text: Chicken and Pumpkin Stir Fry Recipes By Susie Burrell 06 November 2015 Nutritional Facts: Gluten-free Low FODMAPS Dairy-free Nut-free Egg-free Wheat-free Serves 4 339 cals | 7g fat - per serve 40g protein | 26g carbs | 4g fibre - per serve Ingredients: 500g skinless, boneless chicken breast, cut into strips 2 carrots, cut into matchsticks 1 bunch bok choy, chopped 1 cup pumpkin 2 tbsp. chives, chopped finely 2 tbsp. gluten free soy sauce 1 red chili, deseeded and chopped finely Juice of a lemon 1 tsp. brown sugar 1 tsp. sesame oil 1 1/3 cup cooked brown rice Instructions: Get your rice on the go before starting this recipe Steam the pumpkin and carrot in the microwave for four minutes, then set aside. Heat sesame oil in a pan over a medium to high heat and add chives and chicken. When the chicken is browned add the carrots and pumpkin stir frying for a couple of minutes, then stir through the bok choy. Add the soy, lemon, sugar, chilli and season to taste. Add a dash of water to the pan if you feel it needs it. Serve with 1/3 cup of rice. Please note: This blog aims to supply user-friendly nutrition information for busy people without comprising on food taste and quality but should be used as a guide only and not in place of advice from your own dietitian or medical specialist. For further information on this topic, please consult your health professional. The content of this blog, including attachments, may be privileged and confidential. Any un-authorised use of this content is expressly prohibited. Any views that are expressed in this message are those of the individual sender, except where the sender expressly, and with authority, states them to be the views of Susie Burrell Pty Ltd. Tags: Chicken Recipes Dinner Category: Recipes « Back


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Voila Pull-Along Cat
How adorable is this pull-along wooden cat toy? At BuyMeOnce HQ we absolutely fell in love with it, especially when we read that as you pull it along it wags its tail and bobs its head!
Created by Voila, a Thai wooden toy manufacturer, this beautiful toy is not only durable but it's also made from sustainably sourced wood.
- A super cute pull along toy for children
- Shaped like an adorable Pet Cat
- Supported on hard wearing wheels, this toy is extremely durable - take it everywhere with you!
- Made by respected toy manufacturer Voila
- Produced from sustainable sources
- Recommended for children 12 months and older.
(Clicking this button will take you to Amazon's website to buy the cat)

subset: commoncrawl


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17 November 2016,
New York, Rockefeller Center
Price realised USD 199,500
Estimate USD 150,000 - USD 250,000
Marino Marini (1901-1980)
Piccolo giocoliere in policromia
with raised initials 'M.M' (on the top of the base)
bronze with brown patina, hand-chiseled and painted by the artist
Height: 19½ in. (47 cm.)
Conceived in 1953
New York +1 212 636 2000
London +44 (0)20 7839 9060
Hong Kong +852 2760 1766
Shanghai +86 21 6355 1766
The Marino Marini Foundation has confirmed the authenticity of this work.
Acquired by the family of the present owner, circa 1970.
Saleroom Notice
Please note the amended literature for the present lot:G. Carandente, intro., Marino Marini, Catalogue Raisonné of the Sculptures, Milan 1998, p. 269, no. 382 (another version illustrated, p. 268).
Pre-Lot Text
PROPERTY FROM A DISTINGUISHED COLLECTIONThe following hand-chiseled and painted bronzes depicting giocolieri (jugglers) were executed in 1953 when Marini was at the height of his creative power. The artist's exploration of the dissolution of monumental solidity—which had characterized his representation of the horse in earlier sculptures—was reaching its climax. Only several years earlier, Marini's horses were shown in graceful union with their riders sitting steadily on their backs. But from 1951, they began to depict various stages of the rider being thrown from his steed and tumbling to the ground in crisis. The Miracolo (miracle) series, executed between 1952 and 1970, includes some of the most poignant examples of dramatically dissolved form that expresses Marini's anxiety for the human condition (fig. 1). At the same time, however, Marini was absorbed by the antithesis of the drama and discord imbued in his horses and riders. Giovanni Carandente, the author of the Marini catalogue raisonné, has written, "Marino was simultaneously trying another motif that was dear to him, a joyful one this time; the result was the series of nine small sculptures of jugglers and acrobats, veritable masterpieces for the visual keenness, for the chromatic frenzy that animates them" (op. cit., p. 18).The present bronzes are two from a group of only nine sculptures that Marino Marini created on the theme of jugglers and acrobats (fig. 2). According to Carandente, "In those nine models—one could say—Marini reached the apex of his expression" (ibid., p. 18). In them, Marini relinquished the tragic theme of the rider collapsing from the horse that was his most frequent theme in favor of one filled with joy and dynamism. In the giocolieri series, Marini has taken the subject of the juggler and used it as a springboard for an exploration of movement and form. He has rendered the flying balls through the stylistic shorthand of a gentle arc that deftly conveys the sense of motion and effortless action of the performer. Marini has clearly espoused this theme as one of celebration, revelry and fun. The elongated figure, reminiscent of the Rose Period pictures painted half a century earlier by Marini's friend Pablo Picasso, has a waif-like elegance that accentuates the agility that is encompassed both in the theme and in Marini's own exploration of it.Carandente suggests that ultimately, the violence inherent in Marini's equestrian sculptures of the period is complemented by the color and joy of his giocolieri. "Expressionism in the nine jugglers was also, in the end, the other side of the dramatic force of the Miracles. That kind of formal chasm that unites, rather than separating, the rearing horse to the collapsing rider has the same violence that merges form and color in the jugglers" (ibid., p. 18). PROPERTY FROM A DISTINGUISHED COLLECTION
A.M. Hammacher, Marino Marini, Sculpture, Painting, Drawing, New York, 1970 (another version illustrated, pl. 202).
H. Read, P. Waldberg and G. di San Lazzaro, Marino Marini, Complete Works, New York, 1970, p. 369, no. 306 (another version illustrated).
S. Hunter, Marino Marini, The Sculpture, New York, 1993, p. 216.
G. Carandente, intro., Marino Marini, Catalogue Raisonné of the Sculptures, Milan 1998, p. 269, no. 382 (another version illustrated, p. 268).
On 15 May in New York, Christie's will offer this searing portrait of the artist's love and muse, Dora Maar
The first picture from the artist's iconic flag series will be offered in the American Art sale on 23 May
Their passions, motivations and dreams — and advice for anyone hoping to join their exclusive club
A deep dive into the life of Impressionism's founding father, featuring upcoming works offered in New York


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Hitachi Laptop AC Adapter for C, E, MX Series, VisionBook 5000, Elite 8000, Plus 5000, 5280, Pro 7000, 7775
Item No.: Dekcell - AL-3126
Ratings: (1 review).
Availability: In Stock, Ships within 24 Hours
Ships from U.S Warehouse. Most customers receive within one week.
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Note: Order placed before 12:30PM Pacific Standard Time will normally be processed in the same day.
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Product Reviews
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1. woohooo
By Rich from Salem, Oregon on Feb 10, 2010
Great transaction - Lightning fast shipping and excellent product! This is the second time I purchased from Brilliant Store and I am again, leaving as a happy customer. I love you guys!


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And you thought Idris Elba was a beast on HBO's The Wire.
On Luther, he stars as the titular John Luther, a Detective Chief Inspector with London's Metropolitan Police in the Serious Crimes Unit. Accordingly, he's seen some serious shit that's affected him in less than ideal ways—it's all made him into someone who's got a very distinct idea of what good and evil is, and he also operates in an extremely morally gray area.
Luther—tallying at 14 episodes over three seasons—sticks closely to Elba as he solves various crimes and deals with his inability to live a well-adjusted, normal life. It's always refreshing when, as a viewer, you can tell that a TV show's producers aren't underestimating the audience's collective intelligence with hokey dialogue and lazy plot-lines. You'd be hard-pressed to find a character who's as compelling as the genius, paranoid, sociopathic, malignant narcissist Alice Morgan (Ruth Wilson), especially when it comes to her dynamic with Luther.
Although a fourth season won't happen, creator Neil Cross confirmed that a feature film is in the works.


