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Suite Saint Vincent.. 18.1Km
Situated in the centre of a small medieval town, this pleasant guest house, where a personal welcome awaits you, dates back to the XVIth century. Private entrance from the outside / A wide bedroom of 90sq metres, a queen size bed/ There is also a private library, a large living room with a French billiard-table; TV with DVD/ Microwave oven and electric kettle, réfrigérator. Private shower room with toilet (bath towels supplied) Copious breakfast is served in the owners private dining room. Smoking not permitted. Paypal accepted
1Contact More info Add
Gite Napoleon 21.9Km
ALPS OF HIGH PROVENCE - Prox. Gorges du Verdon WORTHY - COL OF Corobin - Outstanding Website! Altitude 1050 m - 4 stars Prefecture Authorised persons-6 Cottage 85 m2 comfortable for 6 / 7 persons with swimming pool (8x4 m)
1Contact More info Add
Le Mas du Loup 23.3Km
Dreaming of sun, peace, comfort and simplicity... The Mas du Loup, nestled in the foothills of Moustiers Sainte Marie (700 meters from city center), will warmly welcome you to rest and relax. After a continental breakfast, you can go hiking, wonder at the provencal markets, refresh yourself along the lake, and if you wish for other activities, we will be glad to guide you... You can also spend your time lazing about (napping, sunbathing, reading...) At the end of the day you will have the pleasure of walking to a restaurant. From simple fare to haute cuisine they are all within walking distance. And on your way back, the song of the crickets will accompany you and lull you to sleep.
68Contact More info Add
La Maison de Julie 25.0Km
On the border of the county of Nice and dominated by its famous citadel, the medieval village of Entrevaux was always wildly attached to its heritage and to its exceptional living environment. "La Maison de Julie" ( Julie's house ), build near the city during the 18th century, and recently restored, embodies marvelously the local hospitable tradition. Guests rooms as well as greedy breakfasts, that smell sweetly the charm, the wealth and the flavours of this magnificent low-alpine soil. In very soon. Carole, Christian and children.
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La Ferme du Petit S.. 25.7Km
Home on the farm in our B&B and cottage living in Moustiers Sainte Marie, Verdon, Provence. Old farm completely renovated by Noël and Sylvie, spacious and tastefully decorated, quiet. You can share dinner at our table and enjoy our Provencal and Mediterraneen cuisine. Guided hikes and mountain bike hire on site, numerous hiking, earthenware from Moustiers to visit, Gorges du Verdon.
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Ferme Para Loù 29.4Km
The Farm Para lou have 4 independent charming rooms and 2 cottage**** The Located near the Verdon canyon and the Lac, surrounded by fields of lavender, olive trees and truffles. Laëtitia et Richard and their son Robin welcome you to their farm Para Loù. We will help you to discover this magnificient region and make your stay with us an enjoyable one. The farm offers safe car parking, a play area for children, a petanque pitch, volley-ball / badminton court, an swimming pool a relaxing sunbathing area. The swimming pool has a panoramic view of the Lake and also walking access to the Lake.
3Contact More info Add
Chambres d'hôtes à .. 0.2Km
Sian aqui ben Bed and Breakfast in Castellane, a village at the gates of the Verdon Gorge
50Contact More info Add
Gite dans Les Gorge.. 7.1Km
Weekly rental in Verdon - Provence, in the Verdon natural park, independent lodging for 3 to 4 guests in a castle lost in the nature. Very close to the famous Verdon Canyon and sentier Martel.
370Contact More info Add
Le Chalet de l'Imag.. 7.7Km
In a wooden house *****, luxurious Bed and Breakfast, steps to the water, with direct access from the garden to the lake and near ski stations at Val d'Allos and Vauplane. The French Chalet is situated in the mountains les Alpes de Haute Provence, 100 km north of Cannes and Nice near the Gorges du Verdon (the grand canyon of Europe) and the Lake of Castillon, at an altitude of 880 meters.
70Contact More info Add
Auberge Le Clos Jam.. 9.8Km
A 20 minutes de Castellane at the foot of the Gorges du Verdon, we welcome you to Jamac closed. We are located on secondary road 4085 has senez and you will discover the detour road towards Barrême napoleon. Jamac the closed structure is a home where you will find five guest rooms including two suites (for a total capacity of 15 persons) + a cottage and a restaurant
1Contact More info Add
Gîte Les Vignes De .. 11.4Km
The GITE "Vineyards of the Tower Saint Blaise" welcomes you with all its comfort in a former sheepfold located in a quiet wilderness. View of the surrounding mountains, south facing 1 km from the village of Trigance. You will enjoy cool nights in summer thanks to the altitude of 960 m from the property. The set consists of 3 bedrooms, 3 bathrooms with toilets, fitted kitchen, living room with fireplace and wood stove, large covered terrace, solarium terrace and barbecue in the garden.
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Le Bois Faé 13.4Km
La Bastide
Near the Gorges du Verdon, in the high var country, the guest rooms "Le bois faé" invites you to discover, in the heart of nature, atypical habitats such as Yurt and teepee. Enjoy the calm & the landscape around wild & preserved of the Natural park of the Verdon! We also propose a traditional guest room with its private entrance. Many leisures & sports activities are available in the Gorges du Verdon. But Le bois faé also propose you some theme holidays & week end, and guided walks from the guest house (to discover on our website)
80Contact More info Add
Haras de Séranon 16.4Km
cottage with indoor pool in a stud farm in the south of France Bed and Breakfast
150Contact More info Add
Domaine des Guernaz.. 18.7Km
Located in Valderoure, this guest house is 10 km from L?Audibergue ski resort. It offers free Wi-Fi access, a garden and a terrace. A living room for guests is also available. All the accommodation types at Domaine des Guernazelles offer mountain views and a private bathroom with a shower. A continental breakfast is served every morning at Domaine des Guernazelles. The cottage includes a kitchen equipped with a microwave, a refrigerator and a stove. Guests have access to an outdoor kitchen during the summer. This guest house offers a children?s playground. Bikes are available for free and guests can go fishing and canoeing in the area. Free private parking is available on site.
Les Cabanes De La M.. 21.9Km
Les Cabanes De La Moulière offers accommodation in Caille. Free private parking is available on site. Certain rooms include views of the mountains or garden. Rooms have a private bathroom fitted with a shower. There is free shuttle service at the property. The area is popular for skiing and cycling. Nice is 42 km from Les Cabanes De La Moulière, while Cannes is 32 km from the property. The nearest airport is Côte d'Azur Airport, 38 km from the property.
La Joia 22.1Km
Private individual welcomes you in a magic place and convenient to the meditation in an arboretum of 5000m2 - Callian in the Var - in 20 minutes of Cannes, Fréjus, Saint Raphael.
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Le Refuge de Sylva 22.5Km
Chalet of hosts entirely in logs, in full nature between the Cote d'Azur and the gorges of Verdon; For sporting or contemplative stays, alone, in family or in a group.
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L'Oustaou de Mousti.. 23.3Km
One tourist apartment in Moustiers-Sainte-Marie, near the Gorges du Verdon Lakes and to discover lavender, faience, nature, and Provence Verdon. . . in the Alpes de Haute-Provence
420Contact More info Add
Gites Marose 23.4Km
Rental of two gites in Andon cigalon Cigalette quiet and greenery comfortable in the Alpes Maritimes region Provence Cote d'Azur
290Contact More info Add
L'Odalyre 23.5Km
The Odalyre is a Provencal house, located 500 m from the village, near the GR4, we welcome you in a friendly, warm and very quiet.
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Les Lauriers 23.6Km
Located in Moustiers-Ste-Marie to the Verdon doors, the room is ideal for your active holiday or relaxing. Quiet 500m from the center of the village or are earthenware workshops, shops and restaurants, you will take the time to admire one of the most beautiful villages in France. leisure, the Verdon (12 km) are a paradise for nature lovers and walking, Mountain bike trails, paragliding, rafting, canyoning, climbing, swimming or Nautical (sailing, pedal boating, canoeing, swimming .... 4 km) all activities that will satisfy you.
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Chambre D'Hôtes à M.. 23.9Km
In Mons, a villa, a guest room can accommodate 2-3 people in a hilltop village in the Var hinterland. The villa is ideally located halfway between the sea in Cannes and Saint Raphael and the prestigious Gorges du Verdon. The room, with bathroom and WC has a separate entrance and overlooks the veranda.
65Contact More info Add
Lou Rigaou 24.7Km
Pretty independent cottages that can accommodate three people. 5 minutes walk to the hilltop village of keyboards in the Var hinterland. Comfortable sofa bed, television, air conditioning, garden terrace, en suite shower room, microwave. . .
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Maison Fontaines 25.5Km
Fountains house is a typical house of a medieval mountain village as Bargemon. Built in 1641, thick ripe provide perfect insulation and leave a genuine impression of romantic nostalgia. A pleasing harmony between noise and quiet village. In this ancient village with its squares and plane trees, we discover and experiment all day. Discover the charm and warm hospitality Bargemon House Fountains.
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L'Estuve Provencale 25.6Km
We have two very nice airconditioned bedrooms with shower rooms ensuite to offer. They both have direct acces to the garden. There is a fitness room (running machine, powerplate and indoor bike) There is even the possibility to use the sauna (heated by infra-red panels) . The panoramic view looks out onto the village and surounding mountains. Parking space infront of the house.
70Contact More info Add
L'Amiradou 25.7Km
The studio is independent but adjoining the house. Its double bed and (twins at the mezzanine) offer nice lodging for 4 persons. It also has a small living room, a kitchenette(gas stove, refrigerator, dishwasher). The hall way leads to the shower and separate toilet. A small balcony gives an unbelievable view over the valley and even over the sea on clear days. Also private parking and garden, boulodrome.........
450Contact More info Add
La Magnanerie de Se.. 25.8Km
At the foot of one of the Most Beautiful perched town of France, Magnanerie, an old silk worm factory just HAS-been renovated to host 4 large and exquisite cottages
120Contact More info Add
La Farigoulette 25.8Km
Near the village of Seillans, var, in a charming house in the heart of the olive trees, the Farigoulette offers accommodation in two rooms. Terrace and pool.
