit-fibronectin all from Abcam, Cambrigde, MA; anti-rabbit-β-catenin (Sigma-Aldrich, St. Louis, MO), CD68-Alexa-488 and F4/80-Alexa-647 (AbD Serotec, Düsseldorf, Germany) and anti-mouse-active-β-catenin (Millipore, Billerica, MA). Secondary antibodies: Goat-anti-rat-IgG-TRITC (Sigma-Aldrich, St. Louis, MO); chicken-anti-rabbit-Alexa-594 (Molecular Probes, Carlsbad, CA); biotin-SP-donkey-anti-rabbit-IgG, biotin-SP-donkey-anti-rat-IgG, and biotin-SP-donkey-anti-mouse-IgG (Jackson ImmunoResearch Laboratories, INC, Suffolk, UK). Streptavidin-HRP (Biolegends, San Diego, CA) was used to detect biotin labeled secondary antibodies. Recombinant TGF-β1 and TGF-β neutralizing antibody was purchased from R&D Biosystems (Minneapolis, MN) and recombinant EGF was kindly provided by Dr. A. Mueller, IMCR, University of Zürich, Switzerland. LEAF (low endotoxin azide free) purified mouse IgG1, κ isotype control antibody was obtained from BioLegends (San Diego, CA). Recombinant IL-4 and IL-13 were from Biosource (Camarillo, CA).
Cell lines and conditioned media
F9-teratocarcinoma cells (ATCC CRL-1720) were grown on 0.01% gelatin. NMuMG-cells (CRL-1636) were kindly provided by Prof. G. Christofori, Center for Biomedicine, University of Basel, Switzerland. Both cell lines were cultured at 37°C, 5% CO2 in DMEM/10% FBS/0.8% penicillin-streptomycin. RAW264.7 macrophages (Sigma-Aldrich, St. Louis, MO) were cultured at 37°C, 5% CO2 in RPMI1640/10% FBS/0.8% penicillin-streptomycin/1% Na-pyruvate (GIBCO, Basel, Switzerland). Conditioned medium was generated by culturing cells at 80% confluence in DMEM/10% FBS/0.8% penicillin-streptomycin for 24 h followed by sterile filtration. RAW264.7 macrophages were M2 polarized by culturing in DMEM/10% FBS plus recombinant IL-4 and IL-13 for 48 h (each 10 ng/ml) as previously described [43].
F9 tumors and macrophage depletion
F9-tumors were generated in female SV129S1 mice (Charles River, Sulzfeld, Germany) and liposomes were prepared as previously described [11]. Mice were kept in standard housing and normal diet at the animal facility of the University of Zürich. Animal studies were approved by the Veterinary Department of the Canton Zürich and performed under license 183/2006 issued to R.A. Schwendener. The control group (n = 6) received empty liposomes (100 μl/20 g body weight, i.p.), the test group (n = 6) clodrolip (1.5 mg clodronate/20 g body weight, i.p.) starting 6 h post tumor inoculation and followed by the same dosage every 3rd day for 20 days. Tumors subjected to immunohistochemistry and protein analysis were stored in Hanks salt buffer (GIBCO, Basel, Switzerland) at -80°C. Tumors subjected to q-PCR were stored in RNAlater as described by the provider (Qiagen, Valencia, CA). Data are shown from two independent experiments and non-responders as assayed by q-PCR of Csfr-1 were excluded from the study unless otherwise noted.
H&E staining, immunohistochemistry and quantification of frozen F9 tissue sections
Frozen sections (8 μm) were acetone fixed. The sections were either stained with haematoxylin and eosin (DAKO, Glostrup, Denmark) following the providers protocol or blocked with 1% BSA/TBS prior to immunostaining. For immunohistochemistry, the sections were incubated with primary and secondary antibodies overnight at 4°C. Nuclei were stained with DAPI (1 μg/ml). The sections were mounted with Vectashield (Vector Labs, Burlingame, CA) and visualized with an Olympus fluorescence microscope (1X81) using the CellR software (Olympus, Hamburg, Germany). The pictures were merged in Adobe Photoshop CS4. Macrophage density was quantitatively estimated by counting the absolute number of CD68+ and F4/80+ cells and the total number of DAPI positive cells in defined areas throughout tumor sections using ImageJ software (NIH, Bethesda, MD). Quantification and correlation of macrophage density and tumor cell expression of EMT-associated markers was similarly done in a quantitative manner, using ImageJ to count the absolute number of CD68+ and EMT-marker positive cells in defined areas throughout the tumor sections. The quantifications were done on 6-10 individual sections from various control and clodrolip treated tumors sampled from two independent experiments.
In vitro induction of EMT and immunofluorescence analysis of F9-and NMuMG-cells
F9-and NMuMG-cells were cultured on sterile glass coverslips in F9-CM, N-CM, M-CM +/- LEAF purified IgG1 control antibody (1 μg/ml) or TGF-β neutralizing antibody (1 μg/ml), DMEM/10% FBS +/- rEGF (50-100 ng/ml) or +/- rTGF-β1 (2 ng/ml). The medium was renewed every 24 h. The cells were harvested at the time points annotated, fixed with 3% formaldehyde, stained and visualized as described for frozen sections.
In vitro invasion assay
The cells were starved in serum free medium for 6 h and seeded (100.000 cells/well) in Boyden chambers (Corning, NY, 8 μm pore size) coated with 50 μl 1% Matrigel (BD Biosciences, Rockville, MD). F9-CM, N-CM and M-CM +/-LEAF purified IgG1 control antibody (1 μg/ml) or +/- TGF-β neutralizing antibody (1 μg/ml) were used as chemoattractants. The assay was incubated for 48 h at 37°C, 5% CO2. The relative number of invading cells was estimated by resazurin live cell detection using the provider's protocol (Invitrogen, Carlsbad, CA). Fold invasion was calculated relative to control conditions.
TOPFLASH reporter assay
The TOPFLASH reporter assay was established as previously described [44]. The fold values were calculated as TOPFLASH/FOPFLASH, where TOPFLASH is the plasmid expressing luciferase downstream of three wild type β-catenin/Tcf binding sites, and FOPFLASH is the plasmid with mutated binding sites. Renilla pRL SV40 was included as transfection control. Luciferase was detected using the Dual Glo Luciferase detection kit (Promega, Madison, WI). The cells were transfected two days prior to luciferase readout using a standard in-house transfection protocol. Fold changes were calculated relative to controls.
Western blots
F9-and NMuMG-cells were lysed 1% NP-40, 100 mM orthovanadate, 100 mM 3-indoleacetic acid (IAA), 100 mM phenylmethylsulfonylfluoride (PMSF) at annotated time points and snap frozen in liquid nitrogen. Frozen tumors were cut into small pieces and soaked in lysis buffer and homogenized using an Ultra Turrax T8 homogenizer (IKA-Werke, Staufen, Germany). Protein concentration was determined by Bradford analysis (Bio-Rad, Reinach BL, Switzerland). The blots were quantified using ImageQuant 5.2 software (Amersham Biosciences, Piscataway, NJ). Protein expression was normalized to β-actin levels.
Quantitative real time PCR
Total RNA was isolated from homogenized F9-tumors using the RNAeasy kit (Qiagen, Valencia, CA). cDNA was synthesized using the Omniscript reverse transcriptase kit (Qiagen, Valencia, CA). Q-PCRs were carried out using the LightCycler 480 instrument (Roche Diagnostics, Rotkreuz, Switzerland). PCR program: 95°C, 5 min, 45 cycles of 10 s 95°C, 25 s annealing and 15 s 72°C. Primers were obtained from Microsynth, Switzerland, (for primer sequences and annealing temperatures, see Additional file 1: Table S1). The quality of the PCR-products was assayed on 1.5% agarose gels. Expression of all target genes was normalized to β-actin and GAPDH. All samples were run in duplicates; n = 5-6/per group. Fold change was calculated as clodrolip treated versus control tumors using the Pfaffl equation [45].
