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Henry Ford
Intro Henry Ford was one of the best men that ever came to this world he created the assembly line.Henry Ford was born on July 30, 1863, on his family's farm in Wayne County, near Dearborn, Michigan. Henry Ford did not have the best education until later on in his life. He went to a small school house with only one room.His mom sadly passed away when he was 12 years old. In the summer he worked on his families farm. At 16 Ford walked to Detroit and apprenticed himself to a mechanic for $2.50 a week. His board was $3.50, so he worked four hours every night for a watchmaker for $2 a week. Later he worked in an engine shop and set up steam engines used on farms.
Compare and Effect The first car that he made all by himself was in 1903 and he named it the tin Lizzy after his mom passed away her maiden name was lizzie aka the Model T. As a result Ford started to blow up with orders. He hired a couple of men from his old mechanics school and got to work. The men were not fast enough to pump out all the orders he needed something revolutionary. Ford soon could make the car flow non stop out of the shop.
Henry Ford was from Michigan. Michigan is also known as the wolverine state because it shows there strength and broad. The great state of Michigan is a wonderful place for water sports like paddle boarding, boating,wake boarding, knee boarding, and water skiing.
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Author: Balin Galbraith
Last updated 1/13/15


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Quick clicks: Basel | Berne | Geneva | Innsbruck | Klagenfurt | Vienna | Zurich
• Photo gallery: Euro 2008 host cities
While Salzburg may be famous as the setting for the epic movie "The Sound of Music" and birthplace of composing giant Wolfgang Amadeus Mozart, Euro 2008 is set to leave its own indelible mark on the city.
This summer, the streets of Salzburg will reverberate to the rhythms of partying Greek, Swedes, Russians, Spaniards and, of course, Austria's own fanatical supporters.
Apart from the city's stadium which will stage three first-round fixtures party central will be the visually appealing Old Town on the left bank of the river Salzach. Big screens are to be set up in three of the main squares Mozartplatz, Kapitelplatz and Residenzplatz. And here there also will be a food and refreshment stands, musical events, competitions and sponsor spinoffs. The fun and games will take place from 2 p.m. to 11 p.m. daily, with room for 25,000 visitors.
Another favorite extra-curricular pursuit for football fans should be the city's numerous beer gardens. Munich may be the beer capital of the world, but much of the nectar flows south to Salzburg, with many of the gardens serving moderately priced meals. Stiegkeller (Festungsgasse 10, off Kapitelplatz) serves great ale and boasts incredible views over the city.
Yet the daddy of the biergharten has to be the Augustinerbrau, located in an old abbey to the west of town. Nothing beats nursing a "Mas," a liter of beer, while sitting under a chestnut tree. To reach this nirvana, take bus 7, 8, 20, 21, 24, 27 or 28 from the city center, alighting at the Landeskrankenhaus stop. More centrally located watering holes are to be found in the Rudolfskai street, which runs parallel to the river in the Old Town.
Salzburg cooking is typically Germanic meaty, hearty and distinctly no frills. Pork in all its forms beef, chicken and game abound, while broths and soups do a roaring trade, too. Also popular are locally caught fish, such as pike (Zander) and trout (Forelle). A local dessert speciality is the Salzburger Nockerl, a large souffle of eggs, sugar and raspberry baked into three mounds to represent the city's three hills the Monchberg, Festungsberg and Kapuzinerberg. However, be warned that one hefty serving is more than enough for four.
For excellent regional food in the Old Town, head for the Goldene Ente on Goldgasse or Alt Salzburg on Burgerspittalgasse, while variety is provided by the numerous Italian, Chinese and Mexican joints.
Salzburg also offers countless Konditoreien (pastry shops) and cafes. One of the most famous is Cafe Furst on Brodgasse, a venue that owes its preeminence to its world-famous Mozart chocolate balls. These can be bought throughout Salzburg, but the Furst's efforts are the original and the best. Another good example of the genre is the classy Cafe Tomaselli (Alter Markt).
Inevitably shopping in the Old Town is all about souvenirs and old-style speciality stores. The central produce markets are found on Universitatsplatz and Mirabellplatz. For malls and supermarkets, you will have to make for the suburbs, such as the Europapark in Klessheim (take bus No. 1 from the central terminus).
Things you have to do here include visiting Mozart's birthplace (Mozarts Geburtshaus) on Getriedegasse, the Schloss Mirabell Palace and Gardens on the right bank and the imposing Hohensalzburg fortress that towers over the city.
Salzburg has a fine public-transport network of trolleys and buses. Tickets can be purchased from the driver or at the ticket office in the bus terminal that sits alongside the main railway station (Hauptbahnhof) on Sudtirolerplatz.
The best bet for Euro 2008 visitors will be to get their hands on a Salzburg Fan Card, which covers six days of public transport in the city and the Salzburger region, plus admission to no fewer than 190 sights and attractions. It's worth noting that the majority of buses leave from Mirabellplatz and the railway station on the right bank, and from Hanuschplatz and Mozartsteg bridge on the left.
Situated on the western outskirts, the Stadium Salzburg Wals-Siezenheim can be reached by trolley buses 1, 20 and 28 from the city center or bus line 1 from the Hauptbahnhof.
Home to reigning Austrian champions FC Red Bull Salzburg, the rectangular 2003-built arena holds 32,800 and its modernity makes for a refreshing change in a place where church spires and medieval turrets reign supreme.
BACK TO FRONT PAGE OF GUIDE | Complete Euro 2008 coverage from ESPNsoccernet


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In this section you'll find all the latest news and data on the UK restaurant market, including dining trends, food and beverage trends, eating-out spend, and restaurant marketing and technology trends.
18-May-2016 - Bake Off: Creme de la Creme, the professional pastry chef contest on BBC Two, has crowned Mark Tilling's team the winners after last night's final.
06-Mar-2015 - A new LA-inspired restaurant offering a menu of low salt, low carb and free of refined sugar dishes will open in London's Shoreditch this month.
10-Feb-2015 - Restaurant reservations system provider ResDiary has launched new technology to help restaurateurs tackle the issue of no-shows.
06-Feb-2015 - Chef and restaurateur Steve Parle has unveiled plans for the next phase of his ambitious Craft London project.
06-Feb-2015 - Dub Jam, the Caribbean bar and restaurant concept, has launched a fundraising round via crowdfunding platform Crowdcube to expand to another eight London venues over the next three years.
02-Feb-2015 - The UK eating out market continues to grow – with the regions showing recovery for the first time – but discount driven consumers remain a challenge for the sector.
30-Jan-2015 - Soaring costs, changing consumer demands and the rise of the big brands mean independent eateries can't afford to rest on their laurels. BigHospitality looks at some innovative ways that restaurants...
30-Jan-2015 - Porky's, the Memphis BBQ restaurant, is rolling out four sites this year as part of its plan to reach 10 over the next two years, according to BigHospitality's sister publication M&C...
30-Jan-2015 - Dishoom Covent Garden has topped a list of the best 100 eateries in the UK compiled by online city guide Yelp.
28-Jan-2015 - Shaker Group has revealed plans to open upmarket restaurant and cocktail bar Gas Street Social in Birmingham this March.
19-Jan-2015 - Active Private Equity, the backer of Leon and Evans Cycles, has taken a 50 per cent stake in Honest Burgers, the London-based better burger concept.
05-Jan-2015 - The UK has seen an unprecedented cocktail boom over recent years, and the category is set to outpace the drinks market in 2015. With this in mind, BigHospitality has compiled...
05-Jan-2015 - Are you seeking out a new look for the New Year? Or opening a new venue? BigHospitality spoke to some of the UK's hottest interior designers to get their top...
23-Dec-2014 - The number of diners reporting lactose or gluten intolerance has risen in 2014, while the number of diners ordering vegetarian or nut-free dishes has fallen, according to data collected by...
22-Dec-2014 - Chef Dave Ahern will open his first restaurant Wahleeah early next year in London's Fulham.
22-Dec-2014 - Quick service is very important for men when dining out during the Christmas period, while women focus more on the whole experience, according to research by CGA Peach and hospitality...
18-Dec-2014 - Taiwanese street food concept Bao will open its first restaurant in Soho next year after securing backing from Gymkhana founders Karam, Jyo and Sunaina Sethi.
18-Dec-2014 - Manchester-based creative studio NoChintz will launch a new coffee concept in the Grade II listed Sevendale House next March.
17-Dec-2014 - First time restaurateurs Lucy Brown and Jenny Quintero will open their first restaurant, Jar Kitchen, on Drury Lane in February 2015.
17-Dec-2014 - Spanish chef Omar Allibhoy will open his third Tapas Revolution restaurant in Shoreditch in February 2015.
17-Dec-2014 - Chef Tom Seller's Restaurant Story in London took the top spot on this year's OpenTable Top 100 Best Restaurants list.
16-Dec-2014 - Michelin-starred chef Richard Allen will take over the running of The Orangery restaurant at Rockliffe Hall hotel in Country Durham in January.
15-Dec-2014 - Maggi Real Chefs has launched a Christmas selfie campaign in partnership with Hospitality Action to raise money for charity.
15-Dec-2014 - All-day Japanese and Peruvian restaurant and takeaway Amaru will open in London's St Katharine Docks on 5 January 2015.
15-Dec-2014 - The Richmond restaurant will open in spring 2015 in London, serving snacks and comfort foods in a relaxed atmosphere.


text: Google signed an agreement with the Italian Ministry of Cultural Heritage to push forward its digital renaissance vision. "Working with National Libraries of Florence and Rome, we'll digitize up to a million out-of-copyright works. The libraries will select the works to be digitized from their collections, which include a wealth of rare historical books, including scientific works, literature from the period of the founding of Italy and the works of Italy's most famous poets and writers. It marks the first time we've ever joined forces with Italian libraries, and the first time we've worked with a ministry of culture. Digitization of books is a tremendous undertaking, requiring the joint effort of a great number of public and private stakeholders. For this reason, we're supportive of many other efforts at digitization, such as European Commission's Europeana. We want to see these books have broadest reach possible — the books we scan are available for inclusion in Europeana, of which the Florence Library is a founding member, and other digital libraries," noted Google.