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More exciting is the reported price: Consumers purchasing the phone with a two year contract will get it for a less than a Benjamin. Before sales tax anyhow. Still, a $99 price point is very aggressive, so clearly Microsoft and Nokia are coming to play this spring. This price positioning reflects the important that Microsoft and Nokia place on the U.S. market for the future of Windows Phone.
Given the lackluster sales of WP7 so far, this is a smart move. It will come at a time when they are reported to be readying a $100 million dollar marketing campaign in the U.S. Both AT&T and Nokia may benefit from the contrast that will be made with Verizon's laughable $300 on-contract price point for Android LTE handsets.
No reports of on-contract pricing for international markets yet, but they will most likely vary from country to country anyhow.
Any U.S. customers that are planning to pick up a Lumia 900 for a hundred dollars?
source: BGR via TechCrunch


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The Question
"He died. He just...died." Jackson spoke though his thoughts felt a million miles away as he stared down at his hands.
"I know, buddy. There was nothing, I mean nothing, you could have done," Minh comforted, though even his thoughts were distracted by the chaos still swirling around them.
Jackson seemed to come gliding back to the present, "Minh, what's it all about? I mean..." He paused, casting his eyes about the behemoths of glass and steel around them and the cold, lifeless concrete at their feet.
Wise beyond his years, Minh looked carefully into his friend's face, "It's found you then, has it? The question."
"What question?" The din seemed to fade away, pushed to the background, leaving only he and Minh.
"The question of life. It finds us all eventually, however much this...well, these distractions tried to pull us away, tell us nothing matters beyond the next shiny toy or the next hot cup of trendy coffee."
The blood on his hands demanded his attention once more, and Jackson realized aloud, "Then the old man, he knew. He really knew. Minh, I want to know. I need to know."
Minh smiled wisely, "Then go. Get away from these distractions and your present cares. Take this with you." He produced an irregularly shaped trinket the size of a racquet ball, covered in gold, ivory and jade.
"What the..."
"It's an ancient Chinese...hrm, sensor, I guess. It will help to keep the worries and cares of this material world at bay, for a time. Bury near by, and only retrieve it when you've answered the question."
"Minh, I don't know what to say."
"Just go. I'll straighten things out with the agency."
"Yes, old friend?"
"I thought you were Vietnamese."
"Shut up and go."


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Tom Dixon has a "bad boy" reputation, but his inner mathematics genius shows through with the delightfully light Etch Candle Holder.
Made from digitally acid etched brass sheets, each modern candle holder displays an intricate pattern that appears to be delicate despite the obviously stable design. When lit from within, this piece casts a sunburst of light and motion across nearby surfaces. This brass candle holder manages to combine the best of geodesic aesthetics with elaborate organic detail.
Combine or arrange more than one Etch Candle Holder to create a fascinating centerpiece, or simply enjoy the beauty of a single glowing ember.


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More than three-fourths (79%) of retailers expect an increase in sales this holiday season – the highest percentage seen since the financial downturn.
Three-fourths (75%) of retailers forecast an increase in holiday sales this year, according to a survey by Hay Group, a global management consultancy.
According to a survey released Tuesday by global management consultancy Hay Group, 68% of retailers expect holiday sales to increase this year.
By Craig Rowley, VP and global practice leader, Hay Group
By Lindsey Lanzisero senior associate, Hay Group's Retail Practice and Craig Rowley, VP and global leader of Hay Group's Retail Practice
A survey released Thursday by global management consultancy Hay Group found that 64% of retailers...
Few, if any, retailers are using the business-management concept of senior leadership teams (SLT)...


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Woman critically injured in RI highway wreck
HOPKINTON, R.I. (AP) — Rhode Island State Police say a woman was critically injured when her car rolled over on Interstate 95 in Hopkinton.
Troopers say the woman was driving erratically in the southbound lanes near exit 2 at about 1 a.m. Tuesday when she lost control of the car and it rolled over. Police say she was thrown from the vehicle during the crash.
The woman's name hasn't been released. Authorities say she is being treated for life-threatening injuries at Rhode Island Hospital. No one else was in the car.
State police say speed was a factor in the crash. The exact cause remains under investigation.
Shutterstock/Stephen B. Goodwin


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Find Hotels in Thoiry
Thoiry Hotels & Accommodation
Browse through the list of Thoiry hotels to find the right hotel at a great price. Each hotel in Thoiry has many photos, reviews and a map of its location in Thoiry to make sure you get the most out of your stay. Booking your hotel in Thoiry couldn't be simpler. Just find a hotel, check the rates and proceed to the checkout. We'll have you enjoying your Thoiry hotel in no time. Quick, easy and secure.


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Kane VS Wester (No Limits)Mature
I have gotten VERY bored, so I have started up this. Unlike my previous attempt at a tournament of protagonists, this will simply be something anyone can add to. Just fight scenes, though. I want to see what you guys will make of this, as well as get some insight on different styles of fight scenes. Enjoy and write, my fellow Protagonizers!
Wester walked into the Arena, irritated and urging to fight. Today would be a glorious day, indeed. It would be the day that the Drakos-El would rid themselves of Kane, the unrivaled storm.
"I see my opponent is here, then," Wester said to himself when he noticed the figure ahead. Standing just half a head shorter than Wester himself, Kane was not too intimidating. It was a ruse, though. Wester had fought the man enough times to know his power.
"Wester, you bastard!" Kane shouted, pulling his large blade. His short auburn hair and dark leather armor made for little to get in the way as he separated the blade into a longer and shorter blade. "Shall I jump right in, or do you want to pull your weapons out first?"
Wester smiled. "Gladly, heathen," he said, easing the twin bladed shields off his own back and onto his forearms. Their weight was confortable there, unlike the silver armor covering his body. Pushing blonde locks out of his face with a bladed shield, Wester smiled slighly. "Are you actually going to cut me this time?"
Kane's face contorted with rage and he sliced the air, sending out wind magic to cut anything in it's path. A dangerous attack, but not unstoppable. In fact, it was a waste. Wester slammed his shield into the ground and summoned his own Earth magic to create a wall of rock. The ground shook and contorted to Wester's whim and took the blunt of the attack.
Wester pulled his shield just in time to block a swing from Kane's larger sword. He had jumped over it, huh? Next time, the wall would be bigger. Wester blocked the shorter blade with his other shield and kicked at Kane's leg. The hit connected and gave Wester a small chance to back away. He took it.
With a backwards roll, Wester had pulled himself a little ways away from Kane. Before the man could react, Wester gathered a flame in his hand and threw it at Kane. Being unable to use his pistol to concentrate and aim the fire, it would be more more clumsy, but still good enough for a heathen, such as Kane.
Kane simply dispersed the fireball with a wind-enhanced swing of his blade and came for Wester. Sword met shield, blade met blade, and warrior met warrior. Wester and Kane exchanged blows, neither striking their opponent with any of them. Wester was forced to focus all his attention on following Kane's two swords, so he hadn't the time to use any magic.
Kane, on the other hand, had had time. With each exchange Wester felt wind cut at his silver armor or a jolt of electricity run across his arm. Although Kane couldn't put a lot of effort into the magic, it was an advantage and both men knew it. Wester had not choice.
Wester caught Kane's arm mid-swing, opening himself up for another attack. Kane took the opening, but Wester was prepared. Wester managed to put his shield between the shorter sword and his own side. Too late, though.
Wester cried out as blade met flesh. Pain. Pain. PAIN!
Wester rolled back, gripping his side. Even though he had purposely opened himself, how could he let that Dynio HEATHEN strike his flesh! It was preposterous! It was unforgivable! It was... horrid.
"What's the matter, Unscarred Champion of the Drakos-El, you get cut?" Kane barked a laugh. He knew of Wester's pride in never being cut. He had tried to ruin the streak for years. Well, he finally had.
"It's nothing compared to your wounds, Heathen!" Wester gathered his magic. It was time to release the Holy Stampede! He would crush this insect! This Heathen!
Kane laughed again and combined his blades. "I have next to no wounds, you Drakos-El dog!" He smiled and allowed visible electricity to run through his large blade. "Should I give you another?"
Wester, finally having enough magic gathered, set to placing it in the right areas. He would have to be quick. While standing still, Wester could hold all the power indefinitely, but moving took away concentration and leaked it out. He would have just over ten minutes to take the Dynio trash out.
Earth magic to strengthen. Wester pushed it to every fiber of his being, then to his shields. Otherwise, they would break. Fire magic to burn. He set it in a barrier around himself. It also went into the tips of each of his bladed shields. That would burn anything near him. And lastly Holy to enhance. He set it to his feat and joints for speed and to his mind and eyes for enhanced thinking and sight. Together, these magics made his an unstoppable stampede of Holy Judgement.
Kane had been doing something as well, Wester noticed. Aside from just calling insults, he had been gathering a mass amount of magic. That electricity earlier wasn't just for show. What could he be doing? Well, it mattered not. Wester was untouchable.
Kane winced in pain, then shouted and charged. Wester followed suite, charging and yelling his own battlecry. The charge seemed to last an eternity, despite only having a few feet from each other. It was as if there was a calm before a storm.
Wester struck out with a magic-enhanced shield, feeling as the Earth and Fire swirled around it, enhanced by Holy increasing speed. Kane's sword, dancing with black wind and lightning, met the shield. Darkness covered all.
After what seemed like hours of darkness, light came into Wester's vision. Ah, the sun was a beautiful sight. With it's majestic rays and constant warmth, it truly was a spectacle of the Source's creation.
Wester pushed his blonde locks from his face and forced himself upright. Pain seared through his body at the movement, but he ignored it, hard as it was to do so. The sight of the arena, however, made it easier to forget the pain, though.
Around Wester, reaching up nearly two hundred paces or more, was what looked like walls of dirt and rock. No, wait, that wasn't right. Then, Wester realized what he was in. In front of him, a few paces off or so, lay a breathing and blinking Kane. With the man's presence, everything was crystal clear.
They had created a crater.


