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"It's not right. I think it's all of our jobs to rectify this travesty."
— Bill Walton on Dennis Johnson not being elected to the Basketball Hall of Fame in 2006
And that's always how I've felt about Dennis Johnson and the Hall of Fame.
I mean, this is DJ we are talking about. He's got the resume that reads perfectly on a Hall of Fame bust, right? A Finals MVP, three championships, five All-Star Games and on the Mount Rushmore of great defensive guards. What am I missing?
With the announcement last week that DJ was a finalist for the Class of 2010, I decided to take a closer look at the case for Dennis Johnson. So I dusted off the Keltner List, a set of 14 questions that has been used mostly to determine if a player deserves to get into the Baseball Hall of Fame. However, it translates fairly well to basketball, so let's take a gander.
1. Has he ever been regarded as the best player in basketball? Has anyone ever suggested that he was the best player in basketball?
Well, no. But that's a really tough standard. During his career (1976-90), the title of Best Player in Basketball was held, at one time or another, by Kareem Abdul-Jabbar, Moses Malone, Larry Bird, Magic Johnson and Michael Jordan. All-time all-timers. But how many Hall of Famers were never near the best player in the league? Joe Dumars played 14 seasons in the NBA and finished in the top 10 in MVP voting once (and that was 10th, in 1993). James Worthy finished 12th in MVP voting in 1986, and that was the only season in his career when he received any votes at all. Lots of guys like that in Springfield. But Dennis Johnson finished fifth in MVP voting in 1980 and eighth in 1981. So for three years or so he was a top seven or eight player in the league. But no, I don't think anyone ever suggested that DJ was the best player in basketball. If those were the only guys you let into the Hall of Fame there would be about 20 players enshrined.
2. Was he the best player on his team?
Sure he was. With the Supersonics he was a second-team All-NBA player in 1980. And he was MVP of the Finals in 1979. Gus Williams and Jack Sikma (the owner of a top five all-time perm) were good players, but I think most people thought that DJ was the best player on those teams. And that first season in Phoenix was his first-team All-NBA year.
(Here's every retired player that has won a Finals MVP award and been named to an All-NBA first team.
Jerry West
Willis Reed
Kareem Abdul-Jabbar
Wilt Chamberlain
John Havlicek
Rick Barry
Bill Walton
Dennis Johnson
Magic Johnson
Moses Malone
Larry Bird
Isiah Thomas
Michael Jordan
Hakeem Abdul Olajuwon
With the exception of DJ, every player on that list is in the Hall of Fame. In fact, except for Rick Barry, every other player was elected on the first ballot. And everyone but DJ was named as one of the NBA's 50 best players in 1996. And although A.C. Green is not on this list, it should be noted that from 1958-2002 he and Wilt Chamberlain combined to sleep with over 20,000 women. Seemed as a good a place as any to mention that.)
3. Has he ever been the best player in basketball at his position?
You could make a case for DJ as the best guard in the NBA during the two years before Magic took over the title. Here's the All-NBA first team of 1981:
Kareem Abdul-Jabbar
Larry Bird
Julius Erving
George Gervin
Dennis Johnson
Again, a bunch of guys in the Hall of Fame and D.J. I'm not sure how to compare DJ and The Iceman. Gervin led the league in scoring four times in a five-year stretch from 1978-82 but played absolutely no defense. By all accounts he was the kind of guy that would rather score 50 and lose than 14 and win. Well, we know that wasn't DJ I'm OK with DJ as the best "all-around" guard in the league at that time. Nearly 20 points a game plus the best defensive player at his position. But I'll allow that we aren't exactly talking about the golden age of guard play.
4. Has he had an impact on a number of NBA Finals or conference finals?
This, as we all know, might be Dennis Johnson's best argument for the Hall of Fame.
The Sonics do not win the NBA title in 1979 without DJ. The Celtics do not win the NBA title in 1984 without DJ. How many players not in the Hall of Fame can claim that they were the difference for two title winners? Just look at these playoff moments from his years with the Celtics:
1) The Celtics were down 2-1 in the 1984 Finals (and save for Gerald Henderson would have been down 3-0) and had just lost Game 3 by 33 points when DJ was assigned to defend Magic Johnson. Four games later, the Celtics were champions (DJ averaged 18-5-3 for the series) and "Tragic" Johnson was born. Magic would later call DJ "the best defensive guard I ever played against."
2) DJ hits a jumper as time expired to give the Celtics a 107-105 win in Game 4 of the 1985 Finals, evening the series at 2-2. He averaged 16.0 points, 9.5 assists and 1.7 steals per game in the six-game series and led all players in with 247 minutes of court time.
(Think about that for a second. In an NBA Finals between the biggest of rivals, at the peak of the league, in a series that included seven Hall of Famers, the player that was on the court the most was Dennis Johnson. And we aren't talking about borderline Hall of Famers, either. Any serious list of the six or seven best players in history has to have Kareem, Bird and Magic on there. Doesn't that have to count for something?)
3) I think the 1986 Celtics would have won the title with Johnny Weir at point guard. We are talking about the best team I have ever seen in any sport. So I can't give DJ a lot of credit for this one, though he did put the clamps on Robert Reid in the Finals. And again, in a series that had five Hall of Famers, only Bird played more minutes than DJ.
4) DJ averaged 18.9 points and 8.9 assists in 23 games during the 1987 playoffs and was the Celtics' best player in the Finals (21.0 ppg, 9.3 apg, shot 48 percent from the floor and 86 percent from the line). And how many players have you seen in your lifetime of watching basketball that would have had the instinct to race to the basket as he did after Bird's steal vs. the Pistons? When Bird called DJ "the best player I have ever played with," THAT was the kind of stuff he had in mind. Sure, Kevin McHale was probably a better player. But DJ was cut in the Bird mold. He was the only player that Bird talked about with a little bit of awe, the way everyone else talked about Larry.
5. Was he good enough that he could play regularly after passing his prime?
He was just OK in his last three years, but, yeah, I would count him as a serviceable NBA guard until he retired (at age 35) in 1990. He was neither a revelation nor an embarrassment during his third act.
6. Is he the very best (eligible) basketball player in history who is not in the Hall of Fame?
Karl Malone is, but he'll get in this year, as will Scottie Pippen. But not counting those guys (each on the ballot for the first time)?
I don't see a single player not in the Hall of Fame (and currently eligible) that is a clear choice over Dennis Johnson. There are some guys that you could argue (Jo Jo White would be one. Very close call. Also a Finals MVP, White was a six-time All-Star and a key part of a couple of title-winners. Also second-team All-NBA twice. Gun to my head, I'd still take DJ, but I think if one gets in the other would have to as well) but there are no locks. Though I can understand the Bernard King argument. So I'd suggest that if Dennis Johnson isn't the best player not in the Hall of Fame, he's somewhere among the top three.
