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ChordBuddy 1.6.1
Guitar chord diagram dictionary tuner
Last update 20 Mar. 2006 Licence Free to try | $10.00 OS Support Mobile Downloads Total: 183 | Last week: 0 Ranking #36 in Multimedia Publisher Randy Wade
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ChordBuddy Publisher's Description
ChordBuddy is a large guitar chord dictionary for the PalmOS. It features large, easy to read, chord diagrams with four different fingerings for most of the 45 different chord types. Optionally, all four fingerings can be viewed at once to see which will be easier for you to play. Several options are available to customize the chord display. The chords can be played through the palm's speaker. Also, acts as a tuner by emitting reference tones.
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Eddie Tolan
Medal record
Thomas Edward "Eddie" Tolan (September 29, 1908 – January 30/31, 1967),[1][2] nicknamed the "Midnight Express", was an American track and field athlete who competed in sprints. He set world records in the 100-yard dash and 100 meters event and Olympic records in the 100 meters and 200 meters events. He was the first non-Euro-American to receive the title of the "world's fastest human" after winning gold medals in the 100 and 200 meters events at the 1932 Summer Olympics in Los Angeles. In March 1935, Tolan won the 75, 100 and 220-yard events at the World Professional Sprint Championships in Melbourne to become the first man to win both the amateur and professional world sprint championships. In his full career as a sprinter, Tolan won 300 races and lost only 7.
- 1 Early years
- 2 Cass Tech High School
- 3 University of Michigan
- 4 Double gold medals at the 1932 Summer Olympics
- 5 Vaudeville and hard times
- 6 Professional sprinting career
- 7 Civil service and teaching career
- 8 Death and family
- 9 Honors and awards
- 10 See also
- 11 References
Early years[edit]
Tolan was born in Denver, Colorado, one of four children. Tolan's father was Thomas Tolan. The family moved to Salt Lake City, Utah when Tolan was young, and moved again to Detroit, Michigan in 1924, when Tolan was 15 years old.[3] Tolan later recalled, "My father read about better opportunities for Negroes here, so he packed up Mom and the four kids and we came here."[3]
Cass Tech High School[edit]
Tolan attended Cass Technical High School in Detroit where he was an outstanding football player and sprinter. While at Cass Tech, Tolan set state records in the 100 and 220-yard dashes.[3] While still in high school, Tolan ran the 100-yard dash in 9.8 seconds and the 220-yard dash in 21.5 seconds.[4] At age of 16, Tolan was a member of a two-man team from Cass Tech that won the 1925 National Interscholastic indoor meet in Chicago.[5] He won his first sprint double at the state meet as a sophomore, and in 1927 he won the 100 and 220-yard dashes at the National Interscholastic Championship at Soldier Field in Chicago.[1][5][6] Despite his accomplishments as a sprinter, Tolan's first love was football, and he often said "the six touchdowns he scored in one game as a 131-pound quarterback at Detroit's Cass Tech High School was his greatest thrill, rather than his double win in the Olympics."[7]
University of Michigan[edit]
Tolan was recruited by several major universities as a football player, but he chose the University of Michigan.[2] There are differing accounts as to why Tolan never played on the varsity football team at Michigan. According to a published account in The Detroit News in 2002, Tolan joined the freshman football team as a freshman in 1927.[2] At that time, no African-American had played on Michigan's varsity football team since George Jewett in the 1890s. Tolan was initially allowed to play, but on the third day of practice, the freshman football coach told him, "Some of the coaches are disagreeing on your chances. Some of them think that you shouldn't be allowed to play football. I'd be tickled to have you but I'm afraid I'm going to be outvoted."[2] The Detroit News noted, that the freshman coach was outvoted: "They took away Eddie Tolan's football uniform and handed him a track suit in exchange."[2]
Other accounts indicate, it was an injury that prevented Tolan from playing football at Michigan. An Associated Press story on Tolan in 1958 stated: "He would have been a football great as a quarterback, had a knee injury in his junior year in high school not forced him to channel all his energies to track."[3] In his obituary, the Associated Press reported that the coaches at Michigan "talked the pint-sized speedster into going out for track."[7] Tolan was also quoted as saying, "The track team did a lot more traveling then, so I saw the opportunity to travel on a Pullman and see the country."[7]
Big Ten and world sprint champion[edit]
At Michigan, Tolan ran track under the mentorship of two of the great sprinters of their generations. Michigan's head coach, Steve Farrell, was considered "the greatest professional footracer this country has ever known" in the 1880s and 1890s.[8] And Michigan's assistant coach Charles B. Hoyt, who took over from Farrell in 1930, was rated "America's best sprinter" in 1913, but lost his opportunity to compete in the 1916 Olympics due to World War I.[9]
As a sophomore in May 1929, Tolan broke the Big Ten Conference record and tied the world's record for the 100 yard dash with a time of 9.6.[6] Press coverage starting with this world record run, and throughout his career, focused on three features – Tolan's race, his eyeglasses, and his short stocky build. Tolan was one of the first African-Americans to have success in sprinting,[10] and he raced with eyeglasses taped to his head.[2] Various accounts put his height anywhere from 5 feet, 4 inches,[7][11] to 5 feet, 7 inches.[2] One writer noted that Tolan "looks like a church deacon."[12] Another writer described Tolan's appearance this way:
"Tolan, known as the 'Midnight Express,' was five feet six inches (1.7 m) tall and weighed 130 pounds (59 kg). He smiled often, raced while chewing gum, and could be easily identified by a bandage around his left knee to protect an old football injury. In addition he wore horn-rimmed glasses held in place with adhesive tape."[10]
Tolan's gum-chewing became part of his routine. He chewed gum before a race to relieve stress. After accidentally running with the gum in his mouth, Tolan found that he was chewing in sync with his stride. Tolan later began chewing gum as part of his routine, chewing the gum faster when he needed to accelerate his leg movements.[10]
At the Big Ten championships in May 1930, Tolan broke the world's record in the 100-yard dash with a time of 9.5.[13] Tolan's performance was accepted by the International Amateur Athletic Federation as the new official world's record.[13]
Seven weeks after breaking the world's record in the 100-yard dash, Tolan also broke the world's record in the 100 meters race. Competing in Vancouver, British Columbia, Tolan shaved two-tenths of a second off the record with a time of 10-1/5 seconds.[14] Track officials in Vancouver announced after the race, that Tolan's record-setting performance was "all the more remarkable in the fact that he ran uphill, the finish mark being thirty inches higher than the starting point."[14]
Tolan's world-record performances in 1930 brought him international fame, as he became known as the "Midnight Express."[14] In May 1931, Tolan again broke the world's record in the 100 meters event with a time of 10.3 seconds in Vancouver.[15] Southern California sprinter Frank Wykoff jumped to a slight lead, but Tolan came from behind to pass Wykoff at the 100-yard mark.[15]
Tolan graduated from the University of Michigan in 1931.
Double gold medals at the 1932 Summer Olympics[edit]
Lead-up to the Olympics[edit]
After graduating from Michigan, Tolan enrolled at West Virginia State College, where he did "graduate work preparatory to teaching and coaching at a Negro institution."[16] Early in 1932, Tolan was not running at his prior level. Despite the slow start, Dean Cromwell, Chairman of the All American Board of Track and Field, predicted great things for Tolan in his column on 1932's "Olympic Prospects." Cromwell wrote of Tolan:
"Just as spring warms into summer Tolan slides from the class of mediocre sprinters to that of the champions. He is a slow starter, but when the weather gets warm so does Eddie, and off he goes."[16]
While press reports regularly referred to Tolan as "stocky," Cromwell took issue with that characterization:
"Eddie is now 24 years of age, five feet six inches tall and weights about 130 pounds. Although he has always been termed 'stocky' by the press, a comparison of his weight and height will show that he cannot properly be so styled. He is well muscled, though, and in action gives the impression of great running power, with his arms and legs working smoothly and strongly in a machine piston-like manner."[16]
The Olympic trials were held at Stanford University, and Ralph Metcalfe won both the 100 and 200 meters finals, with Tolan finishing second to Metcalfe in each case. The results meant that the top two American sprinters in the 1932 Olympics would for the first time be African-Americans. As a result, much of the press attention focused on race. Los Angeles Times sports columnist Braven Dyer wrote: "Metcalfe and Tolan make the ace of spades look positively pale by comparison … But how these boys can run … And they figure to do even better here than they did at Palo Alto because it's warmer now and they enjoy the heat."[17]
100 meters race[edit]
The 100 meters contest at the 1932 Olympics was one of the closest races in Olympic history. Tolan broke the Olympic record in the first heat of the second round with a time of 10.4 seconds, but Metcalfe remained the favorite.[18] In the finals, Japanese sprinter Takayoshi Yoshioka jumped out to a four-yard lead after 40 meters. Tolan passed Yoshioka at the 6 -meter mark and had a two-yard lead over Metcalfe at the 100-yard mark. But Metcalfe passed Tolan at the tape and appeared to the crowd to be the winner. Sports writer Maxwell Stiles described the last strides as follows:
"His powerful legs churning wildly, Metcalfe swept down upon little Tolan like an avenging angel full of fury. Tolan, his left knee in an elastic bandage and his glasses taped to his head near his ears, dug in for one last desperate stride in his effort to hold the lead. Just at the tape, Metcalfe rushed past Tolan and was well ahead a yard beyond the finish. Almost everyone thought Metcalfe had won."[18]
It was hours later, after review of films taken with a "Kirby two-eyed camera," that officials were able to declare Tolan the winner with a time of 10.3 seconds.[10][18] The films showed that Tolan and Metcalfe hit the finish line in a dead heat, but Tolan was declared the winner, because he had his entire torso past the line on the ground before Metcalfe.[18]
200 meters race[edit]