text: Meta Battle Subway PokeBase - Pokemon Q&A Login Register All Activity Questions Unanswered Tags Users Ask a Question Rules Chat How can legendary Pokemon be shiny if there's only one of them? 0 votes 3,079 views There's only one of each legendary. How can any be shiny? shiny legendary asked Dec 27, 2013 by redring345 Please log in or register to add a comment. Please log in or register to answer this question. 2 Answers 3 votes Best answer Actually only a hand full of Legendary Pokémon are consider Unique (One of a Kind). Pokémon that are not considered unique are: Mew (Mewtwo Strikes Back and Lucario and the Mystery of Mew) Mewtwo (Mewtwo Strikes Back and Genesect and the Legend Awakened) Lugia (The Power of One and a young Lugia called Silver EP220, EP221, EP222) Celebi (Pokémon 4Ever and Zoroark: Master of Illusions) Regirock, Regice, Registeel (Brandon's Regis and Lucario and the Mystery of Mew) Latias (Pokémon Heroes) Latios (Pokemon Heroes and Tobias's Latios) Jirachi (Jirachi: Wish Maker and BW132) Deoxys (Destiny Deoxys) Heatran (Arceus and the Jewel of Life and DP169) Regigigas (Giratina and the Sky Warrior and DP129) Manaphy (Pokémon Ranger and the Temple of the Sea) Phione (DP113) Darkrai (The Rise of Darkrai and DP104) Shaymin (Giratina and the Sky Warrior) Genesect (Genesect and the Legend Awakened) Pokémon that are debatable and could end up in either category: Articuno, Zapdos and Moltres- We aren't actually aware if there're unique or not, they have appeared in several different episodes and in The Power of One but they do seem to travel quite often so could be the same. Since Nolan did not officially catch the Articuno he used against Ash as they were just friends we cannot place the Legendary Birds in either section so I deem them in the Debatable Category. Entei, Suicune and Raikou- Although we are aware that Ho-Oh created them from the ashes of Pokémon, Suicune has appeared multiple times and even in different regions. It has appeared in three episodes of the anime and Pokémon 4Ever. Entei has also appeared in several episodes and in Spell of the Unown. Although the Entei in Spell of the Unown was only an illusion created by the Unown. All of the Legendary Beasts also appeared in Zoroark: Master of Illusions where they are shiny. Even though they are normal in the Anime and shiny in Zoroark: Master of Illusions they are still placed in the Debatable Category as Ho-Oh could have potentially changed their forms as it is the individual that created them. Cresselia- One question if there's more than one Darkrai, why not Cresselia? Victini- Victini is in the Debatable Category because there has only been one seen so far, this is in Movie 14. Even though Victini is probably a unique Pokémon, each of the Legendary Pokémon with a overall stat of 600 are in the non unique section so it get's put in the Debatable Category. Meloetta- It has only been seen once in the Anime so far. Diancie- Although Diancie has only appeared once in the Anime, Diancie doesn't seem to be a unique Pokémon, as Diancie is born from a Carbink that undergoes a mutation. Pokémon that are consider unique are: Ho-Oh - Even though its counterpart, Lugia, is able to have offspring, Ho-Oh seems to be a single Pokémon that travels around. Kyogre, Groudon, and Rayquaza - Kyogre and Groudon have appeared in the Team Magma and Team Aqua arc, and Kyogre has appeared in Pokémon Ranger and the Temple of the Sea. Rayquaza could be argued as being more than one of its species, but it is a high probability it is the only one. Azelf, Uxie, and Mesprit - They were created by Arceus to keep Dialga and Palkia in balance. Dialga and Palkia - They are the keepers of Time and Space. Giratina - It is the guardian of the Reverse World, an distorted mirror of the Pokémon World. Although it could be argued that because mirror dimensions exist, that there would be Reverse Worlds for each of these mirror dimensions, that is extremely technical and probably won't be mentioned. Arceus - Creator of the Pokémon Universe. Not much more to say about that. Cobalion, Terrakion, Virizion and Keldeo- Only appearance was in Kyurem VS. The Swords of Justice. Seem to be a unique group. Landorus, Tornadus and Thundurus- Only appearance was in BW059 and BW060 but seem as though they are unique. Zekrom and Reshiram- Even though Zekrom and Reshiram have made several appearances in the Anime and have both appeared in Movie 14 they are considered to be unique as they represent Ying and Yang in the Pokémon World. Kyurem- Part of a trio with Zekrom and Reshiram. Xerneas and Yveltal- They both made an appearance in Diancie and the Cocoon of Destruction, Xerneas also appeared in XY041 although as silhouette, so we can not determine if it was a different Xerneas or not. However Xerneas and Yveltal are considered unique as they represent Life and Death respectively in the Pokémon World. Zygarde- Zygarde has been seen at all so far in the Anime, but it is assumed that it is the the only one of it's kind. answered Dec 27, 2013 by Sir Dan edited Nov 8, 2014 by Sir Dan Please log in or register to add a comment. 0 votes There is not just one of each legendary. In the Pokémon movie Zoroark master of Illusions there are shiny Entei, Raikou, and Suicune as opposed to the non shiny ones seen in the tv show. Also there is a baby Lugia (Silver) shown in the show proving that there are more than just the seen lengendary. As for how they can be shiny it's just that chance though there are shiny locked Pokémon such as Zekrom, Reshiram, Vicitini, Meloetta, etc. answered Dec 27, 2013 by Stella Midnight Please log in or register to add a comment. Related questions Is recieving a shiny legendary always show that the Pokemon is a hacked one?? What is the possibility of finding a shiny legendary? Can there be shiny legendaries? If you make one of the Legendary Birds Faint will they Reappear Can you get shiny Solgaleo/Lunala in Sun/Moon? Can you get shiny legendarys legit in B/W? How do people find shiny legendaries? How do you get shiny legendarys? Useful Meta Posts Vote for Sun/Moon moveset questions How to change your username How to add a user avatar Why was my post hidden? The points system Question etiquette Flags vs Downvotes Anime FAQ


text: Interactive game from McDonald's, I'm lovin' it! I am not a fan of the Golden Arches, but I do have to give McDonald's props for creating Pick 'n Play. Pick 'n Play is a Pong arcade game for the iPhone that allows visitors to Stockholm, Sweden to compete against a computer for coupons for McDonald's menu items. Players connect to the billboard… Read More


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Spacious 3 bedroom townhome with 1 full bath. Freshly painted, new replacement windows, Central Air, Gas Heat, and security system. Unfinished lower level wit hook up for washer and dryer. Extra parking in the rear. Turn key, don't delay - call today!


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David Price Memorabilia
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- David Price Boston Red Sox Autographed Baseball
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About David Price Autographed Memorabilia & Collectibles
A lefty pitcher for the Boston Red Sox, David Price is one of the most dominant players in the MLB. After beginning with the Tampa Bay Rays in 2008, then spending time throwing Aces for the Detroit Tigers and Toronto Blue Jays Price moved his talent to Bean Town, bringing with him some heat.
A five-time All-Star, the 2012 Cy Young Award winner and a two-time AL ERA leader, David Price has brought the heat not only in a World Series appearance with the Rays, but also with an incredible 2015 postseason run with the Blue Jays. Such talent in pitcher has led to a drastic increase in the demand for David Price memorabilia, an investment all MLB fans and collectors should be making. As a player that is just reaching the peak of his game, items with a David Price autograph will prove to be a smart investment as his collectibles acquire worth over the years. Take home a piece of the action with a David Price autographed baseball to star your collection or preserve memorabilia moments from his career with a signed David Price photo. Since all fans can appreciate an athlete of his caliber, David Price autographed memorabilia is perfect for anyone.
Invest in the future of the Red Sox with unique David Price memorabilia that will bring value to any sports collection as he continues to dominate the pitching mound. Enhance your Sox collection by shopping the wide selection of baseball memorabilia for collectibles signed by more current stars, such as David Ortiz and Hanley Ramirez.


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Hour 72
They whisper "one more day"
I wait, I whine, I stare, confined to a
Bleak prison cell, then they clip on the leash and
Death's scent slithers down my throat.
A needle, just a little needle, pain is ending,
Why don't you love me anymore?
You said forever, but I'm evidently just
A nameless number in a dirty cage,
The Green Mile for me 'cause I'm not
Little and cute anymore, you said forever,
This isn't forever.