7. Are most players who have comparable statistics in the Hall of Fame?
If you look at his offensive numbers, then no, not really. Some are in, but most are not. But there's another list. How about the players in NBA history that have made the first or second All-Defensive Team at least nine times:
Tim Duncan
Kareem Abdul-Jabbar
Kevin Garnett
Scottie Pippen
Michael Jordan
Gary Payton
Bobby Jones
Kobe Bryant
Hakeem Abdul-Olajuwon
Jason Kidd
Dennis Johnson
All those active guys are first-ballot locks. Gary Payton will get in, too. So only Bobby Jones and DJ are left out. And while Jones was a really good NBA player (and totally forgotten), he was never an All-NBA guy or Finals MVP.
8. Do the player's numbers meet Hall of Fame standards?
Again, they don't jump off the basketball-reference page and hump your leg or anything, but they are plenty good enough. When he retired in 1990 he was one of just 12 players to score more than 15,000 points and collect over 5,000 assists. And you're never going to guess what the other 11 guys have in common. Yup, all Hall of Famers.
Magic Johnson
Oscar Robertson
Lenny Wilkens
Bob Cousy
Tiny Archibald
Jerry West
John Havlicek
Kareem Abdul-Jabbar
Dave Bing
Julius Erving
Walt Frazier
9. Is there any evidence to suggest that the player is significantly better or worse than is suggested by his statistics?
In 1979-80, the Supersonics won 56 games and lost to the Lakers in the Western Conference finals. They traded Dennis Johnson to the Suns in the offseason (for Paul Westphal) and won 34 games in 1980-81. The Suns, meanwhile, went from third to first in the Pacific Division in 1980-81, finishing three games ahead of the Magic/Kareem Lakers.
In 1982-83, the Suns won 53 games. They traded Dennis Johnson to the Celtics that offseason (for Rick Robey, of course. That's one of those trades that would never happen today. In the Internet/talk radio/ESPN world, I mean. I get that DJ had some baggage, but a 28-year-old, four-time All-Star straight up for a guy that, if everything worked out, would maybe give you 20 minutes a night as a backup center? Is there a 2010 equivalent to this deal? Maybe Joe Johnson for Aaron Gray. That's about right). The Suns won 41 games in 1983-84. The Celtics won 56 games in 1982-83 and were swept by the Bucks in the Eastern Conference semifinals (despite 0.4 points per game from Robey.) In 1983-84, the Celtics won 62 games, beat the Bucks in five games in the Eastern Conference finals and went on to beat the Lakers in seven to win the NBA title.
Teams got better when DJ arrived and got worse when he left. And not just slightly in either direction. So that would be, I think, a "yes" to Question 9.
10. How many MVP-type seasons has he had? Has he ever won an MVP award? If not, how many times has he been close?
Never challenged for an MVP award. The year he finished fifth (1979-80), Kareem was a runaway winner. He was never close to winning, but as I wrote earlier, the Hall of Fame is stuffed with guys who never challenged for an MVP. You think Paul Pierce is a Hall of Fame lock, right? Well, so do I. You know how many first-place votes Pierce has received in his career? Zero. Second-place? None. Third place? One, last year. Since Pierce began his NBA career, 1,359 MVP ballots have been cast, and just one voter thought he was one of the three best players in the league for a given season. But he'll still cruise into the Hall of Fame, probably on the first ballot. MVP voting just doesn't mean a lot in basketball when it comes to the Hall. Unlike baseball, it's a sport that can be dominated by a single person, and that usually is the guy that wins the MVPs. Plus, there rarely is a fluke MVP in hoops. No Zoilo Versalles or Kevin Mitchell. There isn't an NBA MVP who isn't in the Hall of Fame (or will be when eligible.) There are lots of baseball MVPs who haven't even come close to Cooperstown (hello to George Bell, Jeff Burroughs and Willie Hernandez, among others.) This is the one spot where the Keltner List isn't much help and frankly doesn't translate well to basketball.
11. How many All-Star-type seasons has he had? How many All-Star Games has he played in? Did most of the players who played in this many All-Star Games go into the Hall of Fame?â¨
Dennis Johnson played in five All-Star Games. There are 21 other players eligible for the Hall of Fame who have played in five All-Star Games. Nine are have been elected.
I was a little surprised to see that D.J. played in just one All-Star Game for the Celtics, but it makes sense when you consider that A) Jordan and Isiah were the starters every year and B) The Big Three made it every year.
(In case you were wondering, the stone-lock number of All-Star Game appearances you need to get into the Hall of Fame is eight. There have been 37 players eligible for the Hall of Fame that have played in eight. Only Larry Faust isn't in Springfield. In fairness, he did kill four people in 1972, so maybe that's why he isn't in. Kidding, of course. But once you get to eight, you can punch the ticket.)
12. If this man were the best player on his team, would it be likely that the team can win an NBA title?
Well, he was the best player on a team that won an NBA title. And you could at argue that he was the second-best player on the 1984 Celtics. Take a look at all the NBA title winners and figure out the second-best player on those teams. I'll bet 90 percent of them are in the Hall of Fame.
13. What impact has the player had on basketball history? Has he been responsible for any rule changes? Has he introduced any new equipment? Has he changed the game in any way? Was his college and/or international career especially noteworthy?
Not much here, although he was one of the subjects of the famous "Thirteen Johnsons Playing The Game" song from the 1984 Pride And Passion NBA DVD. Come on, sing along:
Thirteen Johnsons With The Same Last Name
Thirteen Johnsons Playing The Game
All Of The Johnsons Shooting Hoop
Too Many Johnsons Spoil The Soup
That final line, by the way, has never been uttered by Nina Hartley.
So Will He Get In?
I have to confess that I thought I would need to play the intangible card with DJ. You know, look past the numbers, was a winner, all that stuff. But his numbers alone hold up pretty well. And there are just too many important lists that have only Hall of Famers and DJ. Can't ignore that. Again, I'm not sure that he's the very best player not in the Hall of Fame, but there aren't five better. He absolutely deserves his day.
I don't think he gets in this year (that'll be Malone, Pippen and The Dream Team — I'm speaking about the 1992 Olympic squad, not the Brutus Beefcake/Greg Valentine tag duo of the late '80s) but I still believe it'll happen sometime in the next couple of years. I bet he sneaks in during a down year.
And that'll make the case for Jo Jo White a lot easier.