The 200 meters race was held on the fourth day of competition, and this time the race was not close, as Tolan beat Metcalfe easily with an Olympic record time of 21.2 seconds – four-tenths of a second better than the prior record of 21.6 seconds.[19] Tolan stumbled slightly with three yards to go, but righted himself and finished with a four-foot lead. With double wins in the 100 and 200 meters contests, Tolan was dubbed the "world's fastest human."[19] Tolan was the first African-American to have that distinction, and press coverage of his Olympic wins focused on his race. The Associated Press called him the "spectacled little American Negro" and "the dusky little thunderbolt."[20] Braven Dyer referred to him as "the stubby colored boy," and noted that "the chunky Detroit Negro" had defeated Arthur Jonath of Germany, "the white-skinned Teuton."[19] Another writer described how the "little black man with horn-rimmed glasses" crossed the finish line, being chased by "a white man of America, George Simpson," and "a brother black, Ralph Metcalfe."[21]
Commentators also noted, that the only other two sprinters to win double gold in the 100 and 200 meters races were also University of Michigan athletes, Ralph Craig and Archie Hahn.[19]
Reaction to Tolan's Accomplishments[edit]
After the sprint competition concluded, a reporter interviewed Tolan and Metcalfe in their shared room at the Olympic Village. When Metcalfe teased Tolan for being lucky, Tolan replied, "Yeah, I had it all right – but it's 'bout time, Ralph; first little ol' luck I had in eight years!"[22] Still in bed at noon wearing pajamas and with a stocking cap on his head, Tolan said he was "in the best condition of my life when the 200 meters final started," and he vowed to give his gold medals to his mother.[22]
Back in Detroit, Mayor Frank Murphy appointed a reception committee to meet Tolan at the train station,[23] and Michigan Governor Wilber M. Brucker declared September 6, 1932 as "Eddie Tolan Day" throughout the state.[24] The governor issued a proclamation stating that Tolan had "brought honor to our commonwealth" and encouraging communities throughout the state to arrange ceremonies "as an expression of Michigan's pride in his achievement."[24]
Tolan's mother noted, that she was proud of her son's accomplishments. She noted that, though she had worked hard as the sole provider for the family, it was worth it.[23] She added, "If my menfolk could only find jobs I could ease up a bit and a mighty big worry would be off Eddie's mind."[23]
In April 1936, Tolan, along with many other sports champions and stand outs, was honored at a banquet in Detroit, MI.[25] This Banquet was the first celebration of Champions Day.
Vaudeville and hard times[edit]
Less than six months after winning Olympic gold medals and the title of the "world's fastest human," Tolan garnered national press when he fell on hard times. Syndicated columnist William H. Beatty wrote that "the heady wine of victory has turned overnight to vinegar" for Tolan.[26][27] Tolan noted that, when he was met at the train station by a welcoming committee, his half-brother was collecting waste paper in the grass of the park in front of the train station. Tolan noted that his half-brother was "luckier than I am," because he had a job.[26] His parents had both been unemployed for many months, and it was not until January 1933 that Tolan was able to get a low-paying job as a filing clerk in a county office.[26] Tolan's lifetime dream of becoming a physician was waning, as he had been "unable to make enough to support himself and his parents."[26]
Desperate to earn a living, Tolan "walked the streets of many cities, seeking work," and even briefly appeared in vaudeville in 1932 with Bill "Bojangles" Robinson.[26] They made a good team; Tolan had set world records for running forwards, and Robinson had set world's records for running backwards: 50 yards backward sprint (6 seconds), 75 yards backwards sprint (8.2 seconds), and 100 yards backwards sprint (13.2 seconds).
Because of his brief appearance in vaudeville, the Michigan Amateur Athletic Association stripped Tolan of his amateur status in June 1933.[28] And in April 1934, Tolan's bad luck continued as an automobile he was driving stuck and seriously injured an 80-year-old pedestrian.[29]
Professional sprinting career[edit]
In November 1934, Tolan took a leave of absence from his job as assistant county registrar of deeds to compete in the Australian sprint program, a series of five professional races, including the Stawell Gift handicap.[30] Tolan returned in April 1935 after having set new Australian records of 21.5 seconds in the 220-yard dash on a full curve track and 7.5 seconds for the 75-yard dash.[31] He won the 75, 100, and 220-yard events at the World Professional Sprint Championships in March 1935 in Melbourne,[1][2][3][4][5][6] and became the first man to win both the amateur and professional world sprint championships.[10]
In his full career as a sprinter, Tolan won 300 races and lost only 7.[1][2] Throughout his career as a sprinter, Tolan worked by a simple creed: "Start fast, run easily, stay in your lane and finish strong."[32]
Civil service and teaching career[edit]
After returning from Australia, Tolan returned to his job in Detroit as a clerk to the Register of Deeds.[31] Tolan worked at a variety of jobs in the 1940s and 1950s.[3][7] In 1956, Tolan became a school teacher in physical and health education. He taught at the Irving Elementary School on Detroit's West Side for several years.[3]
Death and family[edit]
Tolan never married.[11] In 1965, Tolan's kidneys failed, and he was required to undergo weekly dialysis treatments for the rest of his life.[11] In 1967, Tolan died from heart failure at age 58 at Detroit's Mt. Carmel Hospital, while undergoing one of his weekly treatments.[11] At the time of his death, Jesse Owens paid him tribute in Jet magazine:
"When I was in high school, Eddie and Ralph (Metcalfe) were my idols. Eddie and I later became close friends. I used to live in Detroit and every time I'd go back Eddie was one of the first ones I'd look up."[11]
Tolan was survived by his sisters, June Brown and Martha Lombard, and a brother, Hart H. Tolan.[7] Though the two never met, Tolan was also a cousin of former Major League Baseball player Bobby Tolan.[33] Eddie Tolan is interred at United Memorial Gardens in Plymouth, Michigan.
Honors and awards[edit]
In 1958, Tolan was inducted into the Michigan Sports Hall of Fame. He was one of the first 18 persons inducted.[34] He was inducted into the University of Michigan Athletic Hall of Honor in 1980.[35] Only 17 individuals were inducted into the Hall before Tolan.[35]
Tolan was a member of Alpha Phi Alpha fraternity.[36]
Eddie Tolan was inducted into the National Track and Field Hall of Fame in 1982.
See also[edit]
- ^ a b c "Eddie Tolan". USA Track & Field Hall of Fame.
- ^ a b c d e f g h Patricia Zacharias and Vivian M. Baulch (February 2, 2002). "Michigan Athletes have made Olympic history". The Detroit News.
- ^ a b c d e f "Where Are They Now?". Ironwood Daily Globe (AP wire story). August 3, 1961.
- ^ "Two Negro Sophs in Big Ten Appear Certain of Track Fame". Ogden (NEA wire service story). March 12, 1929.
- ^ a b "Cass Flash Is Dash Finalist". Lima News (AP wire story). June 4, 1927.
- ^ a b "Tolan Ties World's Mark: Michigan Negro Runs Century Dash in 9 6-10s; Other Records Tumble in Big Ten Meet". Los Angeles Times. May 25, 1929.
- ^ a b c d e f "Little Eddie Tolan: Track Immortal Dies". Lowell Sun. February 1, 1967.
- ^ Walter Eckersall (June 23, 1918). "Steve Farrell Once Noted as Keen Sprinter: Track Coach Learns Tricks of Trade in Old School". Los Angeles Times.
- ^ "Track & Field Timeline & Overview" (PDF). Iowa High School Athletic Association.
- ^ a b c d e Edward Seldon Sears (2001). Running Through the Ages, pp. 178–181. McFarland. ISBN 0-7864-0971-1.
- ^ a b c d e "Eddie Tolan Dies: Remembered As High School Idol". Jet (magazine). February 1967.
- ^ "Eddie Tolan Steals Spotlight From Metcalfe: Former Wolverine Takes Limelight in Sprints". Los Angeles Times. July 16, 1932.
- ^ a b "Tolan Given Credit For New 100-Yard Mark: Five American Records Get World Recognition". Los Angeles Times. May 21, 1930.
- ^ a b c Frank G. Gorrie (July 2, 1930). "Dash Time Bettered By Tolan: Michigan Flyer Sets New Figure for 100 Meters; Trims Two Rivals". Los Angeles Times.
- ^ a b Frank G. Gorrie (August 23, 1931). "Tolan Defeats Wykoff at Vancouver: Colored Star Breaks Mark; Special 100-Meter Event Won in 10.3s; Michigan Negro Cops Race by Two Yards". Los Angeles Times.
- ^ a b c Dean B. Cromwell (May 18, 1932). "Olympic Prospects". Los Angeles Times.
- ^ Braven Dyer (July 30, 1932). "The Olympic Torch". Los Angeles Times.
- ^ a b c d Maxwell Stiles (April 23, 1948). "Great 100 Meters Duel Won by Tolan in 1932 Olympiad". Long Beach Press-Telegram.
- ^ a b c d Braven Dyer (August 4, 1932). "Tolan Flashes To New Record: Simpson and Metcalfe Decisively Defeated; Negro Wizzes Over 200-Meter Route in 21.2s for Mark; Americans Win Vault". Los Angeles Times.
- ^ "Tolan Wins Sprint Title of World: Bespectacled Little American Negro Races to Decisive Victory in Olympic 200 Meter Final". Daily Capital News (AP wire story). August 4, 1932.
- ^ Jean Bosquet (August 4, 1932). "Day of Amazing Feats Rung Up in Olympics: Tolan Shatters 200 Meters as Babe Didrikson Thrills Huge Crowd with Record Run". Los Angeles Times.
- ^ a b Terrel Delapp (August 5, 1932). Los Angeles Times. Missing or empty
- ^ a b c "Reception Awaits Eddie Tolan After Olympic Victory". Moberly Monitor-Index (AP wire story). August 5, 1932.
- ^ a b "All Michigan Honors Tolan: Colored Star's Achievements in Games to Be Recognized". Los Angeles Times. August 31, 1932.
- ^ http://news.google.com/newspapers?id=Qg8_AAAAIBAJ&sjid=jk4MAAAAIBAJ&pg=6215%2C5649943
- ^ a b c d e William H. Beatty (January 24, 1933). "Eddie Tolan Retired, Is Glad to Have a Job Now". Daily Capital News.
- ^ William H. Beatty (January 24, 1933). "Tolan Sick on Victory Wine: Feted Littled Colored Hero's Dreams of Becoming a Great Physician Shattered as He Toils at County Clerk's Job; Eddie Says He May Never Run Again". Los Angeles Times.
- ^ "Eddie Tolan Ruled 'Pro' by A.A.U.". Los Angeles Times. June 24, 1933.
- ^ "Eddie Tolan Car Injures Man". Los Angeles Times. April 2, 1934.
- ^ "Pro Sprint Career Calls Eddie Tolan". Jefferson City Post-Tribune (AP wire story). November 13, 1934.
- ^ a b "Negro Hailed As Next Olympiad Sprint King: Eddie Tolan Optimistic Over Progress Made by Colored Youth in College Athletics". Los Angeles Times. April 21, 1935.
- ^ "Death Takes Ex-Olympian Eddie Tolan". Oakland Tribune. February 1, 1967.
- ^ Mike Gremaud (June 5, 1966). "Ex-Silver Soxer Bobby Tolan's Fast, But Cousin Was Faster". Nevada State Journal (UPI wire story).
- ^ "Add 3 to State Hall of Fame". Ironwood Daily Globe (AP wire story). May 7, 1958.
- ^ a b "Hall of Honor". M Club.
- ^ "Sports Figures". Alpha Chapter of Alpha Phi Alpha Fraternity, Inc.
- 1908 births
- 1967 deaths
- African-American track and field athletes
- American sprinters
- Cass Technical High School alumni
- Athletes (track and field) at the 1932 Summer Olympics
- Michigan Wolverines track and field athletes
- Olympic track and field athletes of the United States
- Olympic gold medalists for the United States
- Sportspeople from Denver, Colorado
- Sportspeople from Detroit, Michigan
- Sportspeople from Salt Lake City, Utah
- Vaudeville performers
- Olympic medalists in athletics (track and field)