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Chatham Inn At 359 Main
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Travel Blogs from Chatham
Eating a sandwich in Sandwich & cod in Cape Cod!
... plop' went the pink ball in the stream. This must happen a lot as there was a ball fisher set on the side!
But then...A HOLE IN ONE was had by Mrs Smith! Alas, not once, but twice around the course! Would this be enough to claw back and win the championship?
No, it wasn't.
There was only one clear winner – not that you'd ever know who...!
And ...
Home base at South Yarmouth
... see the water plumes of whales not far off the beach. Difficult to actually see the whales even through the telescopes at the visitors centre. Provincetown has been the highlight of our time in Cape Cod, quite old but with new life from the gay community and bohemian themes, and another great place to scoff lobster!
As in Cape May we have squirrels running around and climbing up the trees around the ...
Week 3 9 - 12 Sep
... in an effort to overpower the hijackers. Famous words of Todd Beemer, "Let's Roll!" echo the heroic efforts of these great Americans who died that day! Heroes forever.
There was a large boulder unearthed in the rubble; it was placed near where the Boeing 757-222 crashed traveling about 563 mph. The impact obliterated the plane and everyone on it. The investigators dug 35 ft into the ground, of the once open ...
Family mini vacation in Nantucket
... emotional "excuse" - my angel lost his mother this year, and our little family reunion was in her memory - we thought nothing would have given her more pleasure than seeing her family together, happy and having a good time...besides, her birthday was in July, and we celebrated it there...unfortunately not all the children ...
Back in Cape Cod - Chatham
... both short and the water was up to our thighs at times.
Brian and Ken had decided to bike over. Brian had fixed some bikes and they wanted to try them out. We walked on the beach in the sunset and it was beautiful. I was a little worried of our return through the tidal waters but the water was still going out so it was shallower than before but in the darkness now. Good thing I am not scared of walking in the water at night! It was ...


text:
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Is there a way to create a report that shows any and all files shares being served off my workstations and servers? If anyone has one I would appreciate it, thanks!
1 Reply
· · ·
Feb 19, 2009 at 7:44 UTC
The shares would have to be reported by WMI.
v3.5 has SQL support. You would have to find someone to write the report or make a stab at it yourself.


text:
The Strait of Anian : an exhibit of three maps in the James Ford Bell Collection at the University of Minnesota, portraying sixteenth and eighteenth century concepts of the waterway between Asia and America, which is now known as the Bering Strait
- Language
- English.
- Imprint
- [Minneapolis, 1956]
- Physical description
- 13 p. : 3 maps (1 fold. col. in pocket) ; 22 x 28 cm.
Browse related items
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text:
| May 30, 2006
From the Singapore Cancer Society.
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text:
OLLIS avait besoin d'un nouveau design de logo et a lancé un concours sur 99designs.
Un gagnant a été sélectionné de 44 designs proposés par 10 designers freelance.
Bethel Christian School
Bethel Christian School is a private, non-profit Christian School in McMinnville, Oregon. We service about 100 families and 150 children. Our website http://www.bethelcs.org needs an awesome logo that communicates our purpose. Logo should communicate a fresh look that portrays excellence.
Young families interested in our school. Families are predominantly middle class and protestant.
We need the logo several formats: especially png, jpg, eps. Logo will be used on our website, used in print in a variety of different programs (indesign, word, etc..). Logo will also be used outdoors on large printed signs. Large formats for the files are required.


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Walt Disney World Official 2016 Birnbaum's Guidebook for Kids
Small World
Birnbaum is the most respected name in Disney guides, and the only official guide. This updated edition of Birnbaum's Walt Disney World Resort for Kids takes younger readers through Disney's biggest resort from the peer's eye of a child. See more
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Express shipping not available for this item. This item cannot be shipped internationally or outside the contiguous United States. It can only be shipped to a physical address, not to a P.O. Box, APO or FPO address. Please allow 2-3 weeks for delivery.


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Sunrise on the Montana range, yellow dog at your side, black coffee in your hand. This Shearling Vest by Mountain Khakis takes you there. Its unique stretch canvas exterior (the same fabric as our Camber 107 Pant) is insulated with shearling pile to fend off the pre-dawn chill. Vest features 5 pockets. Imported. 97% cotton/3% spandex body, 80% acrylic/20% poly shearling lining.
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text: i dont care what people say about how good our wr's are.. keyshawn, glenn, and/or morgan wouldn't be any other teams #1 wr. keyshawn looks the part to play a slot wr, not a #1. he lacks speed. i appreciate key's hard work but he shouldnt get over 1000 yards a season. its not really a big threat when he gets the ball. he hardly ever has good YAC (yards after catch), he's to slow. face it ..key NEVER will break a long pass play.. EVER again. who wants that to be your #1 wr? i sense the same problem with mike williams, hes a big possession wr. he'd be better than keyshawn (who isn't).. but still not what we truely need. we need braylon edwards badly, he'd give us youth at the position at most importantly SPEED. i dont see us taking mike williams, hes just so slow for a team lacking speed like ours.