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Sligo is a coastal seaport, and part of the western province of Connacht. The magic of Sligo is there for you to immerse yourself in. The history, culture alongside the industrial and retail services makes Sligo a unique county town. As a result of being situated in an area of outstanding beauty, Sligo has an incredible wealth of scenery to admire to ensure you will never get bored of visiting Sligo. Hiring a car allows you to explore the stories and trails that can be found in and around Sligo. The spectacular scenery expands to outside of the main hub of Sligo. Whilst being developed along the riverside over the past 20 years, Sligo combines modern amenities and attractions with untouched natural beauty encompassing its surrounding areas which are renowned as areas of outstanding natural beauty. Our Sligo branch benefits from being located outside the city centre in order to ensure it is as easy as possible for you to go beyond the centre and explore more that this county has to offer. Hiring a car allows you to experience attractions ranging from the wildlife walks of the Benwiskin Mountains to the ruins of the Carrowmore Megalithic Cemetery. If you can't get to our Sligo branch, we can collect you. With our pick up service, booking in advance ensures that we can come and collect you even if you can't come to us still with our usual low prices.
With our huge range of cars from economy cars to larger people carriers, Enterprise Rent-a-Car always guarantees cheap prices to hire a car with us. Our economy cars are renowned for being fuel efficient as well as promising cheap running costs along with their cheap car rental rates, hiring an economy car is not only environmentally friendly but good for your budget as well. Book online or in our Sligo branch to ensure you get the best offers on car rental in Ireland.
Whether you need a smaller passenger van or a larger commercial van, our Sligo branch has the hire van suitable for you. A day, a week, a month or longer – book online or through our Sligo branch to rent a van for as long as you need it with our usual cheap rates. From moving objects that don't quite fit in your car to moving a house, sometimes a van is necessary – at Enterprise Rent-a-Car we promise to have a vehicle that is suited to your needs.
The Benwiskin Mountain guarantees breath-taking views of the winding rivers to a coastline that you cannot help but be amazed by. The Benwiskin centre is set in a scenic location in the shadows of the mountains, and worth a visit to ensure that you can truly get to experience the beauty of the North West of Ireland. Carrowmore is an attraction in Sligo that just adds to unique charm. Carrowmore complex is a collection of tombs, or they were tombs in its original state, located in the Irra Peninsula approximately 3km west of Sligo. The Carrowmore complex is the one of the oldest cemeteries in Europe, thought to be built between 4600 – 3900 BC. Check out more information on Sligo's great attractions.


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Flowering Time No feminized seeds.
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Australian Story
Alaska And Me - Transcript
PROGRAM TRANSCRIPT: Monday, 17 September , 2012
JAMES CASTRISSION, PRESENTER: Hi Im James Castrission and earlier this year my best mate Jonesy and I undertook the longest unsupported polar expedition of all time. Tonights program is about a fellow adventurer John Cantor. Six years ago John decided to tackle one of the toughest solo expeditions on earth across the Brooks Range in Alaska. After three devastating failures he faced down his demons for one final attempt. This is his story.
JOHN CANTOR: My plan is to traverse the Brooks Range solo. The expedition involves 1,000 kilometres of hiking and then 600 kilometres of paddling a kayak. Its expected to take me two months to complete.
ANDREW SKURKA, ADVENTURER: There are only a handful of people who have hiked across the Brooks Range solo. Its an incredibly difficult adventure. The weathers bad, there are lots of big river crossings, there are bears, there are wolves. It is very possible to die out in the Brooks Range. But Id say the biggest challenge of all in the Brooks Range is that its just you. You are completely on your own, youre completely self-sustainable. Really a good goal is just to make it to tomorrow.
JOHN CANTOR: It's incredibly daunting, having spent six years towards one goal and having had three unsuccessful trips. I don't want to die, I want to make it out of there alive. And part of living is having something to aim for.
CHRIS CANTOR, FATHER: I can well understand him wanting to pursue an adventure, but why Alaska which is hardly sort of familiar territory for an Aussie boy? And why the sort of most God forsaken part of Alaska? People have died out there.
BECKY CANTOR, MOTHER: He has had a very privileged upbringing, you know. He's had the private school, supportive parents. He's had an easy background, I suppose and he needed something more out of life than that.
JOHN CANTOR: Every risky pursuit is selfish. I dont believe you can truly know yourself until youve been put in situation where the decisions that you make are critical.
CHRIS CANTOR, FATHER: We've not put our hands in our pockets for any of this, because we've not wanted to encourage it or make it too easy, because we're very aware of the risks that are involved.
LIZ CANTOR, SISTER, SISTER: It does kind of worry me that hes put every cent hes ever made, like hes worked his arse off like being a waiter in restaurants and working massive hours, and every cent of that has gone into Alaska. Hes now in his mid-20s, he doesnt have a cent to his name. Like he pretty much doesnt even have a car. Like, he doesnt have any home to come back to. The obsession has to stop, and it does drain me thinking like if he doesnt make it this time, is he gonna be able to let go?
BECKY CANTOR, MOTHER: The Cantor family, they are medical practitioners going back generations. They are academic focused. And John is not that, hes chosen a very different path.
JOHN CANTOR: My upbringing was really about surfing and the beach and just getting out in nature.
LIZ CANTOR, SISTER: I think back at parts of his life and I reckon hes been through some huge challenges that he doesnt really acknowledge.
JOHN CANTOR: When I was 18 I was diagnosed with testicular cancer. But fortunately they found it really early on. So six months later I was back in the surf as if it hadnt really happened. But that was kind of the turning point in my life where I no longer felt quite so immortal.
LIZ CANTOR, SISTER: After getting sick, I think he wanted to feel alive again. And pushing the physical boundaries like climbing and everything really gave him that sense of living.
JOHN CANTOR: I did decide to go to university, and did a year of film and TV. During that year I read the book 'Into the Wild' about Chris McCandless unfortunately dying in Alaska by himself.
LIZ CANTOR, SISTER: I think it really just affected him that someone could put themselves in that position of going back to just living off the land and living off basics. And it just sparked something in him.
BECKY CANTOR, MOTHER: I can remember vividly thinking 'great, you know, he's on the path.' And he comes home and he says 'dropping out of uni, I'm going to Alaska.' Not happy.
JOHN CANTOR: So I did some research and found a two and a half month wilderness course.
BECKY CANTOR, MOTHER: He saved up the money to go and do the course. So that was something that we thought, 'Right, he's doing the right thing, he's going and getting some training.'
JOHN CANTOR: It just felt like I had been searching for this all my life, and Alaska was the place I wanted to be. After the wilderness course, I flirted with the idea of crossing the Brooks Range. It was so far beyond my capabilities, but why not at least explore doing it?
ANDREW SKURKA, ADVENTURER: The Brooks Range is a very remote mountain range up in northern Alaska. Most of it lies north of the Arctic Circle. It runs 1,000 miles from east to west. This is not a place where you can make mistakes. You need to have the right maps, you need to have the right gear, you need to have your supplies all figured out. And most importantly you need to, you need to bring your head with you.
CHRIS CANTOR, FATHER: With this trip was, he sort of sprung that on us. I had to scrape myself off the roof, because I was pretty irate that he'd got so advanced without consulting anybody. And I think with that first trip he was, there was a lot of naivety.
BECKY CANTOR, MOTHER: He was utterly, utterly unprepared. When he first told us, he wasn't even going to take a sat phone. He didn't want to be contacted. He was going to go off and be in the wild.
JOHN CANTOR: With all of my gear, I had too much because I was overcautious. I had two cans of bear spray and two compasses in case I lost one. And my pack weight was 39 kilos including all my food. It was way too much weight for me to be able to do this expedition with.
CHRIS CANTOR, FATHER: The pilot, before dropping him off, asked whether he was absolutely sure that he wanted to go because once theyd landed he couldnt take off with two people in the plane. So there was no room for second thoughts. And then, after that I believe the pilot then said well I really hope you make it out alive mate.
(Excerpt from John Cantors video diary of Trip One 2008)
JOHN CANTOR: Im alone. Im terrified right now. I really am. I feel like I dont know what Ive got myself into. Im just so far from anyone. Guess Ive just got to start walking. Ive only been going a few hours but its my first day so I want to take it pretty easy.
(End of excerpt)
ANDREW SKURKA, ADVENTURER: The Brooks Range it's - it's an intimidating place. There are valleys that no one has ever gone off into, there are just endless peaks that dont have names. Youre just constantly reminded that you are the only person that you have to rely on. That youre on your own.
CHRIS CANTOR, FATHER: From what we gather sort of things really started going wrong right from the outset
JOHN CANTOR: I experienced knee pain and that knee pain became patella tendonitis in both knees, which was largely due to the really heavy pack that I had. I ate a lot of fatty foods to try and put on some excess body fat and what didnt know at the time was I was destroying my liver and I had some real bad stomach problems. By the fourth day I hadn't eaten or slept in over two days because of the stomach pain. And they decided that they wanted to come and get me. Ending up in a rescue chopper was so hard to deal with. I remember lying in that bed with the Brooks Range flying past beneath me and my dream was over. At that point I had no plans on ever returning because it had been such a failure.
CHRIS CANTOR, FATHER: Luckily for John the Alaskan authorities paid for the rescue chopper.
BECKY CANTOR, MOTHER: He was devastated. He was humiliated, embarrassed and broken when he came back. But he felt 'no Ive got to go back to do it.' He said, 'this is something thats taken over my life. Im not going to pretend Im doing it for charity and Im raising money. No, Im doing this because I need to do it.'
JOHN CANTOR: So I started training and planning for a second attempt.
(Excerpt from John Cantors video diary of Trip Two - June 2009)
JOHN CANTOR: Well Ive just been dropped off at the Brooks Range again. Im really happy to be back out here. Ive definitely made the right decision in coming out. Well here goes again. Todays the first day back and Ive had to stop because of my knee. It's - Im in agony. Im just in utter disbelief.
(End of excerpt)
JOHN CANTOR: I called my pilot to come and get me. I had no one to blame but myself. Prior to the third attempt I started having panic attacks, probably about four months before I set off for Alaska. I saw a psychologist because it got progressively worse and I wasn't coping with it.
(Excerpt from John Cantors video diary of Trip Three May 2010):
JOHN CANTOR: Well here I go again. Ive been walking just over four hours now. Hey bear. Just going through some brush at the moment which is why Im making the bear calls.
(End of excerpt)
BECKY CANTOR, MOTHER: The third time he went back he just completely freaked. The fear when he was dropped off and realizing he was in trouble set off the panic attacks.
LIZ CANTOR, SISTER: I think through this hes just discovered this battle with anxiety. Like I actually think it might even have got to the point of being a slight mental depression, which is weird with a psychiatrist father. Obviously I shouldnt be diagnosing this! (laughs)
CHRIS CANTOR, FATHER: Im unclear in my own mind as to how much we might describe this as normal anxiety and how much might be more correctly described as panic disorder. But he really beat himself up for having not succeeded.
JOHN STANSBIE, FRIEND: A lot of people would taunt him a lot with it, sort of going 'oh, youre going again' and say oh, youre just going to fail, dont bother going. It constantly sits with him and eats him away. I think even there might be some demons over it. Absolutely. Yeah.
JOHN CANTOR: Ive always prided myself on this image that I had of being a really psychologically strong person. I was always the first guy to jump off the big cliff or paddle out in the big waves or run hard at the biggest player on the football field. And after the third attempt I felt like I wasnt the person that I thought I was. And until I go back to the Brooks Range and become that person that I hope I still can be, I will never be alright with it. After about six months, I started flirting with the idea of returning the next year, because I just knew it would always be with me.
JOHN STANSBIE, FRIEND: His mind's changed. His more mature, absolutely. And I think Sarah's going to play a big part as well. He's never had a girlfriend.
SARAH WIILIAMS, GIRLFRIEND: I think that he's anxious about it, just 'cause he's a bit insecure, really. I mean, I think he's insecure in a couple of aspects of his life, even though he doesn't need to be, he is. Yeah, if he's successful, maybe it will make him feel a bit stronger in other aspects of his life, as well.
JOHN CANTOR: I'm really lucky of the amount of support that I have received from my family and friends. So when I do receive criticism from people for how selfish this expedition is with regards to what I'm putting them through, I have the support of them and I know that they realise that this is something that I have to do. I've put so much into this fourth trip. The planning has been so intense that I feel so much better prepared. At the moment, I've spent over $70,000 over the six years on this expedition. And of I am successful this year, and make it across, it will cost probably another $15,000. At the moment five people have traversed the Brooks Range solo. Andrew Skurka is the most recent. He's potentially the greatest long distance hiker of all time.
ANDREW SKURKA, ADVENTURER: John got a hold of me prior to his fourth attempt. And I was really interested by the idea that someone, especially from Australia would spend that much time and that much money on a successful traverse of the Brooks.
JOHN CANTOR: He really helped me out with my gear and gave me some awesome advice. And Im so indebted to him.
LIZ CANTOR, SISTER: Emotionally its kind of sickening to have to say goodbye to your brother and not know when youll speak to them again. I dont like to say if Ill speak to him again, but when Ill speak to him again.
JOHN CANTOR: Flying in the little bush plane towards the Brooks Range I knew what I was in for from the previous trips.
(Excerpt from John Cantors video diary of Trip Four June 2012)
JOHN CANTOR: I felt alright walking, but as soon as I got into camp I feel like shit. Im just so terrified and my stomachs a mess. (Throws up) Day one.
(End of excerpt
JOHN CANTOR: And I had this sense that I was moving fast because I was running to safety. There was just constantly this voice in my head quit, quit, quit. I was looking at my maps and just always checking to see how far away am I from the next spot where the pilot can pick me up. The pilot flew in my food in a bear proof container. And I got to the first food drop in three-and-a-half days when it was meant to take me seven days. And that felt pretty good. My birthday I woke up, my stomach feels great, first day of the trip I can eat solid food, bodys feeling great, starting to get my hiking fitness. It was an amazing day.
(Excerpt from John Cantors video diary of Trip Four June 2012 Day 5)
JOHN CANTOR (Laughing and crying at the same time): Oh! Three years in a row I planned to be out here on my birthday and I was back in Noosa by my birthday, depressed and miserable about another failed expedition. So to be out here, its just so special. And today for the first time, I actually believe I can do this. I cant believe Im crying! Oh. This is good!
(End of excerpt)
JOHN CANTOR: Every mountain around you is the same brown grey intimidating mountain for just 360 degrees around you. And if you get into trouble, no ones coming to rescue you. And thats when you feel alone. Thats when the Brooks Range is there above you just making you feel so tiny.
LIZ CANTOR, SISTER: Each day his satellite sends through a spot data. There were two days in a row we didnt hear from him. And we literally by the third day Mum wasnt in a good state, Dad wasnt in a good state. On the third day, late in the day, we got confirmation of the spot data and it had been thick cloud coverage prevented it.
JOHN CANTOR: The final day hiking to the river, I hiked for 19 hours and 10 minutes with only one five minute break in the whole day. And I moved faster than I had during the whole trip. A few hours before I got to the Noatak River, the pilot flew in and dropped off my kayak. I thought the river would be easy. I gave the river no respect, and that was a bad mistake. This huge headwind hit me. I had my first meltdown of the trip. Some screaming and swearing and ...
(Excerpt from John Cantors video diary of Trip Four June 2012 - Day 30)
JOHN CANTOR(Crying): This is the first time in the whole trip that I'm crying because Im sad. Its f***** pathetic. I just cant handle this wind. I just want to get to the end. (Crying) Ive only got two days worth of food left. Im exhausted .... and Im pathetic. In the past two days I've slept for about four hours and Im pretty sure Im about two miles from the end of the expedition.
(End of excerpt)
(Excerpt from John Cantors video diary of Trip Four June 2012 - Day 31)
JOHN CANTOR: This is it. I am at the end of the Noatak. Those flashing lights in front, thats Kotzebue (Qikiqtaġruk). I've just traversed the Brooks Range solo.
Yeah! Woo-hoo!
(On phone to his mother): I made it! (emotionally) I just wanted to say that I love you so much and Im so lucky to have you and Dad.
(End of excerpt)
BECKY CANTOR, MOTHER: Now that hes done it we have a lot more faith in him. And half of me is really feeling go, go for it John you know, go for those adventures, the adrenaline's great. And the other half is please marry, have children, settle down. Stay at home
JOHN CANTOR: A slight feeling of emptiness. Six years of my life I was the guy that was trying to traverse the Brooks Range and now its done. But ah, it feels good.
CHRIS CANTOR, FATHER: Very, very happy to have been wrong. Very happy.
ANDREW SKURKA, ADVENTURER: Its difficult to relate to one of these long distance adventurers. We come from good families, we might have good jobs, but I dont think that life sometimes is quite as rich and quite as rewarding as tackling one of these enormous projects. You know this extended period in which were out of our comfort zones. And whenever someones out of their comfort zones they learn a lot about themselves and the world in which they live.
JOHN CANTOR: Now that Im back home and Im so lucky to be here its so beautiful but all I can think about is that Ive got to get back to Alaska. And Ive already started planning it.
Nine days after John Cantor finished; Lukas Grobler, a 38-year-old South African, fell to his death while attempting the Brooks Range traverse.
John says he is now planning to do the trek again in 2014... but in winter.