subset: commoncrawl


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Programs & Events
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New York University's 2010 graduating class owed a total of more than $600 million in student loans. It's unlikely the university will forgive them. But NYU has forgiven portions of mortgages they have extended to President John Sexton, other university executives or star faculty -- money that has been used to buy properties in Manhattan or vacation homes in the Hamptons.
Does this shock you?
Or, how about this: Treasury Secretary Jack Lew, a former executive vice president at NYU, received an "exit bonus" of $685,000. Just to put this in perspective, Lew's NYU exit bonus alone would have provided free tuition for 34 undergraduates.


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Updated: 08/01/2014 9:52 AM
Created: 07/31/2014 4:54 PM KSTP.com
In a one-on-one interview, the Archbishop of the St. Paul-Minneapolis Archdiocese defended himself and his actions as head of the Catholic Church in Minnesota.
"I never covered up allegations of child sexual abuse by priests," Archbishop John Nienstedt told 5 EYEWITNESS NEWS.
Nienstedt and the Catholic Church have been sued for not reporting and then covering up allegations of child sexual abuse by priests in the St. Paul-Minneapolis Archdiocese. ... Read more.


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Earlier this month, Drake released a new song called "Marvin's Room" on his blog, October's Very Own. If you haven't heard it yet, the track consists of an intoxicated Drizzy vulnerably addressing an ex-girlfriend, trying to convince her that she can "do better" than the boo with whom she's currently in a relationship. Coaxing her with his evocative fairy dust, the still-smitten singing rapper can seemingly not let go. Now considered a contemporary drunk-dialing anthem, "Marvin's Room" is
Wheelchair Jimmy's Drake's personal adjusting-to-celebrity confession session, yet still relatable enough to potentially rouse emotional baggage from our own civilian relationships past. Lucky us!
Striking similar chords with female vocalists, pop/R&B singer JoJo decided to remake the song last week, delivering her own version from a female's point of view, and snagging quite a bit of buzz off her naughty lyrics. Teyana Taylor, too, just transformed "Marvin's Room" into "My Room," proving that she clearly didn't give a damn about the poor guy in the original song's title. And speaking of this "Marvin," you probably noticed that Drake doesn't mention him at all on the track, triggering a head-scratcher we found ourselves dealing with: If he's important enough to garnish the song's title, why the EFF don't we know who Marvin is?
Before we overthink this conundrum, it's important to remember that answers are sometimes hiding in plain sight. For example, maybe Drake really, really, really enjoys Looney Tunes' Marvin the Martian. Or perhaps he's taking a page from The Who or Led Zeppelin, giving his tune a title that has absolutely nothing to do with the lyrical content. Word to "Baba O'Riley." A more literal theory that's been tossed around, perhaps the play-turned-film, Marvin's Room, starring Leo DiCaprio and Meryl Streep is a personal favorite for the Canadian rapper? You can just picture him watching black and white romance flicks with popcorn and tissues at the ready, so being a film buff could likely explain it all, right?
Wrong. We don't think any of those hypotheses answer the "Who is Marvin?" question. In fact, although others have speculated and Drake himself has yet to confirm the truth, solid sources have revealed to us that "Marvin" is actually Marvin Gaye, and "Marvin's Room" as a title is referring to the Prince of Soul's personal studio (where Michael Jackson used to record, among others), because…
Wait for it…
Drake recorded the song there (gasp!), in the ridiculously historical location. Not going to make a Thank Me Later joke, but we will say you're welcome; the cat's out of the bag and the case is closed! Just don't tell Drizzy where you heard the scoop- we don't want him and his band of (emo) brothers to get sauced and retaliate with prank phone calls.
[Photo Credit: Getty Images]


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Echino, Decoro 2014, Hide in FAT QUARTERS 4 Total
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|Posted by holmfamilycookbook on March 7, 2012 at 9:25 AM
French dip sandwich made from leftover beef tri-tip
In my teens and twenties the only food I would order when I ate out in restaurants was French dip sandwiches. Not only was my diet very limited, but so was the distance I had traveled. However, at that time I could have told you where you could get the best French dip sandwiches from Livermore (in the San Francisco Bay Area) to Lake Tahoe and south to San Diego. I very rarely order French dip sandwiches these days--I find that a lot of restaurants use beef that looks and tastes like lunch meat in their French dips, and I prefer hand carved roast beef.
Recently my friend Kim Bonde provided a French dip sandwich lunch at a fundraiser that we hosted. Her sandwiches were just delicious and reminded me of how much I used to like them, so when I had some tri-tip roast left over last week, I made French dip sandwiches with the leftover meat.
As long as you have the beef on hand, they are quick and easy to make. It's so easy, you don't need a recipe, just follow the directions under the photos below.
Split open and spray olive or spread some butter on sourdough or ciabatta rolls, place the rolls cut-side down in a skillet on medium heat until toasty brown
Thinly slice left over roast beef
Following the manufacturer's directions, mix up some au jus
Heat up the beef with a tablespoon or two of the au jus
Place the beef on the bread and serve with the au jus.
To dress the sandwiches up a bit, you can add cheese or grilled onions.
That was easy.
Categories: Beef Recipes, Main Dish Recipes
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Pro from top to bottom.
The downside to having a Pro-level bike is finding a seat bag that matches its stylishness. SciCon, long considered a master of saddle bag design, has that covered with the Elan Seat Bag.
The Elan attaches to your seat rails through a hook-and-loop closure with a fit so snug under the seat that it forgoes the traditional seatpost strap. It's manufactured from Polyester 600 and is 210 cubic centimeters, making it unobtrusive, yet big enough to carry your basic essentials -- tube, tire lever, and a CO2. The SciCon Elan Seat Bag is available in Blue, Grey, Black, and Red.
- Cordura
- Single zippered pocket
- Hook-and-loop saddle rail attachment
Tech Specs
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Paul Savala
Compact, questionable durability
- Familiarity: I've used it several times
Here is what I carry in this pack:
- One road tube
- Two Pedro's tire levers (bigger than most tire levers)
- One multi-tool (not one of those tiny ones either, this one has 16 pieces or so)
With a bit of squeezing I can just barely fit all these in there. You're not going to want to open it up regularly with all this stuff, because it's difficult to get it closed again. But the point of this pack is just to handle emergencies, so I'm not too worried about it.
The only problem thus far is that it developed a small hole near the top after only a couple weeks of usage. This may have been from my multitool puncturing it when I squeezed everything in there, so I won't penalize it too much. So far it's just a small hole, and doesn't seem to be getting any bigger.
I should add that if you're hoping to carry what I have listed above PLUS a co2 cartridge and inflator, you will almost surely be out of luck. Even substituting a smaller multitool and tire levers, you would still have a very hard time squeezing in more.
Perfect Size
- Familiarity: I've used it once or twice and have initial impressions
Love this thing. Perfect size for one tube, two tire levers and a multi tool. Strap it on and you're good to go.I have a bigger saddle bag for when I need to take more but this thing is perfect for just the bare essentials.