Greg and Chris talk more offseason happenings with the Pats and their plans. They talk about some of the free agents toward the bottom of the list with Stevan Ridley and Dan Connolly. Price thinks that Connolly could end up back with the Pats and Ridley elsewhere (Cowboys?), but Greg thinks they both could be back. They also chat about the departure of VInce Wilfork and what he meant to the organization, the re-signing of McCourty and more.
The very first airing of the offseason edition of NFL Sunday gets underway with Greg and Chris delving into the free agency period and how the Pats made out. Of course they lost Revis to the Jets, but what else went on? Greg isn't over the loss of Revis yet and the guys discuss what went into that whole ordeal. Price is looking forward to the additions of Chandler and Cadet. They also get a call from Mike Petraglia and get his thoughts on the Pats offseason moves.
We talk to Manish Mehta of the New York Daily News about his column today which basically accuses the Patriots of sour grapes for asking the league to enforce their own rules against tampering.
Brow Buff's Sam Packard and Ben Kichen break down Marcus Smart's unfortunate ball tap, debate leadership in the Celtics locker room, and rehash the great Kevin Love to Boston rumors.
Flannery joins Mut to break down the Isaiah Thomas trade to Boston and what it means for the Celtics this season and in the future. Paul also chats with Mut about the other deals that happened at the NBA's trading deadline
We talk to Chris Mannix from SI to break down the C's acquisition of Isaiah Thomas and the crazy trade deadline in the rest of the NBA.
Mut, Tomase, and Bradford kick things off talking about Shane Victorino taking offense to people reading into some comments he made about trading for Cole Hamels. They also discuss Blake Swihart and how soon he could be up if Christian Vazquez starts the season on the DL.
Joe Kelly joined the Hot Stove show where he talked about being ready for his next spring training start after a biceps ailment forced him out of his last outing, he talks about his NCAA brackets and how teammate Wade Miley has a perfect bracket still.
Mut, Bradford, and Tomase kick off this weeks show by talking to Red Sox pitcher Joe Kelly about his biceps recovery, getting ready for the season and his NCAA brackets. They then talk about the Red Sox depth at closer with Koji Uehara questionable for the start of the season.
Jack Edwards of NESN joins Dale, Michael and Jerry. With 9 games left the Bruins don't have much if any margin of error, and Jack knows it.
DJ, Joe and Pete talk more playoff scenarios in hour 2 and if the Bruins can get in, they'll be a very dangerous team... to the point where DJ thinks teams would much rather face the Senators and are doing their best to oust the Bruins from the equation. It's become apparent now more than ever that Chiarelli probably needed to pull the trigger on a deal for a defenseman at the trade deadline. Also. Bruce Garrioch from the Ottawa Sun joins the boys to discuss the Hamburglar and the Senators and Bruins being neck-and-neck for a playoff spot.
With the Senators hot on the tail of the Bruins for a spot in the playoffs, Bruce Garrioch from the Ottawa Sun calls into Sunday Skate. He talks about "the Hamburglar" craze sweeping through the league as goalie Andrew Hammond has really stepped up for Ottawa. They discuss playoff chances, the fans' reaction in Ottawa and more.
The latest edition of the highly rated segment.
The great Lisa Scherber joined us to discuss today's trip to Fort Myers with 46 Jimmy Fund patients.
D&C's favorite author joined the show to discuss his new book.
We hear more audio from Christian's day between the pipes. He did his best to try and intimidate the small children shooting on him.
After Christian gave away his children's dog, we find out that Lola eventually found a better home.
During the recess of the Aaron Hernandez murder trial, Ted Daniel describes the first half of Shayana Jenkins testimony.
Dale, Michael and Jerry Thornton discuss David Ortiz's self-penned piece which took on such topics as steroids, the media, his contract and more. And we get into a back and forth about the fan perception of him in Boston, and why he can be so polarizing at times, even with the on-field track record he has.
Dale, Michael and Jerry Thornton discuss some of the testimony from Aaron Hernandez' fiancee, and try and judge how her words might change the outcome of this case.
Dale and Michael talk Bruins after they managed to snatch defeat from the claws of victory and blow a late game lead to the Anaheim Ducks. With the playoffs still in question, the Bruins need more efforts like that, and more luck.
Chris Price joins Mut to talk about how Revis will heat up the Jets-Pats rivalry next season
Mut opens his show talking about the New York Jets filing tampering charges on the Patriots
Mikey, Mut, and Lucy are talking about all things New England sports, the Red Sox spring training, more Darrelle Revis and Jets talk, and some Bruins mixed in.
Ben and Adam finish the odyssey that is the history of Wrestlemania. Wrestlemanias 21-30 are discussed and analyzed.
Mike Mulloy joins Chris in the studio to talk Raw and Wrestlemania.
Brow Buff's Sam Packard and Ben Kichen break down Marcus Smart's unfortunate ball tap, debate leadership in the Celtics locker room, and rehash the great Kevin Love to Boston rumors.
The latest edition of the highly rated segment.More from this show
D&C's producers took over for the lazy hosts who declined to do this weeks podcast. Sausage needs to join a dating site.More from this show
The top stories of the day as recounted by Kirk Minihane.More from this show
Ortiz writes a column defending his career.More from this show
Christian does not impress the high school girls hockey team.More from this show


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Patrick Chung won't shy away
Patrick Chung won't shy away
Parental guidance prepped Patriots safety for stardom
Parental guidance prepped Patriots safety for stardom
FOXBORO — There isn't a how-to guide on being a celebrity. There should be, considering the pitfalls and life-shaking changes the famous encounter, but there isn't.
It's trial and error and learning on the fly while striving to continue doing the job that brought one into public consciousness. All of which makes the education Patrick Chung received priceless.
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A Duo Of Peculiar Games Being Ported To Linux
Published on 12 January 2013 08:50 AM EST
Written by
Michael Larabel
55 Comments
Replay Games has written into Phoronix to talk about two commercial game titles that they will be bringing to Linux.
The two games coming out of Replay Games for Linux is "Leisure Suit Larry in the Land of the Lounge Lizards: Reloaded" and "Fester Mudd: The Curse of the Gold" will be out soon for the penguin operating system.
About the Leisure Suit Larry successor, Replay writes, " Replay has been hard at work on the remake of Leisure Suit Larry which had a very successful Kickstarter campaign. Leisure Suit Larry is one of the most iconic characters in the history of computer gaming. The game follows the life of Larry Laffer, a loveable loser who is a balding, dorky, double entendre-speaking, leisure suit-wearing "lady's man". The new Larry game is going to be expanded and enhanced in every detail and ready for mobile devices, PCs, and LINUX!"