70Contact More info Add
L'Oliveraie 25.8Km
Carole & Eric are pleased to welcome you at the Oliveraie, an old and charming provençal house amongs the olive trees. A peacefull property of 5.000 m² with a panoramic view on the Estérel, a pool, only 800 m from the village of Seillans (classified as one of the most beautifull of France)
65Contact More info Add
Residence Les Ferra.. 25.9Km
Appartement Les Ferrages is a one-bedroom apartment located in Seillans, 20 km from Lac de Saint-Cassien. The accommodation features a balcony and terrace with views of the countryside. It includes a satellite, LCD TV and free Wi-Fi access. Featuring a shower, private bathroom also comes with a hairdryer. You can enjoy a garden view from the room. There is an equipped kitchen with a dishwasher and oven. Guests can also use the barbecue facilities on site and a grocer can be found within 100 metres. At Appartement Les Ferrages you will find a garden. The accommodation is also 30 km from Le Muy and from the A8 motorway. The property offers free parking.
Lou Triboulet 25.9Km
quiet and peaceful location with breathtaking views of the valley that leads to the sea. Ideal home for a couple with children. No thank you dog.
120Contact More info Add
Mas la Jaina 26.2Km
Mas la Jaïna is a completely ecological bed and breakfast built recently in the typical style of Provence. Ingrid and Johan reserve you a warm welcome in their villa warmed and cooled by geothermal science.
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Ecogîte du Bivosque 26.3Km
Marie Paule welcomes you in Montferrat Provence, in his green houses built with natural materials (clay, wool, linen, cork) that use renewable energy (solar, wood, air).
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Studio des Muraille.. 26.6Km
Studio des Murailles offers pet-friendly accommodation in Entrevaux. The property boasts views of the mountains is 46 km from Nice. The kitchen is equipped with an oven and there is a private bathroom. A flat-screen TV is featured. You can play tennis at the property, and the area is popular for cycling. Cannes is 47 km from Studio des Murailles, while Antibes is 48 km from the property. You can engage in various activities, such as fishing and canoeing. The nearest airport is Côte d'Azur Airport, 45 km from Studio des Murailles.
La Collette 27.4Km
Four air-conditioned rooms with TV and terrace, bowling alley, heated pool, pool house with kitchen available for guests. . . A dream holiday in an unspoilt, quiet with a view over the Esterel
85Contact More info Add
Villa Vénus 28.0Km
Villa Vénus, a bed and breakfast, is a property located in Châteaudouble. Each accommodation at the bed and breakfast has mountain views, and guests can enjoy access to a seasonal outdoor swimming pool and to barbecue facilities. Guests can make use of a garden. The units in the bed and breakfast are fitted with a flat-screen TV with satellite channels. Rooms are complete with a shared bathroom equipped with a bath, while certain rooms will provide you with a terrace. All units feature a wardrobe. A buffet breakfast can be enjoyed in the breakfast area. Villa Vénus offers accommodation with a hot tub. Hiking is among the activities that guests can enjoy near the accommodation. Cannes is 47 km from Villa Vénus, while Saint-Tropez is 40 km from the property.
La Cabane d'Esteban 28.1Km
Charming guest house completely independent, in a cottage with terrace, bathroom, toilet, parking, swimming pool. In a green, quiet and relaxing. We're here to make your stay as pleasant as possible. .
80Contact More info Add
Maison des Lavandes 28.1Km
Maison des Lavandes is set in the beautiful French countryside surrounded by vineyards and olive groves, close to the picturesque hilltop village of Seillans. There are two stone built shepherds shelters dating back to the 14th century in the large garden surrounding the house, with lavender bushes and ancient olive trees. Our guest rooms are decorated in traditional provencal style, each having its own private terrace overlooking the swimming pool, WiFi, tea/coffee making facilities, satellite television offering English, French and freeview channels, Continental breakfast included
90Contact More info Add
La Guérite 28.1Km
We are pleased to welcome you to our 18th century building in the heart of a picturesque village a hundred souls, nestled in lush greenery at 700 m away from the hubbub of the city.
85Contact More info Add
Chambres d'hôtes L'.. 29.7Km
Bed and breakfast in the Var to Tourrettes de Fayence on the border of the Alpes Maritimes and the Var, near Saint Raphaël. This guest house is located near Fréjus, Grasse, Cannes and Nice. 1 hour from Monaco and Saint Tropez.
89Contact More info Add
La Chrysalide 29.7Km
Featuring an outdoor pool and a hot tub, La Chrysalide offers B&B accommodation in Saint-Cézaire-sur-Siagne. The property offers a terrace, a garden and free WiFi access. Each room features views of the sea and the garden, a flat-screen TV and a desk. The private bathroom has a shower, a hairdryer, free toiletries and bathrobes. Breakfast featuring organic products is included and served every morning. Meals prepared with organic products can be served upon request at an additional charge. Guests can also enjoy the BBQ facilities. La Chrysalide offers a library and free on-site parking. Grasse is 19 km away, Cannes is 32 km away and Antibes is 41.5 km away.
Domaine de la Grang.. 29.9Km
The Domaine de la Grange spreads over 160ha in the beautiful and sunny South of France. There are 1 and 2 bedroom apartments for rent, with on the property a secured heated swimming pool with a man-made beach, a golf driving range and putting green, a lake for fishing and 2 jeux de boules fields. Not far the the Gorges du Verdon. 45 minutes from Med. beaches, 1 hour from St Tropez.
1155Contact More info Add


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Who We Are
Allysia Finley
Allysia Finley is an assistant editor of the OpinionJournal.com. She publishes opinion articles to the web and adds exclusive online material. She is also responsible for expanding the OpinionJournal.com's readership and presence on the web.
Ms. Finley joined the Wall Street Journal in 2009 after graduating from Stanford University with a bachelor's degree in American Studies. During college, she edited the opinions section for the Stanford Review and wrote columns for the Orange County Register....


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Take the Tour
Mark your calendar
This year's tour will be on Saturday, April 29, and Sunday, April 30. The tour will take place from 11am to 5pm each day.
Get your tickets
Tickets are available for a recommended donation of just $5. Please pay what you feel the tour is worth!
Download our Tour Program
The tour program provides maps, photos, descriptions and identifies the green features of each site on the tour! Use this guide to help plan your day.
View online or download
Keep up with us
Like us on Facebook to receive tour updates https://www.facebook.com/NWGreenHomeTour
- The tour is self-guided. Start and end at any of the 18 residential or 2 sustainability sites.
- Walking, biking, and carpooling are all encouraged. Why not invite a friend or two to take the tour with you?
- When you arrive at your first site, we will take your printed ticket or view your ticket on your phone and give you a wristband. You won't have to check in again as long as you are wearing your wristband.
- Your tour wristband will entitle you to free items and discounts at some Sustainability Stops (local businesses and organizations that support the tour and offer further opportunities for learning about green building).
- Look for informative signs inside every home that explain the many green features on display.
- Children are welcome on the tour, but due to space constraints, please park strollers outside.
- Wear shoes that are easy to slip on and off, as many sites have a no-shoes policy.
- The tour is free and open to the public. It is made possible by site hosts, sponsors, and the Northwest EcoBuilding Guild. We ask for a $5 donation to help offset costs. Your donation can be made when you register online for the tour. Please help this annual event continue by becoming a member of the Guild and supporting our site hosts and sponsors.


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Check Out These 2 Brand New Major Lazer Tracks
Major Lazer had more than one thing up its sleeve this week! The new Major Lazer cartoon series on FXX serves a secondary purpose: To Debut new Major Lazer tracks. The cartoon already debuted such tracks as "Bass Drop," and this week's installment unveils another fresh tune. Watch the clip from the Major Lazer cartoon that debuts "Weedman" featuring Trinidad Jame$'s below...
But that's not all... Now, it's time for the new remix! Major Lazer just uploaded their take on Stromae's "Ave Cesaria" to their Soundcloud, and it's available for free download! Take a listen and download below, and remember that the group's upcoming LP Peace Is The Mission is set to release on June 1! You can count on EDM.com to keep you posted as the premiere approaches.
[H/T EDMSauce & FistInTheAir]
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What to Consider Before Retiring Out of State
Taxes Are a Big Factor, but They Aren't the Only Thing
Living in California, I often hear how expensive it is to live here, primarily because of higher taxes. But I've started to debunk that myth for my clients, and provide them with some information about what they need to consider before retiring out of state.
Journal Report
- Insights from The Experts
- Read more at WSJ.com/WealthReport
More in Wealth Management
I'm 61, and last year I had this idea about retiring in Reno, Nev. It doesn't snow much. It's 4,000 feet above sea level, but not so high that I'd get congestive heart failure. And there's no income tax. I thought it had to be the cheapest place.
But I was wrong. I calculated the average cost of the house I'd want to buy, as well as expenditures such as gas, and compared them to what I'm paying in California. The cost of certain taxes were less in Nevada, but I was surprised to find that the property taxes were only slightly less for a house costing the same amount. I decided that taxes shouldn't be the only reason to move to a state.
In general, I think people rely on similar assumptions when they are contemplating a move for retirement. So in deciding whether a move is prudent, people should research everything. Taxes are one of the biggest factors—everything from sales, property and income taxes to cigarette and diesel taxes. Certain states have special tax breaks for seniors. People need to read the fine print.
There also are cost-of-living expenditures for things like food and heat, as well as state-by-state anomalies. For instance, I live on the beach. Salt invades everything. It pops through my driveway and ruins the landscaping. It kills the plants. In Florida, there are so many mosquitoes they could be considered the state bird. You may have a nice pool but you can't enjoy it unless it's screened-in. These are costs you need to consider.
Before deciding on a move, people should first visit the state during the worst part of the year. If you love Maine and it will be your only residence, try living there in the winter and see what happens.