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At one time, the Fine Arts Center had three gifts shops.
Today, it has none.
Earlier this week, Cathy Coleman moved out the remaining books and children's art sets from her Luma store inside the FAC. After operating her eclectic arts store there for nearly five years, she closed shop on Jan. 1. She just wasn't doing enough business to stay open, she said.


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Tours & Packages
- Cruising / Sailing
- Cultural Exploration
- Ecotourism / Green Travel
- Golf
- Learning Activities
- Medical Tourism
- Meditation
- Outdoor and Adventure Activities - Air Activities
- Outdoor and Adventure Activities - Land Activities
- »4WD, Off-Road Driving
- »Absailing/Rappelling, Bungy Jumping
- »Cave Exploration
- »Cycling
- »Elephant Riding
- »Horse Riding
- »Mountain Biking
- »Paintball
- »Rock Climbing
- »Trekking, Hiking
- Outdoor and Adventure Activities - Water Activities
- Self Drive
- Shopping
- Spa and Wellness
- Weddings & Honeymoons
Umphang Jungle Safaris
Tour Overview :
The small town of Umphang lies at the end of an only recently finished road, in the middle of beautiful mountainous jungle. Even by powerful pickup truck, the journey from Mae Sot to Umphang takes about three hours: no wonder this area has yet to be put of the tourist-map.
Umphang and surroundings are mainly inhabited by hill tribes like H'mong, Lisu and Karen. The comfortable, Umphang Hill Resort is beautifully located in a gorge, on the banks of a jungle stream. Without doubt, one of the highlights of a visit to Umphang is the Thilorzu, Thailand's largest and most impressive waterfall.
Highlight :
An exotic adventure!
Departure Date :
Daily with minimum 2 persons
Tour Inclusion :
All mentioned meals & transfers. Transportation by open pickup truck, rubber or bamboo raft and by elephant. Services of an experienced English speaking local guide. Sightseeing as listed in the trip itineraries. Accommodation in tent, floor space and Karen Village bamboo hut both without bathroom facilities or electric.
Tour Exclusion :
Additional meals & (airport) transfers, optional excursions, flight- & travel insurance, luggage handling.
Remark :
- * Under certain conditions (weather, roads, close down of village, uprising) the printed itinerary may change. We reserve the right to make changes as required.
- * Guest are advised to bring some walking shoes which can get wet, flashlight, slippers, mosquito repellent, several copies of the passport, a small bag pack. This trekking is for everybody in a healthy condition. If necessary consult a Physician!
Day by Day Itinerary :
Date 1 : Mae Sot - Umphang
In the morning we will pick you up from you hotel, bus station or airport in Mae Sot. From Mae Sot we will go by pick-up truck to Umphang. A nice drive of about 170 kilometer. On the way we will stop at the Pacharoen Waterfall and visit the village of the Hmong hill tribe. After the lunch we will get to know their traditional everyday life. In the afternoon we will visit upon other things a Karen Village and at the end of the day a spectacular bat cave. In the evening we will have dinner and after that you can relax at a campfire.
Date 2 : Umphang - Mae Klong River
After breakfast we will depart to make a spectacular raft on a bamboo float on the Mae Klong River; along the jungle of Umphang to the Thee Lor Jor Waterfalls and the natural hot spa. In the late afternoon we will arrive in Thasai. Enjoy the stunning nature, the colorful birds and maybe also the gibbons. You will also see the Takubi cataract. Lunch will be served as picnic. Then we will do a 4 hour trekking to the Umphang Wild Reservoir. Together we will make dinner and stay at tents 800 meter away from the waterfalls.
Date 3 : Umphang - Tilorzu Waterfall
After the breakfast we will make a half an hour trekking to the famous Tilorzu Waterfall which is the biggest waterfall of South East Asia and the fifth biggest of the world. The WWF has selected this waterfall to be a 'World Heritage'. You can take a refreshing swim in one of the lower terraces of the waterfall. After lunch we will make a 3 hour trekking to the Kotha-Karen Villages. After dinner we will see how the Karen live. At night we will stay again in tents.
Date 4 : Umphang - Mae Sot
We will get up before the sunrise and walk to an observation point. There you have an amazing overview of the surrounding. At the back of an elephant or by foot we will depart for a 3 hour ride/walk to Palata Karen Village or Mae Lampung. There will be a transfer back to Umphang. After lunch we will transfer you to your hotel, bus station for the VIP night bus (not inclusive) to Bangkok or Chiang Mai or the airport for a flight (not inclusive) to Bangkok.
Optional Day 5: If you have a bit more time it is possible to extend the above mentioned program by 1 day and 1 night. The program is the same as describe in the program of tour 0260. At day 4 of the 5-day program we will make a 4 hour walk through the primeval forest of the Doi Phuwatoo Mountain. You will spend the night in the jungle. The elephant ride is inclusive but 1 hour shorter.


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HealthyOut Is Like A Personal Nutritionist For Healthy Food Deliveries
New York-based startup HealthyOut already has a popular iPhone and Android app for quickly finding nearby restaurants and dishes that users can order and have delivered. Today at Disrupt NY 2013, HealthyOut is unveiling a new service, which will provide its users with personalized menus of food delivered to help them lose weight or just overall eat better. Read More


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|The Usual
Two eggs, choice of sausage or bacon and tater-tots or hashbrowns. 7.5
|Eggs Classic
Two eggs, toast and your choice of tater-tots or hashbrowns 5.5
|Ribeye Steak and Eggs
8 ounce char-grilled ribeye steak, served with two eggs, tater-tots or hashbrowns and toast 10
|Breakfast Burrito
Sausage or bacon with scrambled eggs, tater-tots, cheese and pico de gallo, wrapped in flour tortilla, served with a side of salsa 8
|Creme Brulee French Toast
Two slices of sugar crusted french toast, eggs and bacon or sausage 8
Just French toast 5
|The Scrambler
Bacon, ham or sausage and cheese scrambled into three eggs with hashbrowns or tater-tots and toast 7.5
|Three Pig Breakfast Sandwich
Bacon, ham, sausage, fried egg and cheese on a toasted English muffin 6.5
|Corned Beef Hash
Our slow roasted corned beef, red and green peppers, diced onion and hashbrowns, served with two eggs and toast 9
Just hash 7
|Sausage ©Muffin
Fried egg, sausage patty and american cheese on a toasted english muffin 3.5
Skillets are served with toast and your choice of hashbrowns or tater-tots
Eggs, Sausage, peppers, onions and cheese 7.5
|South Of The Border
Spiced chicken or beef, pico de gallo, cheese, jalapenos and eggs 7.5
|Veggie Lovers
Two eggs, black beans, tomatoes, onions, peppers, mushrooms and shredded cheese 7.5
|Cajun Skillet
Grilled andouille sausage, two eggs, peppers, onions and hollandaise sauce 8
Omelettes are served with toast and your choice of hashbrowns or tater-tots
|Ham and Cheese
Thin sliced ham and shredded cheese 7.5
Ham, green peppers, cheese, onions and mushrooms 8
A little of everything. Turkey, bacon, tomatoes, onions, peppers and cheese 8
|Fresh Fruit Plate
Seasonal fruit served with cottage cheese 5
|The Eye Opener
Fancy up that Bloody Mary with Hard boiled egg, celery, bacon, salami, pickle spears and bleu cheese stuffed olives. Tops up to four drinks 6
|Oats and Honey
Oatmeal, honey, toasted pecans, dried cranberries and a pinch of salt 5


