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I piss excellence!
I piss excellence!
When God made the ass, he didn't say, 'Hey, it's just your basic hinge, let's knock off early.' He said, 'Behold ye angels, I have created the ass. Throughout the ages to come, men and women shall grab hold of these, and shout my name!
-Brent J.
I wanna dip my balls in it!
Ellen Griswold: I honestly don't think we're going to find the Grand Canyon on this road.
Clark: Jesus, it's only the biggest God-damn hole in the world.
Aunt Edna: Clark, watch your language!
Clark: Make that the second biggest.
Well if you can't make it stay hard, stay hungry, stay alive if you can
I think you're all fucked in the head. We're ten hours from the fucking fun park and you want to bail out. Well I'll tell you something. This is no longer a vacation. It's a quest. It's a quest for fun. I'm gonna have fun and you're gonna have fun. We're all gonna have so much fucking fun we'll need plastic surgery to remove our goddamn smiles. You'll be whistling ZipADeeDooDah out of you're assholes! I gotta be crazy! I'm on a pilgrimage to see a moose. Praise Marty Moose! Holy Shit!
Pardon me, um, Homes. Can you give me directions back to the interstate?
F*#! Yo Mama!
It all sounds like some bad movie...
Everyone is responsible for their own happiness.
Need a translation to/from Spanish?
Roll Em Up!
Posted via Mobile Device
me: excuse me where's the aqua sun
man: sorry dude im not an elkbilly im from delaware
me: hey! me too!
man: we better keep quiet before we get shot
I have multiple personalities and none of them like you.
You can only make a mistake once. After that it's a choice.
Pizza..... I LIKE IT!
Gimme a Diablo sammich and a Dr pepper to go little lady...
and make it quick...
I'm in a gottdamned hurry....
I'm in hot pursuit....
"You either die a hero or you live long enough to see yourself become the villain"
Waiting for the first snowflake to fall!!!
Connor, Murphy, Il Duce: And shepherds we shall be, for Thee, my Lord, for Thee. Power hath descended forth from Thy hand, that our feet may swiftly carry out Thy command. So we shall flow a river forth to Thee, and teeming with souls shall it ever be.
Il Duce: In nomine Patri.
Connor: Et Fili.
Murphy: Spiritus Sancti.
************************************************** *********
Il Duce: When I raise my flashing sword, and my hand takes hold on judgment, I will take vengeance upon mine enemies, and I will repay those who haze me. Oh, Lord, raise me to Thy right hand and count me among Thy saints.
Last edited by M.Bush; 08-01-2008 at 01:25 PM.
"Garbage In, Garbage Out"
-G. Carlin
"I'm gonna break your nose with my @ss" - Atlantic City stripper on my bachelor party
-Brent J.
I wanna dip my balls in it!
Woman: [holding a grocery bag] What are you doing?
Frank: You tell anyone about this and I'll fucking kill you. I'm kidding, I'm kidding, we'll have him home by midnight.
[reaches into the grocery bag and takes out cheese balls]
************************************************** *********
Frank: I told my wife I wouldn't drink tonight. Besides, I got a big day tomorrow. You guys have a great time.
College Student: A big day? Doing what?
Frank: Well, um, actually a pretty nice little Saturday, we're going to go to Home Depot. Yeah, buy some wallpaper, maybe get some flooring, stuff like that. Maybe Bed, Bath, & Beyond, I don't know, I don't know if we'll have enough time.
"Garbage In, Garbage Out"
-G. Carlin
Okay. When I nod my head, you hit it.
Peppers: She's a beauty, ain't she?
Frank: Yeah, what kind of gun is this?
Peppers: It's a tranquilizer gun. If any of these little fuckers decide to freak out on the kids, I get to take them down. Ain't that right?
Peppers: [yank's on the mule's reigns]
Peppers: Oh, what? That's what I thought. Shut up.
[Frank cocks the gun]
Peppers: Hey, hey. Careful with that. That's the most powerful tranq gun on the market. Got her in Mexico.
Frank: Cool.
Peppers: Yeah, it is cool. They say it can puncture the skin of a rhino from...
Frank: [Frank shoots himself in the neck with the dart]
Peppers: YES! That's awesome!
Frank: What?
Peppers: You just took one in the jugular, man.
Frank: What? I did.
[feeling his neck]
Peppers: YES!
Frank: Oh my god. Is this bad? Is this bad?
Peppers: You better pull that shit out man. That shit is not cool.
Frank: Wait. What? Pull what out?
Peppers: You got a fucking dart in your neck man.
Frank: [laughing] You're... you're crazy man. I like you, but you're crazy.
"Garbage In, Garbage Out"
-G. Carlin
"All balls itch! It's a FACT!"
"Condemnation without investigation is the height of ignorance." - Albert Einstein
"America lives in the heart of every man everywhere who wishes to find a region where he will be free to work out his destiny as he chooses." - Woodrow Wilson
"I saw this crackhead on my step. So i walked up to this crackhead and said, "Hey crackhead. Get the f*ck off mah step". - Leon
"Condemnation without investigation is the height of ignorance." - Albert Einstein
"America lives in the heart of every man everywhere who wishes to find a region where he will be free to work out his destiny as he chooses." - Woodrow Wilson


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Megalopoli(tic)s | |
By OMA © All rights reserved
Reinier de Graaf |
OMA-partner Reinier de Graaf gave a lecture at the Berlage Institute on Megalopoli(tic)s. De Graaf started by arguing that thinking big is compulsory when thinking about 'the green cause'. One needs to think in a global context, like Buckminster Fuller did with his Spaceship Earth (1968) and Doxiades' global Ecumenopolis city (1967). By showing different mappings of urban growth, De Graaf showed that the Ecumenoplis is, in fact, not that far way. These developments take place, not in the old Western metropolitan areas, but in the megacities of the South and(Far-)East. |
Netherlands, Rotterdam, , 19 April 2012 |
To understand this growth, De Graaf looked at the rise of global economic liberalization. It is generally assumed that this started in the West with the simultaneous election of Margaret Thatcher in the UK and Ronald Reagan in the US. De Graaf argued that it started in China with the coming to power of Deng Xiaoping and the introduction of the 'Open Door Policy'. De Graaf maintained that economic development is inextricably linked to urbanization, questioning if urbanization is a consequence of economic development or a means to economic development. The problems that accompany rapid urban growth were historically addressed by (Western) thinkers writing about urbanization, but when Asia became the main setting for urbanization, these Western thinkers ceased thinking and writing about the topic. The visions of tomorrow's city, are now being seized by consultancy firms. 'Master plans' are now created by technology giants like Siemens and home products companies like IKEA. De Graaf closed his lecture by arguing that the prominence of cities is detrimental to the state of a nation; 'third world' cities like Sao Paolo and Mexico City have a larger GDP compared to 'first world' countries, such as Sweden and Australia. But these cities still have less political power than their respective nations. While the city (polis) was the birth place of politics, the Megalopolis calls for Megalopolitics… |

subset: commoncrawl


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DePauw Blanks Petrels, 3-0
September 21, 2008
September 21, 2008, Greencastle, Ind. - Three different Tigers scored in leading DePauw to a 3-0 Southern Collegiate Athletic Conference victory over Oglethorpe. DePauw improved to 2-4-1 overall and 1-1 in the SCAC, while the Stormy Petrels dropped to 3-2 overall and 0-2 in the conference.
Katy Phillips put the Tigers on the board at 19:48 with an unassisted goal before Sarah McCord followed it up at 36:42 on Lindsay Lund's assist. Lauren Hannan rounded out the scoring at 68:22 with an assist from Phillips.
DePauw outshot Oglethorpe 11-5 and held a 7-0 edge in corners.Three Tigers played in goal with Brooke Shipley, Lauren Palfrey and Christy Fillenwarth assisting with DePauw's second shutout of the season.
The Tigers return to action on Saturday, September 27, when they travel to the University of Chicago for a 6 p.m. CDT contest with the Maroons.


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Loved this course! The river crossing was a blast! The runners and volunteers were so helpful. I ran the 50k
I did the associated 50km but the course only differs in that there was a 5 mile loop added for the ultra. This was my first experience with a wilderness-type run and I loved it. Somehow the distance was not an issue due to constant changes of terrain and elevation. There was a wonderful river crossing that you could swim or wade. The cold water was very welcome so I ducked right under. Great volunteers, easy logistics,unique medal, decent tech shirts and pot-race massage($). Rumor only but there was talk that some runners skipped a short out-back section on the 50km. If true, it could be easily stopped if the volunteers at the turn noted bib numbers. Hope it's not true. Try it, you'll like it!
WMA makes no representations as to the accuracy of information on this site or its suitability for any use. | privacy policy | refund policy