text: Resident Evil: The Final Chapter is based on Capcom's hugely popular video game series comes the final installment in the most successful video game film franchise ever, which has grossed over $1 billion worldwide to date. The movie picks up immediately after the events in Resident Evil: Retribution, Alice (Milla Jovovich) is the only survivor of what was meant to be humanity's final stand against the undead. Now, she must return to where the nightmare began – The Hive in Raccoon City, where the Umbrella Corporation is gathering its forces for a final strike against the only remaining survivors of the apocalypse. William Levy plays Christian and we had a chance to interview him about the film and you can watch that below! Resident Evil: The Final Chapter is now showing in theaters!


text:
Saturday, 14 May 2011
"This is my favourite book."
Cue lump in my throat and tear in my eye.
14 comments:
- Amy said...
What a smart little boy, he knows a good thing when he sees it!
I love how he has placed his little hands and is so engrossed in the album - very precious indeed :-)
- 14 May 2011 at 13:03
- Rachel Holaday said...
That is SO adorable. I hope my little boys learn to love my albums so much!
- 14 May 2011 at 15:15
- ComfyMom~Stacey said...
That is so sweet! My sons love looking at my 365 books.
- 14 May 2011 at 16:11
- Sian said...
Aw, how lovely! And again you have captured the moment perfectly
- 14 May 2011 at 16:30
- Lynn said...
Such a sweet photo - he looks so engrossed. My youngest likes looking at my albums too.
- 14 May 2011 at 17:48
- Kirsty.a said...
So cute. Isn't that exactly why we do it? M loves my pages and is my most honest critic
- 14 May 2011 at 18:58
- Alison said...
Great photo....I would have had a lump in my throat too!
Alison xx
- 14 May 2011 at 19:54
- Sandie said...
That is so nice, Ruth. Are the pages part of a kit or can you buy them seperately?
- 14 May 2011 at 21:07
- Rachel B said...
What a great moment to capture! :)
- 15 May 2011 at 08:29
- ♥♥ Liz ♥♥ said...
He looks like he's really taking it all in. Your hard work is definitely paying off. xxx
- 15 May 2011 at 10:08
- Rhona said...
I love that! I'm sure he will always enjoy looking at it too :) I love the way he's peering at it so intently - too cute! xx
- 15 May 2011 at 11:37
- debs14 said...
Oh how lovely! That photo is just so perfect too, he is totally engrossed in the photos.
- 15 May 2011 at 12:39
- Deb @ PaperTurtle said...
Oh, this is so sweet, Ruth. I love when the kids in my life pull albums off a shelf and enjoy them. I usually try to have a few sitting out within arms reach when we have family get-togethers.
This is such a cute photo of your DS too. xo
- 15 May 2011 at 14:52
- Beverly said...
This is what I call a "forever picture", one that will tug on your heart 30 years from now as much as it does today. And his statement sums up why we do this :)
- 17 May 2011 at 04:28


text:
In the last episode of Kumkum Bhagya, we saw that Abhi took Pragya home and everyone was shocked to see Pragya and Abhi together. Everyone was shocked to see Abhi affected with Pragya. Abhi asked Aaliya that he took her as his secretary. Aaliya tried to convince Abhi that she will bring a new secretary but Abhi said she will remain with me.
Aaliya and Tanu were disappointed with this all. Everyone in Mehra family moved in their rooms and Pragya left standing in the corridor. Tanu started fighting Aaliya and she was blaming Aaliya and she said Pragya moved closer with Pragya. Tanu started crying and Aaliya said she didn't move any step towards them. Aaliya said she got failed in her every step.
Pragya moved to Dadi and Pragya apologised to Dadi. She said she never projects ad of Abhi. Pragya said she tried not to face Abhi. Pragya said Abhi is unaffected by her presence and she tried a lot to stay away from Abhi. Pragya said she never tried to make him recall anything. Dadi said with you many past can come out. Pragya also added that she was unaware that Abhi will take her in this house for a job.
Dadi asked Pragya how can she forget her wordings and how can she take a risk with Abhi and this house. Dadi asked Pragya to get aside from her eyes. Now in the next episode of Kumkum Bhagya, we will see that Aaliya will ask Pragya that everyone will go to torture her. Aaliya added now she will ruin her life along with her family. She also added that she will ruin her family for this mistake. Pragya will remain shocked. Stay tuned for more updates on Kumkum Bhagya and others.