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Recent News
News Archive
Mayor's proposed budget holds the line for arts in 2009
Today, Mayor Greg Nickels announced his proposed 2009-2010 budget. The city's general fund is facing significant challenges due to the national economic slowdown and rising costs. Money is tight for arts organizations, business, families and city government. Many city departments will weather reductions.
Mayor Nickels recognizes the importance of the arts to young people, to economic growth, to the vitality of neighborhoods and communities, and to Seattle residents and visitors. Despite the tough economic climate, the mayor's proposed budget holds the line for the Office of Arts & Cultural Affairs' budget in 2009.
Here's the good news. We will maintain our core programs and continue our current levels of investment in the city's arts and cultural organizations, individual artists, youth arts, neighborhood and community programs. We will also enter into the second year of our groundbreaking Arts Education Partnership Initiative with Seattle Public Schools, with the district matching our $100,000 investment to provide access to a quality arts education for all students. And with more than 40 active public art projects, we will continue to enrich our city's public spaces.
The Office of Arts & Cultural Affairs receives funding from four primary sources.
We receive 20 percent of the city's admissions tax revenues, which primarily fund our grant programs. The current admissions tax is 5 percent on every dollar of ticket sales. Our portion of admissions tax revenues are projected at $1.2 million in 2009.
The city's general fund supports our operations and a portion of our funding programs. The proposed general fund allocation in 2009 is $2.9 million. This amount includes an additional $60,000 added in 2009 and 2010 to make up for a new admissions tax exemption for small music venues.
The municipal art fund—which is comprised of one percent of budgets for eligible city capital improvement projects—supports our public art program. The proposed appropriation for this fund is about $3.4 million in 2009.
The Cumulative Reserve Fund (CRF) funds our public art maintenance, and will remain at the current level of $170,000.
Our total 2009 proposed budget allocation is $7.5 million—down $356,000 from 2008. The 2009 budget does not include several one-time additions in 2008 for capital special projects, which accounts for much of the difference between our 2008 and 2009 budgets.
The situation changes in 2010 when the mayor's budget proposes a four percent reduction to our general fund allocation In effect, we are postponing reductions until 2010 in the hopes that by then the economy will turn around. If not, this gives us a year to figure out the best way to reduce expenses while providing quality core program services.
By working together we will we ensure the continued vitality of Seattle's cultural life. You can learn more about the mayor's proposed 2009-2010 budget on his Web site.
Michael Killoren


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Molly C. Broad
Areas of Expertise
Leadership; strategic planning; economic development
Molly Broad joined the faculty at the School of Government in 2007. Prior to that, she was president of the 16-campus University of North Carolina system for nine years.
An economist, Broad came to UNC from the California State University system, where she served as senior vice chancellor for administration and finance and as executive vice chancellor and chief operating officer. Earlier in her career, Broad served as the chief executive officer for Arizona's three-campus university system and in a succession of administrative posts at Syracuse University, where she was manager of the Office of Budget and Planning, director of institutional research, and vice president for government and corporate relations.
In 2008 Broad was named president of the American Council on Education.
Broad earned a bachelor's degree from the Maxwell School of Citizenship and Public Affairs at Syracuse University and a master's degree from Ohio State University.


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ORLANDO, Florida (AP) -- With a line of NFL scouts and coaches watching his every move and reports swirling that Blake Bortles could be the No. 1 overall pick in May's NFL draft, the UCF quarterback just did what he's done all year.
He focused on completing the next pass.
And Bortles hit enough of them at UCF's Pro Day on Wednesday to keep the discussion going on whether he should be the No. 1 pick - though he says he's not worried about that.
Bortles says he knew Wednesday's pro day "was something on the list of things that I can control, and the last thing before this was the (NFL) combine. Those were the two things that I could control, and that's what I focused on."
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Children's Books → Picture books → Australian picture books
written by Alison Lester
Lothian Books | ISBN 9780733626531
Paperback – 32 pages
$17.00Add to cart +
Member's price: $15.30
When Ruby was a baby her mother made her a beautiful patchwork quilt to keep her safe and warm. But Ruby's quilt also has the special ability to take her on a magical adventure where Ruby must defeat the scary serpent that is terrorising a local island's inhabitants. Join Ruby and Besty on this fantastic adventure, lovingly illustrated by the award-winning Alison Lester.