NSCLC tissue microarrays and patient cohort
The selection of NSCLC patient tissue samples and manufacture of the tissue microarrays (TMAs) were done as previously described [26]. In brief, formalin-fixed and paraffin-embedded tumor tissues of 532 NSCLC patients were reviewed by two pathologists and two representative tissue cores (0.6 mm) were assembled into 3 TMAs. Patients having obtained neo-adjuvant chemotherapy were excluded. Sarcomatoid carcinomas were excluded from this study and EMT was strictly defined by expression of EMT-associated protein markers and not by morphology (n final = 491). The study was approved by the institutional review board of the University Hospital Zürich under reference number StV-29-2009.
NSCLC immunohistochemistry and interpretation
Immunohistochemistry on 4 μm sections from the TMA blocks was performed using automated immunohistochemistry platforms from either Ventana (Ventana Medical Systems, Tucson, AZ) or Bond (Vision Biosystems, Melbourne, Australia). Following primary monoclonal antibodies were used: anti-CD68 (DAKO-Cytomation, clone PG-M1, 1:50 dilution, Glostrup, Denmark), anti-E-cadherin (Cell Marque, clone EP700Y, 1:200), anti-β-catenin (BD Transduction laboratories, clone 14, 1:50, Lexington, KY), anti-vimentin (DAKO-Cytomation, 1:250), Pab anti-periostin (BioVendor, 1:500, Modrice, Czech Republic) and anti-TGF-β1 (Santa Cruz, 1:100 dilution). Detection was done using the UltraVIEW-DAB (Ventana Medical Systems) or the Refine-DAB (Bond) detection kits, including respective secondary antibodies. Distinct intra-epithelial CD68+ macrophage density was quantitatively scored by AKB and by two pathologists (VT and AS) on a multi-headed microscope (Zeiss Axioscope 2 MOT) using a four-tiered system: 0 (negative), 1+ (few to some CD68+ macrophages), 2+ (moderate number of CD68+ macrophages), and 3+ (multiple CD68+ macrophages). Membranous β-catenin (AKB and VT) and membranous E-cadherin (VT and AS) were evaluated for staining intensity according to a four-tiered system: 0 (negative, no detectable staining), 1+ (weak, faint discontinuous membrane staining), 2+ (moderate and continuous membrane staining), 3+ (strong and continuous membrane staining). Cytoplasmic β-catenin (AKB and VT), cytoplasmic vimentin (AKB and AS), cytoplasmic periostin (VT and AS) were scored due to staining intensity: 0 (negative), 1+ (weak), 2+ (moderate), and 3+ (strong) and TGF-β1 (AKB and VT) was scored for intraepithelial staining intensity: 0 (negative), 1+ (weak), 2+ (moderate), and 3+ (strong).
Statistical methods and correlation interpretation
The statistical analyses of all in vitro assays were performed using the GraphPad Prism 5 software (GraphPad Software, La Jolla, CA). All data are reported as mean ± SEM. The significance levels were evaluated by two tailed, unpaired t-tests; *P < 0.05, **P < 0.01. The statistical and correlation analyses of the NSCLC tissue samples were done in SPSS 16.0 for windows (IBM, Somers, NY) using the Spearmann correlation coefficient as a readout for degree of correlation with *P < 0.05.
Depletion of TAMs reduces mesenchymal gene expression in F9-terato-carcinomas
Macrophages are known to infiltrate and locate in clusters rather to being distributed evenly throughout the tumor tissue. Thus, the tumors were analyzed by immunohistochemistry for intra-tumoral macrophage density and expression of EMT markers in adjacent tumor cells (Figure 2E). This analysis identified local correlations between tumor cell expression of EMT markers and intratumoral CD68+ macrophage density. Whereas E-cadherin and β-catenin localized to the plasma membrane of cells in areas with low CD68+ macrophage densities (Figure 2E, upper panel), expression of both proteins was compromised and partially lost in areas with high CD68+ densities (Figure 2E, lower panel). Conversely, fibronectin expression was increased in areas with high CD68+ densities. Thus, intratumoral TAM density correlated locally with a mesenchymal phenotype in F9-tumors.
M2 macrophages induce EMT and stimulate the invasive properties of F9-and NMuMG cells in vitro
We next tested if β-catenin was transcriptionally activated upon long term M-CM culturing. For this purpose we used the TOPFLASH/FOPFLASH reporter assay [44]. M-CM culturing led to an approximately 2-fold increase in β-catenin dependent luciferase activity in both cell lines, confirming that β-catenin became transcriptionally activated upon M-CM treatment (Figure 3E).
A widely accepted physiological consequence of EMT is tumor cell invasion [19, 22, 23, 24, 31, 33]. Thus, the invasive properties of F9-and NMuMG-cells were assessed in vitro using Matrigel coated transwells. Both cell lines were slowly invading under non-stimulated conditions and their invasive properties significantly increased in response to M-CM (Figure 3F). Collectively, the data show that M-CM generated by M2 polarized macrophages induces mesenchymal trans-differentiation, activates the β-catenin pathway and increases the invasive properties of both cell lines.
TGF-β signaling is crucial for M2 macrophage induced tumor cell EMT
CD68+macrophage density correlates with a mesenchymal tumor cell phenotype, intraepithelial TGF-β levels and grade in non small cell lung cancer patients
Clinico-pathologic parameters and correlation with CD68+ macrophage tumor infiltration
CD68+ intra-tumoral TAMs
n = 491
Evaluation 1 Evaluation 2
≤ 3.7 cm
> 3.7 cm
Correlation of EMT-associated protein markers and TGF-β with CD68+ macrophage tumor infiltration
CD68+ intratumoral TAMs
Evaluation 1 Evaluation 2
E-cadherin membrane
β-Catenin membrane
β-Catenin cytoplasm
Vimentin cytoplasm
Periostin cytoplasm
TGF-β intraepithelial
The recognition that disease progression is highly influenced by the tumor microenvironment has lead to the concept that cancer management may be improved by therapeutic targeting of the tumor stroma [11, 52, 53]. We and others have previously demonstrated the potential therapeutic value of macrophages by showing that their depletion or inhibition of their recruitment leads to reduced angiogenesis and tumor growth, increased tumor necrosis and reduced metastasis in tumor bearing mice [11, 51]. Moreover, M1 macrophages have been shown to regulate EMT at the invasive front through paracrine TNF-α signaling and Snail stabilization, linking tumor inflammation to EMT and metastasis [20, 42]. In this study, we show that the role of tumor associated macrophages in tumor cell EMT extends beyond the invasive front.
Gene expression analysis of control and clodrolip treated tumors revealed a positive correlation between macrophage infiltration and mesenchymal marker expression in whole F9-tumors. Moreover, immunohistochemical analysis of the tumors confirmed a positive correlation between macrophage and mesenchymal tumor cell density, suggesting that TAMs modulate the phenotype of tumor cells located in the neighboring microenvironment. This trend was confirmed in vitro using a conditioned medium approach to facilitate trans-differentiation in F9-and NMuMG-cells. As assayed by immunofluorescence, the mesenchymal phenotype was reversible in F9-cells upon M-CM removal in vitro. Fibroblastoid epithelial cancer cells can re-acquire epithelial traits by undergoing mesenchymal-epithelial transition (MET). MET has been assigned with a hypothetical role in metastatic colony formation where plastic tumor cells, in response to micro-environmental changes, reacquire epithelial traits [19, 54]. That the M-CM induced mesenchymal phenotype was reversible in vitro, suggests that TAMs incite tumor cell plasticity and contribute to tumor heterogeneity through regulation of EMT/MET. The occurrence of EMT in tumors may therefore be transient and highly dependent on the local microenvironment.