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The Free-Will of God (12 of 26) by Zach Terry
This content is part of a series.The Free-Will of God (12 of 26)
Series: Romans
Zach Terry
Romans 9:1-26
INTRODUCTION: Today we will look at one of the most difficult passages in God's Word. Not difficult to understand, but difficult to accept. It deals with the radical Free Will of God. Of all the cultures to inhabit this planet perhaps none find this doctrine more difficult to accept that our Modern Western culture. We are taught from our earliest age -
• Self determination
• Self actualization
• We are taught the free-will of man, but we never examine the free-will of God.
As a matter of fact we are willing to allow God to be loving, holy, righteous, good - anything but free. Free to do as he determines as it relates to man.
But God's will is the only purely free will there is.
• For example, your will is not free to fly like superman. You can will it but the law of gravity will override your will.
• But when God wills something the entire universe conspires to bring it to pass.
So Churches don't know what to do with this chapter. I don't know that I have ever in person heard this passage preached in all my life.
But friend if we really believe in the inerrancy of scripture we must embrace and love this chapter as much as any in the bible.
TEXT: Look at how Paul begins... Romans 9:1-5 (ESV) 1 I am speaking the truth in Christ-I am not lying; my conscience bears me witness in the Holy Spirit- 2 that I have great sorrow and unceasing anguish in my heart. 3 For I could wish that I myself were accursed and cut off from Christ for the sake of my brothers, my kinsmen according to the flesh.
One of the greatest criticisms of the doctrine of election as I understand it is simply that it will kill a zeal for evangelism. That seems to make sense, "If God choose those who would believe from before the foundation of the world, 'why witness, why do missions?'". That's a very valid question. I would simply say that the evidence is to the contrary.
Notice that Paul ...
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Like other countries that are both OECD and G20 members, the United States has been fully engaged in the OECD's BEPS project.
Representatives of the US Treasury Department have actively participated in the OECD negotiations and generally expressed support for the goals of the project. Some members of the US Congress have also expressed their support for the project, but others have reserved judgment or expressed concern that the project may have unfairly focused on US multinationals.
The United States has good reason to believe its companies have been disproportionately targeted. Within Europe, much of the public and media attention relating to BEPS has focused on the perceived tax behavior of US-based multinationals that derive profits from high-value marketing intangibles. A significant portion of the OECD Action Plan focuses on tax issues involving intangible property, and the US is home to many of the world's highest value brands.
Many of the OECD's recommendations have been revised to address US concerns about the original proposals.
For example, early versions of the OECD's recommendations for country-by-country reporting sought much more detailed disclosures. Due to concerns expressed by US policy official regarding burden, misuse of information and confidentiality, which are shared by a number of other officials, the OECD's final recommendations on country-by-country reporting are narrower.
The US influence is also evident in the OECD's anti-treaty shopping recommendations. Previously, it appeared the OECD was set to recommend that countries adopt both a limitation on benefits article in their treaties and a domestic principal purpose test under which treaty benefits would be denied where gaining the benefit is one of an arrangement's principal purposes. In line with the general US preference for objective tests over general anti-abuse or anti-avoidance rules, US representatives participating in the BEPS project (among others) felt the domestic principal purpose test would create too much uncertainty. The final recommendations call on countries to adopt either a principal purpose test or an objective limitation on benefits provision coupled with targeted domestic anti-abuse rules, such as anti-conduit rules.
On 22 December 2015, the US Treasury Department and the Internal Revenue Service issued proposed regulations that would require country-by-country reporting by US persons that are the ultimate parent entity of an MNE group that has annual revenue for the preceding annual accounting period of 850 million US dollars (USD) or more. The proposed regulations would be applicable to taxable years of ultimate parent entities of MNE groups beginning on or after the date of publication of the final regulations.
Given the late publication date for the proposed regulations, final regulations are not expected until sometime during 2016, pushing the first reportable period for calendar-year MNE groups to 2017, which is 1 year later than the OECD's recommended first reporting period.
The US Treasury Department released proposals to revise the US model income tax treaty on 22 May 2015. The revisions are designed to respond to changes in US treaty partners' tax regimes that the Treasury Department believes may encourage BEPS. The proposed changes include provisions aimed at inversion transactions, 'special tax regimes', and so-called 'exempt permanent establishments'. The Treasury Department has stated that, for the next US model income tax treaty update, a new article would be introduced for resolving disputes between tax authorities through mandatory binding arbitration, although this measure is not among the current proposals.
Previously, the US indicated that it did not intend to take part in the ad hoc group working on the development of a multilateral instrument, but the US has subsequently enlisted as a member of that group.
Beyond these developments, the Obama Administration has indicated it will consider implementation of the OECD BEPS project results, at least to the extent certain results may be implemented solely through administrative actions. The Administration has suggested it may also choose to propose statutory changes based on the OECD BEPS project results, but the likelihood any such proposed changes would be enacted remains uncertain.
Both former House Ways and Means Chairman Dave Camp and former Senate Finance Committee Chairman Max Baucus had previously introduced proposals for international tax reform that include provisions targeted at base erosion. President Obama's 2017 budget also includes several international tax reform proposals designed to address BEPS concerns.
Common to these proposals are variations on measures that would:
Various legislative proposals for a preferential regime for intellectual property have also been put forward. Presumably, these proposals would be considered in the context of broader international tax reform.
Regardless of whether the US enacts these or other statutory or regulatory changes, US-based companies with foreign operations must comply with BEPS-related changes in the local tax laws of the countries in which they operate. In particular, US-based companies may be required to file a country-by-country report locally in jurisdictions in which they operate or designate a surrogate filing jurisdiction where relevant, prior to the effective date of the requirement in the US.
US-based companies also need to:
These are just a few of the BEPS-related changes that US companies should begin preparing for regardless of whether or not the US adopts them domestically. Other potential effects may result from new limitations on interest deductibility, European Commission state aid cases, evolving views on the digital economy and changes in dispute resolution.
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This is a preview for the NET documentary "loopdiver." The half-hour documentary follows the creative efforts of company members over a two year period as they struggle with the extreme physical and emotional demands of creating an experimental new work.
live streaming schedule & on demand videos
|09:00 am
|Nebraska Department of Education: November 2017 NDE Board Meeting
|November 2017 NDE Board Meeting
|02:00 pm
|Nebraska Department of Education: December 2017 NDE Work Session
|December 2017 NDE Work Session
|09:00 am
|Nebraska Department of Education: December 2017 NDE Board Meeting
|December 2017 NDE Board Meeting
|Nebraska Stories: A Quilt of Honor & More, 813
|"A Quilt of Honor" The story of Caroline Boston is explored through a quilt she inscribed with the...
|Nebraska Stories: Big-Time Radio in Clay Center, 813
|In the 1920s, a chicken incubator baron in Clay Center started a radio station to market his...
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|"Sowing The Prairie" Since the Civil War, nearly 99 percent of Great Plains grasslands have...
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|The story of Caroline Boston is explored through a quilt she inscribed with the names of 318 Union...
|Big Red Wrap-Up: 2017 Spring Practice Week 4 Update
|Spring practice continues at Nebraska as players continue making strides ahead of the annual Red/...
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text:
You can trust the IRS with your medical information.
And:According to new IRS emails obtained through a Freedom of Information Act request from Judicial Watch, former head of tax exempt groups at the IRS Lois Lerner was in contact with the Department of Justice in May 2013 about whether tax exempt groups could be criminally prosecuted for "lying" about political activity."I got a call today from Richard Pilger Director Elections Crimes Branch at DOJ ... He wanted to know who at IRS the DOJ folk s [sic] could talk to about Sen. Whitehouse idea at the hearing that DOJ could piece together false statement cases about applicants who "lied" on their 1024s --saying they weren't planning on doing political activity, and then turning around and making large visible political expenditures. DOJ is feeling like it needs to respond, but want to talk to the right folks at IRS to see whether there are impediments from our side and what, if any damage this might do to IRS programs. I told him that sounded like we might need several folks from IRS," Lerner wrote in a May 8, 2013 email to former Nikole C. Flax, who was former-Acting IRS Commissioner Steven T. Miller's chief of staff.
Just a few short days later on May 10, 2013, Lerner admitted and apologized for the inappropriate targeting of conservative tea party groups during an American Bar Association Conference after answering a planted question. Further according to Judicial Watch, "In an email to an aide responding to a request for information from a Washington Post reporter, Lerner admits that she "can't confirm that there was anyone on the other side of the political spectrum" who had been targeted by the IRS. She then adds that "The one with the names used were only know [sic] because they have been very loud in the press."In other words, only conservative groups were being looked at for criminal prosecution.


text:
Type to Search
Pro Football Teams As Cars - NFC North
America's team, America's sports car.
Inexplicably, people still love them both.
Image via ProductionCars.com.
Pro Football Teams As Cars - AFC West
Both look best in blue, with hardcore fans everywhere.
Skins have a jerk for an owner. Sadly, so do many A6es.
Next Gallery
What if your favorite pro football teams were cars? Here's how...
James Wolfcale


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text:
|Inside Carolina audio is available to IC premium subscribers. To listen, you'll need an updated version of Windows Media Player - click here to download the software.
Opening comments:
"Obviously, it's good to win the game. Coming into this ballgame, our kids had respect for William & Mary. They are who they are and have the record they had and they are a very well-coached football team. I think that our football team also learned that they have to play well, they can't put the ball on the ground, can't make communication mistakes on kickoffs, and you have to execute a lot better than we did. We were fortunate enough to not dig too big of a hole and we put ourselves in a position to dig ourselves out. "At halftime we talked about what it was going to take to win the football game. It was going to take all three phases, there wasn't going to be any margin for error. I think our offensive line showed up tonight and Johnny White ran the ball really well and gave us the play that we needed to flip not only the emotions but also the score."
On how this game typifies the season:
"I think that it would probably be a pretty good analogy. It's been a microcosm of a lot of things that have happened this year. As in the case of this football team, throughout the course of the year, they've showed a lot of resilience. Even though it looked ugly and at times we didn't play as well as we'd have liked, they kept fighting, kept competing. Later on, obviously, some good things started to happen."
On Mike Paulus's play:
"I thought he played very well. I had a chance to talk to him afterwards and told him he played extraordinarily well. He's done a remarkable job this year to help them win those games, and he played well tonight."
On Quan Sturdivant:
"We didn't play Quan Sturdivant tonight. It was a gametime decision. We thought about the possibility of playing him 12 plays each half, but the way the game unfolded we were never able to get him into the game."
On his emotions when White scored his touchdown:
"A lot of relief. We knew it was going to be a struggle going into the second half, but when he busted off that long run, it was definitely a good feeling because we knew we had taken the lead."
On the necessity of getting this win:
"It's really big. If we hadn't have been able to pull this game out, it would have been a big hit for us. We just knew we had to pull it out for the rest of the season because this game was so important for us. We had to come out with the win."
On Paulus and where he's improved:
"Everybody knew he had a lot of skill. He's a very good thrower and he's mobile. His thing was just getting into a system that worked for him and getting comfortable. He showed that he's very confident and very decisive in all of his throws and reading his coverages throughout the game. That's the thing I think he's improved the most on."
On the win:
"Anytime you win, whether it's William & Mary or its USC or Florida State, it doesn't matter - it's a win. That's the thing we got to go into every game looking at. No matter who the opponent is, we have to play the way we know how to play."
On changes in defense:
"You have to know your opponent and how they play. Mike Paulus threw some great balls in the first half and you just have to give him credit for that."
On returning after missing the first seven games:
"With that scenario, everybody makes mistakes and I can admit that we made a mistake coming into the season. I'm just thankful that God gave me a second chance to play football, and we are just going to build as a team and learn a lot later in life about that."
Was the length of your suspension fair?
"As fair as it could possibly be. You can't take anything for granted. I'm back out here, so regardless of whether it was six, seven or eight games – if I didn't play this game and came back next week – just the opportunity to be back out here with my teammates… You just thank God for that and come back out here and play as hard as you can."
On having a career game:
"It was just a great feeling. I just thank God that the offensive line just came together for us in the second half and really blocked their tails off for the tight ends and tailbacks and receivers."
On the team's mentality in the second half:
"We just felt a sense of urgency that we just needed to get it together. I felt like in the second half we couldn't waste any possession because we just played a really good team, no matter if they are I-AA or whatever. They didn't really mess up or miss any picks or blow any coverages or anything, so we knew that we were going to come in and play a team that wouldn't beat themselves."