text: So, in the book, Breaking Dawn, Jacob imprints on Renesmee, what are your views on this? Retrieved from "http://twilightsaga.wikia.com/wiki/User_blog:Twidict4ever/How_do_you_feel_about_Renesmee_and_Jacob%27s_Relationship%3F?oldid=40061" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Category: Blog posts


text:
Kalalou Wall Lights
The Kalalou Wall Light are a beautiful source of illumination for you home. The Kalalou Wall Light finds its expertise in this home furnishing type. There are some never seen before craftwork. The Kalalou Wall Light will surely hold a place of pride in your home décor. The kalaou wall Lights are available in many options one can choose from. There are some simple and rustic ones while others have modish style of circle and domes. Some are hanging wall lights while others are fixed to the wall.


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Frequently Asked Questions
- What is the Runway Development Program? And why does Melbourne Airport need a third runway?
- When will the third runway be operational?
- How did Melbourne Airport decide on the east-west orientation of the third runway?
- Will the third runway operate 24 hours a day?
- What is the planning and approval process?
- What studies are being undertaken to inform the development of the RDP?
- When will flight paths for the third runway become known?
- Which direction will most flights take off and land on the new runway? East or west?
- Will there be an increase in flight activity for residents in Broadmeadows /Westmeadows /Gladstone Park with the new runway?
- What impact will the new runway have on Diggers Rest and areas west of the airport?
- How can I be kept updated about the RDP?
What is the Runway Development Program? And why does Melbourne Airport need a third runway?
The Runway Development Program (RDP) is part of Melbourne Airport's plan to meet the growing demand for air travel to and from Melbourne.
Close to 33 million passengers passed through Melbourne Airport in 2015, and this number is expected to reach 64 million passengers by 2033. To meet this demand, the airport will need additional runway capacity to allow for more arrivals and departures, and reduce the amount of time planes spend on the ground waiting to depart, or in the air waiting to land.
As such, Melbourne Airport is proposing to construct a new east–west runway. This third runway will be located 2 kilometres to the south of the existing east–west runway and will be 3 kilometres long and 60 metres wide and capable of handling all aircraft types.
The existing east–west runway is also proposed to be extended from 2.2 kilometres to 3 kilometres and widened from 45 to 60 metres.
When will the third runway be operational?
If approval is received from the Commonwealth Government, the third runway is projected to be operational sometime between 2022–2024.
How did Melbourne Airport decide on the east–west orientation of the third runway?
The selection of the preferred east–west orientation was based on criteria that recognise the potential impacts the third runway will have on the airport, the community and the environment as well as air traffic management and safety.
The major safety and operational advantage of a second east–west runway is that it eliminates the need for aircraft moving to and from the terminal precinct to cross paths on the runways—as the terminal would be between the parallel runways.
With no runway crossing, there are no additional delays for aircraft waiting to cross the runways. There would also be shorter flight distances for flights as well as shorter taxiing distances and times.
It also means less fuel is burnt, fewer carbon emissions are generated and there is a reduction in aircraft ground noise, which benefits the environment and the community.
Will the third runway operate 24 hours a day?
It is proposed the third runway will be available to planes 24 hours a day, similar to the existing runways. Noise abatement procedures will also be put in place for the new runway to minimise the impacts of plane noise on surrounding residential areas.
What is the planning and approvals process?
The RDP requires the approval of the Commonwealth Government through a Major Development Plan (MDP), which is a detailed planning document that considers the runway's impact on the community and environment.
A draft RDP MDP will be available for public comment before it is submitted to the Commonwealth Government for approval.
What studies are being undertaken to inform the development of the RDP?
The RDP MDP will be informed by multiple studies covering areas such as noise, flight paths, environment, health, and social and economic impacts.
When will flight paths for the third runway become known?
The final design for the flight paths will start around two years before the expected opening of the new runway.
A flight path study will form part of the RDP MDP—this study will provide indicative flight paths for the new runway but ultimately Airservices will determine the final flight paths.
Flight paths are determined by Airservices, who is responsible for air traffic control. At this stage, Airservices forecasts that up to four new flight paths may be needed to service the new runway and maintain efficient operations, but most importantly, maintain the highest safety standards that Melbourne Airport has always operated under.
Which direction will most flights take off and land on the new runway? East or west?
If approved, the majority of flights on the new east–west runway are expected to take off to the west and land from the east. However, it is important to note that it can't be guaranteed that flights won't need to take off to the east, as safety and separation of aircraft is the first priority Weather conditions also impact on flight direction.
An aircraft's origin/destination, the wind strength/direction, air pressure, temperature, runway slope/surface and aircraft weight are all considered when determining which runways are used at different times of the day for different flights.
Airservices and the plane's pilot decide which runway will be used with safety as the guiding principle.
Will there be an increase in flight activity for residents in Broadmeadows /Westmeadows /Gladstone Park with the new runway?
Residents in these areas can expect more planes flying overhead should the proposed third runway be approved.
What impact will the new runway have on Diggers Rest and areas west of the airport?
Some impacts on areas to the west of the airport are expected should the proposed third runway be approved, however, the specifics of flight paths will be made closer to the opening of the runway.
How can I be kept updated about the RDP?
Melbourne Airport will keep the community and stakeholders informed via regular and open communication.
Here are a few ways to stay updated:
- This website, which will be updated on a regular basis.
- Through our social media channels.
- Via Gateway, Melbourne Airport's quarterly community newsletter.
- Community forums such as the Melbourne Airport Community Aviation Consultation Group.
- By emailing your questions to email@example.com.
- Or calling our Community Relations line on 9297 1597.


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Dark Souls
How do I use magic?
I am a Pyromancer and equipped the pyro flame in my right hand, next to my axe. Am I on the right track? Somebody please help, it sucks being a pyromancer that can't use fire!
beausis - 5 years ago
Top Voted Answer
you should be able to press the up arrow on the D pad to cycle thru your memorized spells/miracles/pyromancies. you should have fireball, press the right arrow on the D pad to equip the pyro flame catalyst then lock on target and press R1 to throw a fireball.
persh52 - 5 years ago
You need to have a catalyst or talisman equipped to use magic. If you do not have this yet, then you cannot use magic yet.
Euronymous - 5 years ago
But don't forget to Attune your spells at a bonfire first!
CobaltMonkey - 5 years ago
To cast magic, you need 3 things on top of the stats :
- Learned the spell.
- Having the "weapon" to cast (there are 3 possible + some special ones) :
Pyromancer use one kind
Priest use another
Sorcerer use one last.
Note that PYROMANCER AND SORCERER DON'T USE THE SAME BASE ITEM! There are some weapon that offer dual possibilities, but you need to test them out first.
- "Equip" the spells at bonefire. (One option while resting at bonefires is to manage your known spells)
donoghu - 5 years ago
You actually need 4 things:
-At least 10 Attunement stat to unlock the first spell slot.
-Have the spell (obviously), you can see it in your inventory under what looks like a scrap of paper.
-Have the required weapon equipped and active (Talisman = Miracles. Catalyst = Sorceries. Pyromancy = Pyromancies)
-Have the spell equipped in your attunement slot(s) by managing spells at a Bonfire.
dankathor - 5 years ago
To use magics - you need to have the correct weapon for each of the three types of spells.
Catalysts for Sorceries.
Talismans for Miracles.
And, of course,
Pyromancy Flame for Pyromancies.
For Sorceries and Miracles - you need a certain stat level to cast stronger spells. (Intelligence for sorceries, Faith for miracles.) But first, to cast them, they must be attuned to your magic slot (the top square space to the left.)
But keep in mind that if your attunement level is less than 10 you won't be able to equip any spells. The higher your attunement level, the more spells you will be able to carry with you at one time.
Anyway, to equip your spells, just sit at a bonfire and select "Attune Magic", then select the spells you wish to use.
Then when you are in battle just switch to your Pyromancy Flame or Catalyst/ Talisman and fire off the spell you wish to use.
That's it. That's all there is too it. Have fun, fellow wizards.
RubMyNipples - 3 years ago
Start out as a pyromancer. You'll start with a fire and through the first section you'll find the flame hand once you find the flame hand equip it to either left or right hand. Use left or right on d pad depending on which hand you equipped it. Once the flame hand is chosen as the weapon it will be either r1 or L1 again depending on which hand you equipped it on. Once you progress you'll find other flame spells and those can be equipped through your attunement slots now pyromancy is different so you don't need to level up intelligence or faith you just need to spend souls on upgrading the hand to make the spells more powerful I hope this helped
Jknow35 - 3 years ago
This question has been successfully answered and closed.
More Questions from This Game
|Magic Dmg ?
|What is the difference between Magic and Enchanted?
|Where can I find crystal magic weapon?
|Where can I find the magic casting shield?
|Better for enchanted, magic or +15 weapon for sorcerer?