Mr. Kagawa is a certified financial planner and president of Capital Resources & Insurance Inc. in Huntington Beach, Calif. Email him at email@example.com.
Corrections & Amplifications
The property tax rate in Nevada generally is higher than it is in California. However, it is only applied to 35% of the assessed value of a home. A previous version referred to an incorrect calculation based on the rate being applied to 100% of the assessed value. (June 25, 2014)


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Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly activated by mutation in non-small cell lung cancer. The mechanism of this oncogenic activation is incompletely understood but, in contrast to the WT EGFR, is proposed to be independent of kinase domain dimerization. Mechanistic studies on EGFR have largely relied on cell-based assays or isolated kinase domain measurements. Here we show using purified, near full-length EGFR proteins (tEGFRs) that two oncogenic mutants are fully active in the absence of EGF and highly resistant to the known therapeutic and endogenous inhibitors, Cetuximab, lapatinib, and MIG6. Based on the pattern of inhibition and the effects of additional asymmetric kinase dimer interface mutations, we propose that these oncogenic EGFR mutants drive and strongly depend on the formation of the asymmetric kinase dimer for activation, which has implications for drug design and cancer treatment strategies.
The epidermal growth factor receptor (EGFR) family comprises of four members in humans, EGFR (HER1), HER2/Neu, HER3, and HER41. These receptor tyrosine kinases (RTKs), play consequential roles in a variety of solid cancers and are the targets of many successful antineoplastic therapeutics2,3. The synthetic compound erlotinib targets the active conformation of the kinase domain and is clinically approved for non-small cell lung cancer. Erlotinib is particularly effective in cancers in which the EGFR kinase domain contains activating mutations, the two most common of which are Δ746–750 and L858R4–7. The synthetic compound lapatinib is FDA-approved for the treatment of HER2/Neu-positive breast cancer and is proposed to bind preferentially to the inactive conformations of EGFR and Her2/neu8,9 kinase domains. Cetuximab is an antibody that binds to the EGFR ectodomain, blocking the binding of EGF to the receptor, and is approved for treatment of several EGFR-positive cancers 10,11.
EGFR family members are composed of a ligand-binding extracellular region, a membrane spanning region, a juxtamembrane region, a kinase domain, and a C-tail that can be autophosphorylated12,13(Fig. 1a). Activation of EGFR by EGF involves the formation of a specific dimer of the extracellular ligand-binding regions14–18, which appears to promote an asymmetric dimer interaction between the kinase domains in which the activity of one kinase subunit (acceptor kinase) is stimulated by another (donor kinase)19. The interface of this asymmetric dimer has been defined crystallographically and by mutagenesis and involves the N-terminal lobe (including Ile706) of the acceptor kinase and the C-terminal lobe (including Val948) of the donor kinase19. A peptide segment (segment 1) of the tumor suppressor protein MIG6 (RALT) has been shown to be a moderately potent inhibitor of EGFR kinase activity by binding to the C-lobe of the EGFR kinase domain and sterically blocking asymmetric dimer formation20 (Fig. 1b). Another MIG6 segment C-terminal to segment 1 (segment 2) enhances the inhibitory activity of MIG6 and is believed to interact directly with the EGFR kinase active site20.
Previous in vitro studies of the isolated L858R EGFR kinase domain have shown that it is ~50-fold more active relative to the WT kinase domain but does not appear to depend on asymmetric dimer formation19,21. The L858R EGFR kinase domain is, however, sensitive to erlotinib and MIG6 inhibition20,22. Tyrosine phosphorylation of MIG6 appears to be increased in cancer cell lines containing Δ746–750 or L858R EGFRs, suggesting that in addition to inhibiting EGFR, MIG6 may also be a direct substrate of these mutant receptor EGFRs23. There has been limited enzymologic characterization of the Δ746–750 EGFR kinase domain24. Cell-based assays with full-length L858R and Δ746–750 EGFRs show enhanced autophosphorylation of the EGFR C-terminal tails and other proteins relative to WT EGFR22,25,26, but the enzymologic basis for this increased phosphorylation has been difficult to establish because of the complex environment of the cell.
Previously, we demonstrated the feasibility of expressing, purifying, and analyzing the kinetics for near-full length EGFR (tEGFR, aa25–1022), which lacks only part of the C-terminal tail27. It was shown that the EGF bound form of WT tEGFR had a kcat that was 150-fold greater and a sensitivity to erlotinib that was ~25-fold higher than the Cetuximab–bound form, consistent with EGF–driven activation27. Interestingly, and not readily understood based on the kinase crystal structures, the potencies of lapatinib for EGF– and Cetuximab–bound tEGFRs were found to be within 2-fold of one another27.
To investigate the effects of cancer-associated EGFR mutations on the mechanism and degree of EGFR activation, we examine here the kinase activity of wild-type and mutant EGFRs in the presence and absence of inhibitors targeting different activation states of EGFR. Unexpectedly, we find that EGF-independent activation of L858R and Δ746–750 tEGFRs remains strongly dependent on asymmetric kinase dimer formation.
The cDNAs encoding human EGFR aa 25–1022 (tEGFR) with mutations L858R or Δ746–750 were transiently transfected into 2–4 L of HEK 293 GnTi− cells28, and the mutant tEGFRs were purified from detergent-solubilized cell extracts as previously described using the anti-EGFR Ab 52827,29. Expression levels of the mutant tEGFRs were reduced compared to WT tEGFR (Fig. 1c), leading us to suspect that the oncogenic forms of tEGFR may be cytotoxic at high expression levels owing to excessive kinase activity30,31 or unstable because of the mutation. We thus evaluated expression in the presence of the reversible EGFR inhibitor erlotinib, which indeed led to enhanced expression of both mutant tEGFRs at the relatively low inhibitor concentration of 50 nM (Fig. 1c). Addition of erlotinib to the cell culture media allowed for the purification of ~0.1 mg of L858R and Δ746–750 tEGFRs per liter of cell culture. An EGF–bound and a Cetuximab Fab–bound form of each tEGFR mutant were obtained by eluting the affinity column with either EGF or the Cetuximab Fab. These tEGFR complexes were further subjected to size exclusion chromatography, with the majority of tEGFRs eluting at positions consistent with formation of high molecular weight but self-limited oligomers. We estimated tEGFR purities to be >80% by SDS-PAGE (Fig. 1d). Extensive dialysis and chromatography were used to remove erlotinib prior to storage. Similar ATP Kmapp and kcat values were observed from two different protein batches purified from cells cultured with either a high (2 µM) or low (50 nM, considerably below the tEGFR IC50, vide infra) concentration of erlotinib, indicating that erlotinib was effectively removed during purification.
The mutant tEGFRs were assayed using a direct, radiometric assay in which transfer of phosphate from γ-32P-ATP to a biotinylated peptide was monitored after avidin pull-down of radiolabeled phosphopeptide. Both L858R and Δ746–750 tEGFRs in their EGF and Cetuximab–bound forms display linear kinase activity versus time as well as enzyme concentration (Supplementary Fig. 1), suggesting that these mutant receptors are stable in the conditions of our assay. It is readily apparent from these results that the Cetuximab–bound forms of oncogenic mutant tEGFRs are dramatically more active than WT enzyme in the presence of Cetuximab, which shows poorly detectable kinase activity under similar conditions. The kcat and Kmapp values for peptide and ATP substrates for WT and mutant tEGFRs are shown in Table 1 (Steady-state curves are shown in Supplementary Fig. 2). Striking differences in the kcat values between the oncogenic mutant tEGFRs and WT tEGFR in the Cetuximab–bound complexes are observed. The kcats for Cetuximab–bound oncogenic tEGFRs are within 2-fold of each other but approximately 200-fold greater than the kcat for Cetuximab–bound WT tEGFR. In contrast, the kcats for the EGF–bound WT and mutant tEGFRs are similar to each other and to the Cetuximab–bound forms of L858R and Δ746–750 tEGFRs. These results indicate that the activities of oncogenic tEGFRs are comparable or greater than that of EGF-stimulated WT tEGFR.
The ATP Kms also show marked differences between mutant and WT tEGFRs. Compared to that of the WT EGF–tEGFR complex, the ATP Kms of the L858R and Δ746–750 tEGFRs are 50- to 200-fold higher. The finding of the elevated ATP Km with L858R tEGFR is consistent with previously reported analysis of the isolated L858R kinase domain21,24. Since both Leu858 and the aa746–750 loop are distant from the ATP binding site and from each other, the origin of the elevated ATP Kms is not readily apparent from X-ray crystal structures. In contrast to the widely divergent ATP Kms in WT versus mutant tEGFRs, effects on peptide substrate Kms from the mutations are less dramatic. However, the L858R mutant shows 3–4-fold higher peptide Km value versus WT and Δ746–750 tEGFRs, which may reflect substrate binding interactions involving the activation loop on which L858 resides19,32.
We next examined ability of the ATP mimic AMP-PNP, as well as the therapeutic agents erlotinib and lapatinib, to inhibit oncogenic tEGFRs. AMP-PNP showed similar IC50s for WT and mutant tEGFRs in the range of 80–200 µM (Supplementary Fig. 3). Taking into account the ATP concentration employed (10 µM) and the respective tEGFR ATP Kmapps, the Kis of AMP-PNP are deduced to be ~5- to 8-fold higher for L858R (107 ± 19 µM) and Δ746–750 (160 ± 59 µM) compared with WT (21 ± 5 µM). While clearly an increase, this 5–8-fold change is substantially lower than the 50- to 200-fold Km differences for ATP among these EGFR forms, suggesting that the ATP Km differences result largely from changes in rate-determining steps in catalysis, rather than simply changes in binding affinities for nucleotide.