text:
Lack of HDMI aside the Ferrari One has competent connectivity. Like most netbooks it has three USB ports in total, though none offer eSATA or 'sleep & charge', while a VGA video output, memory card slot, audio jacks (1x headphone, 1x microphone) and an Ethernet port round off the options. This is all pretty consistent with the netbook mantra. Given the price it's hard to complain about the lack of any niceties, including an optical drive, which this machine is far too small and slim to incorporate.
It's not too small or slim to have a decent display, though - quite the opposite in fact. LED backlit and with a roomy 1,366 x 768 native resolution, it's a really great display to work on and to enjoy video content on. We were particularly impressed with the brightness of the display, which went some way to forgiving the predictable glossy, reflective finish. Viewing angles aren't a strong point, but neither are they a great weakness, so overall it's a good'un.
Overall performance is impressive, too. In PCMark Vantage the Ferrari One outperformed the HP Pavilion dv2-1030ea and Acer Aspire Timeline 4810T-353, both of which used single-core ULV CPUs. Until we get a look at Intel's new CULV offerings it's hard to see how this stacks up, but for the money the Ferrari One offers very good performance, particularly in light of its HD video playback and modest gaming abilities.
Unfortunately, where battery life is concerned, things do take a light jolt. In the low-intensity Reader test the Acer managed a creditable four hours and 50 minutes, but this dropped markedly to three hours, 35 minutes in the Productivity segment. Still not terrible and it may be enough for many, but it's clear that when the machine gets busier its battery life takes a large hit. Larger than you'd normally expect at the very least.
A clue to the cause of this difference can be found in how noisy the machine can get. In truth this isn't a massive surprise, AMD laptops tend to run warmer and noisier than their Intel counterparts, but in an ultra-portable/netbook like this it's an important factor. Even when idle the fan runs at a noticeable speed, ramping up considerably when the system is under stress. This constant spinning does keep the unit cool, but clearly it's also having a negative impact on battery life.
Whichever way you look at it, as a netbook or as an ultra-portable, this is an impressive and enticing proposition. For the price the Acer Ferrari One offers excellent performance - including smooth 1080p video playback - while the balance of features, portability and usability is just right. But it does have weaknesses, namely the lack of HDMI, its innate Ferrari-ness and its okay but not outstanding battery life. It would be foolish to dismiss this machine for these problems alone, but they do just preclude it from an award.
Better than the Air then :P.
C'mon, someone was going to say it ;).
Looks great, I would definitely consider it except for one thing - no HDMI! I appreciate that you can still output video through VGA, but then I'd need to output audio separately too. The ability to decode 1080p video is nice, but to me fairly pointless without HDMI.
Can't buy that due to the ferrari logo on the back - like wearing a ferrari baseball cap.
the fact it goes "vroooom!" on startup eliminates the HDMI negative in my books.
The noisy fans is very disappointing. I can live without HDMI but don't like noisy computers. This is my type of netbook/ultra portable, a dual core with dedicated graphics.
They should just make the lid silver. I remember an Acer Ferrari with a silver lid??
I must correct the video, it does not have a noisy fan. It is very quiet. Great little netbook. Had it one week so far and can't find any fault in any way.
I bought one a couple of months ago - it was silent for 3 weeks then developed a noisy fan, something between a rattle and a buzz. This is very disappointing from an otherwise powerful and handy machine. Sadly speedfan and other monitors do not work on this model so I can't adjust the fan - it makes lots of fan noise at temperatures as low as 30 degrees C, temps that shouldn't need a fan to be on at all.
Would be nice to see a performance review where it was pitted against the Acer Ferrari one netbook.
Acer ferrari one vs the Eee pc 1201n.. While looking for reviews of both these netbooks iv seen a few requests by budding netbook owners requesting the same thing.
Would be nice to see a performance review where it was pitted against the Eee pc 1201n. netbook.
Acer ferrari one vs the Eee pc 1201n... best video performance, best gaming performance fastest cpu etc.
I bought one of these laptps yesterday. I've used it a good few hours and so far I cannot say that it has loud fan noise at all and it does not generate large amounts of heat. It is at the most a quiet whirr. This smashing little machine packs some degree of gaming capability, effective video and HD playback and the very fast multasking of a much more expensive ultraportable for £400. Add to that the bonus of a rock solid build quality and great keyboard and crystal clear display on pictures & font. The battery life is just as good as most ultraportables and regular netbooks at 4-5 hours, just as good as my Samsung NC10 which has much lower powered hardware. It is wrong to compare the battery life with the Timeline series, it needs to be compared alongside other regular netbooks and ultraportables.
Yes, the design and colour scheme is like Marmite, you either love it or hate it but it is sure distinctive in a world of homogenous if sleek machines. I disagree having the Ferrari logo makes one appear a wannabee who can't afford the car. So what? One can admire Ferrari branding and perhaps even be a F1 fan. This lovely little cross somwehere between an ultraportable and premium netbook has the performance to go with the branding image. If you like he design but don't want to pay silly prices you cannot go wrong.
Apart from that, the review is very accurate and a pretty fair score, except I'd give it 9/10 at its pricing point.
It seems the owners in this thread are split between noisy and quiet fans. I was in the quiet camp for the first 3 hours the computer was on. Then I heard a clunk like a Ferrari had been mis-shifted and started to make a metallic buzzing noise from the fan similar to how ando321 described it. This happened at idle. I have not heard the quiet (and pleasant) whirr I heard at first use in the week since. It makes the rattly buzzing noise when I boot it up... when it's cool... I'm afraid to take it to class for the noise it makes.
I also own a Lenovo S10, another "loud" netbook that runs hot but this is altogether different. I love everything about this little red beast except for the fan issue :(
I don't have any real problems with this netbook other than the touchpad. I would like to adjust the sensitivity but there doesn't seem to be an option under touchpad properties so I will use my wireless nano mouse most of the time.
My main problem is not with the machine but with the online registration site. Each time I try to submit the Serial Number I get the message (in red) to "check serial number". I have triple checked that it is correct and that the sticker underneath the machine, the SN printed on the box, the one listed in the BIOS and the VCARD are all identical. I only use a 0 (zero) and not the letter O so I don't understand why it isn't recognised?
Another problem I encountered is that when I enter the SNID the online form only accepts 3 digits so it is not capable of taking the full number.
Has anyone else had any trouble registering their products?
my ferrari one heat up fast and shut down with in 20 min .wht is the solution of it?
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text:
Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front
- First Online:
- Accepted:
DOI: 10.1007/s00418-008-0464-1
- Cite this article as:
- De Wever, O., Pauwels, P., De Craene, B. et al. Histochem Cell Biol (2008) 130: 481. doi:10.1007/s00418-008-0464-1
- Citations
- 1.5k Downloads
Reduction of epithelial cell–cell adhesion via the transcriptional repression of cadherins in combination with the acquisition of mesenchymal properties are key determinants of epithelial–mesenchymal transition (EMT). EMT is associated with early stages of carcinogenesis, cancer invasion and recurrence. Furthermore, the tumor stroma dictates EMT through intensive bidirectional communication. The pathological analysis of EMT signatures is critically, especially to determine the presence of cancer cells at the resection margins of a tumor. When diffusion barriers disappear, EMT markers may be detected in sera from cancer patients. The detection of EMT signatures is not only important for diagnosis but can also be exploited to enhance classical chemotherapy treatments. In conclusion, further detailed understanding of the contextual cues and molecular mediators that control EMT will be required in order to develop diagnostic tools and small molecule inhibitors with potential clinical implications.
KeywordsStroma Cadherin EMT Metastasis Therapy