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Roni Scacchi (Ronaldo) – another scamster from Cabarete
Roni Scacchi (Ronaldo) - another scamster from Cabarete
We just got notified from a Swiss editor about another scamster in Cabarete , mainly in the German speaking community, nevertheless Roni Scacchi also damages other nationalities, so be warned. His company he uses to generate the funds for his lavish life style is Palm Hills SA.
He uses this information (tries to somewhat hide under a false name, his REAL FIRST NAME is RONALDO and not ROLANDO as stated below):
Palm Hills
Caribe Real Estate S.A.
Carretera 27
Dominican Republic
Tel.: +1-809-571 0988
Fax: +1-809-571-0986
Internet: www.karibik-invest.de
E-mail: firstname.lastname@example.com
Persönlich haftende Gesellschafterin: Palm Hills Caribe Real Estate S.A.
Vertretungsberechtigter Geschäftsführer: Rolando Scacchi
Registergericht: Santo Domingo, Dominikanische Republik
RNC Nr 1-05-03794-7
Inhaltlich Verantwortlicher gemäß § 6 TDG: Rolando Scacchi
More to come soon, here the link to the German site
Gordon Gannon is about to get slaughtered – finally!
Gordon Gannon is about to get slaughtered - finally!
He was bilking foreigners for years with his unfinished ruins in the heart of Cabarete, now he started to steal land from old Dominican families, and that is a mistake! High politicians, who can be bought..., are now defending the poor Dominican peasant, I am sure Gordon Gannon, the par venue from Canada will not survive that.
Watch the interview with Angel Lockward, and you know Gannon's days are counted.
Total Immersion Spanish Lessons and Surfing in South America or, as They Say in Spanish, "Aprender Espa
Atlanta, GA (Vocus) July 28, 2010
LearnSpanishAndSurf joins EscapeArtist.com as a Strategic Media Partner to help educate their 400,000 subscribers to their EscapeFromAmericaMagazine about the opportunities and advantages for learning Spanish and taking surfing lessons in Central and South America off the warm coastal waters of Costa Rica and Ecuador. This dual opportunity for learning and pleasure offers students of all ages a once-in-a-lifetime and unforgettable experience for taking advantage of a total immersion opportunity.
EscapeArtist, the leading website for International travel, receives more than one million unique visitors a month from their global readership. Recently, EscapeArtist has received an increased interest from their readers regarding opportunities for 'total immersion learning for Spanish,' and are pleased to announce their new partnership with LearnSpanishAndSurf.com so their readers can, "Aprender espa
Oceanfront Duplex
Oceanfront Duplex
and the best surfing beach in the area.
Price: $ 3,078 - $ 4,067 Weekly
1405 Ocean Drive
93035 Oxnard, USA
Surfing Burleigh Heads_3432
Some cool best surfing images:
Surfing Burleigh Heads_3432
Image by Michael Dawes
Surfing Burleigh Heads_3411
Image by Michael Dawes


text:
Marquee Flooring Atlantic Wharf
Find marquee flooring hire in Atlantic Wharf for your next party. Get a quote from companies supplying flooring for marquees in Atlantic Wharf using Add to Event.
41 Marquee Flooring suppliers near Atlantic Wharf
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1. Get Introduced
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2. Compare Suppliers
View an estimate, personal message, reviews and business profile of each company that gets in touch.
3. Hire the Best
Call or message your favourite suppliers and once you're ready simply hire the best match for your event.
We have 41 marquee flooring suppliers near Atlantic Wharf
Contact them all with a single request


text:
News By Tag
* Retail Display
* Slatwall Panels
* Slatwall Fixtures
* Slatwall Accessories
* Merchandising
* More Tags...
Industry News
News By Location
Industry News
Wind Mill Slatwall Products Expands Operations to Serve the Western US Market
Headquartered in Sheboygan Falls, WI, Wind Mill Slatwall Products has expanded its capacity of manufacturing slatwall, panels and component parts to serve the Western United States.
With this new capability, Wind Mill is now positioned to serve the many customers based in the west, including the markets of Seattle, Portland, San Francisco, Los Angeles, Phoenix, Las Vegas and others by offering a manufacturing point for product out of the Seattle, WA area.
Customers located in the west region who would like to work with Wind Mill can simply call the Wind Mill Sales Team based in Wisconsin to discuss their project. Wind Mill will coordinate the production and have the order shipped from the Seattle location.
"Our new manufacturing point is a strategic and important addition to Wind Mill's capacity," states Mark Radtke, Executive Vice President of the company. "We've had many customers who want to do business with us...and the only thing holding them back has been the high cost of freight between our Wisconsin facility and the states located west of the Rocky Mountains. We now can deliver on that request and bring those customers the product line, quality and exceptional customer service and support that Wind Mill has become well known for throughout the retail display industry.
Wind Mill's arrangement with Boise Cascade to sell and market the Anchor™ Core provides a very nice opportunity to west region customers to now acquire this product and experience the great value it offers, as an alternative to MDF...especially as the MDF marketplace becomes tighter.
"Wind Mill's results of introducing, marketing and selling the Anchor™ Core line for Boise Cascade has been nothing short of remarkable,"
Wind Mill Slatwall Products has been manufacturing and marketing slatwall and related component parts since 1980 - serving the store fixture manufactures and distributors in the retail, merchandising and display industries. Wind Mill also has a consumer products division called GarageEscape, with a line of products specific to garage and home organization.
For more information, please visit www.windmillslatwall.com, or www.garageescape.com
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text:
Dr. William Russell MD Patient Reviews
- Pediatrics Alexandria, VA
Overall Rating
9 Patient Reviews
- Friendly Staff
- Promptness
- Wait Time 15 minutes
- Appropriate Followup
- Spends Time With Patients
- Bedside Manner
- Fair and Accurate Diagnosis
- Easy Appointments
Showing 1 - 9 reviews
5.0 of 5
September 9th, 2016
I highly recommend this doctor. Being in the medical field myself, I have a high standard for Healthcare and this doctor goes above and beyond. He is very thorough and takes his time explaining everything. He wants your child to be healthy and also wants you to succeed as a parent. He seems to genuinely care about a parent's concerns and gives great advice.
5.0 of 5
May 1st, 2013
We love Dr. Russell. He is an excellent diagnostician. Whenever we have had anything going on that he wasn't sure about, he immediately set us up with the right person. He is careful, thorough, and conscientious. He always calls me back about test results in a very timely manner. He is always empathic to our situations and is great with my kids.
5.0 of 5
February 2nd, 2011
Dr. Russell is fantastic. We have been seeing him since my children were born and my son is now 9 years.
5.0 of 5
October 26th, 2009
Dr. Russell has been a wonderful pediatrician for my daughter. He came recommended by my sister and I am very impressed with his professionalism and his treatment of my daughter (3 yr old~she has been his patient since we moved to Alex. 2 1/2 yrs ago). He has taken time with me to discuss my concerns; never making me feel rushed. I feel his exams are thorough and his level of care outstanding.
2.3 of 5
November 18th, 2008
He was not good with my little brother nor my little girl
I have gone to "Kidz Docs" in my younger years and Dr. Russell was cold and he did not spend time explaining his diagnoses. My little brother hated to have to see him. Now that I am a mother I started taking my little one to Kidz Docs for check ups and we enjoyed the other Doctors.One day my little girl had an appointment to see her Doctor, however her Doctor had an emergency and could not see us so Dr. Russell saw us. He was ruff on my newborn and he treated me like I did not know anything because I was a young mother.
5.0 of 5
March 24th, 2016
5.0 of 5
December 30th, 2015
2.3 of 5
June 15th, 2014
5.0 of 5
August 24th, 2010
Health Guides
More than 22 million Americans of all ages have asthma. Prepare to talk to your doctor about symptoms, diagnosis and treatment options.
Nearby Doctors
Dr. William Russell, MD is similar to these 3 Doctors near Alexandria, VA.
Alexandria, VA
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The Coral Springs Battle of the Bands -- Plus Donuts!
The Battle of the Bands is a throwback to the days before file-sharing. But the concept -- bands offered in both a showcase and a competition setting -- is still one of the best ways to hear (and then judge) an act. You get a live show and the ability to indulge in some schadenfreude. Now, with the support of Dunkin' Donuts (!!), the Coral Springs Council of Executive Officers presents the first Coral Springs Battle of the Bands at the Coral Springs Center for the Arts.
Each participating high school has the opportunity to showcase two bands, with a line-up including The Fleet, Leave It 2 Us, Kaboozle and Impulse. Mindy Lang of Majic 102.7 is acting as event emcee, along with a slew of co-host celebrity judges: Vinnie Rebecca of Style Entertainment, Richard Sality of Coral Spring's School of Rock, and Denny Artache of Iron Butterfly (truth be told, he was a temporary band member in 1993 -- but that means dude knows his psychedelica).
Follow County Grind on Facebook and Twitter: @CountyGrind.
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text: did anyone see the ESPN 30 for 30 documentary No Mas? if you missed it check it out.... also there's a film in the works which will star Robert DeNiro as Ray Arcel(Duran's trainer) and Usher playing Sugar Ray Leonard. it will be called "Hands of Stone". my question is, will anyone see the film once its released? i know i will watch.


text:
About the Book
All Nature photos from varies places in the United States.
Features & Details
- Category Arts & Photography
Standard Landscape, 10×8 in, 25×20 cm
20 Pages
- Publish Date Jul 06, 2008
See More
About the Creator
Roderick Hudson
Los Angeles, CA United States Of America
Young fun guy that enjoys traveling and spending time friends and my camera. I've resided in southern CA for the past 7 years and enjoy the scenery here. Also, interested in learning more about the camera and lighting techniques. Feel free to email me with any questions regarding my work or book. firstname.lastname@example.com
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Sampson happy with loan spell
Jack Sampson is enjoying life at Southend following the club's decision to extend his loan stay by a further month.
Last Updated: 14/03/12 4:29pm
Bolton Wanderers forward Jack Sampson has revealed he is enjoying life at Southend following the club's decision to extend his loan stay by a further month.
Southend currently lie in fourth position in League Two, challenging for automatic promotion and all but guaranteed a place in this year's play-offs.
Sampson has featured heavily since his arrival at Roots Hall in January, making eight appearances, including five starts.
He told the club's official website: "I'm enjoying playing matches because that is what every player wants, especially in a team that are doing well at the moment.
Positive mentality
"There is a real positive mentality in the squad. I'm enjoying being here and that's why I'm happy to stay for longer. I'm happy to be given the chance to play competitive league football."
Southend are currently in a rich vein of form and Sampson is happy with the part he has played.
He added: "We are unbeaten in our last three matches and I have started in all of them. I'm still looking for my first goal but I'm sure that isn't far away.
"A finish in the top three has to be the aim and everyone is confident that it can be achieved in these last couple of months of the season."