The β-catenin pathway is an important mediator of EMT [19, 34]. Although immunoblotting analysis of whole tumor tissues failed to establish a noticeable difference in the levels of active β-catenin in the two F9-tumor groups, in vitro systems utilizing the TOPFLASH/FOPFLASH reporter system confirmed a significant increase in transcriptional activity in both F9-and NMuMG cells upon long term M-CM culturing. Together with the immunohistochemical data, which indicated that macrophages mainly cluster with cells expressing biochemical EMT markers locally in the tumor, we conclude that the levels of active β-catenin in F9-tumors were too low to be detected by western blotting. Therefore, based on the in vitro data we suggest that M2 macrophages signal EMT in part through activation of the β-catenin pathways.
In a candidate based screen we identified TAM-derived TGF-β as the main cytokine inducing EMT in our assays. TGF-β is a well characterized regulator of EMT and it can induce epithelial trans-differentiation through various pathways. On one hand, TGF-β induces EMT through activation of various intrinsic pathways, e.g. AKT, SMAD and β-catenin [19, 29, 30, 31, 32]. Conversely, it stimulates the production of MMPs which are important stroma-derived inducers of tumor cell EMT [25, 35]. Although being a strong mediator of EMT, TGF-β often signals in conjunction with other cytokines such as TNF-α, Wnt and EGF [40, 55, 56]. We were therefore surprised by the finding that neutralization of TGF-β in M-CM was sufficient to abrogate the invasive, mesenchymal cell phenotype. Although we cannot exclude synergistic effects between TGF-β and other macrophage-derived cytokines, we conclude that TGF-β is indispensable for the induction of EMT in our cell systems. All together, the data suggest a model in which M2 polarized macrophages regulate EMT through TGF-β signaling and consecutive activation of the β-catenin pathway. This finding challenges the previous finding of M1 macrophages signaling EMT at the invasive front through paracrine TNF-α signaling and consecutive SNAIL activation [21, 42]. Our findings suggest that the signaling pathways through which macrophages induce EMT is highly context dependent.
An important aspect of this study was to address the clinical relevance of TAM regulated EMT. For this purpose we analyzed tumor samples of NSCLC patients in which we had previously established significant correlations between tumor cell expression of EMT markers and disease outcome [26]. In the current study, we evaluated the correlation between intra-tumoral CD68+ macrophage density and EMT profile. In concordance with the murine data, the NSCLC study revealed a positive, significant correlation between CD68+ macrophage density, intraepithelial TGF-β levels and expression of EMT markers in adjacent tumor cells. Moreover, intratumoral CD68+ density, intraepithelial TGF-β1 levels and EMT tumor profile correlated with high tumor grade. Although TAMs and tumor cell EMT generally are associated with metastasis, we did not obtain evidence for such correlation (Table 1) and it is important to note that the metastatic process is complex and not exclusively depending on these two factors.
Collectively, the data suggest a model in which TAMs induce EMT in intratumoral epithelial cells through paracrine TGF-β signaling and consecutive activation of the β-catenin pathway. As macrophage infiltration, TGF-β1 expression and pronounced EMT tumor phenotypes correlate with increased grade in NSCLC patients, we propose that TAMs contribute to tumor progression by inducing mesenchymal trans-differentiation in local clusters in tumors and thereby contribute to tumor heterogeneity and grade. As EMT is associated with both drug resistance and patient relapse it is attractive to speculate that therapeutic targeting of tumor associated macrophages could improve disease outcome.
We thank Dr. Sibel Mete (IMCR, University of Zürich) for helpful discussions. The project was supported by the Swiss National Science Foundation (Grant Nr. 31003A-111804 to AKB), the Foundation for the Fight against Cancer (Stiftung zur Krebsbekaempfung, Zurich to AKB) and the Fondation Nuovo-Soldati (VT).
Supplementary material
Copyright information
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Emery Walker
Name: Emery Walker
Other Name: Emport
Age: N/A
Occupation: government party member
Relations: Brother to Phase
Appearance: Dark skinned, dark brown hair and dark brown eyes, his legs are weak because of and accident that occured when he used his ability.
Personality: Doesn't care about good or bad but is riddled with anger against Phase.
Power: Can create empathy links with people and places to travel to them or with them. Also able to travel through dimensions by focusing on power gained through empathy.
Weakness: Links that are not regularly upkept can break, death whilst empathically linked to someone can cause the other to suffer great pain or even die.
Past: After Phase came to this Dimension, Emery tried to teleport to him (unaware of this) and went through the phase dimension which began deteriorating his body and lost him some use of his legs. He blames Phase for this.


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Faulting application sd_serverservice.exe, version 0.0.0.0, time stamp 0x3d295e53, faulting module ntdll.dll, version 6.0.6002.18005, time stamp 0x49e03821, exception code 0xc0000005, fault offset 0x00067279, process id 0x157c, application start time 0x01d0791fbac96f71.
HP openview Service desk 4.4 SP33 email template for service calls
I have been advised that this version of HP openview service desk is only able to support plain text emails (on service call creation and closure) and that modifying the existing email template (phone number) is a lot of work.
Both of these answers surprise me, and I would like to verify the information I have been provided. Can anybody comment on this?
P.S. This thread has been moved from Systems Management (OpenView-OP Mgmt) Support and News Forum to HP Service Desk Support and News Forum. - Hp Forum Moderator
Modify column for search incident or search interaction value is showing for Status as A/P
Hye Guys ,
For Default modify column value of status is properly displayed i.e open or wip etc
But when i modify column , value for status get changed into A/P .
I have checked with my datadict (single field is there Status) , no issue with that .
Appreciated for any HELP .
Urgent .
Rohit Y.
Update ticket via form by email
hello experts
I have a query. a client of ours wants to inject data to SD through a form in Outlook. by this form sends data and SD somehow have to read and update the relevant registration or ticket. is able to perform this task? SD version is 4.5 SP18.
Stop updating closed SC via integration
I have SD-SD integration. It work perfectly. But sometimes Service call already closed in first SD, but second SD updates it (changes status for example) during integration process. How can i prevent this situation?
HP OpenView service desk 4.5 SP25 on Windows 8
Hi all,
I hope someone can help me here.
I have installed hp OpenView service desk 4.5 client and updated to SP25 on windows 8.
It connectes to the server and opens a basic view of calls or changes etc.
When i look at the view i see that the call/change IDs are 0 and when i double click the call or change i get an error.
Error is: You are not allowed to view this service call or this may have been deleted by another user
I have cleared my profile and reinstalled the application and SP25 and i tried running it in compatablity mode to no success.
I have also tried installing the HP OpenView service desk 4.5 Client 2008 (with no updates)
When i launch the Client 2008 i get a message to update my software, to what version i do not know...
I have tried the fixes outlined in these posts:
Note: Screenshots attached.
Please could some one help me with this issue?
Many thanks,
OVSD web client gives issue while adding history to a ticket
Hi All,
OVSD web client gives issue while adding history to a ticket. But this issue sometimes gets resolved by restarting the OVSD webserver.
I have attached a document to explain the details.
Any help/clue will be greatly appreciated and of course kudos :)
Service call Initiator
Is it possible to set Initiator field via web-api functions?
HP OV SD 4.5 Language settings export
we're using HP OV SD 4.5 SP10 and going to migrate to another server platform.
We exported almost all settings via ACES functionality but unfortunately I have no idea of how to export Language settings and respectively how to import them onto new SD installation. Language settings are unavailable to export via ACES (((
Please explain:
1. How to export Language settings?
2. How to import Language settings?
Please help to solve it!