Replay raised $655,182 of a $500k Kickstarter goal to develop this Leisure Suit Larry successor.
About the Fester Medd game, it is described as, "a throwback to the old school adventure games that dominated gaming in the 80's and 90's. With a western theme and strong comedic elements, Fester Mudd will be Replay's first original intellectual property adventure title."
Below are the video trailers on these two peculiar games that are coming natively to Linux that will be distributed via Valve's Steam client.
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Michael Larabel is the principal author of Phoronix.com and founded the web-site in 2004 with a focus on enriching the Linux hardware experience and being the largest web-site devoted to Linux hardware reviews, particularly for products relevant to Linux gamers and enthusiasts but also commonly reviewing servers/workstations and embedded Linux devices. Michael has written more than 10,000 articles covering the state of Linux hardware support, Linux performance, graphics hardware drivers, and other topics. Michael is also the lead developer of the
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Hey Chef, What Can I Do With Sichuan Peppercorns?
If you're not familiar with the numbing, tongue-tingling bite of Sichuan peppercorns, they can be a nerve-wracking ingredient to bring into your kitchen. So we asked chefs around the country to show just how versatile this spice can be, and how to incorporate into food well beyond the Sichuan standards, without the pain. More


text:
Shane Sutton says Joanna Rowsell was not performing at her normal level at the Track World Championships
Joanna Rowsell
Track World Championships round-up: Day three
Two events. Two world titles for François Pervis. Following his peerless display at last year's world championships where he won three world titles his 2015 homecoming is looking every bit…
Joanna Rowsell declares Hour Record interest
Joanna Rowsell has revealed she is interested in attacking the women's Hour Record after the 2016 Olympics. The double world champion told skysports.com that seeing her friend Dame Sarah Storey…
British Riders of the Year 2014 number 3: Joanna Rowsell
Reigning Olympic, World, Commonwealth, European and national champion Joanna Rowsell is third in our countdown
Britain's female team pursuiters start strongly at London Track World Cup
World champions Katie Archibald, Elinor Barker, Joanna Rowsell and Laura Trott qualify fastest in day session.
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British Cycling's technical director Shane Sutton says he has to manage expectations ahead of the track World Cup in London
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LaCavera Produces RBI In Softball Doubleheader March 28, 2015 Megan LaCavera produced RBI singles in both games. Albion collected eight hits in 10-2 and 9-1 losses at Kalamazoo [read more]
'A Little Fight, A Little Drive' March 27, 2015 The way Megan LaCavera persevered through multiple knee surgeries has helped the softball first baseman become one of Albion's most popular student-athletes [read more]
Softball Loses Pair At Madonna March 24, 2015 Ashley Bulter and Julia Anderson collected Albion's hits in losses at Madonna [read more]
Brugnoni, LaCavera Power Softball Rally March 20, 2015 Monica Brugnoni pitched a complete game and produced two RBI and Megan LaCavera slugged a grand slam to help Albion take the first game of a doubleheader from Lourdes [read more]
Softball Team Completes Spring Break Schedule March 12, 2015 Megan LaCavera and Alive Garvin delivered RBI singles and Ashley Butler pitched a complete game in Albion's 3-2 win over Marietta [read more]
Britons Split One-Run Games March 11, 2015 Ashley Butler's walk-off single lifted Albion to a 4-3 win over Beloit. The Britons also lost 3-2 to Illinois College in Wednesday softball action [read more]
Britons Split One-Run Games March 11, 2015 Ashley Butler's walk-off single lifted Albion to a 4-3 win over Beloit. The Britons also lost 3-2 to Illinois College in Wednesday softball action [read more]
Seventh-Inning Rally Fizzles March 9, 2015 Albion scored three times in the seventh, but it stranded the winning run at second base in a 5-4 loss to Hiram [read more]
'We Did A Lot Of Things Well' March 8, 2015 Albion collected 17 hits in Sunday losses to Defiance and Mount Saint Joseph [read more]
Imbier Delivers In The Clutch March 7, 2015 Olivia Imbier delivered a game-winning single as Albion pulled out a 6-5 win over Westminster. The Britons also took a 7-2 loss to Coe on Saturday. [read more]
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text:
Welcome to LMTmag.com, the social and information hub of the dental lab industry. Connect with industry peers and vendors, ask questions, sign up for events, review products, read LMT articles and industry news and more!
Knowing What You Know...Jack Garcia, CDT · Jun 07, 2013
Knowing what you know
doesnât mean you know
more than others know,
or those others know
more than you know.
Maybe they donât know
what you know,
so what you know
might not be what you need to know,
because another one could not know
what others know,
including what you know.
Read More 1 minute read


text:
Narrow your search
The impressive, metal Galaxy S6 is Samsung's hero phone all decked out with worldly looks and sophisticated specs. But stay tuned for our final tests before you make the investment.
Looking for phones? CNET's reviews of the best phones include photos, video, and user reviews.
Samsung has a dizzying array of flagship smartphones. CNET's Marguerite Reardon helps you break down your options.
Though Sprint's Samsung Galaxy Nexus retains the cache of being an official showpiece for Ice Cream Sandwich, it's no longer the only kid on the block. The fact that Sprint's LTE network is not operational yet doesn't help the phone, either.
Samsung's striking, high-end and convenient Galaxy S6 Edge has the beauty, brains and brawn to take down the iPhone 6 and all the Android competition. We're still testing -- but get ready to burn your cash.
These two top flagship smartphones both pack high-end designs and features to boot. Here's how they stack up against each other.
The Samsung Galaxy Nexus is a big step forward for Android, but it's not the giant leap you may have been expecting. As impressive as it is, Ice Cream Sandwich can be messy, and without it, the Galaxy Nexus is just another Nexus device.
Sprint, AT&T and other carriers have lined up with a wide range of pricing options for consumers. Samsung has a lot riding on getting off to a good start.
As the first U.S. phone with Ice Cream Sandwich, Verizon's Samsung Galaxy Nexus takes a coveted, solitary step forward. However, once other premium handsets receive the updated Android OS, the Galaxy Nexus will lose some of its competitive edge.
Although the Nexus 6 trails the slimmer Samsung Galaxy Note 4 in processor performance and native productivity features, it's still the most powerful pure Android handset available and the largest Nexus yet.
The Samsung Galaxy Note 4 will thrill anyone who loves a fast phone with a large screen, but it's best for compulsive scribblers willing to pay a lot for its winning stylus.


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By-Laws/Standing Rules
Past Meeting Minutes
Membership List
Trustees List
Scholar Awards
Welcome to the Hilliard Bradley Athletic Boosters Website
Hilliard Bradley High School parents, family, friends and local business owners make up the Athletic Boosters. They play a vital role in promoting academics, school and community spirit for our athletic program at Bradley. We volunteer our time, talents, and resources in supporting all of our sports teams.