text:
|Home | About | Journals | Submit | Contact Us | Français
Neurofibromatosis type 1 (NF1) is an inherited disease predisposing affected patients to variable numbers of benign neurofibromas. To date there are no effective chemotherapeutic drugs available for this slow growing tumor. Molecularly targeted agents that aim to slow neurofibroma growth are being tested in clinical trials. So preclinical models for testing potential therapies are urgently needed to prioritize drugs for clinical trials of neurofibromas.
We used magnetic resonance imaging (MRI) to monitor neurofibroma development in the Nf1flox/flox;DhhCre mouse model of GEM grade I neurofibroma. Based on studies implicating mTOR and Raf signaling in NF1 mutant cells, we tested the therapeutic effect of RAD001 and Sorafenib in this model. Mice were scanned to establish growth rate followed by eight weeks of drug treatment, then re-imaged after the last dose of drug treatment. Tumor volumes were determined by volumetric measurement.
We found that rate of tumor growth varied among mice, as it does in human patients. RAD001 inhibited its predicted target pS6K, yet there was no significant decrease in the tumor volume in RAD001 treated mice compared to the vehicle control group. Sorafenib inhibited cyclinD1 expression and cell proliferation in tumors, and volumetric measurements identified significant decreases in tumor volume in some mice.
The data demonstrate that volumetric MRI analysis can be used to monitor the therapeutic effect in the pre-clinical neurofibroma drug screening, and suggest that Sorafenib might have clinical activity in some neurofibromas.
Plexiform neurofibromas develop in 25 - 30% of children with neurofibromatosis type 1 (NF1) [1]. Plexiform neurofibromas are benign peripheral nerve Schwann cell tumors that can cause disfigurement, nerve compression, and distortion or infiltration of adjacent structures, and can compress vital structures causing mortality [2]. The only current standard neurofibroma therapy is surgery, which is not always feasible as it necessitates removal of tumors of neurofibroma- integrated nerves. Even after surgery many patients experience tumor recurrence [2]. To date there are no effective chemotherapeutic drugs available for this slow growing tumor, so molecularly targeted agents that aim to slow plexiform neurofibroma growth are being tested in clinical trials. The activity of agents is being analyzed using sequential volumetric imaging of tumors using magnetic resonance imaging (MRI), the most sensitive method available [3]. This method allows to reproducibly (coefficient of variation ≤ 5%) detect smaller changes in plexiform neurofibroma size compared to standard solid tumor response criteria. In currently ongoing clinical trials disease progression is defined as a ≥20% increase, and response as a ≥20% decrease in plexiform neurofibroma volume from baseline prior to initiation of investigational treatments [3-4]. In a mouse model of neurofibroma formation, neurofibroma growth was monitored by Positron Emission Tomography (PET) scanning [5]. Although PET may be more sensitive than MRI for detecting smaller lesions, it cannot directly measure tumor size and is more expensive than MRI. It would be useful to prioritize drugs for clinical testing in a mouse model in preclinical drug trials by monitoring tumor growth over time using sequential volumetric imaging.
NF1 is a tumor suppressor gene that encodes a GTPase activating protein (GAP) for Ras proteins [6]. Complete loss of NF1 in neurofibroma Schwann cells leads to increased levels of Ras-GTP [7] known to activate Raf kinase, phosphatidylinositol 3′-kinase (PI3K), and other signals, regulating cell proliferation, survival and cell death [8]. Research focused on the biology of NF1 and pathogenesis of plexiform neurofibroma and their malignant peripheral nerve sheath tumors (MPNSTs) has identified potential targets including Ras itself, Raf kinase, angiogenesis, growth factor receptors, and mammalian target of rapamycin (mTOR) [9-10]. For example, S6K1 is activated in MPSNT cells with NF1 mutations, and this response is attenuated by rapamycin in MPNST cell lines, MPNST xenografts, and in a genetic engineered mouse model [11-12]. In a mouse sarcoma model in which Nf1 and p53 mutations are in cis on mouse chromosome 11, mice treated with rapamycin showed delayed tumor formation [11]. On this basis, a Phase II trial of rapamycin in plexiform neurofibromas is ongoing.
We developed the Nf1flox/flox;DhhCre neurofibroma mouse model in which loss of both Nf1 alleles in developing Schwann cell precursors at embryonic day 12.5 causes neurofibroma formation in adult mice [13]. The tumors show the loss of axon Schwann cell interaction, mast cell accumulation, and fibrosis, which are characteristics of human plexiform neurofibromas. Four – 20 tumors arise in each mouse and at sacrifice each tumor is >10 mm3. We reasoned that MRI with volumetric analysis could be used to monitor neurofibroma development in the Nf1flox/flox;DhhCre mouse model. Based on previous studies implicating mTOR signaling and Raf signaling in NF1 mutant cells, we tested the therapeutic effect of the rapamycin analog RAD001 [14], an mTOR inhibitor, and Sorafenib, a multi-targeted kinase inhibitor that was originally developed as a raf kinase inhibitor [15], in this model. We demonstrate that volumetric MRI can be used to monitor neurofibroma growth in mice. We also show that RAD001 does not decrease neurofibroma growth, while Sorafenib has significant therapeutic effect on some neurofibromas in this model.
We housed mice in temperature- and humidity-controlled facilities on a 12-hour dark-light cycle with free access to food and water as described previously [13]. The animal care and use committee of Cincinnati Children's Hospital Medical Center approved all animal use. The mice were in a mixed C57/129/FVBN strain background and were interbred to obtain the expected genotype. Mouse genotyping has been described [13].
RAD001 and vehicle carrier were obtained from Novartis Pharmaceuticals Corporation (East Hanover, NJ). RAD001 was in a microemulsion solvent that was diluted to 3 parts 2% carboxyl methylcellulose and 2 parts 6% captisol for in vivo usage [16].
Sorafenib was purchased from LC Laboratories (Woburn, MA). Sorafenib was dissolved in 50% cremophor EL (Sigma, St. Louis, MO) – 50% ethanol (Pharmaco Products, Brookfield, Conn). The mixture was sonicated for 1-2 minutes on ice to dissolve Sorafenib. Once in solution, the aqueous component (75% water) was gradually added and diluted to generate the final dosing solution. Each dose was weighed and stored in dry form away from light and was dissolved to liquid form immediately prior to oral gavage.
RAD001: We used RAD001 instead of its analog rapamycin because of improved oral availability [17]. The RAD001 dose was chosen based on studies in which daily oral administration of RAD001 at 10 mg/kg produced transient tumor stasis in an MPNST xenograft model [12] and after a preliminary tolerated dose study in the neurofibroma mouse model (not shown). Seven-month old Nf1flox/flox;DhhCre mice (n=15) were imaged by MRI followed by daily oral gavage for 8 weeks of RAD001 (10 mg/kg) diluted in 3 vehicle carrier. Vehicle-treated mice (n=5) were gavaged daily with the same solution lacking RAD001. These animals were re-imaged by MRI at 9 months of age after the completion of the last dose.
For the Sorafenib trial, 9-month old Nf1flox/flox;DhhCre mice (n=10) were imaged by MRI then treated with Sorafenib (45mg/kg) daily by oral gavage. This Sorafenib dose was chosen based on preclinical studies in which daily oral administration of Sorafenib at 30 to 60 mg/kg produced complete tumor stasis during treatment in five of six tumor models tested [15,18] and a preliminary maximum tolerated dose test in this neurofibroma mouse model (not shown). A control group (n=4) received 200 μl of vehicle daily.
Mice were anesthetized with 5% isoflurane in air and maintained during imaging on 1% isoflurane in air. Mice were positioned in a linear volume transmit/receive coil using a bite bar to secure their heads. Respiration rate and temperature were monitored with a Model 1025 monitoring and gating system from Small Animal Instruments, Inc. The respiration rate was around 100 breaths/min and the temperature was set to 32°C. All data were acquired with a 7T Bruker Biospec system equipped with 400 G/cm gradients. Localizer images were acquired in 3 planes to position the 3D volume. Fat-suppressed 3D Rapid Acquisition with Refocused Echo (RARE) data were acquired with an effective echo time of 35.39 ms, repetition time of 1000 ms, 1 average, a field-of-view of 51.2 mm × 25.6 mm × 26.5 mm and a matrix size of 256 × 128 × 128. Respiratory gating was used to minimize motion artifacts. The total scan time for each mouse at each time point was approximately 30 minutes.
To determine the reproducibility of the volumetric MRI analysis in tumor bearing mice, one observer (ED) applied the method to the tumors of 10 randomly selected mice on three different days. We obtained mouse MRIs at age of 4, 6, 8 10 and 12 months for a natural history study; at age of 6, 7 and 9 months for the RAD001 treatment groups; and at age 5, 7, 9 and 11 months for the Sorafenib treatment groups. On the above described 3D RARE sequence, the plexiform neurofibromas appear bright in contrast to most other tissues. Medx software (Medical Numerics, Inc., Germantown, MD) was used for volumetric analysis. One observer (ED) manually outlined lesions on each MRI slice containing tumor. Tumor on the left and right side of each mouse was measured separately at the cervical and thoracic levels, where the bulk of tumor was identified. Smaller cauda equine tumors were not included in the analysis, as the resolution in this region limited accuracy. Measurement error increases for tumors with volumes <10mm3, therefore, we report only tumors with volumes >10mm3. The tumor criteria were based on image resolution and MRI section slice thickness similar to those described previously [3]. The program calculated tumor volume from the area of graphic outline and MRI slice thickness. All volumes are reported as combined tumor volume in an individual mouse.
Tumor proteins were extracted using extraction buffer (20 mMNaPO4, 150 mM NaCl, 2 mMMgCl2, 0.1% Nonidet P-40, 10% glycerol, 10 mM sodium fluoride, 0.1 mM sodium orthovanadate, 10 mM sodium pyrophosphate, 100 μM phenylasine oxide, 10 nM okadaic acid, 1 mM dithiothreitol, 10 μg/ml leupeptin, 10 μg/ml aprotinin, 10 μg/ml pepstatin, 10 μg/ml tosyl-L-phenylalanine chloromethyl ketone, and 10 μg/ml N α-tosyl-L-lysine chloromethyl ketone). Protein concentration was estimated using Coomassie® Plus Protein Assay Reagent [19]. Proteins (50 μg/lane) were separated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis on 4–20% tris-glycine gel (Invitrogen, Carlsbad, CA) and electrotransferred to polyvinylidene diflouride membrane. Membranes were blocked with 5% nonfat milk + 0.1% TBST to minimize nonspecific binding. Antibodies recognizing pERK, ERK, CyclinD1, pS6K(ser240/244), total S6, p4E-BP1, total 4E-BP1, and β-actin (Cell Signaling, Danvers, MA) were detected by incubation of the membrane with specific antibodies. Antibody binding to the membrane was visualized using a chemiluminescent detection system (ECL, Amersham, Arlington Heights, IL). The bands obtained were quantified by Kodak 1D Imagine Analysis Software (Eastman Kodak Company, IL). Anti-β-Actin was used as a loading control. At least three different tumor lysates were analyzed for each antigen.
Immunohistochemistry on tumor sections was performed as described previously [20]. Briefly, following deparaffinization and rehydration, we permeabilized sections with 0.2% TX 100 and blocked with 10% normal serum for one hour at room temperature. Primary antibodies were: Ki67, Caspase 3 (Cell Signaling, Danvers, MA), secondary incubations were with host-appropriate secondary antibodies. We acquired microscopic images with Openlab software suites on a Zeiss Axiovert 200.
Samples were prepared and quantified using a validated HPLC/MS/MS method adapted from an assay developed by Jain et al [21]. The lower limit of quantification was 5 ng/mL. Plasma samples were drawn at times 0.5, 1, 2, 4, 8 hours post Sorafenib dose on day 6. Only one time point was sampled in each mouse and each time point was sampled in three mice.
Data shown in the text is presented in tumor volume in mm3. In the plots, data is presented centered at the last pre-treatment value within each mouse. To derive p values, we conducted a random effects model analysis on the log transformed tumor volume data [22] using SAS mixed procedure. The log transformation stabilized the variability of data across time. Tumors grew linearly on a logarithmic scale over the study period in the control group within each mouse and the individual linear growth trajectories were estimated by random coefficients linear regression. We allowed the slope of the linear growth in the treatment groups to be adjusted in the post treatment period. A significantly negative yet small adjustment in the slope indicates reduced growth rate, while a significantly negative and large adjustment indicates tumor shrinkage. The linear random coefficients models accounted for different measurement time points across treatment groups and variability in the growth trajectory across mice. Results are summarized by the plots of mean tumor growth trajectories. To compare statistical significance to data obtained in clinical trials, we also used Pearson's χ2 test of medians.
We used magnetic resonance imaging (MRI) to study tumors in the Nf1flox/flox;DhhCre mouse model. The MRI image characteristics of the Nf1flox/flox;DhhCre neurofibromas strongly resembled those of human neurofibromas as shown in Figure 1. As shown in the lower panels, the tumors could be distinguished from other tissues and could be outlined for use in volumetric measurement.
The median volume of tumors used to determine the reproducibility of the volumetric MRI analysis was 65.6 mm3 (range, 12.5-231.8 mm3), and the coefficient of variation (CV=standard deviation/mean) for repeated analysis of the same tumor by different observers was 5.7% (range 0.7-10.8%). The CV was less than 10% for all but the two smallest tumors (12.5 mm3 and 27.7 mm3) analyzed.
Tumor growth was determined by volumetric measurement [4]. Mice (n=5) were repeatedly imaged at 2 month intervals from 4 - 12 months of age months using a Bruker 7.0T MRI (Figure 2A). All five mice had developed tumors by four months of age, and tumors continued to increase in size. Due to imaging artifact, one animal was excluded from volumetric analysis. Figure 2B shows coronal and axial images of one mouse at 6, 8, and 12 months of age, demonstrating the visible increase in tumor size. A group of 20 mice including those used in the natural history study (n = 5), RAD001 study (n= 4), Sorafenib study (n=4), and other studies (n=7) were pooled and evaluated for growth over time as controls (Figure 2C). Similar to what has been observed for human neurofibromas [4], the growth rate of GEM grade I neurofibromas varied between mice, but appeared constant within individual mice.
About 10% of Nf1flox/flox;DhhCre mice developed large tumor nodules underneath the dermis (Supplemental Figure 1). On histopathology, these tumor nodules showed characteristic GEM-neurofibroma grade 1 (not shown). These tumors sometimes eroded the overlying skin due to inflammatory reaction and were not included in our analyses.
To investigate the utility of the Nf1flox/flox;DhhCre neurofibroma mouse model as a preclinical model we first chose to determine the effect of RAD001 as a single agent. Mice (n=15) born in a cohort within one month of each other were pooled and scanned in a group (beginning at 5 – 6 months of age). One month later they were scanned again and then randomized to control (n = 5) and treatment (n = 10) trial arms. Treatment consisted of eight weeks of daily oral gavage at a dose of 10mg/kg. Mouse weights were obtained twice weekly. Mice were re-imaged after the last dose of drug (Figure 3A). All mice survived the 8 weeks of treatment without lethargy, dehydration or significant weight loss (<5%). Pharmacodynamic measure of efficacy used western blotting for the mTOR effector S6 kinase in tumor lysates taken 2 hours after the final dose of RAD001. RAD001 treatment had the predicted effect on mTOR pathway activation in vivo, shown by decreased activation (phosphorylation) of S6 kinase. However, phosphorylation of another mTOR effector, 4E-BP1, was decreased in RAD001 treated tumors as compared to controls, indicating its activation (Figure 3B) [23]. Consistent with this result in one of two tumors, a band shift to lower mobility was observed on RAD001 exposure. Thus, RAD001 treatment of neurofibromas completely inhibits the activation of p70 S6 kinase but seems to slightly decrease phosphorylation (activate) 4E-BP1 in response to RAD001.
Tumor volumes were determined by volumetric measurement at each time point. As noted above, tumor growth rates varied among mice. There was no significant decrease in tumor volume growth rate in RAD001 treated mice (n=10) compared to the vehicle control group (n=5, and pooled controls p=0.36; Supplemental Figure 2) random effects model analysis or Pearson's χ2 test of medians (Figure 3C. D; Supplemental Table 1 and 2). We also did not detect a difference in cell apoptosis in RAD001 treated mice compared to control treatment in neurofibroma paraffin sections by TUNEL assay. We did not detect any change in cyclin D1 or active caspase 3 by Western blot compared to control tumors (not shown).
To test the therapeutic effect of Sorafenib, a multi-targeted kinase inhibitor that was originally developed as a raf kinase inhibitor, on neurofibroma growth, we treated mice (n=9) with Sorafenib daily or vehicle control (n=4) by daily oral gavage. To ensure that growth rate was accurately represented, an additional scan was included prior to onset of treatment. Thus mice were scanned at 5, 7, and 9 months to establish tumor growth rate. This additional scan demonstrated a constant growth rate, indicating that the intermediate scan is not necessary. The 9 month scan was followed by eight weeks of drug treatment by daily oral gavage. Mice were re-imaged after the last dose of Sorafenib at 11 months of age. Tumor volumes were determined by volumetric measurement. All mice survived the 8 weeks of treatment without weight loss or other obvious side effects.
We monitored plasma drug concentration at various times after oral Sorafenib administration. Sorafenib was readily absorbed and measurable. The median Sorafenib concentration was 23.7 μg/mL (range 16.6 to 945 μg/mL) (Figure 4D). Peak exposure was at 1 hour and drug was maintained through 8 hours (Figure 4D) as previously described [24].
We observed significant decreases in tumor volume (negative slope) in 5 of 9 Sorafenib treated mice (Figure 4C). One mouse receiving Sorafenib stabilized, while 3 others continued to grow with unchanged growth rate. All vehicle control mice had tumors that continued to grow throughout the experiment excluding a carrier effect. The difference between Sorafenib and vehicle controls was significant (p<0.05; Supplemental Figure 2). Pharmacodynamic measurement of Sorafenib efficacy was monitored indirectly by levels of cyclin D1. Western blots showed that Sorafenib inhibited cyclinD1 expression in two of the three evaluated tumor lysates taken 1 hour after the final dose of Sorafenib (Figure 4B). We also found that pERK expression levels were elevated in these two tumors. Intriguingly, cyclin D1 decreased and PERK increased only in the two tumors from mice which responded to Sorafenib treatment with decreased tumor volume (Figure 4B).
To assess the mechanism underlying Sorafenib treatment, we determined if Sorafenib treatment resulted in increased apoptosis and/or decreased proliferation within the neurofibroma specimens by staining active caspase 3 (apoptosis) and ki67 (proliferation). We observed a decrease in the number of ki67-positive cells in Sorafenib treated neurofibromas that were taken out from the mice 1 hour after the final dose of Sorafenib (p<0.05, Figure 5). We did not detect differences in active caspase 3 between Sorafenib and vehicle treated mouse neurofibromas by western blot (not shown). We also did not identify differences in endothelial cell number per high powered field between groups monitored using anti-mouse endothelial cell antibody (not shown).
Plexiform neurofibroma is one of the most debilitating complications of NF1 and is associated with substantial significant morbidity [2]. A preclinical model predicting activity would be useful to prioritize clinical trials for investigational targeted agents in patients with NF1 and plexiform neurofibroma. In the Nf1flox/flox;DhhCre mouse model GEM grade I neurofibromas form in 100% of mice and recapitulate the histology and imaging characteristics of human neurofibromas [13]. In patients, neurofibromas develop along nerve roots and adjacent peripheral nerves, paraspinally, and in deep or superficial locations. Our use of 7 Tesla small-animal MRI enabled our conclusion that the Nf1flox/flox;DhhCre mouse model mimics mainly the paraspinal phenotype, with tumors predominantly related to the cervical and thoracic spine. We assessed tumor growth rate in the Nf1flox/flox;DhhCre mouse model using volumetric MRI analysis. The same volumetric measurement technique is in use in ongoing clinical trials and has been proven to sensitively detect small changes in tumor size over time [3-4]. The reproducibility of this method is similar for tumors in mice and humans, and thus the response criteria used in human trials can be applied to the preclinical evaluation in mice. In humans, growth rate varies between patients but appears to be consistent within an individual. Similarly, in the mouse model we identified fast and slow growing tumors, and steady growth for individual tumors. However, in patients with NF1 enrolling in clinical trials most rapid plexiform neurofibroma growth was in young children; older patients typically had little or no growth [4]. In contrast, in the Nf1flox/flox;DhhCre mouse model, tumors are visible by 4 months on MRI and continue to grow until mice require sacrifice due to spinal cord compression at around 1 year.
We scanned untreated and carrier treated mice at numerous intervals. Based on tumor natural history, we suggest that future preclinical trials using this model will best be accomplished by imaging mice at 5 and 7 months, then using a 2 months treatment followed by a final scan. This paradigm takes into account both the continuous growth of tumors in the model and the time of significant death of Nf1flox/flox;DhhCre mice, occurring mainly after 9 months of age. Because in individual mice tumor size and growth rate differ, another possible paradigm would be to measure tumor growth rate and only treat mice with large tumors, or tumors of roughly the same size. The fact that we have no evidence that large and small tumors respond differently to drugs argues against this approach, and such a restriction would not reflect the heterogeneity of patients seen in clinical settings.
The predictable neurofibroma growth rate in the Nf1flox/flox;DhhCre mouse model enabled pre-clinical drug screening. We did not detect discernable effects on tumor growth, tumor cell proliferation, or cell apoptosis on RAD001 treated mice. Similarly, sirolimus (rapamycin) was not effective in shrinking non-progressive plexiform neurofibromas in a Phase 2 trial in children and adults with NF1 and inoperable plexiform neurofibromas. Whether sirolimus prolongs time to progression in subjects with progressive plexiform neurofibromas remains to be determined, and we await trial results with interest [25]. Mouse tumor cells had adequate exposure to RAD001, as neurofibroma pS6 kinase was blocked by exposure to RAD001. It is known that in some systems mTOR blockade can cause feedback activation of Akt activity [26], and it remains possible that this or alternative compensatory mechanisms might account for the failure of RAD001 to block neurofibroma growth. Mechanisms of drug resistance (cell autonomous and/or non-cell autonomous) in many tumors will be an interesting avenue for follow-up studies.
Sorafenib is a multi-targeted kinase inhibitor being tested in a Phase I trial in pediatric patients with NF1 and plexiform neurofibroma. Mice exposed to Sorafenib with tumor growth inhibition also showed decreased expression of the cell cycle regulator cyclin D1, consistent with an effect on tumor growth. Sorafenib inhibited tumor cell proliferation, as attested by immunostaining. The target(s) of Sorafenib in this model are not clear. Raf is predicted to be activated downstream of Ras activation caused by NF1 loss. Tumor lysates showed increased pERK expression, likely due to a negative feedback loop caused by Raf kinase inhibition [26-29]. Sorafenib also inhibits activity of receptors implicated in neurofibroma cells including c-kit, VGFR2, VGFR3, platelet-derived growth factor receptor ß, and Flt-3, one or more of which might account for some effects of Sorafenib on individual tumors [15]. The reason that 5 of 9 mice responded to Sorafenib exposure by tumor shrinkage while 4 of 9 did not is unknown. Because the mouse strain is a mixed genetic background, there may be co-modifier genes that differ among the animals that alter drug metabolism or target sensitivity, possibilities supported by the variability seen in our individual pharmacodynamic and pharmacokinetic data (Figure 4B and 4D, respectively). Drug penetration into different tumor sites may also vary among mice because of the blood-tumor barrier, or interstitial pressure on selected tumors. Tissue drug levels and pharmacodynamic studies of tumor tissue will be of interest in future preclinical neurofibroma trial design.
Our data demonstrate that Sorafenib can reduce the growth of certain neurofibromas and suggest that Sorafenib might have clinical therapeutic effects on neurofibromas. More importantly, our data show that the Nf1flox/flox;DhhCre mice are useful to monitor tumor response to targeted therapeutics, indicating the potential usage of this model for preclinical drug screening.
This work was supported by the Children's Tumor Foundation NF Preclinical Consortium (TPC and NR), NIH NS28840 (NR), and P50 NS057531 9 (NR). The authors thank the NF Preclinical Consortium members and its Advisory Board for extensive discussions aiding in planning of the experiments. We thank Mr. David W. Eaves and Ms. Deanna Patmore for their endeavors on the mouse work.
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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Health, Kids & Family, News & PoliticsFollow
The programme that offers a female perspective on the world
June 18th, 2015
Episode 275 of 985 episodes
Over 100 years after Sylvia Pankhurst interviewed working women about their lives and their double shifts of work and family. Emma Barnett speaks to women in the same industries now. In the first of a new series she speaks to women in a pottery factory, and is joined by professor Krista Cowman of Lincoln University to discuss Pankhurst and her writings on working women. The case of Rachel Dolezal has caused a huge race row in the US. Dolezal, a civil rights activist, was born to two white parents, but has been presenting herself as black - or "identifying" as black, as she describes it. It has created discussion about how race forms identity, and some seem to have conflated the issue of adopting a different race with the experience of being transgender. Emma Barnett is joined by guests in the studio to discuss gender, race, and identity. Plus, Ambreen Shah of the Big Lottery Fund on their plans to channel money into projects to help women and girls affected by domestic violence, sexual exploitation, homelessness, substance abuse, and mental ill health.
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Welcome to the Brain Training Podcast, the daily audio workout for your head. In this podcast we have two games for you, each with three rounds which get progressively harder. To enjoy the full experience, relax, and avoid distractions whilst you listen.