How to run banner.exe on Windows 7?
In my environment i use banner for visual user notification. Banner properly works on Windows XP.
But if server tries to run banner.exe on Windows 7 machine user gets notification from Interactive Services Detection service.
I tried to disable Interactive Services Detection service - in this case banner is run, but not shown on desktop, it is shown in Processes.
Is it possible to run banner without this notification as on Windows XP?
Strange system behavior - Smart action settings are changed after UI rule call
I created Application, that runs test.bat, after that created Smart action with this application and [ID] in Parameters field. This UI rule works fine until client's restarting, after client's restarting disappears [ID] from Parameter file in Smart action. I can't understand how UI rule itself or client's restarting can affect to Smart action settings?
Delete all Telephones from IPerson
Hi, I need to delete all telephones from existing person using standard HPSD library: web-api.jar
The problem is that even when all Telephones are deleted, the person.getPrimaryTelephoneNumber() still returns the value of the latest phone (it is also showed in GUI) and I don't know how to overcome this erroneous behaviour.
Firstly, I create some person and its telephone:
ApiSDSession session = ApiSDSession.openSession(path, login, password);
// Create new person
// Create a telephone:
After this code is executed, the IPerson with linked ITelephone is created. In the GUI everything looks fine as well.
Now, I need to remove telephone. I tried multiple ways:
1. newPhone.delete():
this deletes phone from person's list, but not from person's primaryTelephoneNumber (it is also can be seen from GUI)
2. newPerson.setPrimaryTelephoneNumber(null) or newPerson.setPrimaryTelephoneNumber(""); newPerson.save();
this throws an error:
Exception in thread "main" java.lang.RuntimeException: Program error: the attribute '
осн. телефон.' of this сотрудник cannot be modified, because the сотрудник item was opened in view mode or because the attribute is read-only.
осн. телефон. = primary telephone
сотрудник = employee
3. #1 followed by #2 - the same mistake as in #2
So, there are 2 questions:
1. Main question. How to delete all phones.
2. Less important question. Is it possible to addTelephone to the just created IPerson when save() was not yet called? (see the second comment to the first code snippet)
Service pack 39
I tried to migrate from service pack 37 to service pack 39. With no luck. After sp installation, i reinstalled service (hp OpenView service desk 4.5 server) and tried to start it - starting failed and logserver.txt was not created.
I tried to reinstall service with default installservice.bat and with full path to jvm.dll in it with same result.
But if i started server via startserver.bat - it started normally.
My environment:
Microsoft Windows Server 2003 R2 Standart Edition service pack 2
Deadline calculation according Workgroup support hours
I have Service desk 4.5 sp37 with next settings:
1) General settings - Oppening hours calendar of assigned workgroup for all items
2) Free day - list of free days
3) Holiday calendar - there is only one day (01/01/2014) with no free days included
4) Oppening schedule - 12x7 (from 8 a.m. to 8 p.m.)
5) Default Service level - Gold (24x7)
6) Workgroup with schedule (3) and holiday calendar (4)
I create SC in friday (31/05) in 10 a.m. with medium priority (16 hours) and assign it to WG. As i think deadline should be saturday 2 p.m. (10 hours today and 6 tomorrow), but deadline is calculated as 03/06 02:00.
As i understood for some reasons free days are included to deadline calculation. But i can't understand why 02:00.
What shoul i do for correct deadline calculation according workgroup support hours and holiday calendar?
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Follow @DaytimeRoyalty
|Viewing Single Post From: Monday, April 29th Daily Discussion
|The Room Stops
|Apr 30 2013, 12:15 PM
Seriously, how are Marlena, John, Bo and Hope not constantly working to take down Stefano? We're just letting the person who tortured us for decades walk around town with a latte now? We just greet him politely in the town square? I mean, seriously.
|Monday, April 29th Daily Discussion · DAYS: News, Spoilers & Discussion


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Entries in 'gay' (4)
Blizzard withholds Overwatch comic from Russia due to gay propaganda law
A Christmas Overwatch comic released yesterday is not available in Russia because of the country's gay propaganda laws.
Nintendo cuts controversial 'gay conversion' plot from Fire Emblem: Fates
A plotline that sees a lesbian drugged and tricked into falling in love with a man – yes, really – will not be included in the Western version of 3DS ...
American televangelist says Pokemon 'is origin of teen homosexuality'
Pastor Creflo Dollar, an American TV religious evangelist, has accused Pokemon of encouraging children to become gay.
Mortal Kombat universe gets its first ever gay character
The cinematic director at developer NetherRealm has (somewhat ambiguously) appeared to confirm rumours that Mortal Kombat X has introduced the first ever gay character to the series.


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This modern city hotel comprises a total of 91 rooms set over five floors. Facilities on offer include a spacious foyer with lifts, a hotel safe, a cloakroom, and a 24-hour reception. A caf�, a cosy bar, and a restaurant serving culinary delicacies can all be found within the hotel, as can an Internet terminal and a range of conference and meeting rooms for guests arriving on business. Room and laundry services complete the offerings, and there are on-site parking spaces for those with cars.
This tastefully appointed hotel is located in Ciudad Real, only 3 km from the city centre. The nearest railway station is 1 km away, while the airport is about 200 km from the hotel.
The pleasantly fitted rooms all come with a spacious en suite bathroom with hairdryer, a direct dial telephone, satellite/ cable TV, a radio, an Internet connection, a minibar/ fridge, and central heating.
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As you may have noticed, we've added dozens of new resorts and hotels to our map! We decided that it was time to start sharing all of the research we have been doing about destinations these past few years.
While many of these new destinations are also applying to be Approved Healthy Destinations, they won't have their official icon on the map until we have certified them! If you have visited any of the hotels or resorts on our map, please feel free to post a review and share your favorite health or wellness-focused amenity, program, service, facility or personnel with our site visitors!
The reason that many of the new postings only have minimal information on them at this point is because some of our research focused on a particular amenity we found intriguing. We searched for destinations that provided that element, and that may be all the verified health and wellness-focused research we have on that individual property thus far.
Many of these destinations have a variety of health-focused assets and it will just be a matter of time before we update their profile to bring you even more information about each hotel/resort. We promise we will be updating the destination profiles as we discover more about the health and wellness-focused amenities, services, programs, facilities and personnel available at each destination!
For our Road Warriors — our business travel advisers often point out that their travel schedules can be exhausting, we're doing the research so you can know the healthy options that are available to you on-site, at the airport, or around your destination!
For those leisure travelers, health and wellness may not be your primary reason for travel but we want you to know where you can find fun and interesting health and wellness-focused options whenever and wherever possible!
Feel free to post a favorite destination that you've visited, or review and share your favorite health or wellness-focused amenity, program, service, facility or personnel on one of the destinations already posted on the map!
There is so much health and wellness-focused information out there to share…let's work together to make this a helpful travel resource for all of us!
Travel healthy!!
Mary Ellen


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Angry Ham's Octane Bar & GrillTraditional American, Burgers, American (New)
2 Beacon St
(508) 620-8888
Aaron R.
This place is OK. I've met friends and co workers and family here on numerous occasions. It's slowly turning into a local townie hot spot but they still...read more
Keith N.
We were told that behind the bad name and facade, this was a place that actually served up good food. So, since we really don't care for the corporate...read more
Scott J.
We had lunch here today and sat next to a young, attractive hearing impaired couple who were signing to each other during their meal. I was jealous of them...read more
Tina B.
Finger Cuff at Angry Hams Famingham, MA Saturday, May 12, 2012read more
Joe G.
Eggs Benny is delish! And the spicy home fries are a must.read more
Nicole F.