The apparent Kis for erlotinib and lapatinib were also measured for each tEGFR mutant (Table 2, Supplementary Fig. 4). The L858R and Δ746–750 tEGFR forms were potently inhibited by erlotinib with apparent Kis in the range of 0.1–0.4 µM, about equal to the apparent Ki of erlotinib for WT tEGFR complexed with EGF. However, compared with WT tEGFR, the oncogenic mutant tEGFRs showed similar potencies regardless of EGF or Cetuximab ligand. In contrast to the behavior of erlotinib, the L858R and Δ746–750 tEGFR forms were highly resistant to lapatinib with apparent Kis in the range of 2–6 µM. Taken together, these results suggest a model in which the L858R and Δ746–750 mutations drive tEGFR into an active conformation with diminished access to the inactive state, even relative to EGF–bound WT tEGFR.
The tumor suppressor protein MIG6 contains a 77 aa region composed of two functional regions, termed segments 1 and 2, that potently inhibits EGFR kinase activity in part by binding the C-lobe of the EGFR kinase domain and blocking asymmetric dimer formation20. Recent cellular proteomic studies have suggested that this region of MIG6 is also tyrosine phosphorylated in response to EGF23. We find that tEGFR efficiently phosphorylates MIG6 segment 1+2 on Tyr residues (Fig. 2a–b) and that both L858R and Δ746–750 tEGFRs catalyze the reaction ~10-fold better than WT tEGFR (Table 3, Supplementary Figs. 5). Interestingly, the level of autophosphorylation of WT tEGFR in reactions that contained MIG6 segment 1+2 was substantially inhibited relative to the oncogenic tEGFR forms (Fig. 2a). To more precisely measure the effects of MIG6 inhibition, we investigated the effects of both segment 1 (aa 334–364) and the entire 77 aa region (segment 1+2, aa 336–412) of MIG6 on phosphorylation of our biotinylated EGFR substrate peptide, which could be readily separated from MIG6 using streptavidin-containing resin. In prior binding and inhibitory studies on the EGFR catalytic domain, segment 1 of MIG6 was sufficient to bind the C-lobe surface of the kinase domain but bound with ~100-fold weaker affinity relative to segment 1+220. Segment 1 of MIG6 is a moderate inhibitor of EGF–bound WT tEGFR (IC50 = 100 µM) whereas L858R and Δ746–750 tEGFR are essentially resistant to inhibition by segment 1 (Supplementary Fig. 6). Segment 1+2 of MIG6 was a considerably more potent inhibitor of EGF–bound WT tEGFR with an IC50 of 0.5 µM, similar to its potency versus the isolated EGFR kinase domain (Fig. 2c) and the previously determined value versus the L858R EGFR kinase domain20. However, MIG6 segment 1+2 showed an IC50 of ~20 µM versus both L858R tEGFR and Δ746–750 tEGFR (Fig. 2c). Since the IC50 of MIG6 segment 1+2 is 0.4 µM for the isolated kinase domain of L858R20, the far weaker inhibition of L858R tEGFR by MIG6 segment 1+2 suggests that the C-lobe of the kinase domain in the near full-length mutant protein is much less accessible to MIG6 interaction.
Mutations in the N-lobe (I706Q) or C-lobe (V948R) region of the asymmetric kinase dimer interface have been shown to impair EGF induced activation of WT EGFR in cells19,20. However, the double mutant L858R V948R in the isolated EGFR kinase domain has been shown to have essentially identical catalytic activity to the isolated L858R EGFR kinase domain suggesting that dimerization is not important for its constitutive activation20. To investigate this issue in tEGFR, we introduced simultaneous L858R and I706Q substitutions into tEGFR and measured their effects on catalytic activity in the presence of EGF (Fig. 3a–b, Supplementary Fig. 2b). In the presence of EGF, this double mutant tEGFR showed a kinase rate that was ~30-fold lower than the single mutant L858R tEGFR, but showed a similar ATP Km (Table 1, Supplementary Fig. 2b). Interestingly, in the presence of Cetuximab, the kinase rate of L858R/I706Q tEGFR was about 10-fold lower than the EGF–bound form, close to the limit of detection (Fig. 3a–b). These results suggest that the kinase domain asymmetric dimer interface in L858R tEGFR contributes substantially to its constitutive kinase activity and that EGF can still promote dimerization in the presence of an N-lobe interface mutation.
To exclude the possibility that I706Q was affecting tEGFR kinase activity independent of dimer interface effects, we prepared and analyzed L858R/V948R tEGFR. As shown in Figure 3a–b, the kinase activities of L858R/V948R tEGFR in its EGF– and Cetuximab–bound forms were reduced substantially compared to that of L858R tEGFR, indicating that mutation of either the N-lobe or C-lobe face of the dimer interface of L858R results in a 10- to 30-fold decrease in catalytic rate. To probe the conformational properties of L858R/I706Q tEGFR further, we examined its sensitivity to inhibition by lapatinib (Supplementary Fig. 4b). As shown in Table 2, the apparent Ki of lapatinib for EGF–bound L858R I706Q tEGFR is 700 nM, about 6-fold lower than the apparent Ki of lapatinib for EGF–bound L858R tEGFR. These observations indicate that activation by the L858R substitution is coupled to kinase dimer formation and that inhibiting dimer formation by mutation increases accessibility of the inactive kinase conformation.
Next, we investigated the kinase activity of Δ(746–750) I706Q tEGFR (Fig. 3c). In the EGF–bound form, Δ(746–750) I706Q tEGFR showed a kinase rate that was 5-fold lower than that of Δ746–750 tEGFR. There was a further 3-fold reduction in kinase activity with the Cetuximab–bound form of Δ(746–750) I706Q tEGFR relative to the EGF–bound form. Taken together, these data suggest that the asymmetric dimer interface also remains important for activation of tEGFR with the aa746–750 loop deletion, although it appears that there is a larger amount of residual kinase activation in Δ(746–750) I706Q tEGFR relative to L858R I706Q tEGFR.
This study finds that the two most common EGFR mutations in non-small cell lung cancer (L858R and Δ746–750) result in EGF–independent tEGFR activities comparable to, or greater than, the activity of EGF–stimulated WT EGFR, and that tEGFR activation resulting from these mutations remains strongly coupled to asymmetric kinase dimer formation (Fig. 3d). This model differs from prior enzymatic studies on the isolated L858R EGFR kinase domain20 that suggested the asymmetric dimer interaction is dispensable for stimulation of catalysis. In contrast to the isolated L858R kinase domain results, we observe that mutation of residues in the dimer interface in tEGFR dramatically reduces the activity of both the L858R and Δ746–750 tEGFRs, indicating that this dimerization event is critical for activation of both of these oncogenic mutants.
Strong resistance to MIG6 inhibition further highlights the loss of accessibility of the asymmetric kinase dimer interface in the purified oncogenic EGFRs, as activation appears to both remain coupled to and drive kinase dimer formation. Size exclusion chromatography suggests that L858R and Δ746–750 tEGFR proteins are oligomeric, presumably reflecting chains of tEGFR formed through a series of asymmetric kinase interactions. However, the fact that these mutants do not shift completely to the column void volume suggests that the chains are self-limiting even in the absence of membrane. The thermodynamic inter-dependency of the active kinase conformation and dimerization provides a plausible model for these results (Fig. 3d). The previous report that activation is dimer-independent in the isolated EGFR kinase domain underscores the limitations of attempting to understand the regulation of this complex receptor by studying isolated fragments. The multiple domains of full length EGFR clearly contribute to a web of intra- and inter-molecular interactions, including the juxtamembrane region13,33–35, that couple the effects of activating mutations and dimer formation and are central to the regulation mechanism. The lack of a membrane bilayer and the truncation of the C-tail in our tEGFR studies may affect the results, but the fact that we recapitulate a high degree of kinase activation with the wild type EGFR enzyme in its EGF– vs. Cetuximab–bound forms increases confidence in the relevance of our findings with the mutant proteins.
The observation that L858R EGFR transfected in cells retains EGF dependency20,23 differs from our findings with purified tEGFR. This difference may result from the indirect measurement of kinase activity in cells, EGF effects on cellular trafficking/internalization, or the presence of inhibitory feedback mechanisms that EGF is able to override in cells. In any event, we believe that our data indicating loss of EGF–dependence for L858R reflect the intrinsic properties of the purified oncogenic mutant EGFRs and set a benchmark for analyzing cellular behavior of these molecules. The presence of heterodimers of oncogenic forms of EGFR with WT EGFR or HER2–4 may also affect the ligand-dependency of oncogenic EGFR variants in a cellular context.
The studies reported here also enhance our understanding of the paradoxical inhibitory properties of lapatinib with WT tEGFR in its EGF– and Cetuximab–bound forms27. The unexplained parity in potency of lapatinib between the EGF– and Cetuximab–bound WT tEGFR forms was initially interpreted as potentially due to lapatinib binding favorably in distinct modes to active as well as inactive kinase conformations. Based on the >20-fold reduced potencies of lapatinib for the L858R and Δ746–750 tEGFRs compared to EGF–bound WT tEGFR, we hypothesize now that the kinase active conformation of EGF–bound WT EGFR may be nearly isoenergetic with the kinase inactive state of EGF–bound WT EGFR and largely present in the donor kinase. In this way, there would be little thermodynamic impediment to lapatinib accessing the kinase inactive conformation of EGF–bound WT EGFR. Consistent with this model, we have found that MIG6 segment 1+2 potently inhibits EGF–bound WT tEGFR, presumably because this asymmetric dimer is not highly stabilized, allowing access of the C-lobe of the kinase domain to efficiently bind segment 1 of MIG6. In contrast, MIG6 segment 1+2 cannot effectively inhibit the oncogenic mutant tEGFRs, presumably because the C-lobe is less accessible in conditions more strongly favoring formation of asymmetric kinase dimers.
We also show here that MIG6 is tyrosine phosphorylated by tEGFR, particularly the L858R and Δ746–750 forms. These results extend a prior study showing how specific increases in these substrates in isogenic, mutant EGFR tumor cell lines resulted in enhanced tyrosine-phosphorylation of MIG623. How tyrosine phosphorylation of MIG6 might impact its interaction with EGFR or have other influences in signaling is an important direction for future studies. It is also interesting that the apparent Km of L858R tEGFR for substrate peptide is ~4-fold greater than for WT and Δ746–750 tEGFRs. This difference implies that oncogenic EGFR mutations may affect the specificity or extent of substrate phosphorylation, which will be an interesting question to address with future proteomics studies36–38.