Epithelial–mesenchymal transition (EMT) is a type of plasticity during which epithelial cells lose many of their epithelial characteristics and acquire properties that are typical of mesenchymal cells. Multiple terms, including epithelial–mesenchymal transformation and transdifferentiation have been used to refer to EMT. To understand this, it is important to review the terms epithelium and mesenchyme. An epithelium is a sheet of cells that adhere laterally to each other by cell-to-cell junctions. The epithelial layer is polarized in such a way that bottom and top can be defined as basal and apical (inside and outside). The filamentous actin cytoskeleton is apicobasally polarized and shows circumferential organization. Cytokeratins are the main intermediate filaments. The matrix-binding sites are on the basal face, mediating adhesion mainly to the basal lamina protein, laminin. In contrast, mesenchymal cells form a diffuse network with certain points on their surface adhering to their neighbors. Actin filaments form a dense cortical network of interacting fibers, and perhaps trans-cytoplasmic actin bundles. Vimentin is prominently expressed as an intermediate filament. Contact sites to the extracellular matrix (ECM) are widely distributed all around the cells. The ECM forms a dense meshwork involving proteins like collagens and fibronectin. In contrast to epithelial cells, mesenchymal cells also have a more extended and elongated shape, and they have front-to-back leading edge polarity (Tarin et al. 2005; Lee et al. 2006; Thiery and Sleeman 2006; Hugo et al. 2007; Berx et al. 2007). In clinical practice pathologists use the terms "sarcomatous/sarcomatoid dedifferentiation" (i.e., "—resembling a sarcoma—", a malignant mesenchymal tumor) or anaplasia (meaning "—to form backward—") (Van Marck and Bracke 2005). EMT is not considered a requisite for invasion and metastasis, but compelling evidence shows that it can play an important role in determining the dissemination of tumors (Berx et al. 2007). In animal models, single non-dividing migratory cells delaminate from primary tumors as evidenced by powerful imaging techniques such as multiphoton microscopy (Condeelis and Segall 2003). The characterization of specific markers will undoubtedly help to identify the nature and origin of all mesenchymal-like cells found in the stroma and near the primary tumor.
Molecular and functional signatures of EMT
Extracellular cues regulating EMT
Bi-directional communication between cancer cells and their microenvironment, profoundly influences their behavior and fate. Primary tumors are heterogenous and EMT is observed particularly at the cancer invasion front, suggesting the micro-environment as being essential in regulating EMT. For example, melanoma cells that give rise to invasive tumors when implanted into adult animals are reprogrammed into a non-aggressive phenotype when implanted into embryonic tissue (Hendrix et al. 2007). The stroma is essential for tissue integrity and in cancer it drives tissue invasion. Myofibroblasts (also called cancer-associated fibroblasts) are important components of the tumor stroma at the invasion front (De Wever and Mareel 2003; De Wever et al. 2008). In squamous cervix and colon carcinomas, Snail expression is restricted to cancer cells near stromal cells (Francí et al. 2006). Similarly, cancer cells accumulating nuclear β-catenin are distributed throughout the tumor mass but particularly along the invasion front (reviewed by Le et al. 2008). These results suggest that myofibroblasts docking at the invasion front regulate EMT of nearby cancer cells. This myofibroblast-induced EMT may be caused by transient heterotypic cell–cell contacts or by paracrine signals. In vitro, paracrine factors derived from breast tumor myofibroblasts induce EMT in PMC42-LA breast cancer cells, with upregulation of vimentin, loss of E-cadherin staining at cellular contacts and increased nuclear β-catenin signaling (Lebret et al. 2007). We previously demonstrated that tenascin C and SF/HGF produced by myofibroblasts provide convergent pro-invasive signaling to colon cancer cells (De Wever et al. 2004; Denys et al. 2008). ECM remodeling by myofibroblasts is implicated in progression of prostate cancer xenografts (Verona et al. 2007). Furthermore, increased collagen production and expression of α11β1 integrin in combination with α-SMA mediated contractility has a profound effect on the tumor stiffness that is linked with malignancy (Zhu et al. 2007). Matrix stiffness perturbs epithelial morphogenesis by clustering integrins to enhance ILK activation and increase Rho-kinase (ROCK)-generated contractility and focal adhesions (Paszek et al. 2005; Hannigan et al. 2005). Furthermore, engagement of collagen-binding integrins promotes MMP-9-dependent shedding of the E-cadherin ectodomain in ovarian carcinoma cells (Symowicz et al. 2007). Another factor that is receiving considerable attention as an inducer of tumor metastasis is hypoxia (reduced oxygen). There is a strong correlation between tumor hypoxia on the one hand, and metastasis, poor prognosis and patient mortality on the other. This hypoxic response is mainly regulated by the hypoxia-inducible factor (HIF-1), a basic HLH transcription factor composed of two subunits, HIF-1α and HIF-1β. The HIF-1α subunit is regulated by oxygen tension, whereas HIF-1β is constitutively expressed. In breast MCF-7 and ovarian SKOV-3 carcinoma cell lines, Notch signaling is required to convert the hypoxia stimulus into a Snail dependent EMT program leading to increased motility and invasion (Sahlgren et al. 2008). Similarly, hypoxia or overexpression of HIF-1α promotes EMT and metastatic phenotypes in human carcinoma cells via direct induction of the E-cadherin repressor and EMT inducer Twist by direct binding of HIF-1α at the hypoxia response element in the TWIST proximal promoter (Yang et al. 2008). Accordingly, E-cadherin levels were down-regulated while vimentin and N-cadherin were induced in these hypoxic cancer cells. Importantly, these observations were extended in hypoxic human breast cancer cells showing cellular scattering, cell dissemination in vivo, high vimentin levels, translocation of E-cadherin in intracellular pools and nuclear translocation of the EMT inducer Snail (Lester et al. 2007). Furthermore, co-expression of HIF-1α and TWIST in primary tumors of head and neck cancer patients correlates with metastasis (Yang et al. 2008).
EMT signatures at early stages of carcinogenesis and cancer recurrence in vivo
Epidemiologic and clinical studies indicate that a strong association exists between estrogen exposure and increased breast cancer risk. Estrogen and/or estrogen metabolites may act as procarcinogens through ER-α—dependent or —independent mechanisms, and may induce genotoxic effects to initiate breast, prostate or other cancers (Yager and Davidson 2006; Huang et al. 2007). In support of these observations, long-term treatment of spontaneously immortalized human breast epithelial cells by estradiol induced several phenotypic traits characteristic of EMT, including invasiveness, lower expression of the epithelial markers E-cadherin, keratins, and induction of Snail, vimentin, and the EMT inducer TGF-β (Huang et al. 2007).
To identify early events associated with myc-induced breast cancer, mouse mammary epithelial cells and stromal cells were distinguished using fibroblast specific protein (FSP) and epithelial-specific whey acidic protein (WAP) promoter driving transgenic expression of Cre recombinase constructs in transgenic animals, respectively (Trimboli et al. 2008). These two lineages were identified histologically by expression of the LacZ reporter gene from the Rosa26LoxP locus. Of note, early EMT events occurred in 25–50% of myc-initiated breast cancer in WAP-myc; FSP-cre; Rosa26LoxP mammary glands. The frequency of EMT in tumor mice with the FSP-cre transgene was slightly higher than in mice with the WAP-cre transgene, consistent with the concept that Fsp-1 expression is an early event in the EMT process. The MYC locus in the 131 patient samples was therefore analyzed for genome-wide LOH, using the adjacent polymorphic marker D8S1128. Trimboli et al. (2008) concluded that MYC amplification is associated with a predisposition of the epithelium to undergo EMT in human breast cancer.
Early appearance of several molecular alterations characteristic of EMT has been described in benign adenomas of the multiple intestinal neoplasia (Min) mouse model of familial adenomatous polyposis disease (Chen et al. 2008). Inactivation of the adenomatous polyposis coli tumor suppressor protein in this preclinical model recapitulates early events underlying the progression of human colorectal cancer. A strong vimentin signal was observed in the cytoplasm of Min colonic neoplastic cells with characteristic epithelial organization in 74 out of 79 tumors. Vimentin staining was absent from the adjacent normal epithelium. Microadenomas involving only three to five crypts in the colon and small intestine displayed elevated vimentin mRNA levels, suggesting that the classical EMT marker, vimentin can be detected at an early stage of tumorigenesis. Of note, Min mice on a tumor-resistant genetic background have reduced tumor multiplicities, longer life-span, and develop invasive intestinal tumors, that reached the submucosa and muscle layers. In this model, immunohistochemistry demonstrated strong vimentin expression in the epithelia of the primary tumor and in the neoplastic cells invading the submucosa and muscular layers (Chen et al. 2008). Vimentin expression was not systematically distributed in all neoplastic cells, but was present in patches in both central and peripheral tumor regions.
Breast cancer recurrence is an essential clinical manifestation of tumor progression and represents the principal cause of death from this disease. Using a conditional transgenic HER2/neu mouse model showing recurrence of HER2/neu-induced mammary tumors, Moody et al. (2005) demonstrated that the transcriptional repressor Snail is spontaneously upregulated in recurrent tumors in vivo and that recurrence is accompanied by EMT as evidenced by spindle shaped morphology with downregulation of cytokeratin and E-cadherin and upregulation of FSP. Furthermore, Snail is sufficient to promote recurrence of mammary tumors in vivo, and high levels of Snail are predictive of shorter relapse-free survival in breast cancer patients.
Pathological signatures of EMT in tissue samples