Our goal is to increase the awareness and encourage involvement in our booster club. Participation not only increases the success of Jaguar Athletics, but provides the opportunity to teach our children the importance of community involvement.
Our nonprofit organization conducts fundraising, award annual awards, purchase trophies, plaques, pins, chevrons, numbers, letters and certificates. We support all of our athletic teams.
We have monthly meeting the 2nd Monday of the month at 7:00 p.m.. Currently being held at Bradley High School near the commons. Everyone is welcome to attend!
2015 Mulch Sale
It's mulch season! Our annual Hilliard Bradley Athletic Booster Association Mulch Sale starts Sunday, March 1 with sales running through Saturday, April 4. Delivery is scheduled for April 11 and 12. Please continue your support of Jaguar Student-Athletes by purchasing mulch.
Click on Mulch Sale on the navigation bar on the left side of this page. Mail a completed order form or order online. Click here for additional information.
Scholar-Athlete Award Packet
The Athletic Boosters Scholar-Athlete Award packet for 2014-2015 is now available, click on Scholar Awards on the navigation bar on the left side of this page.
Graduation Banners!
Click here for information on this year''s graduation banner fundraiser. 100% of the profits go to the 2016 Senior Class.
Gameday Broadcasting
Listen to every exciting Hilliard Bradley varsity football game live on www.gamedaybroadcasting.com. The pre-game show starts at 7:00 pm, for each home and away game this season. Each game will also be archived for a year, so don't miss a second of Bradley football. Tune in to the "Hometown Voice" of the Jaguars on the Gameday Broadcasting Sports Network.
AmazonSmile Foundation
Use this link and purchase as you would on Amazon.com, but by ordering through this link, Amazon will donate 0.5% of eligible purchases to the Hilliard Bradley Athletic Boosters. The 0.5% will be automatically be deposited into the Boosters General account. Happy shopping!
HIlliard Bradley High School
2800 Walker Rd.
Hilliard Ohio 43026
President - John Krochmal - firstname.lastname@example.com
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Secretary - Maria Satre - email@example.com
Web Editor:
Jim Banaag - firstname.lastname@example.com


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SD activities group adopts changes to constitution
PIERRE (AP) — Members of the South Dakota High School Activities Association voted to pass three of five new amendments to the organization's constitution.
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Stirring eggs into simmering broth is a classic technique for adding nourishment and body to soup. Asparagus gives it a mild, sweet flavor and a bit of texture. Serve this quick soup with Parmesan crisps or sprinkle with grated Parmesan.
- 8 cups homemade chicken broth, fat skimmed, or reduced-sodium chicken broth
- 1/2 cup pastina or other tiny pasta, such as alphabet or stars
- 12 ounces asparagus, trimmed and cut into 1 1/2-inch diagonal pieces (2 cups)
- 4 large eggs
- 1/2 teaspoon lemon juice
- 1/4 teaspoon salt, optional
Bring the broth to a boil in a Dutch oven or soup pot. Stir in the pasta. Cook, uncovered, over medium-high heat, stirring occasionally, until the pasta is just tender, about 5 minutes. Stir in the asparagus; cook for 2 minutes. Reduce heat to medium.
Break the eggs into a large measuring cup and whisk until well blended. Add to the gently boiling soup in a thin, steady stream, stirring constantly with a fork. (Slow stirring will produce large threads; rapid stirring will break the threads up into small pieces). Remove from heat and stir in the lemon juice. Taste, adding salt if desired.
Recipe reprinted by permission of Publisher. All rights reserved.
RecID 7397
nutrition information per serving
116 calories; 8g total fat; 4g total saturated fat; 123mg cholesterol; 566mg sodium; 11g carbohydrates; 1g fiber; 17g protein
These nutrition facts are calculated according to the ingredients listed in this recipe. Any substitutions will change these facts. Although we strive for accuracy, please note that food manufacturers occasionally change their food formulas, which could affect the calculations as shown.
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Report highlights housing woes for low-income Minnesotans
DULUTH -- Shannon Redbrook spent a year homeless in Duluth.
Finding housing has been difficult the past eight years she's lived here. With four children, she's struggled to afford a rental large enough for her family. There are application fees and, worst of all, too many apartments and homes "not in good shape."
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StoryCorps Interview App Announced at TED 2015
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ResearchKit for iPhone Improves Medical Research
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Tag Archives: Question of the Week
Question of the Week: February 23
This week's question comes from Chris Kolakowski: Throughout my career I have drawn great lessons and inspiration from historical personalities and events. From the Civil War, General Grant's campaign against Vicksburg stands out for me in this regard. What Civil War … Continue reading
Posted in Personalities, Question of the Week Tagged Question of the Week 8 Comments
Question of the Week-16 February 2015
This edition of Question of the Week comes from our own Dan Welch: Was there a defining or pivotal political moment in 1865 or was the end of slavery and the restoration of the Union inevitable by then?
Posted in Memory, Politics Tagged 1865, Question of the Week 6 Comments
Question of the Week: February 2, 2015
Saturday, January 31 marked the 150th anniversary of the passage of the Thirteenth Amendment, abolishing slavery. The Fourteenth and Fifteenth would grant former slaves citizenship and give them the right to vote. I have called the Thirteenth Amendment "arguably the … Continue reading
Posted in Question of the Week, Slavery Tagged Question of the Week, slavery, Thirteenth Amendment 8 Comments
Question of the Week: January 19, 2015
This week's question actually comes from ECW's business officer, Jennifer Mackowski. Pondering some of the discussions and controversies that have swirled around Virginia this past weekend in relation to Lee-Jackson Day and Martin Luther King, Jr., Day, she asks: What … Continue reading
Question of the Week—January 12, 2015
This week's question of the week comes from ECW reader Dwight Hughes: I have a question for you experts: Everyone talks about Jackson's brilliance at Chancellorsville. What about Second Manassas? The flanking movement at Chancellorsville was excellently conceived and executed, … Continue reading
Question of the Week—January 5, 2015
In his book Such Troops As These, author Bevin Alexander calls Confederate Lt. Gen. Thomas J. "Stonewall" Jackson "by far the greatest general ever produced by the American people." Later, he refers to Jackson as "one of the supreme military … Continue reading
Question of the Week: July 28, 2014
Historians have given much attention to the decision to replace Joseph Johnston with John Bell Hood, but little attention is given to the Federal command change that happens at the same time. When Army of the Tennessee commander James McPherson is killed, several … Continue reading
Posted in Emerging Civil War Tagged Question of the Week 8 Comments
Question of the Week for July 7, 2014
This week's Question of the Week comes to us from a reader. Some readers might find its tone impertinent, but we couldn't deny that it was, indeed, a thought-provoking question: With the 151st Anniversary of the Battle of Gettysburg last week, all … Continue reading
Posted in Question of the Week Tagged Gettysburg, Question of the Week, what-if 2 Comments
Question of the Week for June 23, 2014
We've heard historians at Petersburg refer to their battlefield as "the red-headed stepchild" of the Virginia battlefield parks. The story they tell doesn't get the attention other battles and campaigns do. Or does it? What do you think: does Petersburg get … Continue reading
Posted in Question of the Week Tagged Petersburg, Petersburg National Battlefield, Question of the Week 9 Comments
Question of the Week for April 14, 2014
At the outset of the spring 1864 campaigns, do you believe that the Confederacy still had a fighting chance to win the war, or do you believe victory was a forlorn hope?