Based on the findings here, the dramatic increase in ATP Km for L858R and Δ746–750 tEGFR forms can be understood to be partially related to altered nucleotide affinities but also likely to result from changes in microscopic rate constants for the enzymatic transformation. For example, if the chemical (phosphoryl transfer) step in the mutant kinases is greatly accelerated relative to the WT reaction, this rate increase might result in an elevated ATP Km39. From a functional perspective, however, ATP Kms in the 200–700 µM range are of little consequence in the cell since ATP concentrations are in the millimolar range.
These studies have several implications for cancer therapeutic strategies. Given their resistance to lapatinib and Cetuximab, there appears to be little rationale for the use of these agents in non-small cell lung cancer containing L858R and Δ746–750 EGFR mutations whereas erlotinib's clinical benefit in these cases is readily understood. Furthermore, targeting cancers with these oncogenic mutations with MIG6 peptidomimetics appears to be a challenging proposition since competition for this dimer interface will be difficult. In future experiments with tEGFRs, it will be interesting to determine the effects of the gatekeeper T790M drug resistance mutation40 on the relative activation and inhibitor sensitivities of these enzymes.
We thank the NIH (GM099321 to D.J.L. and CA074305 to P.A.C.) for financial support and A. Mildvan and J. Stivers for helpful discussions.
Competing financial interests
The authors declare no competing financial interests.
AUTHOR CONTRIBUTIONSZ.W., D.J.L., and P.A.C. conceived of the project and designed the research. Z.W., M.K.T., P.A.L., K.K., and S.H. performed experiments. All authors helped analyze the results and write the paper.
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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Shenzhen, China (PressExposure) August 17, 2009 -- Spy cameras boost in popularity nowadays due to their constantly-dropping prices, technology improvement, and people's increasing awareness of safety and security. Do you know what the basic types of spy cameras are? This article will introduce five basic types. Plus, it also recommends 5 hot spy cameras products selected from different wholesale electronics [http://www.actfind.com/] online stores/retail.
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One of the true hitmakers of the 1990s, Collin Raye still continues to crank out soulful, heartfelt material with the honesty and richness that is signature to his vocals on his newly formed label StarPointe Records.
His new �Selected Hits� CD that is now exclusively at Walmart contains two new songs, �A Soldier�s Prayer� and �Quitters�. �A Soldier�s Prayer� rides that prevalent theme during wartime, but rather than beating a dead horse, this song takes a slightly different approach and states a truth to all of us, not just those in uniform, but that hope is alive and is strong and is Our Heavenly Father.
�Quitters� is just flat out inspirational delivered in fine vocal form and the hook is catchy. Collin says, �I�m a big fan of live material . . . and as a matter of fact, I�d like to see more live music released by country artists. These tracks featured the Salt Lake Symphony, an 80-piece orchestra, along with four more of my previous hits - �That�s My Story�, �Little Rock�, �I Think About You�, and �Love Me� - and it made me wonder how they�d mock up the arrangement. It�s really a flawless presentation of the originals, but with a high energy exciting feel to the up-tempo songs and an intimacy in the slower songs.�
And if that is not enough, Collin recently contributed to the Newly Released Album, Songs 4 Worship: Country that was released in 2008. This wonderful collection of songs from other artists besides Collin was co-produced by Teddy Gentry and Michael Curtis. Collin�s song on the album is �Get Up In Jesus Name� which is not only inspirational but will have you toe tapping and hand clapping to the music.
At every sold-out concert, at every radio-station visit, the mega hit maker gets asked by fans and industry professionals alike, �Hey, man, when are you going to put out a new record?�
�My recording career isn�t done by a long shot,� Collin promises them. �I didn�t go away into hibernation. I tour all the time, so I know there�s a demand for a new album. I wouldn�t put out records again unless I thought that people really wanted them. And they do.�
Actually, he�s been working on his new Twenty Years and Change collection all along. In between the constant concert appearances, he began traveling to Nashville three years ago. During each visit, he would record a song or two.
�One of the great things about making this album was having the freedom of going into the studio with no one looking over my shoulder,� comments Collin. �I didn�t feel like I was on some kind of treadmill. I didn�t set out any timetable. I didn�t think, �Let�s make a hit single, right now.� I said, �Let�s just make this as good as it can be, to where it sounds good to us. Then we�ll step back and look at the whole thing.�
�In the end, we wound up with 23 songs. And these twelve are the best of those 23.�
Those twelve include some instant classics, as well as some bona fide classics. In the latter category are Collin Raye�s island-flavored reinterpretation of The Bellamy Brothers� chestnut �Let Your Love Flow�, a heartfelt �It�s Only Make Believe� tribute to the late Conway Twitty, a powerful reworking of the 1985 Survivor hit �The Search Is Over� and a remake of Don Henley�s �You�re Not Drinkin� Enough� that takes the tune straight into a honky-tonk.
Always a masterful ballad singer, Collin pours emotion into the wistful �Forgotten�, the reassuring �We�ll Be Alright� and the lovely romantic �All I Can Do Is Love You�. �Hurricane Jane�, on the other hand, is a good-time rocker. �Heart� has a lusciously melodic, mid-tempo groove.
�I Know That�s Right�, the collection�s first single, has a stirring message lyric. Two other standouts are story songs. �Josephine� tells the tale of a frightened Civil War soldier writing a letter home. �Twenty Years and Change�, written by the artist, is the portrait of a man who has replaced his youthful ideals with a resigned acceptance of his older, more satisfying reality.
Working with a variety of co-producers, Collin Raye is behind every note of music that�s heard on Twenty Years and Change. That, he says, is a first for him. He is proud of his five prior Platinum albums, 25 Top Ten hits, 15 Number One smashes and twelve chart-topping videos. However, maintaining his high standards wasn�t always easy.
�The last record I made for Sony, I�ll never forget the meeting where they said, �We took a poll around the building and 70% voted for this song as your single.� I said, �You took a vote around the building? I thought it was between the executive, the producer, the radio-promotion department and me. The receptionist has a vote? The art department?� It seemed that everybody was getting a say-so about song selection. You can�t make records that way.
Collin Raye is nothing, if not passionate. His fiery delivery has made country standards of such searing ballads as �Love, Me�, �In This Life�, �Not That Different� and �Little Rock�. Always an electrifying showman, he has also blazed through such vivid rockers as �My Kind of Girl�, �That�s My Story�, �I Can Still Feel You� and �I Want You Bad�.
His commitment to music has been life-long. Collin has been singing professionally since he was a teenager. He has never held any other job.
�I grew up steeped in traditional country music,� Collin reports. �I knew every song on Johnny Horton�s Greatest Hits by heart. To this day, I can sing them to you. I think that�s where I got my love of story songs.
�We never missed a country package show when one came through Little Rock. I remember seeing Porter Wagoner & The Wagonmasters with Dolly Parton, George Jones & The Jones Boys, Merle Haggard, Charley Pride and Conway Twitty, all on the same bill! Ray Price, Buck Owens, I loved them all.�
His mother, Lois Wray, was a country singer, and he was on stage with her by the age of seven. The family moved from Arkansas to Texas when he was young, and at age thirteen he and his older brother Scott formed The Wray Brothers band to entertain in the Lone Star State.
The brothers migrated to lucrative casino work in Reno, Nevada. Billed as �Bubba Wray,� Collin became a master of stagecraft and a �human jukebox� whose repertoire included thousands of songs from across the American musical landscape. The Wrays first attracted Nashville�s attention with a string of independent-label singles recorded in the Pacific Northwest in the 1980s. Mercury Records signed them and issued a couple of singles in 1986-87.
But Scott tired of the road, and the band broke up. Collin had married in 1980 and fathered daughter Brittany in 1983 and son Jacob in 1985. Like his brother, he also considered giving up music. That all changed when he began making solo records in 1990. Scott, by the way, is now bandleader for new Nashville star Miranda Lambert.
Collin shot to fame with �Love, Me� in 1991. Listeners were so touched that they used its lyrics at funerals and memorial services. That set the cornerstone for a career built on meaningful songs. �Little Rock� was an anthem for the recovery community. �Not That Different� pleaded for tolerance. �In This Life� became a wedding favorite. He won awards for the child-advocacy video �I Think About You�.
Five times nominated as country music�s Male Vocalist of the Year, Collin Raye has consistently used his stardom to advance social causes. Among the organizations he has supported are Boys Town, First Steps, Al-Anon, Special Olympics, Country Cares About AIDS, Catholic Relief Services, Parade of Pennies, Vanderbilt Children�s Hospital, The Tennessee Task Force Against Domestic Violence, The Emily Harrison Foundation, Childhelp USA, Silent Witness National Initiative, Easter Seals and Make a Difference Day. At the 2001 Country Radio Seminar, Clint Black presented Collin Raye with the organization�s Humanitarian of the Year award in recognition of Collin�s issue-oriented music and his tireless charity work.
But when the album he released later that year wasn�t successfully promoted, Collin asked for his release from Sony. Contractual roadblocks didn�t allow Collin to seek a new record deal for a period of time. Eventually he was able to aggressively try to get back in the record business.
Thus, Collin Raye began looking for a home for Twenty Years and Change. He turned down major-label overtures to sign with Infinity Records in 2004, but that company folded, further delaying his return to disc. The Navarre-distributed Aspirion picked up his recording contract in August 2005.
The man who has topped the charts with such great songs as �On the Verge�, �One Boy, One Girl�, �What the Heart Wants�, �Every Second� and �That Was a River� is finally ready for another round of successes.