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© 2013 Womad Ltd
Company Reg. No. 2734599
Place of registration : England
Registered address :
Box Mill,
Mill Lane,
...and the title of the this tread was... oh never mind.
Sc is correct the fiscal costs of treating a smoker with lung cancer are less than the tax they paid in, but the societal costs are higher as the loss of the deceased skills and the extra costs to the family that becomes a single parent family are higher.
Oh and before we get on our high horses about smokers, bear in mind 80% of things people consult their GP over are lifestyle related ie they caused it them selves. exercise , diet, drinking, stress, preventable accidents, relationships. Fortunatly there is a cure , for some but not all ,according to the thread title, available in July for 5 days WOMAD.
May be taken in tents ivly with dust or mud accompied by music and mirth,
and drums.
Side effects include children collecting glasses, drumming, the smell of fags and maybe weed, tripping over chairs in radio 3 , seeing famous people wandering around un hindered, out breaks of mass chilling in the heat. Smiles. Hearing music in your ears for days.
We are really sure that we going this year ,tickets have arrived and the weather has improved, time to dust down the tent , and a big thank you to Desert Traveller for getting us back on track, well done!
Excellent news! So good they named you twice!
oh yes, SC just seen the list there will many things to like, I'll ensure I get to feed the world this year- at the front. Thought about being a Talkng Book but when I walk thro the Red Gate I'm a customer ; all that work stuff floats away.
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As founder and president of the Error Prevention Institute, Jay Hopkins provides safety, quality and effectiveness training to businesses, government agencies, hospitals, police and fire departments, and air medical transport operators throughout the country. His Human Factor column in Flying allows pilots to benefit from his uniquely effective approach to error prevention.
Jay received his BA in social psychology from Lehigh University, and lived in many different parts of the country before settling in Payson, Arizona. When he is not flying around the country doing seminars on Error Prevention, he likes to hike in the mountains around his home, go kayaking or take adventures like riding his bicycle across the country.
Jay has experience in virtually all facets of civil aviation, including line service, aerial photography, glider towing and instruction, along with charter, airline and corporate jet operations. His work training military instructors has given him experience with all branches of the U.S. military as well.
Jay has owned and operated a Part 141 flight school and Part 135 charter service. He served as chief pilot of an international corporate flight department and flew copilot for a commuter airline. Jay has over 5,000 hours of flying time with experience in 45 different types of aircraft, from gliders and Cubs to Metroliners and Learjets. He holds an ATP certificate with type ratings in Learjets and Westwinds, and is a certified instrument flight instructor as well as a commercial glider pilot and instructor.
At FlightSafety International in Tucson, in addition to instructing in the Learjet 35 and 55 simulators, Jay developed and presented the Jet Transition Course and the Learjet 55 Initial Course. He was one of the first instructors hired by SimuFlite Training International, where he was chosen as the first standardization instructor and also served as manager of instructional design.
For several years Jay flew a Turbo Twin Comanche around the country to his training assignments. While he is now back on the airlines, he is still very active in aviation as a mission pilot, instructor and check pilot for the Civil Air Patrol in Arizona, flying a brand new Cessna 182T with a G-1000 glass cockpit.


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Jan. 31, 2011 at 7:13 PM ET
As dark UFO videos go, this clip showing flashing lights over Jerusalem is certainly a puzzler. A bright speck seems to descend toward the skyline, around the location of the Dome of the Rock (also known as the Temple Mount). A minute into the clip, there's a bright flash, then the speck shoots up from the skyline. This version of the Jan. 28 clip shows two side-by-side videos, captured by observers who were virtually side-by-side as well. "Have fun debunking this one," the YouTube user who posted the video writes.
Here's another version, which sounds as if it was shot by a group of tourists. "We've seen 'em in Mississippi like this," one observer can be heard saying.
Debunkers might note that the views come from perspectives that could make nearby objects seem farther away and faster-moving. Or they might wonder whether the whole thing was faked. Over at HowStuffWorks, Marshall Brain offers a smorgasbord of videos aimed at pointing out the traces of image processing.
I think this is going to be one of those shaky-camera sightings that will live on in UFO lore without making much of an impact in the wider world. But what do you think? Feel free to leave your comments about the Jerusalem Lights.
More about UFOs:


text:
Stonemasons Arms
Time Out rating:
Venue details
Stonemasons Arms 54 Cambridge Grove
- Venue phone:
020 8748 1397
- Opening hours:
Open 11am-11pm Mon-Sat; noon-11pm Sun. Food served noon-3pm, 6-10pm Mon-Fri; noon-10pm Sat; noon-9.30pm Sun
- Transport:
Tube: Hammersmith tube
Stonemasons Arms
- 54 Cambridge Grove
- 51.493484,-0.230069
- 54 Cambridge Grove
Stonemasons Arms
Reviews & ratings
Very nice environment,
very good food and service.
It's becoming my local.Sophie Sat Dec 1 2012Rated as: 5/5 -
I had a meal here on Saturday night. The service was quite slow and haphazard though the staff were pleasant. We had finished our starter before our wine arrived for example - and it only arrived then because we went to the bar to request it.
I think if a bar cannot offer restaurant service then they should not try - I would have been happy to order my meal at the bar and I am sure it would have been much quicker.
The food was good quality but I will not be returning in a hurry even though I live around the corner. As the reviews below speak highly of the service perhaps it was just an off night though it was not particularly busy.
Also the Hammersmith Privilege Card website states that there is 10% off of food when you present your card but the staff said that they do not accept the card which I found irritating.Buicke Tue Nov 13 2012Rated as: 3/5 -
Booked a table here due to the great reviews (was going to the Apollo) on Saturday - the reviews do not do this place justice, the food is excellent, yes a little pricey but well worth it, the staff are fantastic! wish i lived closer so i could go here more often, will make an effort to go back as had a fabulous meal thankyou The Stonemasons Arms, keep up the good work
Tina Mon Mar 14 2011Rated as: 5/5 -
This is one of my locals and I have been to the Stonemasons quite a few times. In an area that has a lot of excellent gastropubs, this one holds its own and comes up trumps when it comes to value for money. Pleasant atmosphere, never too busy (good if you want to score a table, bad if you are looking for adventure), excellent food, good choice of beers on tap, decent wine list (bit pricey though), really nice staff and film club once a week. 10mn to Hammersmith tube - and open till midnight a few days a week.
Ivana Wed Feb 16 2011 -
Have visited the Stonemasons a few time before and this time was no disappointment. Welcoming, friendly attentative, polite staff providing very good service. The food was fabulous squid and tender lamb to perfection. On top of that great atmosphere!! Best reserve a table or be disappointed.
John Wed Feb 2 2011


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Light to medium bodied wines that are high in acid and light to medium fruit. Typically no oak.
Light to medium bodied wines with lots of juicy fruit, typically medium acid and medium oak.
Full bodied wines that have typically undergone malo-lactic fermentation and/or spent time in oak.
The wine shows an abundance of tropical fruit, pear, grapefruit and lime aromas on the nose that carry through to the palette. The mouth feel is crisp, yet rich and fruity, and coats the pallet evenly. The well-balanced acid and lingering aftertaste will make you come back for more.
"Lively, with a bright core of grapefruit and lemon peel notes backed by mouthwatering acidity. The long, floral-tinged finish lets it all linger. Very tasty. Drink now. 5,000 cases made. " 89 Points Wine Spectator
Warwick Estate lies in a valley enclosed by the Simonsberg, Kanonkop and Klapmutskop. Originally part of a vast piece of land known as Good Success, this eighteenth century farm belonged to Colonel Alexander Gordon who renamed his portion in honour of the Warwickshire regiment which he commanded during the Boer War. Years later in 1964, Stan Ratcliffe bought Warwick, where,...Read More About Warwick Estate
South Africa A long history of growing grapes and making wine, but less of a history on exporting it, and even lesser on the quality aspect. At the turn of the century (1900, that is), a surplus of wine in South Africa created a hierarchy of cooperatives, the biggest and best known being KWV. This organization seemed to favor quantity over quality and had most...Read More About South Africa
Sauvignon Blanc (so-veen-YAWN blahnk) One of the most distinctive grapes, Sauvignon Blanc is a highly aromatic variety that does well in both the old and new world. From the Loire Valley of France to Marlborough in New Zealand, Sauvignon Blanc has found many regions that bring out its unique and delicious flavors. Notable Facts Sauvignon Blanc's home...Read More About Sauvignon Blanc
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Product Details:
Manufacturer: Paris Watch
Mfg Part#: PW0000000001
Sku: 249369153
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Paris Watch Silicone Green Fashion Sport Quartz Calendar Date for Women and Men Watch Designed in France with 13 Colors to choose from. Most known for their vibrant colors, this Genuine Paris Watch also comes in traditional colors so there is sure to be one to go with any outfit. This is a Stunning Authentic Fashion Watch by Paris Watch. 100% Authentic Genuine Watch by Paris Watch Unisex Soft Silicone watch suitable for women, men and teens from any ages. This watch is designed with a stylish and exquisite appearance. Silicon strap design, makes it soft and comfortable to wear. Rotatable bezel design, elegant and fashionable. Traditional time with date display. Suitable for both women, men and teens. |


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Kirk Foley
Kirk Foley, 57, of Superior, formerly of Dodgeville, Wis. passed away unexpectedly on Dec. 14, 2012.
Kirk Foley, 57, of Superior, formerly of Dodgeville, Wis. passed away unexpectedly on Dec. 14, 2012.
He was born on Jan. 4, 1955 in Viroqua, Wis., son of John and Helen (Moeller) Foley of Dodgeville.
Our hearts are heavy to lose you, yet we know you are now with Nancy and your five angels, Kelly, Tim, Katie, Lauren and Shawn. Kirk tragically lost his family in a house fire in 1996.
Kirk will be dearly missed by his lovely daughter, Lora Foley, age eleven. He was a devoted father and loved his daughter dearly. He is survived by his ex-wife Lori Randa, and his many adoring family members. His sisters, Delores (Mort) Moyer of Middleton, Wis., Kathy (Dale) Chellevold of Dodgeville, Wis. His nieces and nephews, K. Jonathan Moyer, Joel Moyer, Karen (Chellevold) Fisher, Lori (Chellevold) Meudt.
Kirk was a man of many talents, skills and accomplishments. He graduated from University of Wisconsin-Platteville and from Drake University with a JD in law. He had a law practice in Hurley Wis. for many years, was an Administrative Law Judge for the county courts and did pro bono work as a public defender. In his later years he did real estate development.
He was a dedicated father and husband. He enjoyed reading, politics, and was a ski instructor. He was a hobby farmer with a yearly vegetable garden, raising pigs and various small animals and loved planting and harvesting his fruit trees.
Kirk, you have gone before us yet we know we will meet again - you will watch over us and be our guardian angel - gone but never forgotten.
Friends may call from 9 a.m. until the 11 a.m. Mass of Christian burial which will be celebrated on Friday, Dec. 28 at St. Joseph's Catholic Church, 306 Ellwood St., Dodgeville, Wis.. Father Patrick Wendler will officiate. Burial will be held in St. Joseph's Cemetery.
In lieu of flowers, the family suggests that memorials be made to an education fund for Kirk's daughter, Lora.
Tags: obituaries