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User Interface and Experience Designer
Closed - This job posting has been filled and work has been completed.
Job Description
We are looking for someone who can help us determine the UI for a new application we are developing. We have determined the functionality for the application, so you're job will involve determining the user flows, navigation, and laying out the various pages of the application.
You will start out by working with wireframes, then move to a photoshop design and then finally, code the HTML.
Please submit at least 3 samples of applications you have designed with your application.


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San Francisco adds green building labels
- Staff Portland Business Journal
San Francisco is greening its real estate records.
Ecologically-sustainable building practices — "green labels" —will now be included on official land records maintained by the city, according to Assessor-Recorder Phil Ting and Department of Environment Director Melanie Nutter. That means that along with information on square footage and assessment and complaints about things like bed bugs and rat infestations, with a few clicks you will be able to check out whether a building has a LEED or Energystar certification.
There are more than 1,000 properties and 250 buildings in San Francisco that have earned some sort of green label. These properties cover more than 60 million square feet of commercial space. At least 35 percent of San Francisco's commercial square-footage now has a LEED or Energystar certification, according to Ting.
Green Labels being recorded by the Assessor's office are U.S. Green Building Council's Leadership in Energy and Environmental Design (LEED), Build It Green's Green Point Rated, Home Energy Rating System II (HERS II), Home Energy Score (US Dept of Energy) and Energystar.
"We are making San Francisco history by including Green Labels in our official property records," said Ting. "The Green Label information now maintained in our files is an important first step in the universal adoption of ecologically-sustainable building practices. Reducing the ecological impact of our built environment is a top priority for so many of us in San Francisco."
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ZHANJIANG -- Roc (China) Oil Company, said that final stage of the Beibu Gulf Block 22/12 development drilling has been completed with the successful conclusion of the five well drilling programme on the WZ 12-8 West field and the demobilisation of the jack up drilling rig COSL HYSY 931.
Commenting on delivery of this strategic milestone, ROC's CEO Mr Alan Linn said: "The demobilisation of the COSL HYSY 931 drilling rig completes the fifteen well Beibu Gulf development programme, designed to maximise production from both the original field development plan and development of the additional reserves discovered during the successful 2012 Beibu near field exploration campaign.
All fifteen wells are expected to be online during Q3 2013 delivering daily project production rate of 15,000 bopd (2,940 bopd net to ROC).
The integrated project development, with CNOOC as Operator and ROC providing part of the project management team produced very positive outcomes for all Joint Venture Partners, with the development drilling campaign completed safely, ahead of schedule and within budget. I'm delighted with the project and offer my congratulations to all of the teams who have been involved with the project for a job well done."
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- Easter 'Blood Moon' to turn sky red this weekend – but was it predicted in the Bible?
- Pastor Cruz: 'We Are on The Brink of The Destruction of This Country'
- Rev. Graham: Pence Attacked by LGBT & 'Liberal Media Who Don't Want Christians' Freedoms Protected'
- Lavrov Claims Agreement with Iran Reached
- Iran's Basij Commander: Israel Must Be Wiped Off the Map
- China's new bank….Is this the start of a New World Order?
- Experts: Iran Housing Nuke Materials in North Korea, Syria
FBI Changes 'Primary' Mission From "Law Enforcement" to "National Security"
The FBI's creeping advance into the world of counterterrorism is nothing new. But quietly and without notice, the agency has finally decided to make it official in one of its organizational fact sheets. Instead of declaring "law enforcement" as its "primary function," as it has for years, the FBI fact sheet now lists "national security" as its chief mission. The changes largely reflect the FBI reforms put in place after September 11, 2001, which some have criticized for de-prioritizing law enforcement activities. Regardless, with the 9/11 attacks more than a decade in the past, the timing of the edits is baffling some FBI-watchers.
"What happened in the last year that changed?" asked Kel McClanahan, a Washington-based national security lawyer.
McClanahan noticed the change last month while reviewing a Freedom of Information Act (FOIA) request from the agency. The FBI fact sheet accompanies every FOIA response and highlights a variety of facts about the agency. After noticing the change, McClanahan reviewed his records and saw that the revised fact sheets began going out this summer. "I think they're trying to rebrand," he said. "So many good things happen to your agency when you tie it to national security."
Although a spokesman with the agency declined to weigh in on the timing of the change, he said the agency is just keeping up with the times. "When our mission changed after 9/11, our fact sheet changed to reflect that," FBI spokesman Paul Bresson told Foreign Policy. He noted that the FBI's website has long-emphasized the agency's national security focus. "We rank our top 10 priorities and CT [counterterrorism] is first, counterintel is second, cyber is third," he said. "So it is certainly accurate to say our primary function is national security." On numerous occasions, former FBI Director Robert Mueller also emphasized the FBI's national security focus in speeches and statements.
FBI historian and Marquette University professor Athan Theoharis agreed that the changes reflect what's really happening at the agency, but said the timing isn't clear. "I can't explain why FBI officials decided to change the fact sheet… unless in the current political climate that change benefits the FBI politically and undercuts criticisms," he said. He mentioned the negative attention surrounding the FBI's failure in April to foil the bomb plot at the Boston Marathon by Dzhokhar and Tamerlan Tsarnaev.


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Was £89.00
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Dark pink cowl front jersey dress
Item No.0080102348
In a rich shade of dark pink, this jersey wrap dress from Debut has a fabulously flattering design. The draped cowl neck and wrapped waist accentuate feminine curves and forgive all else. A diamante brooch subtly embellishes the gathered waterfall at the side. For sophisticated evening style, just team with silver and diamond-look jewellery.