$8 lunch special soup, salad or fries and full sandwich!read more
Tina B.
Must See Finger Cuff on Thursday Nights. Karaoke with a Live Band.read more
Shannon D.
The fried pickles are incredibly delicious. Unfortunately, they only come with a sandwich order.read more
Bill C.
Seriously bound for glory at angry hams? This is not New Jersey ... Not waiting for snookie and jwowread more
Mark E.
The Turkey Tips are simply unbelievable...a must have.read more
Joe G.
Mavericks are recruiting for the next Semi-Pro football season. Don't just watch - live it!read more
Excellent service --- French onion soup is one if the best I ever had!read more
Try the Carnivore Pizza and spot it on Foodspotting!read more
Alyssa H.
Fried cheese curd with gravy - yumread more
Michelle E.
$1 coors light draftsread more
Paul F.
Hotty mayor alert!!read more
Chris B.
As seen on TV!read more
Peter G.
Try their 20" pizzas. So good. Mmmmmread more
Kyle K.
Consistently delicious! It's that simple.read more
Try the Meat Lollipops and spot it on Foodspotting!read more
Tina B.
Finger Cuff Live Band Karoke Every Thursday Night.read more
John B.
You can ask for a side order of frickles - yumread more
Gary N.
Beer and burger or near gourmet. Excellentread more
Jason R.
Best eggrollsread more


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: Post-Game Talk:
Devils 3 - Penguins 1
View Single Post
Registered User
Join Date: Feb 2013
Location: upstate ny
Posts: 1,001
vCash: 500
Everyone seems to think Kovy and Zajac are in a funk. With Zajac I think this is true, but with Kovy--he gets points, or is a factor in every game. Today was a blessing with an absurd amount of PP opportunities (seriously 10 PPs, whoa), where Kovy can really dictate from the point. What is so awesome about the Devils is the contributions they get from every player in the line-up. Clarkson/Bernier set up awesome screens down front, while random players pick-up the goals. Today having guys like Butler (who's been great in Albany) and Matteau score is what makes the Devils a great team. Production can come from anyone at any time. These guys are playing as a team, which makes them dangerous, every game.
Did anyone else have a weird/painful flashback when Matteau scored? I was surprised Lou kept the kid after 5 games. Nice for him to get his 1st.
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Northstar Ratings are powered by Northstar Travel Media and are based on objective and unbiased evaluations from experienced editors that individually analyze, research, and evaluate hotels. Hotels and suppliers are not required to pay any fees or pay for memberships to have their property rated.
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The Milan Hotel Monopole is strategically located just 100 metres from the central railway station Milano Centrale and within easy reach of shuttle buses leaving every 10 minutes for Linate, Malpensa and Orio al Serio Airports. Located on Via Fabio Filzi 43 in the commercial district of Milan the H...
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ED Magedson – Founder
Ripoff Report
union workers credit servicesp o box569410 dallas, Texas USA
union workers credit services credit card services dallas Texas
Does your business have a bad reputation?
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by there information they give you it makes it sound like a credit card, but it isn't . Its like a service that you buy merchandise out of their catalog. No card. for the low price of 37.oo dollars , in which I paid thinking I would be getting a card.
This report was posted on Ripoff Report on 03/10/2014 11:15 AM and is a permanent record located here: http://www.ripoffreport.com/reports/union-workers-credit-services/dallas-texas-75356-9410/union-workers-credit-services-credit-card-services-dallas-texas-1129584. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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Our view: Avoid
Share price: 1,353p (-182p)
Admiral's shares suffered yesterday. The company reported high headline numbers: first-half profits of £16.6m were 27 per cent ahead of the same period last year, while turnover rose by 53 per cent to £1.1bn.
But some analysts expected better for the shares to justify their lofty rating. Their main worry was the cost of big personal injury claims from prior years, which appear to have increased considerably.
To be fair, the company said that these sorts of claims do sometimes unexpectedly increase, but the news caused a flutter in the market given this was a bullet Admiral appeared to have dodged.
Still, Admiral's underwriting is solid, with a combined ratio of something "in the low 80s" expected for the full year. That means that for every £1 in premiums, Admiral expects to pay out something under 85p in costs and claims. Good by industry standards.
The price comparison website Confused.com, which had been hit by its rivals' meerkats and opera singers, has started to hold its own. But the ad spend increased sharply. So while turnover was up, profits were down.
We worry about Admiral. This column's own experience suggests renewal notices aren't always sent out correctly, which could lead to customers facing heavy fines. Not good for a company's reputation.
And while Admiral's costs came down because it has grown and volumes have increased, questions remain over whether it can continue its impressive growth.
We said avoid back in March, with the shares at 1,665p. That has proved to be sound advice. However, even after their recent falls, the shares still trade at 17 times full-year earnings.
Given that premium prices are slowing and the increase in those injury claims, the fact that the company is going to find it tough to maintain its growth levels, and our concerns over service, the shares are too pricey.
Our view: Buy
Share price: 323p (+11.7p)
Carillion, the building and support services group, is something of a jack of all trades. If you need transport to a hospital, it often provides the ambulance, maintains the roads down which you travel, employs the porters who get you to the clinic and, finally, the people who keep that clinic clean.
Yesterday's interims were ahead of some analysts' expectations, with first-half pre-tax profits coming in at £72.5m, 10 per cent ahead of the first six months of last year. The company had already flagged that it was doing rather well and expects to meet full- year forecasts.
It has an order book (confirmed and probable) of £19.4bn and plenty of outsourcing opportunities. Businesses in the Middle East and Canada will provide good international reach. Chief Executive John McDonough will retire at the end of the year, but the company will replace him with current Chief Operating Officer Richard Howson.
That sort of seamless succession process speaks of a well-run company. We said buy in March at 357.4p. The shares were trading ahead of that up until the recent financial turmoil.
Along with the good results, the company also appears to be in good financial health, with relatively little in the way of borrowings. Moreover, the shares are now trading at just 7.5 times the forecast earnings, with a very respectable prospective yield of 5.3 per cent. That's far too cheap for a business that boasts a rapidly growing pipeline and good opportunities.
Derwent London
Our view: Buy
Share price: 1,570p (+15p)
You would never have guessed from its name, but while many property companies may be sensitive to the state of the market across the country, Derwent London is only really bothered with how the capital is doing.
And the answer to that, at least according to yesterday's half-yearly results, is pretty well indeed. As well as a 10 per cent jump in its net asset value, the largest of all the central London-focused real estate investment trusts revealed that it had made new lettings in the period worth £8.5m in annual income, already more than it managed during the whole of 2010.
The group's impressive figures were driven by demand for its offices in the West End, and although it did make some cautious noises over the economic outlook, importantly it said it had not yet seen signs of a slowdown in the area. Its shares may have more than tripled since 2009, but the results suggest that there is more to come.