�I believe in Providence,� says Collin Raye. �I believe there�s a reason things happen the way they do. I also believe that if you�ve treated people right and you continue to work hard at your craft, things will happen. I want to keep going. I want hit records. I want to make music.�
Mixing up the laid back rock and folk of mid-seventies Southern California with country and rock n roll, Collin Raye creates a sophisticated and diverse album on Never Going Back (2009). Full of songs that subtly recall the great, organic music of that era, Raye pulls them right into the future with his distinctive sound and style.Recorded in Alabama�s historic Muscle Shoals, the album feels guided by the ghosts of the country, rock, blues and pop albums that the region cultivated throughout the�70s. And like a fantastic LP, this CD is great from start to finish. From the roaring, feel-good romp of �Mid-LifeChrysler�, and the powerful reworking of �Without You� (a duet with Grammy nominee Susan Ashton) to the unforgettable, intensely personal �She�s With Me�, every tune is finely crafted, sure to connect with his legions of fans.


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Europe Carrier Quarterly Update Q3 2015
Jan 19, 2016, 16:15 ET from Reportlinker
NEW YORK, Jan. 19, 2016 /PRNewswire/ --
Key Developments in the European Telecommunications Market
The research provides an overview of key mobile and fixed communications developments by major European mobile operators in Q3 2015. It covers both qualitative (product launches, infrastructure development, partnerships/alliances, M&A activity, key client wins, change in personnel) and quantitative (mobile and fixed broadband subscribers, mobile ARPU, operating profit margin, market capitalisation) information. The research is a continuation of Frost & Sullivan's regular quarterly updates on the industry.
Top 3 European Carrier Highlights Q3 2015
Wind and 3 Italia Agree on Italian Merger
- VimpelCom and CK Hutchison have agreed to form a joint venture of their Italian telecommunications operations, Wind and Italia.
- With more than Million mobile customers, the combined entity will be the largest mobile operator in Italy.
It is expected to generate significant operational efficiencies and will compete more aggressively against its rivals, Telecom Italia and Vodafone.
Turkcell Acquires LTE Spectrum
- Turkcell secured MHz of spectrum in Turkey's long-awaited 4G auction held on 26 August 2015. It spent a total of € Billion to acquire the highest amount of spectrum acquired among the country's three
operators. The operator will use the spectrum to launch LTE-Advanced by April 2016.
Vodafone UK Launches WiFi Calling
- The service makes calls available in more places connected to WiFi (and/or lacking mobile signal) and eliminates the need of running an app as in the case of over-the-top (OTT) services. There is no additional
cost involved.
- With this move, Vodafone is catching up with its main rival, EE, which was the first UK operator to launch WiFi calling.
Read the full report: http://www.reportlinker.com/p03571238-summary/view-report.html
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Anais B is a professional tattoo artist who works out of Spa, Belgium and specializes in a variety of primarily black-and-grey styles. She's probably best known for her jewel and lace designs that strategically add a splash of color and show off her amazing shading ability that is a great example of how less can indeed be more. If you find yourself in or around Belgium and looking for a tattoo by one of the best tattoo artists in the world, look up Anais B. You certainly won't be disappointed. Belgium Anaïs B Tattoo IG – https://www.instagram.com/anaisbtattoo/?hl=en FB – www.facebook.com/anaisbtattooRead More »
Tag Archives: tattoo artist
Artist Spotlight – Zack Taylor
Zack Taylor is a professional tattoo artist who works out of Evermore Tattoo in Los Angeles, California. He's a massive fan of bold, classic traditional tattoos and have brought that style into the new school with his own work. If you're looking for a phenomenal artist to get your own colorful new school tattoo, then look no further than Zack Taylor. In addition to tattoos, Zack is also a fan of motorcycles, surfing, his dog, and family and friends. Chances are, you have something in common with this great artist and can together come up with a one-of-a-kind tattoo design you can both be proud of. Evermoretattoo Los Angeles CA www.machine13tattoo.com IG – https://www.instagram.com/themachine13/?hl=en FB – https://www.facebook.com/loveandinkRead More »
Artist Spotlight – Carlos Montilla
Carlos Montilla @closmontilla Carlos Montilla graduated with honors from Massachusetts School of Art and Design in 2013 and currently tattoos at Visible Ink in Malden, Massachusetts. He specializes in colorful new school tattoos but, as you'll see in the gallery below, is no strangers to black-and-grey tattoo design either. Montilla is a budding, eclectic tattoo artist you should definitely keep your eye on and get a tattoo from as he gets even better than he already is. Visible Ink Malden, MA IG – https://www.instagram.com/closmontilla/?hl=en FB – https://www.facebook.com/carlos.montilla.9?fref=tsRead More »
Artist Spotlight – Victoria Benea
Victoria Benea is a phenomenal tattoo artist who creates designs in a variety of forms and styles. Any sort of tattoo you could possibly want is within her range of abilities, and she'll even take your moderate or poor tattoo and turn into a wonderful work of art. If you have a chance to get a tattoo done by Victoria Benea, we suggest you don't pass up the opportunity. Riga, Latvia Home of Tattoos IG – https://www.instagram.com/beneatattoo/ FB – www.facebook.com/victoria.benea Read More »
Artist Spotlight – Jhon Rodriguez
Jhon Rodriguez @jhonrodriguez Before moving to the US, Jhon Rodriguez owned one of the first tattoo shops in Bogota, Colombia for 16 years. He moved to the US in 2012 and started Rosa Negra in 2015. The walls of the studio is full of paintings created by Jhon and various other tattoo artists over the years. Jhon's 21 years of professional tattooing experience are evident in each design he creates. He specializes in bold, clean lined tattoos and enjoys drawing animal tattoos more than anything else. If you're in the Wynwood area of Miami, Florida, stop by Rosa Negra and get a tattoo or commission a painting from this masterful artist. You won't be disappointed. http://www.rosanegratattoo.com/ IG – https://www.instagram.com/jhonrodriguez/?hl=en FB – https://www.facebook.com/JHONRODRIGUEZTATTOO?fref=ts Read More »
Artist Spotlight – Marco Canelas
Marco Canelas is a tattoo artist who utilizes a variety of different styles and forms from client to client. He's mostly known for the spiritual designs he creates that explore both the light and dark sides of life and death. IG – https://www.instagram.com/marcocanelas_tattooartist/?hl=en FB – https://www.facebook.com/Marco-Canelas-Tattoo-Artist-323215221221042/photos_stream Read More »
Artist Spotlight – Shannon Pagliarini
Shannon Pagliarini is an American tattoo artist who works out of Crown & Anchor Tattoo Parlor in Point Pleasant, New Jersey. She specializes in new school tattoos and even has her own Tumblr page where fans of her work can contact her directly. Crown & Anchor Tattoo Parlor Point Pleasant, NJ IG – https://www.instagram.com/shannontattooer/?hl=en FB – https://www.facebook.com/shannonpagliarini?fref=tsRead More »
Artist Spotlight – Josh Bodwell
Josh Bodwell @joshbodwell If Josh Bodwell looks familiar then you probably saw him on A&E's "Epic Ink" or a convention somewhere, be it tattoo-related or Comic-Con. He currently tattoos at Funhouse Tattooing in Tannersville, PA and has been known to tattoo during conventions too, be them tattoo-focused or not. As you'll see in the gallery below, Josh specializes in realism, primarily where some form of pop culture is involved. If you're looking for that badass Star Wars, Disney, Marvel or tattoo related to your favorite film or franchise, Josh has you covered and then some. His love for all things pop culture-related shows in his work, and you'd be crazy not to get a tattoo done by him if given half a chance. Tannersville , PA www.joshbodwell.com ig – https://www.instagram.com/joshbodwell/?hl=en fb – https://www.facebook.com/joshbodwelltattoos/?fref=tsRead More »
The Phenomenal Benjamin Lloyd Collection
New Zealand tattoo artist Benjamin Lloyd is bringing smiles to sick children's faces through the use of tattoos. No, he's not actually tattooing young children. He utilizes a special non-toxic ink and airbrushes the tattoos on. Each one takes about nine minutes to create and washes off in the shower. However, while the tattoos may be temporary, the joy and confidence boost they bring to the children and people in need isn't. Mr. Lloyd knows as much from first-hand experience. As a child, he was often bullied and teased at school over a burn he had on his hand. In an effort to avoid the bullying, young Benjamin would draw intricate designs over his hand and up his sleeve. Over time and a lot of practice, he became a talented artist. What you see in the videos and galleries below is his way of giving back, of using the lessons he learned throughout his life to better the lives of others. All you have to do is see the smiles on these children's faces to know he's making a positive difference in their lives. And it's all done through tattoos. Sure, they may not be permanent, but the core idea and values still remain. The next time you see someone looking down on tattoos and tattoo culture, politely point them towards the Benjamin Lloyd Collection. It may not change their minds, but it's might at least bring some positivity to their life – and that's something we could all use ...Read More »
Artist Spotlight – Andrea Lanzi
Andrea Lanzi @antikorpo Andrea Lanzi is a self-taught artist who has been tattooing for over 20 years and is practiced in all forms of art from simple drawings to sculptures. He specializes in a sort of new school realism tattoo style that he's cultivated through over a decade of tattooing and made his own. A lot of his designs are inspired by random pictures he finds online. Lanzi's first tattoo, which he did at 17, was a six-pointed star he drew on his subject's forearm. He wasn't a dedicated tattoo artist at the time, but it's been his primary focus even since he opened his tattoo studio, ANTIKORPO, in Italy over 15 years ago. Orzinuovi, Lombardy, Italy IG – https://www.instagram.com/antikorpo/?hl=en FB – https://www.facebook.com/andrea.lanzi.5?fref=tsRead More »
Artist Spotlight – Becky Foster
Becky Foster @beckyfostertattoo Becky Foster is a phenomenal tattoo artist who works out of Norwich, England and doesn't tend to specialize in any given form of tattooing. One day she'll design a traditional portrait realism piece, the next she might be working on a watercolor abstract tattoo. You'll see the high variance of her abilities in the gallery below. Like a lot of tattoo artists, Becky prefers for people to focus more on her art than herself, so we'll let the tattoos speak for her from here on out. We just hope you enjoy the gallery, and if you ever find yourself in Norwich, England you should look her up for a badass Becky Foster original of your own. Norwich UK IG – https://www.instagram.com/beckyfostertattoo/?hl=en FB – https://www.facebook.com/BeckyFosterArtDesign/?fref=tsRead More »