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- Designed in a midi length, back measurement 100cm / 39.25 inches
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- Model wears: size 10
- Model Height: 5'9", Bust 32B, Waist 24", Hips 35"


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If the binding engine cannot convert the entered text into the bound property's data type in a DataGridTextColumn (binding below), the cell gets a red border, and you cannot edit any other cells until the error is fixed. The border remains even if you tab out of the cell.
<DataGridTextColumn Binding="{Binding IntegerProperty, UpdateSourceTrigger=PropertyChanged, NotifyOnValidationError=True, ValidatesOnExceptions=True}" />
This is all great in my setup. The problem is that if I throw an exception in a property setter, the behavior is different. First the red border (validation error) is removed immediately when I tab out from the cell and I can continue to edit the rest of the grid's cells.
Is there any way to make the exception thrown in property setter behave similarly as the binding engine's way of handling FormatExceptions? The biggest annoyance is that the validation error is removed after moving out from the cell.


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A treatment regimen for cancers having cells which are susceptible to an interleukin-2 activated natural killer cell mediated anti-cancer effect, the method comprises administering to a patient an effective amount of a combination of interleukin 2 and flavone-8-acetic acid. The treatment regimen is particularly effective in the treatment of renal carcinoma. Synergistic pharmaceutical compositions are also provided. effective in the treatment of renal carcinoma. Synergistic pharmaceutical compositions are also provided.
1. A synergistic method for treating a renal carcinoma in a rodent or a human, said method comprising administering by injection to said rodent or human an effective renal carcinoma treating amount of flavone-8-acetic acid, and an effective renal carcinoma treating amount of interleukin 2.
2. The method of claim 1 wherein a rodent is treated for a renal carcinoma.
3. The method of claim 1, wherein a human is treated for a renal carcinoma.
4. A synergistic pharmaceutical composition comprising an effective amount of flavone-8-acetic acid, and an effective amount of interleukin-2, and a pharmaceutically acceptable carrier.
The present invention relates to a treatment regimen for cancers having cells which are susceptible to an interleukin-2 activated natural killer cell mediated anti-cancer effect, and, more particularly, to a treatment regimen for renal carcinoma.
Attempts have been made recently to develop immunotherapies for the treatment of cancer based on stimulating the host immune response to the tumor. These approaches were based on attempts to immunize against specific tumor cells or with nonspecific stimulants in the hope that general immune stimulation would concomitantly increase the host antitumor response. Although some experimental evidence indicated that this approach might be feasible in the therapy of established tumors, the inability to stimulate sufficiently strong responses to putative tumor antigens and the general immunoincompetence of the tumor bearing host argued against the success of this approach.
An alternative therapeutic approach to the immunologic treatment of cancer is that of the adoptive transfer of immune cells. Adoptive immunotherapy is defined as the transfer to the tumor-bearing host of active immunologic reagents, such as cells with antitumor reactivity that can mediate, either directly or indirectly, antitumor effects. Adoptive immunotherapy represents an attractive approach to cancer therapy and to other conditions related to immune dysfunction. Because active immunologic reagents are transferred to the host, complete host immunocompetence is not required. Thus, the immunosuppression generally associated with the tumor bearing state does not represent a major problem to this therapeutic alternative. Since host immunocompetence is not required, and in fact may be beneficial to the effects of the adoptive transfer of immune cells, adoptive immunotherapy can be easily combined with other therapies such as chemotherapy and radiation therapy. Since the transferred reagents are immunologically specific, this treatment modality predicts a high degree of specificity and consequently a low morbidity. Further, in contrast to most other therapies, no immunosuppression is likely to result from this treatment.
A review of previous attempts to perform adoptive immunotherapy of cancer in animals and humans can be found in Rosenberg et al.; 1977 Adv. Cancer Res. 25: 323-388.
Recent studies have demonstrated that the adoptive transfer of specifically immune or broadly cytotoxic lymphocytes generated in the presence of human recombinant interleukin 2 (rIL2) can result in the regression of established tumors in mice and humans. Similarly, the administration of rIL2 alone, in the absence of adoptive immunotherapy, also has been shown to produce some antitumor effects in mice and humans. However, the use of adoptive immunotherapy and rIL2 to treat cancer patients is a complicated, expensive, and toxic form of therapy.
The disadvantage of the use of large amounts of rIL2 either by itself or in combination with adoptive immunotherapy induces a variety of severe and dose-limiting toxic side effects. Therefore, much attention has recently focused on alternative strategies that could exploit the therapeutic benefits of rIL2 while decreasing the expense and logistic difficulties associated with adoptive immunotherapy, as well as decreasing the toxic sequelae associated with high-dose rIL2 therapy.
Renca murine renal cancer has successfully been treated by a therapeutic regimen which combines doxorubin hydrochloride (DOX) and adoptive immunotherapy (AIT) with rIL2, as described in Salup et al., J. Immunol. 138: 641 (1987) and Salup et al., Cancer Res., 46: 3358 (1986). This approach has the advantage of requiring daily administration of a moderate amount of rIL2 rather than the larger amounts required to demonstrate therapeutic effects with rIL2 alone.
It is an object of the present invention to overcome deficiencies in the prior art, such as noted above.
It is another object of the present invention to provide an improved regimen for treating cancers having cells which are susceptible to an interleukin-2 activated natural killer cell mediated anti-cancer effect.
It is a further object of the present invention to provide an improved regimen for treating renal cancer.
Yet another object of the invention is to provide for improved cancer therapy when treating cancers having cells which are susceptible to an interleukin-2 activated natural killer cell mediated anti-cancer effect.
The present invention provides a method and regimen for treating a cancer having cells which are susceptible to an interleukin-2 activated natural killer cell mediated anti-cancer effect, the method comprising administering an effecting amount of flavone-8-acetic acid, and recombinant human interleukin 2 (rIL2) to treat the cancer.
According to the present invention, the investigational drug, flavone-8-acetic acid, potently augments the natural killer cell (NK) activity in the spleen, liver, lungs, and peritoneum in a dose-dependent manner following intravenous or intraperitoneal administration. Combined treatment of established cancers susceptible to treatment (i.e., an interleukin-2 activated natural killer cell mediated anti-cancer effect) with flavone-8-acetic acid and recombinant human interleukin 2 results in up to 80% long-term survival, while the use of flavone-8-acetic acid or recombinant interleukin 2 alone was unable to induce any long-term survival. The use of the combination of flavone-8-acetic acid and recombinant interleukin 2 provides significant antitumor efficacy against tumors having cells susceptible to treatment (i.e., an interleukin-2 activated natural killer cell mediated anti-cancer effect) using subtoxic doses of rIL2 even without accompanying adoptive immunotherapy.