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|Half Baths
|4,000 sq. ft.
|Property type
|chateau / country house
|Minimum Stay
|2 - 3 nights
As you leave the oh so hip village of Woodstock and you start up the side of Overlook Mountain, you're on your way to a rare treat. Hanging on the side of this mountain, drenched in the sun, is one very incredible dwell style home that you'll be lucky to call home. The mountain side road is a bit of a challenge but once you arrive Wow is all you'll be able to utter. This place is one of a kind and the owner has spared no expense building this beauty. This home was built with a nice southern exposure so that all the rooms face a breath taking view of Ulster County and far, far beyond the Ashokan Reservoir and the Hudson River. The entry way to this beauty is high lighted with an exterior stairway and bridge over the driveway. This gives you the first taste of that oh so awesome view and brings you into a two story atrium space. Ascend that stairway and you'll arrive in a large glass great-room that will make you feel like you're on top of the world. This design is known as a Neo-Modern style and was designed by a well known local architect named Les Walker. The materials used here are varied and soothing. On the lower level you'll find a comfy TV room with granite floors, fireplace, big 3-D flat screen TV, Playstation 3 that will play 3D, Blue Ray movies. The Bose system will also play movies, DVDs and all with surround sound and Sirius stations. There's a half bath on this floor and a nice fourth bedroom. Head on upstairs and check out those Cherry hard wood floors and the chefs kitchen with gorgeous Ceaserstone counters, breakfast nook and stainless appliances. Next to it is a nice laundry room. The living room is wide open and has it's own fire place. From there you can walk out onto the big deck and try out that 6 person hot tub!! Also on this floor is a childs bedroom with two race car beds and a guest bedroom with a queen sized bed. You'll also find a killer bath room with gorgeous marble tile work and a huge sky lite. The stair case in the great room takes you to the master suite on the next level. There you'll find a king sized bed and the best view around. The master bath is to drool for. Huge glass shower with steam and a big jetted soaking tub. The owner has built a beauty here. Check out the custom Maple cabinets built in throughout the home. Slip off your shoes and experience the radiant heated floors. Nothing has been over looked here. Even the grill on the deck is tied into the propane tank. If you ever leave the mountain side to explore Mohonk or Minnewaska or to hike some of the famous Catskill Mountain trails or to carve some trails on the local ski slopes, you'll know something incredible is waiting for your return home.
We lead very busy lives in the city and always try to escape when possible. We fell in love with this area and decided to build a weekend home here. This place is incredible and has really given us the ultimate escape. We can't use it every weekend and are willing to share it with those that really appreciate what we've created here.
Bruce Stalnaker purchased this chateau / country house in 2009
We wanted an awesome view year round and to be close to I-87 and Woodstock. We selected this 4 plus acre mtn side lot and carefully built into the side of the mtn.
We get such incredible light here and that view changes with the clouds. All four seasons are special here. Night time is dark up here for maximum star gazing. The hot tub is inviting in any season. You won't want to leave.
This house has amazing view of Woodstock valley with Catskill mountains in back round. It is hard to walk away from. The architectural design of this house is very cool. From the open living area to the secluded bedrooms, you will not be disappointed. The deck and bridge add to the awesome character of this property. I look forward to returning. Property manager was most helpful, easy to reach, and quick to reply.
Great house. Views fantastic, house is private and well kept. The house manager very friendly and helpful. 5 minutes to town. Very comfortable.
The house was really nice. It is just a very cool house in general. The setup with the bridge from the driveway to the home is really different. The views are amazing. The house is very comfortable. The house manager was easy to work with and had everything ready. Although we didnt spend much time inside (we were taking advantage of all the catskills have to offer), I thought the accomodations were great and could easily fit a family, three couples, etc. The road to the house is steep, but that adds to the feel of the area. You are in the mountains. Would definitely rent again and may try for some winter skiing this year.
This house is absolutely stunning and everything that we wanted when searching for a perfect summer house for 5 nights away from NYC. It's super modern (new), open layout, clean, amazing views, and conveniently located a few minutes from Woodstock town. We were a party of 5 adults and 3 kids (ages 7, 3, 15 months old). The living space was so so so spacious; plenty of room for the kids to run around or play outside on the huge balcony. There is a nice-sized hot tub on the balcony, but we didn't use it - we opted to set up an inflatable kiddie pool instead (so much fun!). Because we have young kids, we picked up grocery from a local market and made all our meals. The well-stocked kitchen was a joy to cook in. A bonus is that the house has TONS of really cool toys that helped entertain our kids for hours. We couldn't be more glad we chose to stay here. Bruce, the property manager was such a pleasure to work with; he was very responsive, easy going, and accommodating.
The pictures do no do this home justice. There is an open floor plan on the main floor: which includes a gorgeous kitchen, huge fire place, exceptionally large living/dining room and million dollar view. It was perfect because our large group could all be together, while not being on top of one another. The other floor has two huge leather reclining couches, another large fireplace with a TV and a bar -- downstairs was ideal for Football Sunday. The beds, bathrooms and everything else are all very nice. Plenty of wood in the garage too. Oh, I almost forget the best part: Huge, sunken hot tub that overlooks the picturesque landscape that only Woodstock can offer. We had a bunch of food delivered to the house, great Italian food and BBQ. If there is snow, drive an SUV. My only hope is to be able to rent this magnificent home again. The property manager/owner is also very easy to work with, a good communicator and returned 100% of my deposit only days after my rental ended. If I had something negative to say, I would have (I'm not shy!)
We loved this place and had a wonderful stay. It's location is fantastic because it's on the side of mountain with great views and feels very private but at the same time Woodstock is only 5 minutes drive away. Sitting in the hot tub on the side of the mountain on a cool winters night with the snow around you is magical. Plenty of space for the family and the driveway made a great sled run for the kids after some snow fall. Bruce the property manager is great and very responsive and attentive both when booking and during our stay. The only negative is that the 4th bedroom downstairs is next to the boiler room so it's a bit noisy for light sleepers. That said this was a unique and special place to stay and my favorite house and location, to date, in Woodstock.
This area is full of things to do. You're in the famous Catskill Mountains here. There are miles of trails to hike and several mountains to ski. We've got incredible parks to explore like Mohonk and Minnewaska with countless miles of old carriage roads to bike and pristine lakes to swim. Local hikes to places like the Overlook Fire Tower will test your metal but reward you with views to droll over. Eclectic local villages like Woodstock, Saugerties and Phoenicia are great to explore. Kingston has one of everything as far as stores go. Fine restaurants can be found in all of them. Time will slip by you here and this house is just soooo amazing you won't want to leave!! Sit out on the deck or in that huge hot tub and just drink in the view and serenity.
|Rate Period
|Weekend Night
Mar 31 2017 - Jan 1 2018
3 night minimum stay
My Standard Rate
2 night minimum stay
|Refundable damage deposit
Three night minimum for all National Holidays and $ 550 per night
Sheets and towels included
Tiny dog considered


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Skip to comments.SEE IT: Transportation Department video teaches kids proper ways to cross the street (NYC}
Posted on 05/07/2014 3:04:47 PM PDT by SMGFan
The Cross This Way hip-hop song got the video treatment and showcases visuals of the best ways to cross the dangerous city streets. The video will be aired in public schools as part of Mayor de Blasios Vision Zero initiative and is also available on YouTube.
(Excerpt) Read more at nydailynews.com ...
I guess the expert educators are right. Today's kids are different. When I was that age, all that had to be done was for someone to tell me how to cross the street. And, that was it. Period!
My parents weren't very educated but they somehow managed to teach me how to cross streets. Have been doing it for years.
https://www.youtube.com/watch?v=5SAopqAmuFI Here is "Cross at the Green, not in Between"
I thought the Australian rail system had the right idea
"Dumb ways to die, so many dumb ways to die"
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.


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Not her, oh GodMature
"Can you get that?" Michael asked me as he was washing the plates we used for breakfast.
"Sure, hun." I answered the phone in the hallway, which had been ringing loudly throughout the house.
"Hello?" I used my "posh-telephone voice".
"Lee? Is that you? Its Sandra." I immediately hung up, eyes wide with fear.
"Who was it?" Michael popped his head around the door from the kitchen, still scrubbing a plate.
I snapped out of the state I was in.
"No one. Wrong number." I said a bit too quickly. "Mike. You're dripping." I pushed the call to the back of my mind and helped put away the breakfast goods.
"Are you ok, Lee?" Michael knew me too well, he could see when I was worried about something.
"Yep. I'm fine." I put on my most convincing face.
I could tell that Michael didn't believe me, but he carried on with what he was doing.
The phone rang again a few hours later. I knew who it was.