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Rugs America Sardinia 5125 Aztect Rust Rug
Item #: 2635125-P Add to Wishlist
$239 - $1999 + FREE SHIPPINGDescription: With an enthusiasm for designs of the past and a taste for colors of today, the Sardinia collection is a unique tribute to quality, design, and texture. The brilliantly rich color palettes and superlative hand carved texture help introduce a unique beauty to the world of floor covering design. Each rug is hand carved and hand tufted in India with 100% premium sardinian wool.
- Collection: Sardinia
- Brand: Rugs America
- Material: 100% Sardinian Wool
- Weave: Hand Tufted & Carved
- Styles: Traditional Rugs
- Origin: India
- Available in the following sizes: 3' x 5', 10' x 13' and 6' Round
- Clean & Care: Vacuum regularly as new wool rugs can shed yarn fibers for up to three months. Avoid direct and continuous exposure to sunlight. Do not pull loose ends, clip them with scissors to remove. Clean liquid spills immediately by blotting with cloth or sponge. For hard to remove stains, professional rug cleaning is recommended.
I was disappointed in this rug. The color is more like a burgundy than the soft rust pictured and reinforced by the color name. I purchased it for the foyer but can't use it there because the quality is too good: the pile is too high for the door to clear. Luckily I have another place for it, but keeping it is a compromise in order to avoid the expense and bother of a return.
RECOMMENDED: No, I would not recommend this to a friend.Fill out the information below.


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December 21, 2011
Steve Jones CatsIllustrated.com
Paul Hornung presented the award named for him to UK commit Patrick Towles, who expressed great optimism about the Cats' future. ...More... To continue reading this article you must be a member. Sign Up Now for a FREE Trial
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text:
Is Kraken. He wants to turtle? Kill Engineer in 4 steps with Kraken.
2)Blink into his base of turret or ult (silence doesn't stop his Ult).
3)Kill the defenseless Engineer once he is pulled.
4)Type, "A lot of good that gun did you" in all talk.
This tactic counter every single hero, so not really much of a tip.
In life we are all created equal. It just so happens, some of us were created more equal then others.
The real hard counter for Engineer is Forsaken Archer, with his 8 skeletons.
except forsaken archer is a bad hero (imo) and ophelia is way better since you can acctually controll your minions with her. I guess defiler would work pretty well too.
Or anything with summons.
In life we are all created equal. It just so happens, some of us were created more equal then others.
Best counter for Engineer is a nuke on his head, then another nuke, then another nuke, then another nuke till he die.
Dumb thread much.
Warbeast. Path his 2 wolves to hit the gadget/turret while warbeast goes for the hero. Max ms those wolves will get to the gadget/turret and own it fast.
How to counter turret with any hero.
1. Buy barbed armour.
2. Activate barbed armour.
3. Walk into turret range so it shoots you.
4. ????
5. Profit.
No seriously, the turret explodes like instantly if it shoots anyone with barbed active.
Looks like Blademail/Barbed Armor actually has a good use now!
S2 Games: Dedicated employees serving dedicated gamers. Continuous development. Never-ending improvement.
Tech Support and Customer Support: https://www.heroesofnewerth.com/support/
Look for my highlighted text (important information) and grey text (interesting but not required information).
well, there is even cheaper counter for turret - void talisman. 4 seconds is enough to kill the turret.
imho engineer owns only in 1500- games, he is really easily countered and doesn't need a nerf.
but he is so much fun to play. not that kind of "press a button get a profit" hero.
Other than destroying DPS heroes with Legionaire?
Wait, so the damage barbed armor is received from turret is redirected towards the turret or the engineer? And how would you counter if he has more hp than you?
lego + barbed armor = anti carry
That?s so NOT true lol.
Playing a pro game with an Engineer that has shieldbreaker, thunderclaw, savage mace and riftshards = win. the only thing you need to do is place a turret, send somone in to lure, and if they come the turret finishes them all /easy genocide.
Tempest minions could counter it mayB. But most Engineers get a thunderclaw straight up and if they do they take down entire creepwaves in a blink of an eye.
Logics are hard to come by these days.


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why not? and make it 24 bit while you're at it…i'd buy that for a dollar.
:idea: I'll see your dollar and raise you 50
"...the gnomes have found a NEW way to say Hooooraaaaaay…" http://www.kramerkreations.com/images/shpongle_emo.gif
A very interesting thread to start and yes 5.1 would sound amazing. Futrue Sound of London are releasing a 5.1 project this year which should be well nice.
The only personal problem I have with it is that I've spent a hell of lot of cash on hi fi over the past 17 years and it means extra speakers and 5.1 amp etc and a decent shaped room for it.
However I think it's only a matter of time before everything does go surround and psy music is perfect for it, the possibilities and directions for effects is limitless.
'My god it's full of stars'
I interviewed Simon when he came to Western Australia and I asked him that very same question:
or perhaps even the use of a Neumann head a la Tchad Blake, if it's not used already…
Not purely surround, but if you have an X-Fi (Creative) Soundcard, you can "Enable CMSS-3DSurround" and "Stereo Surround", to get it on all the speakers, I like it a lot!
http://img364.imageshack.us/img364/1962/halmainaniml7smallertmqfn4.gif ...from the cave man to the rave man…—Raja Ram
[quote author="Adam Brown"]I interviewed Simon when he came to Western Australia and I asked him that very same question:
Artists such as Nine Inch Nails have been experimenting with music in 5.1 surround; this sort of project seems to have your name written all over it. Do you one day hope to produce a psychedelic album this way? I shudder to think what sort of trickery you could unleash if you mastered the art of producing music in surround sound. The guys from Blue Room did a lot of work with B&W on this prior to the DVD explosion. Sure it provides a variation on the usual format, but the original music quality has to be available. I know a lot of people who have very ordinary sounding 5.1 systems in rooms that are not configured correctly. If it was a choice between dodgy 5.1 there is no comparison. The possibility of pushing the experience I will always welcome.
Kind of an opened ended reply, don't ya think? :wink:
Heya Pynts, long time no read.
Glad you replied, because I wanted to post this (two posts in row might seem a bit pushy)
In the Mixing Engineer's Handbook, by Bobby Owsinski, Greg Penny (one of Elton John's best engineers) states:
"As Nate Kunkel (protege of George Massenburg) says, you've got to make records for the guys that have the right system, because if you back off from that and try to dilute the vision down to the most common denominator, we'll never get anywhere. You have to somehow set the benchmark. More often than not on these blogs on the Internet about Elton's mixes, I either get slammed for being sacrilegious or lauded as a genius. They always talk about how the use of the surrounds is extreme on Elton's records, but then a lot of guys say, "Finally I'm able to figure out my system. I've got some stuff that puts something through all of my speakers." So my objective is to use the system entirely and not be too timid, but there are some songs where you don't have enough data to put in all the speakers and have it make sense without it seeming lopsided."
I think most people would agree that Shpongle has set a benchmark already. Why not raise it even higher? Who knows, people might be inspired to buy a surround system just to hear this album. I know I would.
Me too.
Good to see you too.
[quote author="digitalex"] I think most people would agree that Shpongle has set a benchmark already. Why not raise it even higher? Who knows, people might be inspired to buy a surround system just to hear this album. I know I would.
Good point. I have no plans to buy surround yet but if they did release something like that, it would influence me greatly too.


text:
Apache is the most prevalent web server operating on the internet and there's good reason for this. It's robust, secure, stable and easy to configure with a myriad of add-ons (mods) to allow you to set up websites running PHP, Java and Ruby amongst many other uses such as a reverse proxy or web application firewall. Getting a website up and running is very easy with Apache as all Linux distributions give you access to Apache using the distributions installation tools such as Yum (Red Hat based) or apt (Debian based).
SSH Access Using Keys
Aug 9, 2011 by 1 Comment
Access to Linux and Unix systems via Secure Shell (SSH) is standard practice. It offers encrypted access to enable you to administer your server which is vital over the big bad internet. There are different ways to access SSH: password, user keys and host-based keys. Passwords are the most common but are less secure than [...]


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A commercial aviation company is about to start calling the Dothan Regional Airport home.
Commercial Jet, incorporated announced today it would be landing soon.
The Miami-based aircraft repair and maintenance company will take over the old Pemco building that shut down a year ago.
It could bring hundreds of new jobs to the area over the next 3-years and 15 hundred additional jobs.
Those jobs could bring workers, who had to leave the area to find other work, back home.
Get the ingredients you need to cook with Rach all week long. | |
Full length exclusive concerts from hot artists. | |
Take a break! Classic Pacman, Frogger, Asteroids and more. |
FREE Listings Sell almost anything locally. |