Artist Spotlight – Renan Batista
Renan Batista @renanbatistatattoo , which is of course located in Berlin, Germany, where he creates stunning artworks on skin and paper. Renan is a well-rounded artist who has stunning artwork to offer everyone, even if they're not interested in getting a tattoo. That being said, you'd be crazy to pass up the opportunity to get a tattoo done by this masterful artist. If you find yourself in or around Berlin, you should definitely stop by Berlin Ink Tattooing and see what Renan can do for you. Berlin Berlin Ink IG – https://www.instagram.com/renanbatistatattoo/?hl=en FB – https://www.facebook.com/renanbatistatattoo/?fref=tsRead More »
Artist Spotlight – Derek Turcotte
Derek Turcotte is a tattoo artist who specializes in new school tattoos and works out of Canmore, Alberta Canada. He's so good that many people consider him to be the new school tattoo master, and be sure to check out the pictures in the gallery below before you start to disagree. That being said, his style isn't entirely new school focused. It's a unique blend of realism and new school coupled with over-exaggerated illustrative drawings that combine to create unique collages you won't see anywhere else. He excels with color and his talent oozes out of each tattoo he designs. If you have a chance to get a tattoo done by Derek Turcotte, do not pass up the opportunity. Canmore, Alberta Canada Electric Grizzly Tattoo IG – https://www.instagram.com/drkturcotte/?hl=en FB – https://www.facebook.com/derek.turcotte.3 www.frostbackcollective.com Read More »
Artist Spotlight – Tony Sklepic
Tony Sklepic @tonysklepictattoo Tony Sklepic started tattooing in 2002 after he graduated high school and hasn't stopped since. The realism that inspired him to become a tattoo artist in the first place, such as the work by artists like Nikko Hurtado and Paul Acker, is readily evident in the work you'll see in his gallery featured below. In addition to being an avid tattoo enthusiast, Tony is also a self-proclaimed comic book, movie and music nerd who specializes in applying his full-color realism tattooing skills to large pop-culture influenced designs. Some of his biggest artistic influences outside of the tattoo world are comic book artists, like Jim Lee, Tony Moore and Ryan Ottley. In 2014 he founded Sanitarium Studios with fellow tattoo artist Karl Sundquist and has been tattooing from the Edmonton studio ever since. EDMONTON ALBERTA CANADA SANITARIUM STUDIOS IG – https://www.instagram.com/tonysklepictattoo/?hl=en FB – https://www.facebook.com/tsklepic?fref=tsRead More »
Artist Spotlight – Timmy B
Timmy B @timmy_b_413 Timmy B started tattooing in 2005, but not in the traditional sense some would assume. He didn't undergo an apprenticeship. Instead, Timmy started his tattoo career by working out of other people's kitchens and participating in tattoo parties every weekend he could. He used a toaster oven as an autoclave and scrubbed tubes bare-handed. He couldn't find a shop that would take him under their wing so, determined to start learning how to tattoo, Timmy B bothered a kitchen magician tattoo artist for months until he finally agreed to hire Timmy for $100 a day, with parties often running up to 12 hours. Timmy specializes in a blend of realism and new school art styles, which you can see characterized in his work that's featured throughout this gallery. He works out of Tattoo Afterlife, also known as NiteOwl Tattoo, in downtown Northampton, MA on the corner of Pleasant and Pearl St. NiteOwl Tattoo http://www.niteowltattoo.com/ Northampton Massachusetts IG – https://www.instagram.com/timmy_b_413/?hl=enRead More »


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Rumer Willis has rubbished away rumours of her engagement with model Micah Alberti.
Rumer, daughter of gorgeous Hollywood actors Demi Moore and Bruce Willis, declined the engagement rumours with her long time boyfriend, model Micah Alberti.
"She is not engaged," contactmusic.com quoted a spokesperson for Willis as saying.
Demi Moore and Bruce Willis were rumoured to have been celebrating after their 21-year-old daughter accepted a marriage proposal from her longtime boyfriend, model Micah Alberti.


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Chasity ~ Chad * Sneak Peek / Columbus Ohio Wedding Photographer
Wednesday, November 12, 2008
Chasity and Chad had a beautiful evening for their wedding reception back home in Columbus. Wonderful light.... fun setting... perfect evening. Here are a few shots from that evening!
No Comments Yet, Leave Yours!
- leaca said...
wow. these are gorgeous.
- November 12, 2008 at 4:45 PM
- Denise Olson said...
beautiful fall wedding for November!! The weather is perfect!!! gorgeous coloring and lighting. lov'n the flare!!!
- November 19, 2008 at 10:58 PM
- Brudaddy said...
What a beautiful picture and couple! Thanks for sharing...
- December 15, 2008 at 2:27 PM


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MOVIE SYNOPSIS [ General Audiences ] Film of Michael Tracy. Introduced in movie theaters in 2013, with a production coming from UK. You can watch Question online on TV cable or theaters with original audio in English at different dates. This film premiered in theaters in 2013.
Rating: 5 by 67 users./
Runtime: 30 minutes
John Gilchrist, Chris McCann, David Robertson and Christy St. John.
Short film, Romantic.
30-minute film (full movie) directed by Michael Tracy.
The original audio of Question has dialogues in Dolby Digital, it was produced in UK.
It premiered in cinemas or television in 2013.
Screenplay written by Michael Tracy.
Emma McCall.
Michael Tracy, David Robertson and Emma McCall.
Composed by Landon Austin.
Without commercial breaks, the full movie Question has a duration of 30 minutes; the official trailer can be watched in streaming on the Internet. You can watch this full movie free in EnglishDolby Digital 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, Question in FULLTV Movies.


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Congress is considering some form of tax relief to help the nation's sputtering economy, but not all tax cuts are created equal. Some proposals, such as temporary tax cuts, tax rebates, and "tax holidays," will do little or nothing to restore economic growth. It also is a bad idea to increase federal spending. Though such spending may result in increased economic activity in one sector, it shifts resources from more productive uses in the private sector. To boost the growth of national income, tax relief should permanently reduce marginal tax rates on work, savings, investment, risk-taking, and entrepreneurship.
A stimulus bill that fails to include a significant reduction in all tax rates might be worse than doing nothing. A package comprised of new spending and gimmicks like rebates and temporary tax cuts will not enhance long-term economic growth. Indeed, such proposals will increase the risk of continued recession and high unemployment. Adding insult to injury, lawmakers who block supply-side tax cuts this year might point to the economy's poor performance next year and argue that this is "proof" that pro-growth tax cuts do not work. Such misguided claims, if taken seriously, would jeopardize important tax rate reductions that are scheduled to take effect in 2004 and 2006.
Taxes and
Some policymakers do not understand the relationship between fiscal policy and economic growth. Advocates of tax rebates and tax holidays argue that quickly putting more money in people's pockets will trigger more consumer spending and jump-start the economy. This is also the rationale of those who believe that increased federal spending will boost growth by putting more money in the economy.
While superficially plausible, this approach has a dismal track record, as is evident in the failed policies that many Western nations adopted during the 1960s and 1970s. During that time, many countries, especially in Europe, relied on government spending and targeted tax breaks to increase "aggregate demand." But instead of boosting growth, those Keynesian policies resulted in stagnating economies. In more recent times, Japan's economy has been mired in a ten-year stagnation in spite of--perhaps because of--repeated doses of additional government spending.
The Keynesian view is fundamentally flawed because it fails to consider both sides of the equation. More specifically, it does not recognize that government cannot give a consumer a dollar--either in the form of new spending or as a tax rebate--without first taking that dollar from someone else. Every dollar used for tax rebates and tax holidays means that one less dollar can be used to pay down debt, so Keynesian policies merely take money that would have wound up in the pockets of bondholders and instead put that money in the pockets of selected taxpayers. There is no increase in total spending power.
In any event, the Keynesian preoccupation with consumer spending makes no sense. Economic growth occurs when there is an increase in national income. Efforts that simply alter the use of income by encouraging people to spend instead of save do nothing to increase the economy's overall output. Moreover, because less saving translates into decreased investment spending, the Keynesian approach is flawed from both a theoretical and a practical perspective.
The only way to increase national income is to encourage more work, saving, investment, risk-taking, and entrepreneurship. This is why incentive-driven supply-side economics has a successful track record. When tax rates are reduced, people have more motivation to be productive and create wealth. And when they earn more income, they are able to spend more and save more.
An Effective
Advocates of faster economic growth should insist on a stimulus package that satisfies the following three criteria:
- All personal income tax rates should be reduced permanently, and those lower tax rates should take effect immediately . Across-the-board tax rate reductions are one of the strongest tonics for an ailing economy. It is particularly important to reduce the top tax rate, since it is this levy that imposes the greatest disincentive on investors, entrepreneurs, and small-business owners.
- There should be
firm limits on the growth of domestic spending since a bigger
government is likely to harm economic
performance . In times of war, it is both necessary and desirable to increase spending on programs that help defend the nation, but lawmakers should not delude themselves by believing that such new spending, by itself, will help the economy. Government spending--even for legitimate purposes--diverts resources from the productive sectors of the economy. And under no circumstances should special interests be allowed to hijack a national emergency to increase domestic spending.
- Temporary tax cuts and "tax holidays" have no effect on growth and should be kept out of a stimulus bill . Such proposals would temporarily suspend a tax (the Social Security payroll tax and state sales taxes are the two most frequently mentioned options) in an effort to boost consumer spending. As discussed above, this is a counterproductive approach. Lawmakers should devise policies that increase national income. Proposals that merely seek to alter how income is used, by contrast, will do nothing to improve the economy's overall performance.