"I'll get it!" I volunteered, running for the phone.
I answered it in silence.
"Lee? Are you there?" Her voice came through. "Lee. I know you're there. I can hear your breathing."
"Alright, fine. What do you want?" I demanded.
"I need money." Sandra said simply.
I took the phone into the living room before answering her, Michael was in the kitchen, preparing lunch.
"I can't. I'm broke!" I took care to speak quietly.
"What about your partner?" She put emphasis on the last word.
"I can't take money from him!" I was speaking carefully.
"You know, Lee. Now that we have been talking for more than a minute, I can track you."
"Oh shit." I clapped a hand to my forehead.
"Forgot I'm an ex-policewoman, did you?" She laughed at me down the phone.
Her voice suddenly got very deep and sinister. "I'm coming for you." She started cackling again as she hung up.
I walked slowly to the hallway and slammed the phone down in anger.
"You ok?" Michael called while chopping carrots.
"Oh yeah. Fine." I shouted, holding back fury.


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(H/T) If you've followed my blog for very long, then you know there are few things that Mark Driscoll and I agree about. I have unapologetically taken him to task for both the absurd and egregious...
Pat Robertson: You Gotta Be Deaf, Dumb, & Blind To Believe In Young Earth Creationism
Dear John (An Open Letter To John Calvin)
Dear John, Ok, first off I know, "Dear John" letters are usually written between former lovers and we were never even friends. But, John, I tried. I really, really did. I've heard for so long that my frustrations with Calvinism were really due...Read more
This Week In Jesus – Volume 3
In an ongoing effort to keep you abreast of all the important and entertaining Jesus news, here's everything you need to know/see/experience as we start a new week. First up, and prepare yourself because this might come as a shock if you didn't know about his awesome Jesus tattoos, Justin Bieber...Read more
You've probably heard it said, "There's no "I" in team." But did you know there's no "Jesus Saves" without "USA"? Yeah, me either. But thanks to a heads up from one of my readers, I'm sad to report that this is indeed the case. In fact, it seems it's something of...Read more
A Good For Nothing God
What If It Was My Daughter? #bringbackourgirls
Having kids has a way of changing the way you look at things. Sometimes it emerges in silly ways, like suddenly not being able to make it through a movie like Saving Mr. Banks without letting a few tears slip out. Other times, it's more serious. Like when I turn on CNN and...Read more
The Antichrist Wins The Kentucky Derby, Pope Francis Comes In Last
Ah, the Kentucky Derby. That great American tradition where one day of the year everybody comes together to wear silly hats, drink fancy drinks, and pretend like they care anything at all about horse racing. Well, as it turns out, we should all care about this year's Kentucky Derby. Why? Because it was won...Read more
Albert Mohler Has No Use For Jesus
H/T) You may have heard about the awful botched execution in Oklahoma the other day. Many people took it as yet another reason for America to reconsider whether or not putting our neighbors to death actually...Read more
Sarah Palin: "Waterboarding Is How We Baptize Terrorists"
At Christmas last year I had the great privilege of baptizing my daughter. It was a deeply meaningful and powerful moment for me and my family. As it is for countless other disciples of Jesus. Except Sarah Palin, apparently. After...Read more


text:
1,600 people in 24 cities living 4 values for 1 goal:
To use design to help our clients succeed.
We create exceptional environments that meet our clients' most complex design challenges.
We inspire people through our work by expressing timeless cultural, organizational and personal values.
We connect people and place with ideas that come from many minds and imaginations.
We care about serving our clients, enriching lives, improving communities and protecting our natural environment through design.
We are a global architecture, design, engineering and planning firm.
The design makes extensive use of digital output for custom-created murals printed to various media.
Fabric, furniture and finishes communicate the messages of "global" and "creative."
The four briefing rooms are named How, World, Shares and Ideas, with Shares being appropriately sub-dividable. One wall in each room displays a custom mural. Monitor displays and dynamic media content are balanced with more traditional, passive graphics and custom furniture tools including graphic embellishments.
15,625 sq. ft. / 1,450 sq. m.
Display Environments


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'Why are you dressed as one of The Ramones?' My husband and I are stacking the dishwasher one Sunday morning, listening to The Archers. It's a tricky one. How can I explain that drainpipe jeans are tout la rage? Or how a friend of mine wore Converse All Star baseball boots the other evening and looked so rock'n'roll, so Chrissie Hynde, that I was powerless to resist.
'Doesn't David Cameron wear Converse?' continues husband conversationally, as he scrapes Rice Krispies into the Brabantia. 'And what's with that weird skinny tie?'
He's right, of course. There comes a time in life when wearing full-on fashion - the kind of entertaining kit you find in the pages of the glossies, worn by teenage Russian models with complicated names and no breasts - starts to look ridiculous if you attempt the look at home. Pinafores, say. Or culottes. Berets. Braces. Bubble skirts. To make my point, almost as a eulogy for my lost youth, I wore my rock-god outfit on a family kite-flying trip on the Downs that afternoon. Passers-by probably thought I was wearing the skinny tie for a bet. Or a joke. Up there on that hill, it dawned on me that I am too old for clothes.
Not all clothes, of course. But the silly, slavish stuff which has been the lifeblood of my wardrobe for nearly three decades. At the age of 38, certain trends are beginning to look wrong. It's a realisation which creeps up slowly, like hair loss or weight gain, until one day the mirror shows you a stranger. 'Mutton,' mused one similarly afflicted friend, 'dressed as goat.'
Yasmin Yusuf, 45, formerly creative director for womenswear at Marks & Spencer, had a similar epiphany in the company of a pair of Costume National boots not long ago. 'I was wearing my superfine narrow jeans tucked into the boots - and I got home and suddenly felt it was all too young. I had a defining moment. Something had to give.'
While fashion pundits are terribly gung-ho these days about the agelessness of clothes, about how the taboos of dress have been broken, and how mother and daughter can now wear the same jeans to the same party where they'll dance to the same tune around the same handbag... the bottom line is that there are still boundaries. Not, perhaps, enforced by a society of strictures and codes, but by the fact that a 40-year-old woman wearing a pork-pie hat in homage to Pete Doherty looks daft. There is, and I say this with a sigh, undoubtedly a time to put away childish things.
But what to wear instead? Turn 35 and you're supposed to instinctively know how to dress your age, just as you're expected to know how to file a tax return and how to produce a tasty coq au vin - and no one, least of all the media, the mags, the designers, the retailers, the icons, is giving much away on the matter.
The brutal fact is that everything gets more complicated as you edge towards 40, particularly if you've had children. You blithely expect to return from maternity leave and resume shopping, as though nothing has changed. But everything has.
Throughout my twenties and early thirties, I shopped as a hobby, like some folk do crosswords or crochet. I loved it. I loved dressing up, posing, changing three times a day. But, it dawned on me not long after my kids arrived, there's not a whole lot of point in dressing up as a Ramone or Edie Sedgwick or Frida bloody Kahlo to catch the News at Ten headlines or do the nursery run. If you work at home, as I do, only the postman will get to see your witty take on military chic. To add insult to injury, just as your lifestyle goes all domestic, your body goes to pot. Mine, like most, became pliable and comfortable, like something from the soft-furnishings department at John Lewis. Saddled with a mum's bum, dressing becomes a game of hide and seek, reveal and conceal.
While we're struggling with the mirror, the fashion world remains haughtily besotted with youth, enthralled by its milky skin and pretty feet. 'Things are improving,' says Alexandra Shulman, editor of Vogue, optimistically, 'but it's nowhere near enough. Designers are still enormously youth-orientated. As soon as you say you're creating for a specifically older market, you start to put people off... As you age, it's certainly harder to get away with flinging anything on and looking great, like you might have done in your twenties. Your body changes. Your arms aren't so great, you get shorter in the torso. These changes, generally speaking, are being ignored.'