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Dairy free saute main dish recipes
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Thai Fish Curry or Kaeng Khieu Wan PlaA very quick meal to use green curry paste with, Kaeng Khieu Wan Pla or green curry of fish.This hassle free… |
Spicie Foodie
Feb 2010 Intermediate |
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Farrell May Podgorsek
Oct 2009 Advanced |
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Ham & Cabbage HashThis is a fast dinner-in-a-skillet recipe, and a good way to use up leftover ham or roast beef. Lots of vegetables make the meat go further and keep… |
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Jan 2013 Professional |
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Spicy Sweet Potato MedleySweet potatoes with sausage and bell peppers with an Indian flare. |
Piper Seeger
Sep 2008 Advanced |
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Pasta with Fresh Tomato SauceLast weekend it snowed in New York, about 4-6 inches. I felt snowed it. Too lazy to shovel, too lazy to go out, and too lazy to change into normal… |
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Engineering: University Transfer
Program Description
Engineering is the art of applying scientific and mathematical principles to make things that benefit people. Essentially everything that people use in a given day was designed or developed by engineers.
Umpqua Community College (UCC) offers an engineering transfer program that closely follows the first two years of study for students transferring to many public and private universities, including Oregon State University, Oregon Institute of Technology, Portland State University, and University of Portland.
Programs offered at OSU include Electrical and Computer Engineering, Civil Engineering, Construction Engineering Management, Environmental Engineering, Mechanical, Industrial and Manufacturing, and Chemical Engineering, as well as BioMedical, Forest, Geological, Mining, Metallurgical, and Nuclear Engineering. PSU and OIT offer programs in Civil and Environmental, Mechanical, Electrical and Computer Engineering. OIT also offers programs in Geomatics (Surveying) and Renewable Energy.
Program Details:
Engineering Brochure
Advising Guides
Catalog Information
Why UCC?
The freshman and sophomore years at most universities are designated pre-engineering, with the junior and senior years designated professional engineering. Many of the transfer courses during the first two years of study are math, science and elective courses. Students at UCC can take the core courses required for transfer in smaller class room settings and at lower cost than at four-year institutions. The Associate of Science (AS) degree is awarded to UCC students once all required courses, electives and general education requirements are successfully completed.
Pre-Engineering and Certificates
Students who are not prepared to begin Calculus in their first year of engineering transfer program should consider starting with the Certificate of Completion Program as an Engineering and Drafting Technician. The one-year program can serve as a pre-engineering program for students interested in future transfer. A Drafting Pathways Certificate can also be acquired by completing 16 hours of drafting courses. The Pathways and Completion Certificates provide stand-alone, job-ready skills and provide expanded opportunities for summer internships. Students interested in certificates and the engineering technology program should see the Engineering Technology web page.
Contact for More Information
Prospective students should see an engineering faculty adviser, or Advising and Career Planning Services, to develop your educational plan.
Clay Baumgartner, PE - Contact
Department Chair, Engineering and Computer Science
Phone: (541)440-4683


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Penna Dutch Hex Card
Welcome Hex Growing up in the heart of PA Dutch country and having our shop located right off of the Hex Highway(Hex Highway Tour Map), we have an affinity for Hex Signs. Hex Hwy is the adopted name of the scenic Old Route 22 in Berks County, famous for its large amount of Hex Sign covered barns and out buildings. This folk art is exclusive of the PA Dutch; the heavy concentration of German... Read More


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12" Hub-and-drum assembly features 6 on 5-1/2 bolt pattern and includes races, inner and outer bearings, seal, bolts and grease cap.
Determining the Bolt Pattern
The first number in the bolt pattern is the number of bolt holes. The second number denotes the diameter, in inches, of the circle on which the bolt holes sit.
To determine the bolt-circle diameter on wheels with an odd number of bolt holes, measure from the center of any bolt hole to the point halfway between the two bolt holes directly across from the first. (Example: "5 on 4-1/2" means 5 bolt holes with 4-1/2" measured to a point halfway between the opposite bolt holes.)
On wheels with an even number of bolt holes, measure from the center of one bolt hole to the center of the hole directly across from it. (Example: "8 on 6-1/2" means 8 bolt holes with 6-1/2" from the center of one hole to the center of another on the opposite side.)
Measuring the distance from the center of one bolt hole on the wheel to the center of a bolt hole right next to it can also help to determine the bolt pattern.
Ask the Experts about this Titan Trailer Hubs and Drums
Info for this part was:
At etrailer.com we provide the best information available about the products we sell. We take the quality of our information seriously so that you can get the right part the first time.Let us know if anything is missing or if you have any questions.


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The Naughtiest Boy?
Here's former Colombia midfielder Gerardo Bedoya getting sent off in the Bogota derby playing for Indediente Santa Fe against big rivals Millonarios, for a cheeky elbow/boot to the head combo. Remarkably, this was the 41st red card of his career, more than any professional footballer in history.
Hi excuse after the game? "I'm not normally like that". Course you aren't, Gerardo.


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The GUIShell project is a collection of utilities facilitating the use of the GTK+ toolkit in shell scripts through the gtkshell utility. The ACE configuration environment provides sample scripts utilizing gtkshell for desktop utilities. rootcat provides the ability to display messages to the root window using Xft, allowing one to write status display scripts.
Granite Data Services (GraniteDS) is a comprehensive development and integration solution for building Flex / JavaEE RIA applications. The primary goal of this project is to provide a framework for Flex 3+/EJB3/Seam/Spring/Guice/POJO application development with full AMF3/RemoteObject benefits. It also features a Comet-like Data Push implementation (AMF3 requests sent over HTTP) and ActionScript3 code generation tools (Ant task and Eclipse Builder).


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Browse our mobile site for the best experience on your device.
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Teddy Geiger
Teddy Geiger
Singer/songwriter/actor Teddy Geiger makes heartfelt, contemporary pop. When he started out, his raspy vocals and sophisticated lyrics disguised the fact that the budding pop sensation wasn't even old enough to vote. The self-taught Rochester, NY, native had a stockpile of material by the age of eight and a recording contract at 16. The former finalist on VH1's In Search of the New Partridge Family -- later attracting attention in the role of Wayne, a budding songwriting prodigy on the short-lived CBS dramedy Love Monkey -- caught the attention of high-profile producer Billy Mann and formed a partnership that landed him a deal with Columbia Records. His debut, Underage Thinking, was released in 2006, and its lead single, "For You I Will (Confidence)," quickly found a spot in the Top 40. Geiger made his feature film debut alongside Emma Stone and Rainn Wilson in The Rocker. Two years later, he delivered the EP, Living Alone. In 2013, Geiger returned with the full-length studio album The Last Fears, which featured the single, "Walking In the Sun." ~ James Christopher Monger, Rovi
Similar Artists
David Gray
Landon Pigg
Tyler Hilton
James Blunt
Daniel Powter
Jonathan Balas
Ronnie Day
John Mayer
Dashboard Confessional


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Keane Tickets
Without question one of the UK's best loved bands - Keane tickets are now available as they come back to the UK with their largest tour in a couple of years. We love Keane and one of the reasons we love them so much is that they always deliver live performances of fire, emotion and magnetism
Their LP Strangeland entered the UK charts at number one and has been considered one of their best pieces of work to date. Electric vocals, moving harmonies - the lot - it's all there and in abundance.
Don't miss Keane on their tour in 2012! and hopefully into 2013
Keane Tickets are available on Seatwave with a 100% Guarantee, so snap up your tickets today!


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(2740 North Clarkson)
The experienced therapists and friendly staff at Excel provide the highest levels of physical therapy and service in Fremont.
To schedule an appointment or to learn more …
Call: 402.721.0235
Fax: 402.721.6167
Email: firstname.lastname@example.com
We're here to help
Chris Wormuth, PT
Director & Physical Therapist:
Additional Physical Therapists:
Troy Post, PT
Jamie Crow, PT
2740 North Clarkson Street, Suite 2
Fremont, NE 68025
Hours: Monday-Friday 7:30-5:30
Chris Wormuth, PT, Director
Fremont (2740 N. Clarkson)
A native of Blue Hill, NE., Chris completed his undergraduate studies at The University of Nebraska-Lincoln. Chris then went on to earn his Doctoral degree in Physical Therapy from Creighton University in 1996.
Chris is a Board Certified Orthopedic Clinical Specialist and has been a clinic director for Excel Physical Therapy since 2000.
Injuries. Nagging pain. Surgery rehab.
Back & Neck | Shoulder | Elbow | Hand & Wrist | Hip | Knee | Ankle & Foot


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I'm incredibly pleased to report that the first poem I ever submitted to a publisher, "Reflections: The Mirror Speaks," was bought by Enchanted Conversation and will appear in the Snow White issue. * * * My story "Not the Best Neighbors" will appear in Marion Zimmer Bradley's Sword and Sorceress XXVI, coming out in November from Norilana Books. * * * My story "Soul Walls" is in Norilana Books' anthology Marion Zimmer Bradley's Sword and Sorceress XXIV, edited by Elisabeth Waters. (Scroll down the page for the proper volume.) S&S 24 is also available as an ebook in many formats at Fictionwise. Publishers Weekly has this to say about Sword and Sorceress XXIV: "Waters ably continues the feminist anthology series founded by Bradley (1930-1999) to showcase short-form fantasy with a wide variety of heroic female characters. Of the 17 stories featured, standout selections include "A Curious Case" by Annclaire Livoti, a literary gem of a paranormal fantasy that pits a magic-practicing PI against a serial killer targeting succubae, and Julia H. West's "Soul Walls," which brilliantly fuses magic, art and Native American mysticism. A disorganized wizard and his unhappy wife are at the heart of the charming "Merlin's Clutter" by Helen E. Davis, and a princess solves the mystery of her father's murder through a magical tapestry in Brenta Blevins's "Material Witness." Though some of the selections are less than stellar, fantasy fans looking for original stories will find much to enjoy." (emphasis mine) (Scroll to the bottom if you're looking for the review on PW's page.) Jonathan Moeller interviewed me about the story; that interview is at his blog (which also contains interviews with many of the other authors from S&S 24). |
This iteration of the homepage created 20 April 2011
Last updated 12 June 2011 97782 people have visited this page since July 15, 1996. |