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Know how to prevent, treat and control the symptoms of various diseases and medical conditions. We explain what's happening in your body when disease strikes, and what you can do to feel better faster.
Food, animal dander and the environment are all reasons that some people experience allergic reactions. Learn about the types of allergies and treatment options.
Asthma can be a debilitating condition, and a number of factors can trigger an attack. Fortunately, there are treatments available to help those with asthma lead relatively normal lives.
Arthritis is defined as the inflammation of joints, and symptoms include stiffness and pain. It often afflicts older people's hands, inhibiting mobility and fine motor skills. Learn about the causes of arthritis and how it can be treated.
This section covers cancer types, causes and symptoms as well as the signs of cancer, tests and treatments.
From atrial fibrillation to heart attacks and congestive heart failure, the articles in this section cover cardiovascular conditions and the treatments available.
Cold and flu can be extremely contagious and are usually more common at certain times of the year. Learn about the differences between the common cold and the flu, as well as symptoms and effective treatment methods.
From minor tension headaches to severe migraines, the articles in this section explain what's behind your headache and how it can be effectively -- and safely -- treated.
Understand diabetes and how your body uses insulin to handle glucose. You'll also find information about the impact of diabetes on other systems in the body.
Chronic fatigue inhibits everyday functions and routines, and it can be a symptom of several serious health conditions. Learn about the possible causes of chronic fatigue and what you can do to overcome it.
Osteoporosis, the thinning of bone tissue and loss of bone density over time, can be prevented with proper nutrition and lifestyle choices. Learn about the causes of osteoporosis as well as effective methods for treatment and prevention.
Urinary tract infections can affect any of the organs associated with urination, from the kidneys to the urea. Learn about the causes of urinary tract infections as well as effective methods for treatment and prevention.
Digestive acids that end up in the wrong place can cause heartburn and stomach ulcers. Find out how to maintain your digestive health and treat uncomfortable conditions such as reflux, gas, upset stomach and more.
Whether your pain is the result of a health condition or not, learning to manage your pain can make everyday life more bearable. Learn about pain management through lifestyle choices and modern medicine.
Bird flu, malaria, plague and West Nile virus are infectious diseases we've all heard of. Find information on these epidemics and more in this section.
Musculoskeletal conditions affect the movement of the body through the muscles, joints, ligaments or bones. Learn about common ailments here.
Rare diseases may not be common, but they are no less painful or difficult than conditions you've heard of. Learn about the causes and symptoms of rare diseases as well as how patients can find treatments for their unusual conditions.
Respiratory conditions impact the lungs and the ability to breath. In this section, find out about the symptoms and treatment of apnea, orthopnea and more.
Death is an inevitable fact of life. Learn about life expectancy, the different ways to die, in this section.