To be worth implementing, a stimulus bill should stimulate the economy, not curry political favor with high-profile "tax holidays" or spending projects. The Administration's proposal--including reductions in all tax rates, elimination of the corporate alternative minimum tax, and depreciation reform--would improve incentives to work, save, and invest. Yet some Members of Congress would blunt the pro-growth nature of this package by gutting key provisions.
Proponents of economic recovery in the Administration and on Capitol Hill should insist that the stimulus package meet the conditions described above and reject any proposal that does not. Most important, the legislation must fully reduce all personal income tax rates to the levels in the tax package approved in June. The President should not sign a bill that does not include this provision.
Daniel J. Mitchell, Ph.D., is McKenna Senior Fellow in Political Economy in the Thomas A. Roe Institute for Economic Policy Studies at The Heritage Foundation.


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The Scottish Society of New Zealand Commemoration Service Of World War I 1914 – 1918
To commemorate the Scottish Society of NZ involment in World War I
Scottish Society Hall Cnr Edgeware & Caledonian Roads Christchurch
May 10th, 2015 at 10.30am
Heritage New Zealand is excited to offer a tour visiting a number of World War I country memorials in the Waimakariri District, Canterbury. 2015 is the centenary of the ANZAC landings on the Gallipoli Peninsula in Turkey. So why not get a head start on Anzac Day this year by exploring how local communities in Kaiapoi, Oxford, Cust, Birch Hill Station, and Rangiora chose to remember their lost men?
The new version of Auckland Museum's Cenotaph Database website is finally up! Take a look here http://www.aucklandmuseum.com/war-memorial/online-cenotaph
As part of a national project being organised by the Fields of Remembrance Trust the Timaru WWOne Centenary Committee are producing 1,500 white crosses.
The crosses represent every man and woman from the region who died in the First World War.
The crosses will be on display in various sites throughout South Canterbury when they are completed and will be a major feature in Anzac Day commemorations in South Canterbury.
There will be 100 riders for the 100 year anniversary of the Gallipoli landings. 52 of these riders will be dressed in full military uniform representing the 52 soldiers from this area who didn't return home.
Friday 24th April 2015 - Day 1 - Will see us all assembled near "The Peaks Hall" for an introduction, run through with the organisers re: rider placement, formation etc. Riders, support crew and horses will stay over night in their own tents / horse floats etc. All food will be provided for them. There will be more info provided on this once we have our rider numbers.
The Rannerdale World War One Commemorative Centre Regimental Dinner is a premier Christchurch event supported by the New Zealand Defence Force to honour our First World War Veterans.
The Regimental Dinner will be held at the Air Force Museum, Wigram, Christchurch on the 28 February 2015 and will be attended by Chief of Defence Lieutenant General Timothy (Tim) Keating, MNZM, Chief of Army Major General A.D. Gawn, MBE, Her Worship the Mayor of Christchurch Lianne Dalziel along with other dignitaries.
The Royal New Zealand Ballet is honoured to collaborate with the New Zealand Army Band and distinguished New Zealand composers and choreographers Dwayne Bloomfield, Gareth Farr, Neil Ieremia and Andrew Simmons, in this special programme of works to mark the centenary of the Gallipoli landings.
Alongside classic pieces by Johan Kobborg (Salute, New Zealand premiere), Neil Ieremia and Andrew Simmons will create two world premieres.
From December 2014 to February 2015, Christchurch City Libraries is hosting a World War One Exhibition at Central Library Peterborough, 85-87 Peterborough Street. The Exhibition includes a Uniform, holdall, and a collection of Christmas postcards, menus and cards.
Help us tell the story of Canterbury
at home and at war
during 1914 -1918.
Katie Pickles, Associate Professor in History, University of Canterbury
2pm 12 October 2014 Air Force Museum (45 Harvard Avenue)


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We help to build, market and sell your solutions with our online, remote, and face-to-face training and assistance. Port and test solutions, close deals with your clients, and collaborate with IBM, Business Partners, academic leaders, and IT professionals.
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US pushing Iran to walk away from JCPOA: Analyst
In a new provocative move to derail a nuclear deal between Iran and the six world powers, the American authorities have pushed a Luxembourg court to freeze $1.6 billion dollars of Iranian assets, says Stephen Lendman, author and journalist from Chicago.
Iran and the P5+1 group of countries - the United States, Britain, France, China, Russia and Germany - signed the nuclear deal dubbed the Joint Comprehensive Plan of Action (JCPOA) in 2015.
"What we've seen after the passage of the JCPOA (Iran-P5+1 nuclear deal) repeated attempts by America and [pressure on] European allies to keep going after Iran and bashing Iran and accusing Iran of all kinds of things," Lendman told Press TV on Wednesday.
The United States wants "to keep punishing the country and pressuring the country" in order "to inflict enough pain to get Iran to back off from the JCPOA and then blame it for walking away instead of the countries that are responsible for doing all of these things to the Iranian government," he added.
Under the JCPOA, Iran agreed to put a cap on its nuclear activities in return for the removal of nuclear-related sanctions imposed on it.
"[US President Donald] Trump has made it very clear that ... he is opposed to Iran and he despises the nuclear deal," he noted.
Tehran says it has honored its commitments under the JCPOA, as repeatedly confirmed by the UN nuclear agency, but the United States has been dodging its obligations and has even imposed new sanctions on Iranians.
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The imposition of new sanctions, seizure of Iranian assets and provocation of Iranian military forces in the Persian Gulf are among the tactics that the United States has used to prompt Tehran to walk away from the JCPOA, the analyst said.
According to the analyst, the US sends warships near Iranian territorial waters to prompt Iran to respond to their aggression and then misrepresents Iran's self-defense response to antagonize Tehran.
Warning about the American imperialist agenda in the world, he concluded, "They (US officials) want the ongoing imperial wars continued and there could be all kinds of targets including Iran."


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Pet Sitter in Niagara Falls
Hello pet owners ! I am new to this scene, but not new to caring for pets. I absolutely adore animals and as long as they're not aggressive I'll shower them with all the love and attention they can possibly handle. I am flexible and easy-going, willing to meet you halfway to reach an ideal arrangement that suits all involved. I cannot host, but I'm happy to travel to your place (I live in Niagara Falls - the closer the better, unless it's an extended stay). At the present time I'm unemployed so I have fully open availability. I drive, I don't smoke, I am very clean, and I am very approachable. I am positive that your furry friend will feel comfortable with me in no time. Cheers !
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Van Gaal: I will not walk away from Man United job
Louis van Gaal has forced Manchester United's board to make the final decision on his future by making clear that he will not resign.
The United manager, whose job is under threat after a run of only three wins in 13 matches, is continuing to insist that he can revive the club's fortunes. He made a speech to his players at their Christmas lunch on Monday calling for unity ahead of a key run of fixtures, beginning at Stoke on St Stephen's Day.
The former Netherlands coach declared over the weekend that he felt he still had the support of the players and the board, despite his team's poor form, and retains belief that he can save his job, even though the odds are against him.
With Van Gaal determined to fight on, executive vice-chairman Ed Woodward and club owners the Glazer family must decide whether to sack the manager, and face the prospect of a compensation payment of around £10m to terminate his contract.
The manager is scheduled to hold a press conference this afternoon to preview the trip to Stoke. He is set to lose his job if United lose either at the Britannia Stadium, or against Chelsea at Old Trafford on Monday.
United declined to comment on reports surfacing yesterday that Woodward was in a meeting in London to discuss the future of the manager, although the club's board are continuing to consider their options.
Jose Mourinho has made clear that he is keen to take charge if United do decide on a change, while Bayern Munich's Pep Guardiola and United assistant boss Ryan Giggs are also in contention.
Mourinho, a free agent after being sacked by Chelsea last Thursday, remains the leading candidate if Van Gaal leaves, despite reservations from some United directors about his capacity to attract controversy.
However, his success in winning domestic titles in England, Spain, Italy and Portugal, in addition to lifting the Champions League title with Inter Milan in 2010, still makes him an attractive candidate for a club whose season is in danger of crumbling. (© Daily Telegraph, London)
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20a Winifred Street Preston 3072 VIC
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Leading Marketing Automation
Marketing automation solutions have become the standard for many companies. Leading marketing automation providers include Salesforce, Marketo, and Eloqua. These marketing automation providers are great for generating leads, nurture leads, and sending hot leads to sales. But, marketing automation systems do not help marketers reach buyers who have not heard of your brand.
Being able to engage new buyers with your brand is critical for your company's success. With the change in the buying process the most effective way of reaching buyers is through content. Marketers should be creating informative, relevant, and valuable content to keep buyers wanting to learn more about your brand. Most marketers tend to guess about what content to produce and do not have the data to see campaign performance, thus marketers tend on loosing out on pipeline growth.
Captora works with leading marketing automation to ensure marketers are engaging and capturing as many potential buyers as possible. Captora combines data, process, and top of the funnel to ensure more leads are going into your marketing automation system.
Digital Marketing Acceleration Video


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I got my bag back from SparkleHorse today!! I'm sorry that this sets the bar so high future bag swaps can't even dream of obtaining results like these.... I took a bunch of pictures because I was SO EXCITED about the bag. If you dont want to look at all of my pics, tough- close your eyes
I FREAKIN LOVE THE BAG!!! Honestly, If I saw it in a store I would pay way too much for it. I can't believe what SparkleHorse has done. It's perfect and I now have no need for any other purse. (Except the rad bag Alison made me for https://www.craftster.org/forum/index.php?topic=58952.20)
This is the canvas mess that I sent to SparkleHorse (ugh why did I buy such a bag?)
And if you can believe it; This my friends is what came back to me:
The back:
The front in action:
But the fun doesnt stop there. Each pocket had something in it!!!
Soap, nail polish, my favorite gum, a candy cane and a cute lipstick holder with mirror.
SO I'm totally in love. But the real test is the cat stamp of approval:
"it smells good"
"it feels good"
"I'm afraid this bag now belongs to me, Gabey the cat"
So there she blows. This swap has been AWESOME. I LOVE MY BAG. Round 2's got a lot to live up to....