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Call 311 or go to 311 Online to request street tree services, including reporting emergencies, pruning, removals, and planting. Your request will be fulfilled based on the following schedule:
Call 311 or go to 311 Online to request street tree services, including reporting emergencies, pruning, removals, and planting.
Your request will be fulfilled based on the following schedule:
DDOT's Urban Forestry Administration (UFA) is on-call 24 hours a day to respond to tree emergencies that are blocking transportation corridors. Call 311 (311.dc.gov) to report any fallen trees or limbs in public space.
Private property trees and limbs that fall are the responsibility of the property owner. The owner should call a private tree contractor to remove any of their fallen trees or limbs.
If wires are involved, contact Pepco immediately at (202) 872-3432 and do not touch the tree or wire. Trees can become energized and dangerous. Pepco and its contractors are the only entities in the District of Columbia authorized to conduct tree work within 10 feet of power lines.
During events with multiple tree incidents, DDOT will clear, in order of priority, major arterial streets, minor streets, alleys for emergency vehicle access, and sidewalks.
UFA's primary mission is to plant and maintain the city's street trees. Street trees are those located between the curb and sidewalk. UFA also clears fallen trees and limbs from roadways and sidewalks, and moves or removes fallen trees or limbs that impede vehicular passage through alleys. UFA does not conduct work on private property trees, nor does it maintain or remove trees from alleys; these are private property issues that must be addressed by the affected property owner.
UFA plants between 3,000 and 4,000 street trees each year. Residents may request a tree for an existing, empty tree box or continuous planting strip (grass strip) in front of their residence or trees for an entire block by calling 311. All planting requests must be submitted before June 15th to be processed for the upcoming fall/winter planting season.
UFA prunes the District's street trees to maintain the trees' overall health, form, and safety for the area around the tree. UFA also prunes to give clearance over sidewalks and roadways, followed by minor roadways, alleys (to allow passage for sanitation and emergency vehicles), and pedestrian walkways. UFA inspects any street trees that may have fallen on homes or vehicles and will clear them in a timely manner.
Private property trees that fall into public space are the owner's responsibility to clear within 24 hours.
UFA removes trees that are dead, dying/diseased, or unsafe (those that have structural and/or dangerous root defects which cannot be corrected).
UFA removes trees in a three part process
UFA follows this removal sequence because of the different equipment needed for each part of the tree.
For more information about Dutch Elm Disease, see the page called Tree Diseases.
The public space trees that are marked with a yellow dot are female Ginkgo biloba trees. The Urban Forestry Administration treats these trees with Pincher PGR to inhibit the fruit development. In the past the Urban Forestry Administration has sprayed these trees to provide the same effect. By injecting the trees, we reduce the amount of water used and that allows us to directly apply the chemical to the internal parts of the tree.
For more information about female ginkgo management, see the page called Female Gingko Tree Removal Policy.


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"After my first month of Bios Life Slim I had to
return a recently purchased pair of pants because
they were too big! I'm wearing clothes I haven't been
able to wear in years."
- Eleanor L., Georgia
"I remember when I was fat, and I
would have paid any amount of money to feel the
way I do now."
- Roy R., Hawaii
"I will continue to take Bios Life Slim because it curbs
my appetite with no jitters, it tastes delicious, but
more importantly, it has improved my quality of life."
- Rolanda B., Tennessee


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Upon Further(er) Review with JoeSportsFan
It's bizarre that the "Pardon the Interruption" paradigm still has so much appeal, given that it first aired in 2001. It's not a unique concept. Dan Caesar is employed by the Post-Dispatch, there's very little chance that he'll look at his institution's new installment with a critical eye. Thus, we continue our series entitled, "Upon Further(er) Review".
Read moreWhen we interviewed Rally STL head honcho Aaron Perlut in Episode 28 of the JoeSportsFan Show, he indicated that the ideas submitted by citizens of St. Louis suggesting ways to improve our city were already streaming in. He wasn't exaggerating. Since the voting was opened on December 1st, ideas have been unveiled daily on the [...]
Read moreOn the "Bob and TJ Raines Show" this afternoon on 1390 AM, newcomer Randy Choate was asked about the little-known fact on his Wikipedia page. What transpired is pretty tremendous. Listen here.
Read moreUpon Further(er) Review with JoeSportsFan
The intersection of old school talent with new school media is fascinating and the bar for uniquely-produced video in St. Louis needs to be pushed. We're excited for the release of Bryan Burwell's online video series, but cynical of the execution. Since the Post-Dispatch's own media critic is unlikely to document the evolution of this series, we're taking it upon ourselves to do so.
Read moreRoughing the Passer Call on Robert Quinn Deemed Legitimate
St. Louis Rams defensive end Robert Quinn was the victim of what many believed was an extremely poor call when he was flagged for roughing San Francisco 49ers quarterback Colin Kaepernick late in the fourth quarter of Sunday's 16-13 overtime Rams victory. The call was part of a drive that culminated in a field goal [...]
Read moreWe posted this list a few years ago, but given the recent accolade as the "best sitcom of all-time", it was worth recalling. That is, a comprehensive list of baseball players mentioned throughout the storied history of "Seinfeld". Spoiler alert: Willie McGee, included.
Read moreThe End of the Dave Yost Photoshop Era
When word came out yesterday that Mizzou Offensive Coordinator Dave Yost resigned from his position for "personal reasons", Tigers fans knew we had lost a unique character. Whether it was his long blonde hair or the baseless accusations that he was listening to Phish songs on his headset during games, Yost was a frequent target for the message board hecklers' most effective weapon – Photoshop.
Read moreJoe Strauss recently transitioned into the #2 columnist slot after serving as the lead Cardinals honcho since coming to the paper in 2002. We brought him aboard this digital jamboree to chat about his promotion, his favorite athlete to cover, the best press box in the country and where the industry is headed.
Read moreThe Siren Song of Howard Griffith
Even before the glory days of Patrick, Kilborn, and yes, even Olbermann, sports highlight show anchors have long been notorious for coming up with "catch phrases" or recurring bits to use in their highlight segments. Some are good. Some are bad. Some start out as good, but after hearing them 100,000 times make you wish [...]
Read moreWe've talked about it before; horribly produced and/or insanely bizarre videos are typically the ones that go viral on the internet. But this one crosses that line. Admittedly, we felt a little awkward for watching this thing to its finality.
Read more


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Copyright FAQS
This is a brief overview of common questions. For more infomation please contact the University Copyright Officer.
How much can I copy from a book?
No more than one chapter or 10%
Can I put the one chapter or 10% I have copied in Blackboard?
No. No more than one chapter or 10% of a book may be posted online at the same time across the entire University. The University must also provide a central register of this material. To manage this process it is a requirement that all material copied from books is managed via Short Loans.
I want my students to read a chapter from a book urgently and I don't have time to put it into Short Loans. What should I do?
Always check Newcat first. The book may be available electronically, or another lecturer may have requested that the chapter is put into Short Loans already.
Contact Short Loans. They will be able to advise how long the item will take to process. It may be quicker than you think.
You may also hand out copies of the chapter in tutorials provided you do not hand out more than one chapter or 10% from a book in any one course during the one semester.
What if the "book" is a play or a script?
Plays are literary works and treated the same as books for the purpose of copyright
Can I copy a whole music score?
Music scores are literary works and treated the same as books for the purpose of copyright. So you may only copy 10% of a score.
Journal articles
How much of a journal article can I copy?
You may copy an entire article.
Can I copy more than one article from the same issue of a journal?
You may only copy more than one article from a single issue of a journal if the articles are on the same subject matter.
Can I copy an entire issue of a journal from for example the journal Biology because all the articles are about Biology?
No. To be permitted to copy more than one article the articles must be about the same specific subject, not a general subject area.
Can I copy an article from a print journal and post it in Blackboard?
No. No more than one copy of the article may be posted online at the same time across the entire University. The University must also provide a central register of this material. To manage this process it is a requirement that journal articles are handled via Short Loans.
Can I scan a copy of an article from a database and post this in Blackboard?
In most cases the answer is no, but it will depend on the licence agreement the University has with the particular database publishers. We recommend that you get Short Loans to manage this process for you.
What is an artwork for the purposes of copyright?
Artworks include maps, diagrams, charts, drawings, paintings, cartoons, prints, engravings, photographs, illustrations.
What if I wrote the book or the article or created the artwork? Doesn't this mean I can do what I like with it?
Not necessarily. If the item has been published, copyright may now belong to your publisher. Check your publishing contract or contact your publisher to find out what your rights are.
Can I use whatever I want from the internet?
No. Copyright law doesn't change because something is available on the Internet. You are subejct to the same restrictions as in other forms. If someone posts something on the Internet that they are happy for you to use then they will usually make it clear on the page that other people have a licence to use it.. You are also not permitted to put something on the Internet when you do not own the copyright.
Can I show a DVD in a lecture?
Can I show a Youtube clip in a lecture?
Yes, You may show Youtube clips and other material from the Internet in lectures. You may do this by streaming from the website. You are not permitted to mak copies without permission from the Copyright owner.