And so, fashion deserts us just when we need it most, like a redneck cowboy skipping town. When everything is edging towards the floor, it ups and leaves, abandoning women to fend for themselves in an image-obsessed world. No wonder Trinny and Susannah make £1.2million a piece for offering style direction to this lost generation.
Yasmin Yusuf agrees that there's a dearth of ideas for women who are too old for clubbing but too young to make their own chutney: 'There isn't anything really slick and sexy for this market yet. It's such an opportunity. What is available is generally expensive - it's all about beautiful cut, something to give confidence, and that comes at a price. The middle-market retailers should be looking at this: the 35-plus group aren't going to stop loving fashion just because they've had another birthday.'
This year for the first time, women over 40 will make up more than 50 per cent of the UK female population. Many have money. Most have perfectly adequate bodies, thanks to a regime of regular exercise and sensible diet. If anything, we're the future of fashion. Interestingly, there are signs that some of the major fashion and beauty companies are beginning to recognise the spending power of this influential age group. Now that the Pink Pound and the Grey Pound have been truly tapped, attention is at last being turned to the Navy Pound.
Miuccia Prada, as if to seize the moment, has installed 52-year-old Kim Basinger to front the Miu Miu label this spring. Elsewhere, Sharon Stone (47) has just been hired as the new face of Dior's Capture skincare range; 51-year-old Christie Brinkley is the new girl at Cover Girl cosmetics. Suddenly, companies are interested in women who've lived a little, who have the depth and maturity of a good wine rather than the fizz of a bottle of pop. Model agencies are reporting a significant increase in demand for models in the 35-plus bracket. Witness Twiggy's rebirth for Marks & Spencer at the age of 56; even Paula Hamilton is back in circulation, 20 years after that famous VW ad.
Just look, too, at 'the muse of the moment', as designated by the influential industry magazine Women's Wear Daily: Carine Roitfeld - the 50-year-old editor of French Vogue. She has lush eyebrows, punch-black eyes, and a curtain of hair which constantly threatens to close off her face from public view. Her look is imitated everywhere - on the catwalk, in the ad pages of the glossies, in the windows of department stores. 'Right now,' said a recent paean, 'Carine Roitfeld is the most stylish woman in the world.'
The point is - and here's the rub - that she has always looked this way. She didn't arrive in her fifth decade and think, 'Hmm, time to drop the ra-ra skirts and opt for something more swank.' Roitfeld's look is timeless and personal, the living embodiment of Yves Saint Laurent's aphorism that 'Fashions fade; style is eternal'.
The question for mere mortals, tugged between the pull of jazzy earrings and the push of crow's feet, is quite how to win a slice of this ceaseless style for yourself.
Well, over to Roitfeld herself:
'Leather?' she says firmly. 'No good as you get older... For normal woman, with not big money, if I would give advice: buy mainly classic pieces and a new pair of shoes each season. A Burberry trenchcoat is always beautiful. Maybe you change the belt and this season you put an Indian scarf on.'
She doesn't counsel, you will notice, the purchase of a skinny tie and a pair of Converse baseball boots. Shulman, meanwhile, is less prescriptive: 'I don't think there are specific things you can't wear after a certain age. It's entirely up to the individual to make the judgment. Some people are more successful at judging than others, of course. But if you've got great legs, I don't see why you shouldn't wear a short skirt. As you get older, though, you can no longer follow fashion in a craven way... but I rather think you shouldn't do that at any age.'
For the lucky few, of course, the progression happens naturally. I remember seeing a picture of Plum Sykes not long ago. We worked on Vogue together in the early Nineties - and here she was, toast of Manhattan, a genuine It girl, with her glossy mane of hair and her thoroughbred legs. But what caught my eye was her clothes. A striped sweater in coffee'n'cream cashmere. Tailored pants in a tantalising shade of cocoa.
In short, Plum (five years my junior) looked like a grown-up.
My wardrobe, by woeful contrast, still looks like a dressing-up box. Just recently, I was seriously toying with the idea of wearing leggings under a strapless dress. I had the idea that I'd look a bit like Laura Bailey in this get-up, though there's a distinct possibility I'd look like a turnip. The fact is that it's simply not an appropriate look for a mother of two, a woman with a large mortgage, a substantial garden, a subscription to The Economist and a growing knowledge of oenology. The overall effect will, I know, be discordant and off-key.
Perhaps Quentin Crisp was right when he remarked, 'fashion is what you adopt when you don't know who you are.' Once you're old enough to know thyself, you simply have to stop hiding, to start letting go, just as you have already forsaken your intimate knowledge of chart tunes, dance moves, street vernacular and who's snogging who in Hollyoaks.
But - blissfully - just as some things look terribly wrong, others begin to look absolutely right. Take tailoring, for example. Won't give you the time of day until you're 33, and then it's all over you like an expensive suit. 'It helps to know the designers that suit you, to find your shop, so you're not starting from scratch every time,' says Shulman. 'Having some idea of your own style, your strengths and weakness, helps - although, of course, they do change as you get older. Personally, I find it much harder to get away with boho dressing than I once did. You can so easily look like an ageing Mystic Meg. There is a temptation to go for simpler, cleaner shapes as you age. A few great cashmere sweaters really will take you a long way. Jewellery becomes more important.'
Some retailers are getting it right, says Shulman. 'There's a lot of money in this age group. Zara has been very clever and has tapped it well. Chanel and Armani are always going to have things that work - there's a core offer there. I have found that, on the whole, women designers are kinder and more sympathetic - they seem to understand and acknowledge what is happening to a body.'
Yusuf recommends Feathers, 'for top-end ideas - it's beautifully bought and put together. The Cross in West London dresses this age group beautifully. Go to Joseph for real modern classics. In New York, stores edit collections very closely for particular age groups, making it so much easier to shop. Bergdorf's, for example, really knows its customer base and buys accordingly. The UK hasn't quite caught on to that yet.'
There are individuals, of course, who will do the editing for you. Style consultants Campbell & Bathurst fillet and refresh the wardrobes of women in precisely my predicament. Their advice is to go easy. 'Many women over 35 make the mistake of clinging on to a style they should have ditched long ago,' they say. 'So steer clear of frosted lipstick and plunge-V necklines. Avoid acid colours, bubble-gum pink, logo T-shirts, tight anything, hot pants and micro-minis, stonewashed jeans, animal prints (keep to accessories only), midriff-bearing tops and low-slung trousers, girlie frills, black leather. We advise our clients to edit their wardrobe every six months and to keep an eye on things like hair colour. As you get older, you have to tone everything down.'
This season, then, I'll be treading gingerly through the traps and trips of spring fashion... Chloe's wooden stack heels? I think not. Those darling little broderie Anglaise dresses at Miu Miu? Nah. They yell youth. Wear one over the age of 21, and you run the distinct risk of looking like Grayson Perry. As you slide down the razor blade of life towards 40, it's heartening to know that ethnic works well into old age; folkloric, however, doesn't.
Meanwhile, my skinny tie and drainpipes are finished. The animal prints will be escorted from the building and shot. The amusing slogan T-shirts ('Brunettes Have More Fun') are banished. 'Give them to the au pair,' said one friend in what she imagined was a helpful manner. I don't even have an au pair. But if I did, you can be sure she'd look a dish in my drainpipes.
· Mimi Spencer is a columnist for You magazine.
Make-up: Kaz Simler.
Shoes: Christian Louboutin, 020 7245 6510.
Wallpaper: Cole & Sons, 020 8442 8844, Cole-and-son.com.
Blanket: SCP, 020 7739 1869, Scp.co.uk