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Pet friendly Nashville hotels and motels are listed below along with the pet policy if available. Search for cheap and discount pet friendly hotel rates in or near Nashville, IL for your upcoming individual or group travel with your pets. We list the best petfriendly Nashville Illinois hotel and motel rooms allowing pets or dogs. Review the dog friendly Nashville hotel list below to find the perfect lodging for you and your pets. Planning group travel? Find Nashville IL Group Hotel Rates
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Methods for fabricating dense arrays of polymeric molecules in a highly multiplexed manner are provided using semiconductor-processing-derived lithographic methods. Advantageously, the methods are adaptable to the synthesis of a variety of polymeric compounds. For example, arrays of branched peptides and polymers joined by peptide bonds may be fabricated in a highly multiplexed manner. Additionally, peptides that adopt helical structures are synthesized on a substrate surface and arrays are created having one or more features containing peptides capable of forming helixes.
1. An array of polymers attached to a substrate wherein the array comprises a support structure having a surface, wherein the surface has a plurality of features, wherein each of the features comprises a plurality of peptides of known sequence attached to the substrate surface, wherein the sequence of peptides in a first feature of the array is different from the sequence of peptides in a second feature of the array, wherein at least one feature of the array comprises a first peptide and a second peptide attached to the surface of the support structure through a bifurcation molecule or a trifunctional linker molecule, and wherein the first and second peptide are capable of forming a helical structure, and wherein the bifurcation molecule or the trifunctional linker molecule is attached to the first and to the second peptide.
2. The array of
3. The array of
4. The array of
5. The array of
6. The array of
7. The array of
8. The array of
9. The array of
10. An object comprising a substrate having a surface wherein a polymer is attached to the substrate surface, wherein the polymer is comprised of a first and a second peptide and the first and the second peptides are attached to the substrate through a single bifurcation molecule or a trifunctional linker molecule and wherein the first and the second peptides are capable of forming a helical structure, and wherein the bifurcation molecule or the trifunctional linker molecule is attached to the first and to the second peptide.
11. The object of
12. The object of
13. The object of
14. The object of
15. The object of
16. The object of
The present application is related to U.S. application Ser. No. 11/395,899, entitled "Massively Parallel Synthesis of Proteinaceous Biomolecules," filed Mar. 30, 2006, now pending, which is a continuation-in-part of U.S. application Ser. No. 11/291,296, filed Nov. 30, 2005, entitled "Massively Parallel Synthesis of Proteinaceous Biomolecules," filed Jun. 6, 2005, now pending; U.S. application Ser No. 11/322,268, entitled "Massively Parallel Synthesis of Biopolymeric Arrays," filed Dec. 29, 2005, now pending; U.S. application Ser. No. 11/529,573, entitled "Method for High Throughput, High Volume Manufacturing of Biomolecule Micro Arrays," filed Sep. 29, 2006, now pending; and U.S. application Ser. No. 11/585,413, entitled "Solid-phase Mediated Synthesis of Molecular Microarrays," filed Oct. 23, 2006, now pending, the disclosures of which are incorporated herein by reference.
1. Field of the Invention
Embodiments of the invention relate generally semiconductor lithographic technology, to solid-phase synthesis of microarrays of bio-polymers, peptides and peptide structure, and synthetic organic chemistry.
2. Background Information
Microarrays of oligonucleotides, peptides, proteins, and or oligosaccharides continue to gain importance as powerful tools for research and diagnostic applications in the biomedical sciences. Oligonucleotide microarrays can be used to monitor gene expression and discover genotypes and mutations in a massively parallel manner. Proteinaceous microarrays provide the ability, for example, to characterize the molecular progression of disease, research cellular pathways, and perform high throughput screening in drug discovery applications. Peptide-containing arrays can serve as molecular probes for a variety of biological events, such as for example, the arrays can serve as antigens for antibody-antigen systems, ligands for cell receptor-ligand systems, and substrates for enzyme-protein systems. The ability to collect large volumes of information is an integral part of biomarker discovery and personalization of medical treatments. Further, other applications in bioscience, such as for example, the analysis of the proteomic content of an organism, disease detection, pathogen detection, environmental protection, food safety, and biodefense are capable of benefiting from tools that allow rapid multiplexed interrogation of analyte samples.
As the genomic and proteomic knowledge base expands and the drive toward personalized medicine continues, so does the need for methods to collect, understand, and apply biologically relevant information. Methods, such as analyses using microarrays that allow the use of small volumes of sample for highly multiplexed analyses, are valuable tools. Thus amplifying the value of methods that provide for the controllable automated manufacture of arrays.
One challenge that exists in the design and implementation of peptide microarrays is the tendency of peptides synthesized in vitro and on solid surfaces to adopt random conformations. Three dimensional molecular structure often plays an important role in determining biological function. The random conformation adopted by a peptide synthesized in vitro is not necessarily a biologically active conformation.
An array is an intentionally-created collection of molecules situated on a solid support in which the identity or source of a group of molecules is known based on its location on the array. The molecules housed on the array and within a feature of an array can be identical to or different from each other. Embodiments of the present invention provide methods for the synthesis of polymers on a solid support. Polymer synthesis according to embodiments of the invention can be accomplished in a manner that provides controlled-density microarrays comprised of peptides, peptoids, peptidemimetics, branched peptides, and or other small bio-molecules. Embodiments of the present invention provide arrays of biopolymers of known sequence and controllable molecular density. Additionally, the methods described in embodiments of the invention are highly scalable for array manufacture on a wafer or chip as are used in to fabricated devices in the semiconductor industry.
The features, regions, or sectors of an array in which the bio-polymers are located may have any convenient shape, for example, the features of the array may be circular, square, rectangular, elliptical, or wedge-shaped. In some embodiments, the region in which each distinct biomolecule is synthesized within a feature is smaller than about 1 mm2, or less than 0.5 mm2. In further embodiments the features have an area less than about 10,000 μm2 or less than 2.5 μm2. Additionally, multiple copies of a polymer will typically be located within any feature. The number of copies of a polymer can be in the thousands to the millions within a feature. In general, an array can have any number of features, and the number of features contained in an array may be selected to address such considerations as, for example, experimental objectives, information-gathering objectives, and cost effectiveness. An array could be, for example, a 20×20 matrix having 400 regions, 64×32 matrix having 2,048 regions, or a 640×320 array having 204,800 regions. Advantageously, the present invention is not limited to a particular size or configuration for the array.
A method for synthesizing polymers within one or more selected region(s) of a solid support is shown in
Referring now to
The exposure of the photoresist 4 to radiation generates cleaving reagents (species that catalyze the removal of a protective group, for example) in the exposed portion of the photoresist layer 4. The generation of cleaving reagents in the photoresist may be the result of a number of processes. For example, the cleaving reagent may result from the direct radiation-induced decomposition of or chemical transformation of a photoactive cleavage reagent precursor compound. Alternatively or in addition, generation of the cleaving reagent may occur through the absorption of light by a photosensitizer followed by reaction of the photosensitizer with the cleavage reagent precursor, energy transfer from the photosensitizer to the cleavage reagent precursor, or a combination of two or more different mechanisms.
As a result of the radiation-induced generation of the cleaving reagent, the protecting groups 3 are cleaved from the molecules 2 under the exposed area(s) of the photoresist. The molecules 2 located under the unexposed masked regions remain unreacted. The cleaving process leading to the removal of the protecting groups 3 may, for example, be acid-catalyzed cleavage or base-catalyzed cleavage. The chemistry of the process will depend on the type of protecting groups 3 and on the type of cleaving reagents that are generated in the photoresist upon radiation exposure. For example, if the protecting group 3 is t-BOC, acid cleavage can be used. Acids may be generated in the photoresist, for example, through the exposure of sulfonium or halonium salts to radiation. If the protecting group is FMOC, for example, then base cleavage can be used. Cleavage can be accomplished through the reaction of a photogenerated amine or diamine through a decarboxylation process. The rate of protecting group removal can be accelerated by heating the substrate after the exposure to radiation (post exposure bake). The post exposure bake (PEB) serves multiple purposes in photoresist processing. First, the elevated temperature of the bake drives diffusion of the photoproducts. A small amount of diffusion can be useful in minimizing the effects of standing waves, periodic variations in exposure dose throughout the depth of the film that result from interference of incident and reflected radiation. The other main purpose of the PEB is to drive the acid-catalyzed reaction. Chemical amplification is important because it allows a single photoproduct to cause many solubility-switching reactions, thus increasing the sensitivity of these photoresist systems.
Subsequent to the exposure of the masked substrate to radiation, the photoresist is removed. The photoresist layer 4 may be removed using acetone or another similar suitable solvent. The resulting surface-modified substrate is shown schematically in
The processes illustrated in
Any unreacted deprotected chemical functional groups may be capped at any point during a synthesis reaction to avoid or to prevent further bonding at such molecule. In general, capping reagents can be a reagent that prevents further reactivity at the site of polymer chain formation such as, for example, an acid anhydride without further reactive functionalities. Capping groups cap deprotected functional groups by, for example, binding with the unreacted amino functions to form amides. Capping agents suitable for use in an embodiment of the invention include: acetic anhydride, n-acetylimidizole, isopropenyl formate, fluorescamine, 3-nitrophthalic anhydride and 3-sulfoproponic anhydride.
In general, peptides are polymers of amino acids, amino acid mimics or derivatives, and/or unnatural amino acids. The amino acids can be any amino acids, including α, β, or ω-amino acids and modified amino acids. When the amino acids are α-amino acids, either the L-optical isomer or the D-optical isomer may be used. In general, an amino acid contains an amine group, a carboxylic group, and an R group. The R group can be a group found on a natural amino acid or a group that is similar in size to a natural amino acid R group. Additionally, unnatural amino acids, for example, β-alanine, phenylglycine, homoarginine, aminobutyric acid, aminohexanoic acid, aminoisobutyric acid, butylglycine, citrulline, cyclohexylalanine, diaminopropionic acid, hydroxyproline, norleucine, norvaline, ornithine, penicillamine, pyroglutamic acid, sarcosine, and thienylalanine are also contemplated by the embodiments of the invention. These and other natural and unnatural amino acids are available from, for example, EMD Biosciences, Inc., San Diego, Calif.
A peptide is a polymer in which the monomers are amino acids, a group of molecules which includes natural or unnatural amino acids, amino acid mimetics, and amino acid derivatives, which are generally joined together through amide (peptide) bonds. A peptide can alternatively be referred to as a polypeptide. Peptides contain two or more amino acid monomers, and often more than 50 amino acid monomers (building blocks).
A protein is a long polymer of amino acids linked via peptide bonds and which may be composed of one or more polypeptide chains. More specifically, the term protein refers to a molecule comprised of one or more polymers of amino acids. Proteins are essential for the structure, function, and regulation of the body's cells, tissues, and organs, and each protein has unique functions. Examples of proteins include some hormones, enzymes, and antibodies.
A protecting group is a group which is bound to a molecule and designed to block a reactive site in a molecule, but may be removed upon exposure to an activator or a deprotecting reagent. Deprotecting reagents include, for example, acids and bases. Protecting groups can be bound to a monomer, a polymer, a linker molecule or a monomer, or polymer, or a linker molecule attached to a solid support to protect a reactive functionality on the monomer, polymer, or linker molecule. Protective groups that may be used in accordance with an embodiment of the invention include all acid and base labile protecting groups. For example, peptide amine groups are preferably protected by t-butoxycarbonyl (t-BOC or BOC) or benzyloxycarbonyl (CBZ), both of which are acid labile, or by 9-fluorenylmethoxycarbonyl (FMOC), which is base labile.
Additional protecting groups that may be used in accordance with embodiments of the invention include acid labile groups for protecting amino moieties: tert-amyloxycarbonyl, adamantyloxycarbonyl, 1-methylcyclobutyloxycarbonyl, 2-(p-biphenyl)propyl(2)oxycarbonyl, 2-(p-phenylazophenylyl)propyl(2)oxycarbonyl, .alpha.,.alpha.-dimethyl-3,5-dimethyloxybenzyloxy-carbonyl, 2-phenylpropyl(2)oxycarbonyl, 4-methyloxybenzyloxycarbonyl, furfuryloxycarbonyl, triphenylmethyl(trityl), p-toluenesulfenylaminocarbonyl, dimethylphosphinothioyl, diphenylphosphinothioyl, 2-benzoyl-1-methylvinyl, o-nitrophenylsulfenyl, and 1-naphthylidene; as base labile groups for protecting amino moieties: 9-fluorenylmethyloxycarbonyl, methylsulfonylethyloxycarbonyl, and 5-benzisoazolylmethyleneoxycarbonyl; as groups for protecting amino moieties that are labile when reduced: dithiasuccinoyl, p-toluene sulfonyl, and piperidino-oxycarbonyl; as groups for protecting amino moieties that are labile when oxidized: (ethylthio)carbonyl; as groups for protecting amino moieties that are labile to miscellaneous reagents, the appropriate agent is listed in parenthesis after the group: phthaloyl (hydrazine), trifluoroacetyl (piperidine), and chloroacetyl (2-aminothiophenol); acid labile groups for protecting carboxylic acids: tert-butyl ester; acid labile groups for protecting hydroxyl groups: dimethyltrityl. See also, Greene, T. W., Protective Groups in Organic Synthesis, Wiley-Interscience, NY, (1981).
A linker molecule typically is a molecule inserted into the growing polymer that does not necessarily convey functionality to the resulting peptide, such as molecular recognition functionality, but instead elongates the distance between the substrate surface and the peptide functionality to enhance the exposure of the peptide functionality on the surface of the substrate. Preferably a linker should be about 4 to about 40 atoms long to provide exposure. The linker molecules may be, for example, aryl acetylene, ethylene glycol oligomers containing 2-10 monomer units (PEGs), diamines, diacids, amino acids, among others, and combinations thereof. Examples of diamines include ethylene diamine and diamino propane. Alternatively, the linkers may be the same molecule type as that being synthesized (i.e., nascent polymers), such as polypeptides and polymers of amino acid derivatives such as for example, amino hexanoic acids.