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The fastest way to learn about another culture is by immersing yourself in its life and language. Join us on our affordable study abroad program next summer to visit a rich landscape of volcanoes, cloud forests and tropical beaches. Earn college credits while recording your impressions through travel journals, learning to draw and write with EvCC instructors Linda Berkley, Studio Art and Phebe Shen, English.
After flying into San Jose, we soon meet our host families for our first week's stay in San Joaquín, suburb of Heredia. San Joaquín offers a typical "Tico" or local Costa Rican life style surrounded by countryside of coffee and sugar plantations, while only 30 minutes away from Costa Rica's capital. Each morning we attend semi-private Spanish language classes held at the prestigious Centro Panamericano de Idiomas (CPI), Heredia campus complimented with Art/English studies and daily tours or cultural activities. We will cook a typical Latin lunch, visit museums in San Jose, tour botanical gardens and a traditional ox cart workshop in Sarchi, sketch nature and wildlife on site at the Poas Volcano and the La Paz Waterfall gardens and take a Latin dance class.
We walk guided nature hikes through local trails and national reserves, visit local coffee plantations, sustainable farms and arts and craft cooperatives, soar over the rainforest canopy on ziplines and encounter tropical wonders of plant and wildlife; hummingbirds, orchids, monkeys, quetzals, wild cats, 5% of the world's biological diversity. Our observations expand in Art/English travel journals, recording the peaceful beauty of the rainforest in sketch and prose.
We descend from the mountains by private van to the southern coast, via a river tour on Rio Tarcoles, crucial habitat for the American crocodile. Our travels conclude with a weekend at Manuel Antonio, with a guided nature hike in the National Park and time to relax on the beach or at the hotel pool before returning to San Jose and flights home.
2013 Summer Program Dates:June 15 – 30, 2013Program Cost as of October 2012:$2,000 Not included: Airfare, EvCC tuition, passport and personal expenses.
Students earn EvCC credits by enrolling Spring Term 2013 for ART 299 (1 credit) and ENGL 299 (1 credit) as part of their regular class schedule. Regular tuition policies apply for all EvCC credits and are not included in the quoted program costs.
Students who already meet EvCC's requirements for financial aid and who are interested in participating in the study abroad program should speak with an EvCC Financial Aid advisor for further information on available funding.
For more information or for an application, contact Linda Berkley, Studio Art Faculty, (425) 388-9318 or Phebe Shen, English Faculty, (425) 388-9410 at Everett Community College.
Additional Links:CPI Helpful Information 2013 How to Apply for a US Passport USPS Passport Application
Costa Rica Study Abroad
Program Faculty
Linda BerkleyStudio Art Faculty 425-388-9318 Whitehorse Hall 308
Phebe ShenEnglish Faculty 425-388-9410 Gray Wolf Hall 216
Program LinksBrochure Application Participation Agreement and Liability Waiver Trip Contract and Payment Schedule Payment Instructions Scholarship Study Abroad
Additional LinksCPI Helpful Information CPI Spanish Immersion School UGA Costa Rica Campus Manuel Antonio National Park USPS Passport Application How to Apply for a US Passport


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La Mirage in Apartment Rentals in San Diego, CA
6554 Ambrosia Dr
San Diego,
Find Your Apartment Now
Popular Nearby Apartments:
Property Description:
La Mirage Apartments Description
La Mirage apartments are located atop a secluded hill overlooking Mission Valley and is a unique, pet friendly community offering the best of recreation and urban lifestyle! Choose from a variety of apartments and two-story town homes featuring gourmet kitchens, spacious closets, washers/dryers and reserved parking. Relax in the luxurious pools or visit with friends at the cappuccino and smoothie bar. Try a free yoga or aerobics class at our state-of-the-art fitness center or head to the jogging trail, lighted tennis courts or sand volleyball court. La Mirage apartments are convenient to all major freeways, upscale shopping, dining and night spots.
Pet Policy:
Cats and Dogs are allowed.
- Pool
- Spa
- Sauna
- Fitness Center
- Elevator
- High Speed Internet Available
- Business Center
- Basketball Court
- Tennis Court
- Volleyball Court
Search Nearby Cities
- Carlsbad Apartments
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Search Nearby Zip Codes
Search Nearby Neighborhoods
Apartment Rentals Near San Diego, CA
- Avalon Fashion Valley 7084 Friars Road San Diego, CA 92108 Phone Number: (619) 268-6624
- AVA Cortez Hill 1399 Ninth Ave San Diego, CA 92101 Phone Number: (619) 450-1264
- The Promenade Rio Vista 2185 Station Village Way San Diego, CA 92108 Phone Number: (877) 941-0531
- The Reserve At 4s Ranch 10411 Reserve Dr San Diego, CA 92127 Phone Number: (877) 941-0427


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Since I last posted, much has changed, and I'm on the verge of yet another career transition.
Midway through last year, I finished my degree and will be graduating in April at which point I will Margaret Morgan B.A. LL.B B.Adv.Sc. Probably enough letters to be going on with, although I confess I have been thinking deeply about whether or not to continue formal studies.There were two possibilities: staying with science and moving into post-grad, or starting a PhD in Media Studies (creative practice).
Both had their allure. The former, because, well, science. But that would have entailed another five or so years of study and grunt work, with some opportunity for original research, but essentially I'd end up just as a baby scientist and given my er... maturity, I don't want to be a baby again. The latter would have given me an opportunity to write the science fiction novel that's been gurgling around my brain for the last year or so, but would also have required writing a 40,000 word thesis (exegesis) which wasn't too attractive a concept. I want to write, but I want to write what I want to write.
So the decision has been made. I'm writing the novel.
Meanwhile, I've started writing for the Australian Independent Media Network, on science. My first piece, on plants and climate change, will be up there soon. I'll be publishing here everything I publish there, but it'd be great if you could visit the AIMN site and comment there, if you're inclined. It's a worthy site, devoted to providing a forum for non-mainstream media Australian writers and journalists.
And because I hate a blog post without graphics, here's a shot of my husband and me on our recent trip to Europe, visiting his family in the Netherlands. Snow!
I hope you'll continue to follow my blog and meandering career, in their new incarnation!