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Third Class Steamship Ticket, 1912, Cunard Line S.S. Laconia
This is an Agent's Record of a Third Class -Steerage Ticket for one adult and one child from Liverpool, England to New York on the Cunard Steamship S.S. Laconia (I)
Record to be kept by Agent
No. 118545
Cunard Line
Third Class Outward
- Date of Issue: 10.Aug.1912
- For Steamer: Laconia
- Sailing: 20 August 1912
- Booked to: Liverpool
Names of Passengers and Age:
- Mrs. A. Ambler (32)
- Ethel Ambler (5)
1 Adult 1 Children 0 Infant
Amount Paid: $52.50
Commission: $3
Advised: $49.50
Address: 318 Woonas Quacket Avenue Lymansvide (Linesville Rd)
Dated: 24 August 1912
|First Name:
|Last Name:
|USC (Note 4)
|Last Place of Residence:
|Date of Arrival:
|November 04, 1912
|Age at Arrival: 32 y Gender: F Marital Status: M
|Ship of Travel:
|Laconia (1912)
|Port of Departure:
|Manifest Line Number:
Note 4: Naturalized US Citizen by virtue of Marriage
Information on Document
- Date: 1912 August 10
- Agent Receipt No. 118545
- Dimensions: 9.7 x 19.8 cm
Relative Cost of Passage Ticket in Today's Currency Value
In 2013, the relative value of $52.50 from 1912 ranges from $925.00 to $23,300.00.
In 2013, the relative worth of $52.50 from 1912 is:
|using the Consumer Price Index
|using the GDP deflator
|using the unskilled wage
|using the Production Worker Compensation
|using the nominal GDP per capita
|using the relative share of GDP
Samuel H. Williamson, "Seven Ways to Compute the Relative Value of a U.S. Dollar Amount, 1774 to present," MeasuringWorth, 2014.


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Antique Micro Mosaic lidded box of excellent quality and craftmanship. The round Micro Mosaic is depicting white flowers on a turquoise ground. The box is fine and detailed crafted and in excellent condition. Two tiny tesserae are missing. The box itself is made of gilded metal and has fine floral adornment with glass cabochons. In the center is written "Ricordo(Souvenir)". Inside the lid ,which is a little bent, is a small mirror. The box is in excellent condition and dated at the 19th century. Diameter: 2,8inch (70mm), Height: 2 inch ( 50mm)
3 other shoppers have this item in their Cart or Wish List .
High quality Micro Mosaics, Silver, Paintings and Decorative Art
Objects bought with love and treasured for a life time!


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Belgrade Phone: 064/142-7307
E-mail: firstname.lastname@example.com
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