Solid support, support, and substrate refer to a material or group of materials having a rigid or semi-rigid surface or surfaces. In some aspects, at least one surface of the solid support will be substantially flat, although in some aspects it may be desirable to physically separate synthesis regions for different molecules with, for example, wells, raised regions, pins, etched trenches, or the like. In certain embodiments, the solid support may be porous.
Substrate materials useful in embodiments of the present invention include, for example, silicon, bio-compatible polymers such as, for example poly(methyl methacrylate) (PMMA) and polydimethylsiloxane (PDMS), glass, SiO2 (such as, for example, a thermal oxide silicon wafer such as that used by the semiconductor industry), quartz, silicon nitride, functionalized glass, gold, platinum, and aluminum. Functionalized surfaces include for example, amino-functionalized glass, carboxy functionalized glass, and hydroxy functionalized glass. Additionally, a substrate may optionally be coated with one or more layers to provide a surface for molecular attachment or functionalization, increased or decreased reactivity, binding detection, or other specialized application. Substrate materials and or layer(s) may be porous or non-porous. For example, a substrate may be comprised of porous silicon. Additionally, the substrate may be a silicon wafer or chip such as those used in the semiconductor device fabrication industry. In the case of a wafer or chip, a plurality of arrays may be synthesized on the wafer.
Photoresist formulations useful in the present invention include a polymer, a solvent, and a radiation-activated cleaving reagent. Useful polymers include, for example, poly(methyl methacrylate) (PMMA), poly-(methyl isopropenyl ketone) (PMPIK), poly-(butene-1-sulfone) (PBS), poly-(trifluoroethyl chloroacrylate) (TFECA), copolymer-(α-cyano ethyl acrylate-α-amido ethyl acrylate (COP), and poly-(2-methyl pentene-1-sulfone). Useful solvents include, for example, propylene glycol methyl ether acetate (PGMEA), ethyl lactate, and ethoxyethyl acetate. The solvent used in fabricating the photoresist may be selected depending on the particular polymer, photosensitizer, and photo-active compound that are selected. For example, when the polymer used in the photoresist is PMMA, the photosensitizer is isopropyl-thioxanthenone, and the photoactive compound is diphenyliodonium chloride, PGMEA or ethyl lactate may be used as the solvent.
In exemplary photoresist formulations, the mass concentration of the polymer may between about 5% and about 50%, the mass concentration of a photosensitizer may be up to about 20%, the mass concentration of the photo-active compound may be between about 1% and 10%, the balance comprising a suitable solvent. After the photoresist is deposited on the substrate, the substrate typically is heated to form the photoresist layer. Any method known in the art of semiconductor fabrication may be used to for depositing the photoresist solution. For example, the spin coating method may be used in which the substrate is spun typically at speeds between about 1,000 and about 5,000 revolutions per minute for about 30 to about 60 seconds. The resulting wet photoresist layer has a thickness ranging between about 0.1 μm to about 2.5 μm.
Catalysts for protective group removal (also referred to as cleaving reagents) useful in the present invention include acids and bases. For example, acids can be generated photochemically from sulfonium salts, halonium salts, and polonium salts. Sulfonium ions are positive ions, R3S+, where R is, for example, a hydrogen or alkyl group, such as methyl, phenyl, or other aryl group. For example, trimethyl sulfonium iodide and triaryl sulfonium hexafluroantimonatate (TASSbF6) are useful sulfonium ion containing compounds. In general, halonium ions are bivalent halogens, R2X+, where R is a hydrogen or an alkyl group, such as methyl, phenyl, or other aryl group, and X is a halogen atom. The halonium ion may be linear or cyclic. Polonium salt refers to a halonium salt where the halogen is iodine, the compound R2I+Y−, where Y is an anion, for example, a nitrate, chloride, or bromide. For example, diphenyliodonium chloride and diphenyliodonium nitrate are useful halonium salt containing compounds. See also, Frechet, J. M. J., Ito, H., Willson, C. G., Proc. Microcircuit Eng., 260, (1982); Shirai, M., Tsunooka, M., Prog. Polym. Sci., 21:1, (1996); Frechet, J. M. J., Eichler, E, Ito, H., Willson, C. G., Polymer, 24:995, (1983); and Frechet, J. M. J., Ito, H., Willson, C. G., Tessier, T. G., Houlihan, F. M. J., J. of Electrochem. Soc., 133:181 (1986).
Photogenerated bases include amines and diamines having photolabile protecting groups. See for example, Shirai, M., Tsunooka, M., Prog. Polym. Sci., 21:1, (1996); Comeron, J. F., Frechet, J. M. J., J. Org. Chem., 55:5919, (1990); Comeron, J. F., Frechet, J. M. J., J. Am. Chem. Soc., 113:4303, (1991); and Arimitsu, K. and Ichimura, K., J. Mat. Chem,. 14:336, (2004).
Optionally, the photoresists useful in the present invention may also include a photosensistizer. In general, a photosensitizer absorbs light and interacts with the cleavage reagent precursor, through one or more mechanisms, including, reaction with the cleavage reagent precursor and energy transfer from the photosensitizer to the cleavage reagent precursor. Useful photosensitizers include, for example, benzophenone and other similar diphenyl ketones, thioxanthenone, isopropyl-thioxanthenone, anthraquinone, fluorenone, acetophenone, and perylene.
In general, a bifurcation molecule is a molecule that when it is attached to a growing polymer provides more than one location for further polymer growth or extension. In other words, a bifurcation molecule is a polymeric building block that creates a branch point in a polymer.
Some examples of wavelength controlled orthogonal protecting groups are described in "Wavelength-Controlled Orthogonal Photolysis of Protecting Groups," Blanc, A. and Bochte, C., J. Org. Chem., 67:5567 (2002). Additional examples of photo-cleavable protecting groups can be found in: Photogenerated Reagents in Biochemistry and Molecular Biology, Bayley, H., Laboratory Techniques in Biochemistry and Molecular Biology, 12, Elsevier (2002); and Clark, M. A. and Romoff, T. T., Synthesis of peptides and peptidomimetics, Methods of Organic Chemistry, E22a:276 (2004). The most common photocleavable groups are 2-nitrobenzyl-derived carbamates, esters, and ethers. Examples include Z(2-NO2), Nvoc, Ndmoc, Dnboc, Menpoc, Ddz. Other examples include tosyl, phenacyl-based esters, and the 5-bromo-7-nitro-indolinyl group. Many amino acids with photocleavable protecting groups are available from Chem-Impex International, Wood Dale, Ill.
In further embodiments of the present invention, methods are provided to synthesize biopolymers on an array wherein the synthesis is assisted by microwave radiation. Organic synthesis reactions that are assisted by microwave radiation generally demonstrate faster rates and improved fidelity. Synthesis of biopolymers, particularly parallel synthesis methodologies can encounter difficulties, depending on the species being synthesized, from intermolecular aggregation, hydrogen bonded secondary structures (such as, for example, beta-sheet formation in peptides), steric hindrance from bulky side chain protecting groups, and hence premature termination of the sequence. Referring now to
Protein activity is directly associated with its three-dimensional structure. The active site of a protein is usually comprised of a few amino acid residues that can be close to each other (continuous site) or far apart (discontinuous sites) in the primary amino acid sequence of the protein. The activity of a peptide sequence (short amino acid sequence) containing the sequence of a continuous active site is almost never similar to the activity of the folded protein. The lack of activity found for peptides is most often because peptides do not adopt specific conformations (three-dimensional structures). Short peptides sequences synthesized in vitro adopt random conformations (mixtures of many conformations), consequently their activity can be poor even if, for example, the peptide corresponds to the amino acid sequence found at the active or binding site of an enzyme. One of the most common three dimensional structural motifs for peptides in vivo is an a helix. For example, 60% of the segments of proteins around the phosphorylation sites for PKA and PKC kinases display helix motifs. See J. Mo.l Model, 11:431-438 (2005). Helix motifs are commonly found in segments of proteins involved in protein-protein interactions or protein-DNA interactions. The a helix structure is also found in transmembrane proteins, proteins involved in fusion processes (gp 41 from HIV), and antimicrobial sequences, among others.
Examination of the protein structures that contain helix motifs has lead to the formulation of general rules for helix folding. See for example, "De Novo design of helix bundles," J. Mol. Biol., 281, 379-391 (1998). Further structural studies of de novo design helix bundles have generated rules for residue location that favor a particular helix-helix association (dimers, trimers, tetramers, etc). See Protein Science, 6, 80-88, (1997).
Helixes built from two peptide chains may be created from a branch point created by inserting a bifurcation group into a peptide being synthesized on a solid surface or through the use of a trifunctional linker molecule. In general, a trifunctional linker molecule is a molecule having three functional groups, one capable of attaching to a solid surface or a derivatized solid surface, and two that are capable of coupling to an amino acid or peptide chain. A trifunctional linker molecule typically is a molecule having a molecular weight less than about 300 Daltons. The trifunctional linker molecule allows the synthesis of two peptide chains in close proximity. The trifunctional linker could comprise, for example, a carboxy group for surface attachment and two amino groups upon which to grow peptide chains. Exemplary trifunctional linkers include di-Fmoc or di-Boc protected: lysine, ornithine, diaminopropionic acid, and diaminobutanoic acid. Optionally, a linker molecule may be first attached to the substrate surface and the trifunctional linker attached to the linker molecule. Further, linker molecules may optionally be attached to the arms of the trifunctional linker molecule.
Arrays of peptides may be built having features that comprise helical peptide dimers and features that comprise peptides that do not form helical dimers. An array could contain as few as one feature or region having peptides that are designed to fold into helixes. Thus, some regions or features of the array may have trifunctional linkers attached to the surface or bifurcation points inserted into growing peptide chains and some regions may not have these features.
A glass substrate was silanated using a solution of 5% APTES (aminopropyl triethoxy silane) in 95% ethanol. The surface of the substrate was then washed and annealed at about 100° C. for about 1 hour. The substrate was then treated with a 5% solution of DIEA (diisopropyl ethyl amine) in DMF (dimethylformamide). A spacer molecule was then coupled by submerging the surface into a solution of O—(N-Boc-2-aminoethyl)-O′—(N-diglycolyl-2-aminoethyl)hexaethyleneglycol, 0.1 M HOBt, and 0.1 M DIC (diisopropylcarbodiimide) in NMP (N-methyl pyrrolidone) with gentle agitation for about 30 min. After coupling was complete, the surface was washed with NMP. Unreacted amine groups on the surface were capped by treatment with 2% acetic anhydride in DMF solution for about 30 minutes. The surface was then washed with DMF and isopropanol.
A photoresist was prepared by mixing about 2.5% by mass of PMMA, 10% by mass of Bis(4-tert-butylphenyl)iodonium triflate and 10% by mass of isopropyl-9H-thioxanthen-9-one in PGMEA solvent and spin coating the mixture over the amino acid derivatized glass surface for about 60 seconds at 2,000 rpm. The photoresist layer was baked at about 85° C. for about 90 seconds. The resulting photoresist layer had a thickness of about 2 μm.
Acid was generated in the photoresist layer by irradiation of the surface of the substrate with 50 mJ at 365 nm UV light through a mask. The reaction was accelerated by a post exposure bake at about 65° C. for about 60 seconds. After the photogenerated acid deprotection was achieved, the surface of the substrate was rinsed with acetone to strip the photoresist and the surface was dried. The surface was neutralized by treatment in 5% DIEA/DMF for about 5-10 minutes and then washed in DMF.
A trifunctional amino acid (Fmoc-Lys(Fmoc)-OH) was coupled to the surface of the substrate using a 0.1 M solution of Fmoc-Lys(Fmoc)-OH, HOBt, and DIC as above. Fmoc was then removed by treating the surface with 20 piperidine in DMF for 15 min followed by DMF wash. Subsequent rounds of coupling and deprotection were accomplished by repeating the above procedures to generate peptides of a desired length. As a result, an octamer peptide, EIYGEFKK an Src kinase substrate, was synthesized on an APTES surface derivatized with a PEG (polyethylene glycol) spacer. Once the synthesis was completed side chain protecting groups were removed by treating the surface with a solution of TFA/HBr containing pentamethylbenzene and thioanisol as scavengers. Src kinase assay was then performed on the side chain deprotected surface. Phosphorylation detection with ProQ staining showed that the phosphoryl transfer reaction took placed.
An array of wildtype (SDLHKL) and mutant (AGLHKL) peptide was synthesized on an aminated glass surface with a linker molecule, O—(N-Boc-2-aminoethyl)-O′—(N-diglycolyl-2-aminoethyl)hexaethyleneglycol, for spacing the peptides from the surface. The peptides were synthesized in a checkerboard pattern using uniform photodeprotection of t-Boc protecting groups through an open grid mask till the second leucine and spatially localized deprotection through a checkerboard mask for the last two amino acid couplings.
The photodeprotection and coupling of linker molecules and amino acids was carried out as described in Example 1.
The peptide array was incubated for 1 hour with 5 μg/ml monoclonal antibody known to specifically recognize the SDLHKL epitope of human p53 protein. A second incubation was performed with fluorescein-labeled rabbit antibody raised against mouse antibody at a 1:100 dilution in phosphate buffered saline with 0.05% Tween 20. A fluorescent checker board pattern was detected on fluorescence scanning of the array suggesting specific interaction of antibody with the wildtype sequence.
Photoresist formulations may include a sensitizer in addition to the photogenerated acid catalyst to generate the acid deprotection catalysts. In general, the amount of PMMA in the resist in these exemplary formulations may vary between about 3% and about 50%.
Useful photoresists may be made using diaryliodonium salts (DAI) and photosensitizers. The mass ration between DAI and photosensitizer may be between about 1:10 and 1:1. For instance, (tolylcumyl)polonium tetrakis (pentafluorophenyl)borate with isopropyl-9H-thioxanthen-9-one may be formulated in a 1:10 or 1:1 (or a ratio there between) in PMMA and PGMEA to form final concentrations of between about 0.5% to 10% by mass DAI. The formulation selected may be spun coated on the substrate surface and baked. The radiation exposure dose may be between about 0.02 J and about 10 J. Post exposure baking may be conducted for about 30 to 60 seconds at about 40° C. to about 85° C.
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High school students of the Ridgway Area School District will give their final performance of "Beauty and the Beast" tonight, March 2, in the auditorium of the high school at 7 p.m.
JEFFERSON CO. - A Ridgway man headed to trial on arson, attempted murder and drug charges in Elk County has been remanded into federal custody by the U.S. Marshals Office on weapons charges filed against him and a Johnsonburg man in federal court.
Cameron County residents are welcome to bring their electronic devices to the Elk County Community Recycling Center and efforts have been made to clear up a recent miscommunication on the matter.
Chronic Wasting Disease (CWD), a neurological disease that impacts members of the Cervidae family, which includes whitetail deer and elk, has been detected in deer harvested in Blair and Bedford counties, the Pennsylvania Game Commission (PGC) announced Friday. So far, a total of three deer-- two from Blair County and one from Bedford County-- have reportedly tested positive for the disease.
HORTON TWP. – The Ridgway-based state police report responding to a two-vehicle crash that resulted in a fatality at 10:47 a.m. on Feb. 28 on SR 153, 246 feet south of an unnamed street in Horton Township. Desiree M. Smith, 26, of Falls Creek, was killed as a result of the crash.