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23 photos Featured
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Great value here! Incredibly planned out 1 and 2 bedroom apartment homes with washer, dryer, dishwasher, disposal, wood-burning fireplace, huge private …
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Haes AJ, Chang L, Klein WL, Van Duyne RP. Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensor. J Am Chem Soc. 2005 Feb 23;127(7):2264-71. PubMed Abstract
These are observations of great importance, because they help bridge the gap between the amyloid hypothesis and the neuroinflammatory hypothesis of AD. These interrelated mechanisms may help explain the positive clinical effects my colleagues and I have observed using anatomically targeted anti-TNF treatment in AD (Tobinick et al., 2006) and underscores the need to further... Read more
These are observations of great importance, because they help bridge the gap between the amyloid hypothesis and the neuroinflammatory hypothesis of AD. These interrelated mechanisms may help explain the positive clinical effects my colleagues and I have observed using anatomically targeted anti-TNF treatment in AD (Tobinick et al., 2006) and underscores the need to further investigate this treatment approach (see also Tweedie et al., 2007). References:Rowan MJ, Klyubin I, Wang Q, Hu NW, Anwyl R. Synaptic memory mechanisms: Alzheimer's disease amyloid beta-peptide-induced dysfunction. Biochem Soc Trans 2007 Oct; 35(Pt 5):1219-23. Abstract
Wang Q, Wu J, Rowan MJ, Anwyl R. Beta-amyloid inhibition of long-term potentiation is mediated via tumor necrosis factor. Eur J Neurosci 2005 Dec; 22(11):2827-32. Abstract
Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha Modulation for Treatment of Alzheimer's Disease: A 6-Month Pilot Study. MedGenMed 2006; 8(2):25. Abstract
Tweedie D, Sambamurti K, Greig NH. TNF-alpha Inhibition as a Treatment Strategy for Neurodegenerative Disorders: New Drug Candidates and Targets. Curr Alzheimer Res 2007 Sep; 4(4):375-8. Abstract View all comments by E T
There are at least two explanations for the difference observed:
1. The dimer is broken down from a larger oligomeric species through immunoprecipitation and Western blot.
2. The dimer is bound to a larger protein which gives a molecular weight of more than 65 kDa.
[Editor's note: see Oligo report Part 2] View all comments by Lars Lannfelt
It is true that during my Minisymposium talk, I reported a greater than 3-fold increase in Aβ*56 levels in brains of individuals clinically diagnosed with MCI or AD. Aβ*56 levels in both MCI and AD groups were not different compared to each other, suggesting that Aβ*56 may be a molecule initiating Aβ-induced cognitive decline. I also mentioned that we did not observe changes in levels of soluble monomeric Aβ, nor in levels of Aβ trimers. Finally, we reported that cerebral levels of Aβ*56 are inversely correlated with MMSE score, while soluble Aβ monomers, Aβ trimers, or amyloid burden were not associated with neurological status.
As for our poster presentation, we demonstrated that Aβ*56 was not associated with changes in levels of synaptophysin or drebrin (among other pre- and... Read more
As for our poster presentation, we demonstrated that Aβ*56 was not associated with changes in levels of synaptophysin or drebrin (among other pre- and postsynaptic markers), suggesting that Aβ*56 is not triggering synaptic loss (contrary to 7PA2 CM-derived Aβ dimers/trimers). In addition, we reported that in human tissues, trimeric Aβ levels were dependent on monomeric Aβ levels. Finally, Aβ dimers were not detected in soluble fractions of protein extracts from human or transgenic mouse brains. View all comments by Sylvain Lesne
That the three oligomeric forms of Aβ (7PA2 derived small oligomers; high "n"-oligomers termed ADDLs; and "star"-oligomers) exhibit deleterious effects at various concentrations, in various experimental paradigms, is not surprising, and perhaps, not significant. After all, the literature of the 1990s is littered with reports of Aβ monomers or fibrils being toxic to cells. What is important (to come out of the San Diego meeting) is that two studies found the presence of Aβ oligomers in the AD brains but not in the control tissues. Surely, this should silence the critics, right?
In oral and poster presentations, Lesne et al. reported increased levels of Aβ*56... Read more
In oral and poster presentations, Lesne et al. reported increased levels of Aβ*56 oligomers in brains from AD patients but apparently did not find a similar increase in the small oligomers. Conversely, Shankar et al. found increased levels of Aβ dimers/trimers in AD patients but detected no star oligomers. If Aβ oligomers are the causative factors of the disease and exist in AD brains, one wonders whether this is too much of a coincidence that these two groups observed only "their" type of oligomers from AD brains.
An important assumption underlying both these studies is that the oligomeric forms of Aβ, detected at the end of a Western blot protocol, already exist in the diseased tissue prior to homogenization/isolation/purification/detection. However, Aβ is an amphipathic peptide (hydrophobic at one end and hydrophilic at the other), and work by Teplow, Bitan, and colleagues has conclusively shown how easily Aβ can create different higher-order multimers depending on experimental conditions. Some may consider this to be hypercritical, but the observation that two productive and respected groups in the field find only their favorite oligomers in AD brains should raise alarm bells: do oligomers exist in vivo or are they created by the very experimental manipulations that are used to detect their presence? Surely, two different protocols are likely to yield two different higher-order forms.
It is a common observation that naysayers are often irritating and sometimes wrong, but objective, dispassionate criticism is essential for the relevance of the amyloid hypothesis (which has been instrumental in promoting AD research) to AD pathogenesis. Shrek, the large, green, intimidating giant also caught our attention and we have come to like it. However, unless ogres exist in real life, Shrek adds little value to our lives other than entertainment. References:Bitan G, Fradinger EA, Spring SM, Teplow DB. Neurotoxic protein oligomers--what you see is not always what you get. Amyloid. 2005 Jun 1;12(2):88-95. AbstractView all comments by Sanjay W. Pimplikar
1. We observe entry into the cell cycle (as evidenced by expression of cell cycle proteins and DNA replication by FISH) of selected neuronal populations in our APP YAC transgenic mouse model of AD at 6 months of age. This cell cycle entry is dependent upon amyloidogenic processing of APP and occurs about 6 months prior to Aβ deposition.
2. We can identify the presence of Aβ oligomers at this age (bands on SDS-PAGE) recognized by both 6E10 and the oligomer-specific antibodies NU1 and A11, including the presence of dimers and trimers as well as higher-MW Aβ species.
3. In-vitro preparations of oligomeric Aβ (prepared in Hams F12 media or purified via SEC) and, to a much lesser extent, monomeric Aβ, induced concentration-dependent aberrant neuronal cell cycle entry as measured by BrdU incorporation and expression of cell cycle proteins, in primary cortical neurons. Oligomeric Aβ also induced loss of... Read more
3. In-vitro preparations of oligomeric Aβ (prepared in Hams F12 media or purified via SEC) and, to a much lesser extent, monomeric Aβ, induced concentration-dependent aberrant neuronal cell cycle entry as measured by BrdU incorporation and expression of cell cycle proteins, in primary cortical neurons. Oligomeric Aβ also induced loss of neurites.
4. Exposure to increasing concentrations of in-vitro preparations of oligomeric Aβ induced altered morphology of primary microglia, consistent with activation and similar to that observed with lipopolysaccharide (LPS). Conditioned media from oligomer-exposed or LPS-stimulated microglia also induced neuronal cell cycle entry, suggesting that Aβ oligomers may act both directly on neurons and perhaps indirectly through activation of microglia.
[Editor's note: See also ARF conference story on cell cycle symposium.] View all comments by Kiran BhaskarView all comments by Karl HerrupView all comments by Bruce LambView all comments by Nicholas H. Varvel
Oligomers as Alzheimer's toxins. Thanks to the work of many labs, we now know that soluble Aβ oligomers are long-lived, neurologically active molecules, not simply... Read more
Oligomers as Alzheimer's toxins. Thanks to the work of many labs, we now know that soluble Aβ oligomers are long-lived, neurologically active molecules, not simply intermediates in fibrillogenesis. Oligomers accumulate in brains and CSF of individuals afflicted by AD, where they are believed responsible for dementia-producing neuron damage (see, e.g., the "Pathway to Harm," in the Progress Report on Alzheimer's Disease published by the Department of Health and Human Services). Neurologically active oligomers have been given many names—we initially called them ADDLs, for Aβ-derived diffusible ligands. (The pronunciation, by the way, is "addles," as in "Not paying attention to the Alzheimer Research Forum addles the brain.") Their oligomeric structure endows ADDLs with the capacity to attack particular synapses, mainly at spines and near NMDA receptors. In essence, extracellular ADDLs act as gain-of-function pathogenic ligands. This capacity for highly specific synaptic targeting provides a putative mechanism to explain why AD is a disease of memory. Binding disrupts synaptic plasticity, causes overexpression of the memory-linked immediate early gene Arc, and triggers pathological changes in synapse shape and composition. Because ADDL binding also instigates synapse loss, oxidative damage, AD-type tau hyperphosphorylation, and selective nerve cell death, the attack on synapses provides a plausible mechanism unifying memory dysfunction with major features of AD neuropathology. Most recently, ADDLs were shown to trigger downregulation of synaptic insulin receptors, providing a mechanism to explain insulin resistance in AD brain ("type 3 diabetes"; Zhao et al., 2007). Acting as novel neurotoxins that putatively account for memory loss and neuropathology, ADDLs present significant targets for disease-modifying therapeutics in AD, with proof-of-concept already evident from animal models.
Structurally speaking, Aβ is the peptide from hell. I've lost track of who wrote this first, but the truth still holds. Aβ is one-third hydrophobic, two-thirds hydrophilic, and almost 100 percent erratic in its biochemistry, which is why the problem of how Aβ produces Alzheimer's dementia is still unsolved after almost 25 years. Darwin may have been thinking of something like Aβ when he said, "Nature will tell you a direct lie when she can."
The challenges in working with Aβ are exemplified by the remarkable contentiousness of the early 1990s regarding whether Aβ was or was not toxic—some evidence said yes, other evidence said no. Fortunately, despite Aβ's recalcitrance, insightful research can outsmart it. Seminal work by Christian Pike and Carl Cotman, Alfredo Lorenzo and Bruce Yankner, and their colleagues, resolved the controversy by showing that Aβ preparations are indeed toxic but only if monomers undergo a process of self-assembly. Since their toxic solutions showed amyloid fibrils, it was concluded that toxicity required these emergent fibrils. The apparent requirement for fibrils, certainly consistent with Occam's razor, provided major support for the original amyloid cascade hypothesis. It made good sense at the time that Alzheimer's was a pathology of nerve cell death instigated by large insoluble amyloid fibrils.
In keeping with this concept, the first reports of SDS-stable oligomers in AD brain regarded oligomers simply as subunits responsible for ongoing formation of fibrils. Colin Masters, Konrad Beyreuther, and colleagues found that formic acid extracts of isolated amyloid plaques contained dimers and tetramers, as well as a pH-sensitive presence of larger oligomers (Masters et al., 1985). Janusz Frackowiak et al. in 1994 showed SDS-stable dimers and tetramers in extracts of meningeal blood vessels; they concluded that during amyloid formation in AD vessel walls, non-fibrillar oligomers accumulate (Frackowiak et al., 1994). However, 1994 also brought a glimmer of an extremely different concept for structure and toxicity. Tomiichiro Oda and colleagues, working in Tuck Finch's lab, mixed Aβ with clusterin (ApoJ) and found large fibrils were blocked from forming (Oda et al., 1994). They anticipated a protective effect. To their surprise, their non-pelleting material robustly impaired the ability of PC12 cells to metabolize MTT. They wrote, "Inhibition of Aβ aggregation and enhancement of Aβ toxicity by clusterin suggest new mechanisms in AD." Supporting this possibility, Alex Roher and colleagues reported that dimers chemically extracted from amyloid deposits were capable of killing neurons via a mechanism requiring microglia (Roher et al., 1996).