A large-scale tissue microarray-based immunohistochemical study of 479 invasive breast carcinomas revealed upregulation of mesenchymal markers (vimentin, α-SMA, N-cadherin and cadherin-11) and overexpression of proteins involved in ECM remodeling and invasion (SPARC, laminin and fascin), together with reduction of characteristic epithelial markers (E-cadherin and cytokeratin) particularly in breast tumors with the "basal-like phenotype" (Sarrió et al., 2008). Gene expression analysis using cDNA Oncochip microarray of metastatic versus non-metastatic melanomas identified differentially expressed genes implicated in EMT. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin and SPARC) was significantly associated with metastasis development (Alonso et al. 2007). A similar oligonucleotide microarray study on papillary thyroid carcinoma from central and invasive regions and of normal thyroid tissue was performed. The invasion fronts were consistently characterized by the presence of mesenchymal markers and absence of epithelial markers. Furthermore, immunohistochemical analysis revealed that overexpression of vimentin associated with papillary thyroid carcinoma cell invasion (Vasko et al. 2007). Molecular classification of fresh-frozen and formalin-fixed head and neck squamous cell carcinomas showed that genes involved in EMT are the most prominent molecular characteristics of high-risk tumors (Chung et al. 2006). In conclusion, we strongly insist that the occurrence of the EMT signature should be explored in large-scale studies of human clinical tumors in order to predict their metastatic potential.
Pathological signatures of EMT in biological fluids
Organ-related application of circulating EMT markers
Organ or tissue/marker
Anti- p53
Bile ducts
Head and neck
Lung (small cell)
Lung (non-small cell)
Scatter factor/hepatocyte growth factor concentrations in serum are correlated with metastatic spread, they possess prognostic value, and they are useful for monitoring therapy. They can also be used as a urine parameter for diagnosis of transitional carcinoma of the bladder. Fibroblast growth factor-2 (FGF-2), another tyrosine kinase receptor ligand, is an endothelial-to-mesenchymal transformation marker, its serum concentrations correlate with tumor growth rate, volume, grading and staging. Its main clinical usefulness, however, resides in monitoring the effect of angiogenesis inhibitors. In prostatic cancer an inverse correlation between prostate-specific antigen (PSA) and FGF-2 has repeatedly been observed (Usami et al. 2008). While the EMT inducer TGF-β as a circulating marker is difficult to interprete, the serum concentrations of its functional activators, MMP-9 and CD44 (mainly its spliced isoform v6), have proven to possess prognostic information. Assessment of the urine concentrations of MMP-9 was claimed to contribute to the diagnosis of bladder cancer. Circulating tenascin-C, a matricellular protein acting in concert with SF/HGF, can discriminate between good and bad prognosis in numerous cancers, and its cut-off level was determined at 96 ng/ml. Tenascin-C serum concentrations also correlated with the vascularization of the tumors. A central player in cancer progression is p53, and this tumor suppressor's level in circulation was found to be higher in cancer patients than in normal individuals. This is presumably the result of the increased biological half-life of many p53 mutants. Moreover, mutations in exons 5 and 6 are particularly immunogenic, and elicit detectable auto-immune anti-p53 antibodies in the circulation (IgM and IgG). Although p53 and its antibodies were shown to correlate with prognosis and therapeutic response of head- and neck cancer, their major applicability is in epidemiological studies, where mutagenic pressure from the environment has to be assessed.
The switch from E- to N-cadherin is considered typical for EMT, and enzymatically shed, soluble ectodomains from both cadherins have been detected at elevated levels in the serum of cancer patients reviewed in (De Wever et al. 2007). Conceptually the measurement of soluble E-cadherin (sE-cad) may be less straightforward, because E-cadherin is downregulated in carcinomas. Soluble N-cadherin (sN-cad), however, may be a very sensitive circulating marker, because it is upregulated in cancer cells and in stromal myofibroblasts. Two members of the kallikrein family, hK3 (or PSA) and hK4 (prostase) were shown to induce EMT in prostatic carcinoma cells in vitro (Lawrence et al. 2007), and both members are tumor markers for prostatic carcinoma. PSA is not only useful for the monitoring and follow up of therapy, it even contributes to the diagnosis and staging of prostatic carcinoma patients. Additional measurements have refined the interpretation of PSA values. These additional measurements include the rate of the PSA increase (more or less than 0.75 ng/ml or 20% a year), PSA density (serum PSA/prostatic volume), age-related reference values, determination of free/complexed PSA in serum and neural network assistance.
Loss of epithelial cell polarity and of junctional contacts in cancer, in combination with basement membrane breakdown, removes the barriers for apical markers to diffuse into the extracellular fluids. Some high molecular weight apical mucins, which normally circulate at extremely low concentrations, are sensitive markers for loss of cell–cell contact in cancer. Nowadays, they belong to the most frequently prescribed tumor markers in clinical chemistry, and are known as carcino-embryonic antigen (CEA), CA 15-3, CA 19-9 and CA 125. As a result of cell–cell contact loss in hepatocellular carcinoma, α-fetoprotein (AFP) is upregulated (Gleiberman et al. 1989), and has proven to be an excellent serum marker for this type of cancer.
Does EMT affect cancer treatment regimens?
Selective tyrosine kinase inhibitors are promising to treat cancers driven by activated tyrosine kinases such as Bcr-Abl in chronic myelogenous leukemia, c-Kit in gastrointestinal stromal tumors and EGF receptor (EGFR) in non-small cell lung cancer (NSCLC). Gefitinib (Iressa) and erlotinib (Tarceva) are selective inhibitors of the EGFR receptor tyrosine kinase and is currently used to treat NSCLC patients (Guo et al. 2008). Although most NSCLC tumors express EGFR, only a fraction of patients with tumors dependent on EGFR for growth and survival respond clinically to EGFR inhibitors. These tumors appear to contain EGFR-activating mutations or have undergone amplification of EGFR gene copy number. Furthermore, a subset of non-small cell lung carcinomas that do not respond to erlotinib therapy have low levels of E-cadherin and higher levels of mesenchymal type transcripts such as vimentin and fibronectin (Thomson et al. 2005). The bulk of Thomson's evidence is derived from NSCLC cell lines, but some confirmatory evidence comes from immunohistochemical staining of sections of human tumors (Yauch et al. 2005). Furthermore, ILK-mediated EMT predicts hepatocellular carcinoma sensitivity to EGFR-targeted therapies (Fuchs et al. 2008).
Alternatively, many routine cancer treatments may stimulate EMT and thus enhance invasion and metastasis. Chronic chemotherapy with oxaliplatin (a third generation platinum compound) induces EMT in colorectal cancer cell lines (Yang et al. 2006). In another example, ionizing radiation induces changes associated with EMT such as increased migration, F-actin stress fiber formation, and disturbed E-cadherin pattern in A549 lung epithelial cells in vitro (Jung et al. 2007). Human malignant gliomas are lethal neoplasms. Involved-field radiotherapy is the most important therapeutic measure. Most relapses originate from the close vicinity of the irradiated target field. Interestingly, sublethal doses of irradiation enhance the migration and invasiveness of human malignant glioma cell lines in vitro. IR-induced migration is p53-independent, and involves enhanced expression of αvβ3 integrin, altered MMP-2 and MMP-9 expression and activity profiles, altered expression of membrane type 1 MMP and tissue inhibitor of metalloproteinases-2, and altered BCL-2/BAX balance favoring resistance to apoptosis (Wild-Bode et al. 2001). Current approaches to cancer treatment involving more intensive radiotherapy regimens have been suggested to be associated with a higher incidence of local or distant metastasis (Jung et al. 2007). Therefore, a subset of patients may benefit from a combination of radiotherapy and EMT inhibitors. We did not find prospective randomized clinical trials providing level 1 evidence in favor of or against such side effects of treatment so our discussion is admittedly speculative.
Epithelial–mesenchymal transition signatures can be exploited to enhance classical chemotherapy treatments. Gain of N-cadherin expression is a typical example of the EMT signature and it has been linked with drug resistance (Zhang et al. 2007). Interestingly, ADH-1 (an N-cadherin cyclic pentapeptide antagonist) sensitizes N-cadherin-expressing melanoma cells to the anti-tumor activity of melphalan in melanoma models (Mariotti et al. 2007; Augustine et al. 2008). Recent work provides evidence to support the possibility of exploiting EMT as a potential therapeutic target in cancer (Sabbah et al. 2008).
Converging evidence using in vitro cell culture models, transgenic mouse models, gene signature microarray analysis and immunohistochemistry points out that EMT, amongst other mechanisms, is implicated in early steps of carcinogenesis, cancer cell invasion and metastasis and recurrence. The list of molecular signatures defining EMT is growing and will eventually lead to a clear definition useful for daily practice in pathology and clinical biology. Understanding the molecular basis of EMT is essential for designing small-molecule inhibitors targeting the EMT response. These can be used to enhance classical chemotherapy treatments.
G. De Bruyne is gratefully acknowledged for reference management. This work was funded by Fonds Wetenschappelijk Onderzoek (FWO)-Vlaanderen (Brussels, Belgium), Geconcerteerde Onderzoek Aangelegenheden (GOA, University Ghent, Belgium). The Association for International Cancer Research (Scotland), the Scientific Exchange Program between the Flemish community and France (Grant I.2007.03) and FP7 (TUMIC) of the European Union. O. De Wever and B. De Craene were supported by Bijzonder Onderzoeks Fonds (BOF, University Ghent, Belgium).


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