text: Well, I take a dirty, dirty victory over an beautiful loss any day the week. ^^ So I would be more than happy if we are somewhere in the top5 at the end of the season. After all we were third 10points before Hamburg just two years ago with a dreadfull attacking play.


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Sanctuary BenchmarkCurrent version: 2.3 (2010-05-25)
Sanctuary Benchmark is a first GPU benchmark based on advanced Unigine engine from Unigine Corp., original version was released in 2007.
A gothic chapel with sorrowful statues stand in solemn stillness lit by the trembling light of torches. Only few rays of sun coming through the stained glass windows slide over the biblical fresco and ominous creatures carved in cold stone.
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Welcome to the website of Blue Cedar Art Gallery. Glastonbury, has a large creative community and we shall be putting on exhibitions featuring some of the best art from the area, though we shall also feature artists from further afield from time to time.
We opened our first gallery in 2010 on the High Street, but this closed down in 2012. The new Gallery is located on Silver Street, which is only a short walk from the High Street. We have got a number of exhibitions planned and we were a venue for Somerset Arts Weeks in September 2013.
Our current exhibition is called "Through the Lens" and features the work of Roger Manthorp.
You can also see examples of the work of over 90 local artists at Blue Cedar Online
Blue Cedar promotes a celebration of all forms of arts, nature, colour and life in all of its glorious forms.
All of the Exhibitions since April 2011 have been put online, click on the appropriate exhibition in the column on the left to go on a virtual tour.


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ACA Update: Webcast on Plugging into Consumer Assistance Programs in the Affordable Care Act
ACA Update: Webcast on Plugging into Consumer Assistance Programs in the Affordable Care Act
Event Date: Thursday, March 21, 2013 - 3:00pm to 4:00pm EDT
Webcast on how LGBT community based organizations and organizations supporting communities of color can plug into Affordable Care Act enrollment efforts across the country. This "Navigators 101" will explain an upcoming federal opportunity to fund Navigators to help consumers understand health insurance options and enroll in coverage.
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Can You Work Out With a Cold?
Your nose is running, your head aches, and your throat feels like it's been rubbed with sandpaper. So should you hit the gym—or your snooze button? The answer depends on your symptoms, your workout, and the steps you'll take to keep from sharing your infection with your workout buddy.
Most experts agree a moderate workout can't hurt, and may even help, a common cold. Use the above-the-neck rule as a guide. If your symptoms are all in your head, such as sniffles and sneezing, go ahead and take a walk or do another easy routine.
If you have any of the following signs, lay off of physical activity until you feel better:Learn more about exercising with a cold ›


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Bared to You: A Crossfire NovelPaperback Crossfire Novel
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- Publisher: Berkley Publishing Group
- Format: Paperback | 352 pages
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- Publication date: 12 June 2012
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`If I were to recommend any book today to readers who enjoyed `50 Shades.`..this would be the first one I would offer....scorching love scenes.`--`Dear Author ` THE `NEW YORK TIMES `BESTSELLER ` ``Gideon Cross came into my life like lightning in the darkness... ` He was beautiful and brilliant, jagged and white-hot. I was drawn to him as I'd never been to anything or anyone in my life. I craved his touch like a drug, even knowing it would weaken me. I was flawed and damaged, and he opened those cracks in me so easily... Gideon `knew. `He had demons of his own. And we would become the mirrors that reflected each other's most private wounds...and desires.The bonds of his love transformed me, even as i prayed that the torment of our pasts didn't tear us apart...
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Sylvia Day is the #1 "New York Times" and #1 international bestselling author of over 20 award-winning novels sold in more than 40 countries. She is a #1 bestselling author in 21 countries, with tens of millions of copies of her books in print. Her "Crossfire" series has been optioned for television by Lionsgate, and she has been nominated for the Goodreads Choice Award for Best Author. Visit her at www.sylviaday.com, Facebook.com/AuthorSylviaDay and on Twitter @SylDay.
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By Fran Wright 19 Dec 2012
If you have or have not read Fifty Shades, the Crossfire Series is a must to read.
A very intense love story any women would want. Yummy.
By kimberley 19 Jul 2012
One word " Obsessed ". This is just amazing any woman whose read the fifty shades trilogy so needs to read this... So eager for the next book !!
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