Stimulated by the clue provided by Oda et al., our group collaborated closely with Tuck Finch and Grant Krafft in studies that lead to the first ADDL paper (Lambert et al., 1998). Together, we identified small Aβ oligomers as a new type of neurotoxin structurally distinct from amyloid fibrils and protofibrils. We coined the name ADDLs to broadly cover this new class of soluble Aβ-derived molecules showing potent CNS neurotoxicity. We described three different preparative methods, and all yielded solutions of neurotoxic Aβ assemblies that were totally free of fibrils and protofibrils. By atomic force microscopy, ADDLs comprised globular structures roughly comparable in size to soluble proteins smaller than 50 kDa. SDS-PAGE with Tris-glycine gels indicated the assemblies were made of SDS-resistant tetramers and pentamers. Currently, Western blots using Tris-tricine gels with BioRad markers routinely show trimers, tetramers, and 12mers. Native, non-denaturing gels also showed fibril-free oligomers, so oligomers were neither SDS-induced nor products of protofibril breakdown. A later study confirmed that fresh Aβ42, never put in aqueous solution, migrates as monomer in SDS-PAGE (Chromy et al., 2003). In terms of structure-function, the bottom line was that certain conditions promote assembly of Aβ into potent CNS neurotoxins that comprise long-lived soluble oligomers.
The Lambert paper revealed an aspect of ADDL activity that, because of its clear relevance to memory mechanisms, made this new toxin particularly exciting. Within minutes, and greatly in advance of cellular degeneration, ADDLs inhibited long-term potentiation (LTP). We hypothesized that memory dysfunction in early Alzheimer's was the result of impaired synaptic plasticity caused by ADDLs.
At the end of our Discussion we wrote, "ADDLs thus have profound neurological effects well in advance of tissue damage. If Aβ derivatives such as ADDLs prove to be part of Alzheimer's pathogenesis, these results suggest that it would be theoretically feasible to halt or reverse the disease during its early stages." Our prediction that memory loss could be reversed was confirmed 4 years later in mouse model passive immunization experiments by Steve Paul's group at Eli Lilly (Dodart et al., 2002) and Karen Ashe's group at Minnesota (Kotilinek et al., 2002). Most recently, the use of conformation-sensitive antibodies targeting non-monomeric Aβ in memory recovery experiments by Trojanowski and Lee specifically supported the pathogenic role of oligomers (Lee et al., 2006).
A PubMed search of amyloid-β oligomer(s) now yields over 500 hits. Knowing what is implied structurally by "toxic oligomer" has become a central issue. There clearly is a wide variety of preparations, resultant structures, and even nomenclature. With respect to ADDLs, the name is generic and broadly encompasses oligomers associated with dementing activity. It was chosen to sharply distinguish AD-relevant globular assemblies from fibrillar toxins.
A neurologically active ADDL preparation typically comprises two classes of oligomers by HPLC-SEC in aqueous buffer. Some migrate in a peak near putative 12mers and some migrate in a peak near putative 3- and 4mers. The relative abundance of the peaks varies from preparation to preparation. The two peaks also can be separated by ultrafiltration. Both peaks are SDS-resistant but not completely SDS-stable, as indicated originally in the Lambert paper. Silver stains from each peak show prominent 4mers, 3mers, and monomers; this is the case even for the larger peak, which contains oligomers that do not pass a 50 kDa cutoff filter in aqueous solution. Ultrafiltration actually indicates that ADDL preparations in physiological buffer contain almost undetectable amounts of monomer (compared, e.g., with positive controls using Aβ40 monomers). The fraction comprising larger oligomers, when analyzed by Western blots with our conformation-sensitive antibodies, shows 12mers. In overexposed Western blots of ADDLs, it is possible to detect a full spectrum of oligomers up to 24mers, although particular species (3- and 4mers, and 12mers) are favored in a temperature-dependent manner (Klein, 2002). We note that some non-toxic Aβ preparations also show oligomers (Chromy et al., 2003), so quality control monitoring both structure and function is essential. Greatly increased SDS-resistance in the 12mer fraction is promoted by incubation with certain prostaglandins or levuglandins (Boutaud et al., 2002; Boutaud et al., 2006) or by copper and H202 (Atwood et al., 2004).
The fraction with 12mers is particularly interesting to us, because it contains the most striking ligand activity, detected as binding to particular synapses in cell biology experiments (Lacor et al., 2004; 2007). The 12mer fraction also gives the most robust induction of drebrin loss and synaptic spine degeneration (Lacor et al., 2007). Regarding our fraction of 3- and 4mers, current data suggest much less binding and pathogenicity, although absence of evidence is not necessarily evidence of absence. We are investigating possible neuronal responses to the small ADDLs. The findings of Walsh, Selkoe, and colleagues are extremely significant and certainly substantiate a robust pathogenicity for trimers produced by cellular metabolism.
Oligomers in AD brain. The salient issue is the nature of toxins in human brain—what are the neurologically significant oligomers in AD-afflicted brain tissue? Can these molecules explain why early Alzheimer's is a disease of memory, and can they account for AD's other major pathologies?
Our studies of human brain samples using physiological buffer for gentle extraction showed that human brain-derived ADDLs and synthetic ADDLs are biologically and structurally equivalent (Gong et al., 2003). Whether obtained from Alzheimer-affected brain or prepared in vitro, ADDLs act in cell biology experiments as specific ligands that bind to particular synapses (Lacor et al., 2004), a specificity that strongly suggests equivalent conformation in solution. After binding, both ADDLs stimulate AD-type hyperphosphorylation of tau (De Felice et al., 2007). With respect to direct structural comparisons (Gong et al., 2003), human ADDLs are readily detected by conformation-sensitive antibodies that we previously generated against synthetic ADDLs (Lambert et al., 2001). The antibodies, which recognize assembled Aβ but not monomers, bind human and mouse brain-derived and synthetic ADDLs in blots, in solution, and when attached as ligands to synapses, consistent with conformational equivalence. The antibodies also prevent both types of ADDLs from binding to synapses and triggering tau hyperphosphorylation. With respect to precedents for conformational-sensitive antibodies, several years earlier Austin Yang, Charlie Glabe, and colleagues found that antibodies they produced could discriminate in Western blots between monomers and larger structures they called insoluble amyloidogenic fragments—which we now would recognize as Aβ oligomers. They noted their blots were consistent with conformational epitopes being uniquely present in the larger structures (Yang et al.,1995).
When we used 2D gel analysis to look further at structure, we found that both brain-derived and synthetic ADDLs show pIs of 5.6. Of greatest interest, given current attention to oligomer size, both brain-derived and synthetic ADDLs were found to comprise prominent 12mers (54 kDa).
The fact that AD brain manifests 12mers that act as pathogenic synaptic ligands is particularly significant given the subsequent detection of neurologically active 12mers in transgenic mouse models (Lesne et al., 2006). The mouse 12mers become detectable roughly coincident with the onset of memory dysfunction. The 12mers in the mouse model have been referred to as Aβ*56 by Sylvain Lesne, Karen Ashe, and colleagues. The extent to which the mouse 12mer differs from the pathogenic human 12mer has not yet been determined.
Isolation of neurologically active dimers from Alzheimer's brain tissue reported at the SfN meeting by Ganesh Shankar, Dennis Selkoe, and colleagues, and summarized by Gabrielle for ARF in this news series, is the latest important addition to our understanding of the involvement of oligomers in dementia.
For all the oligomers—whether dimers, 12mers, or other pathogenic species still to be characterized—we'll need to learn how they form, why they accumulate, how they target particular neurons, and the extent to which they give a unifying mechanism that explains AD memory loss and brain pathology. These are still big questions for small toxins….
As if that were not enough, one final point makes these questions even more important. We should remember that Aβ oligomers represent a whole new type of toxic structure derived from a fibrillogenic protein. Now a number of other fibrillogenic, disease-causing proteins have been found to generate sub-fibrillar, oligomeric toxins (see Gabrielle's latest SfN story about α-synuclein and also Klein WL. [2006] Cytotoxic intermediates in the fibrillation pathway: Aβ oligomers in Alzheimer's disease as a case study. In Protein Misfolding, Aggregation, and Conformational Diseases. Vol. 1. V. Uversky, ed. Kluwer Academic/Plenum Publishers, New York, NY). Even innocuous proteins can turn toxic when forced to form oligomers (Vieira et al., 2007). Toxic Aβ oligomers were just the first of many. View all comments by William Klein
"For all the oligomers—whether dimers, 12mers, or other pathogenic species still to be characterized—we'll need to learn how they form, why they accumulate, how they target particular neurons,..."
Our lab has been interested in characterizing axonal transport in neurodegenerative diseases, in particular in Alzheimer disease (AD). We wanted to ask whether the Aβ deposition in AD might result from a deficient axonal transport, a question that Dr. Larry Goldstein's lab—and other labs as well—are also trying to answer. Experimentally, this question is difficult to address in animal models of AD, due to the difficulty of identifying early modifications in individual neurons. To circumvent this problem, we have employed a cell culture system, where CAD cells (a mouse neuronal cell line derived from the locus coeruleus) [1] produce and accumulate within their processes large... Read more
Our lab has been interested in characterizing axonal transport in neurodegenerative diseases, in particular in Alzheimer disease (AD). We wanted to ask whether the Aβ deposition in AD might result from a deficient axonal transport, a question that Dr. Larry Goldstein's lab—and other labs as well—are also trying to answer. Experimentally, this question is difficult to address in animal models of AD, due to the difficulty of identifying early modifications in individual neurons. To circumvent this problem, we have employed a cell culture system, where CAD cells (a mouse neuronal cell line derived from the locus coeruleus) [1] produce and accumulate within their processes large amounts of Aβ, similar to what may occur in brain neurons, in the initial phases of AD [2]. Using this system, we showed that accumulation of Aβ likely begins within neurites, prior to any detectable signs of neurodegeneration or abnormal vesicular transport, and long before Aβ deposits are detected extracellularly. We found that neuritic accumulation of Aβ is restricted to a small population of neighboring cells that express normal levels of APP, but show redistribution of BACE1 to the neurites, where it colocalizes with Aβ and markers of late endosomes and autophagic vacuoles. Importantly, cells that accumulate Aβ appeared in isolated islets, indicating that Aβ accumulation is initiated in a small number of neurons, probably by intracellular determinants that alter APP metabolism and lead to Aβ aggregation.
We found the fact that CAD cells occasionally produce and accumulate large amounts of Aβ remarkable, since these are cells that express normal levels of APP (they are not transfected, and only express endogenous APP). Previously, such neuritic accumulations have been mostly found in neuronal cultures derived from mice that largely overexpress mutated human APP (e.g., Tg2576 mice). We found it also very interesting that CAD cells that show neuritic Aβ accumulations may contain such high levels of Aβ that it is detectable by Western blots in whole cell lysates, without immunoprecipitation. Most importantly, this Aβ is oligomeric (we found dimers, trimers, as well as higher-number oligomers detectable with Dr. Charles Glabe's anti-oligomer antibody, A11).
We are now using the CAD cell system to investigate what leads to the formation of these accumulations of Aβ at the neurite terminals, and—most importantly—why these accumulations appear in clusters of cells. Do these cells originate from a few progenitors present in the culture? Are there intrinsic or extrinsic factors that determine this phenotype? Certainly, CAD cells appear to recapitulate some of the biochemical processes leading to Aβ aggregation, and may thus provide an experimental in vitro system for studying the molecular pathobiology of AD. References:1. Qi Y, Wang JK, McMillian M, Chikaraishi DM. Characterization of a CNS cell line, CAD, in which morphological differentiation is initiated by serum deprivation. J Neurosci. 1997 Feb 15;17(4):1217-25. Abstract
2. Muresan Z, Muresan V. Neuritic deposits of amyloid-beta peptide in a subpopulation of central nervous system-derived neuronal cells. Mol Cell Biol. 2006 Jul;26(13):4982-97. Abstract View all comments by Zoia MuresanView all comments by Virgil Muresan
REAGENTS/MATERIAL: Antibodies targeting ADDLs in the LSPR immunoassay (polyclonal M71 and monoclonal 20C2) were generated and characterized as previously described (Lambert, 2001). For the first time, a sandwich assay has been accomplished using the LSPR nanosensor technology.
Antibodies targeting ADDLs in the LSPR immunoassay (polyclonal M71 and monoclonal 20C2) were generated and characterized as previously described (Lambert, 2001). For the first time, a sandwich assay has been accomplished using the LSPR nanosensor technology.
PRIMARY NEWSNanosensor Sizes up Amyloid-β Oligomers in CSF
RELATED NEWSSan Diego: Oligomers Live Up to Bad Reputation, Part 1