FIG. 1 shows the effect of treatment with flavone-8-acetic acid and/or rIL2 on the survival of Renca-bearing mice.
FIG. 2 shows the control group of mice, who received no flavone-8-acetic acid or rIL2.
According to the present invention, a treatment regimen for cancers having cells which are susceptible to an interleukin-2 activated natural killer cell mediated anti-cancer effect is provided to enhance the effectiveness of interleukin therapy. The flavone-8-acetic acid is desirably administered by bolus injection, continuous infusion, or delivery from an osmotic pump in close proximity to the administration of IL2 by any of the above routes to treat cancers susceptible to treatment in rodents and humans. The doses of flavone-8-acetic acid and IL2 used and the route of administration and the carriers and/or adjuvants used may vary based on the tumor type which is susceptible to treatment and being treated, and in view of known procedures for treatment of such tumors. The combination of flavone-8-acetic acid and IL2 provides synergistic antitumor activity against tumors having cells which are susceptible to treatment (i.e., an interleukin-2 activated natural killer cell mediated anti-cancer effect).
Flavone-8-acetic acid was initially selected for clinical testing in cancer patients based upon an unusual spectrum of activity against murine solid tumors which were refractory to conventional chemotherapeutic agents, and favorable preclinical pharmacologic and toxicologic profiles.
It was found that the administration of flavone-8-acetic acid results in a potent systemic augmentation of NK activity, as well as that the combination of flavone-8-acetic acid plus rIL2 exhibits dramatically improved therapeutic effects, comparable to those achieved previously with chemotherapeutic drugs and adoptive immunotherapy against renal cancer.
In all of the experiments described below, male BALB/C mice were housed under specific pathogen free conditions and were used routinely at 7-10 weeks of age.
The flavone-8-acetic acid (FAA) was synthesized by Lyonnaise Industrielle Pharmaceutique.
The rIL2 (3�106 BRMP units per mg protein) was supplied by Cetus Corporation, Emeryville, Calif.
Polyinosinic-polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose (poly ICLC) was provided by the National Institute of Allergy and Infectious Diseases of Frederick, Md.
All reagents were diluted in Hanks Balanced Salt Solution (HBSS) for administration to the mice.
Augmentation of NK activity by FAA was assessed in a four hour 51 Cr release assay against the YAC-1 tumor target. Effector leukocytes were isolated from spleen, peritoneal cavity, lungs, and liver as described by Wiltrout et al., J. Exp. Med. 160: 1431 (1984). The NK activity was expressed as lytic units (LU)/1�107 cells, with one LU being the number of effector cells required to lyse 20% of the target cells. Statistical comparisons in NK activity were performed by Student's T test.
The tumor model utilized for the present studies is the renca renal adenocarcinoma, a tumor which originated spontaneously and which is maintained by serial transplant in BALC/C mice. The growth characteristics of this tumor have been described in detail in Salup et al., J. Immunol. 138: 641 (1987).
The particular Renca line used for the studies reported hereinafter was isolated form a spontaneous liver metastasis derived form the parental line. Following injection of 1�105 tumor cells under the renal capsule, the solid tumor mass develops rapidly with direct extension to the peritoneal cavity by days 7-9 and metastasis to regional lymph nodes and liver shortly thereafter. Surgical resection of the primary tumor-bearing kidney is potentially curative prior to day 8, but not thereafter, when mice succumb to peritoneal carcinomatosis and subsequent metastatic disease.
The FAA was administered by injection of 125 mg/kg intravenously and 125 mg/kg intraperitoneally, while various doses of rIL2 were delivered intraperitoneally. Routinely, FAA was administered two to four hours after nephrectomy of the primary tumor-bearing kidney on day 11, and rIL2 was administered one time per day for four successive days beginning on the day after nephrectomy and FAA treatment. Statistical analysis of the survival data was performed by the X2 test.
Table 1 illustrates that a single intravenous dose of FAA (250 mg/kg), which has been shown previously to be both active against murine solid tumors and relatively nontoxic, strikingly augmented NK activity in the spleen and liver (p<0.01). The maximum enhancement (51.2 and 236 LU, respectively) of NK activity occurred in both tissues by day 1, remained significantly (p<0.01) augmented through day 3, and returned to near background levels by day 6.
Further studies, shown in Table 2, illustrate that NK stimulation (p<0.01-0.001) by FAA was similarly demonstratable in the lungs and peritoneum, and that the effects were dose dependent in all tissues examined.
TABLE 1______________________________________Augmentation of NK activity in the Spleen and Liverafter Administration of FAATreatment Lu20 /1 � 107 leukocytesin Vivo* Spleen Liver______________________________________None 10.3 <10FAA (-1d) 51.2 236.0FAA (-3d) 34.5 150.8FAA (-6d) 17.4 21.3______________________________________ *FAA (250 mg/kg) was administered i.v. 1, 3, or 6 days prior to the assessment of NK activity in leukocytes isolated from the spleen and liver. All groups consisted of 5 mice and NK activity was assessed agains YAC1. Significantly greater than control, P < 0.001. Significantly greater than control, P < 0.01.
TABLE II______________________________________Augmentation of NK Activity in Different Sites afterAdministration of Various Doses of FAATreatment LU20 /1 � 107 leukocytesIn Vivo* (Dose) Spleen Peritoneum Liver Lungs______________________________________HBSS <10 <10 <10 <10Poly ICLC 64.2 137.4 211.7 84.3(0.5 mg/kg)FAA (250 mg/kg) 56.4 108.2 103.4 39.9FAA (125 mg/kg) 37.6 94.8 20.1 10.2FAA (25 mg/kg) <10 76.1 <10 ND______________________________________ *BRM were administered i.v. (for assessment of NK activity in spleen, liver, and lungs) or i.p. (for assessment of NK in the peritoneum) 24 hrs prior to the isolation of effector leukocyte. All groups consisted of 5 mice and NK activity was assessed against YAC1. Significantly greater than control, p < 0.001. Significantly greater than control, p < 0.01.
FIG. 1 shows the effect of treatment with FAA and/or rIL2 on the survival of Renca-bearing mice. BALB/C mice, 8-10 per group, were injected intrarenally with 1�105 Renca tumor cells on day 0. On day 11, the tumor-bearing kidney was removed and 2-4 hours later 125 mg/kg FAA was administered intravenously and 125 mg/kg FAA was administered intraperitoneally to appropriate groups.
Subsequently, beginning on day 12, some of the FAA pretreated mice and two groups of previously untreated mice received four daily intraperitoneal injections of rIL2 at doses of either 10,000 U or 100,000 U/day, as shown in FIG. 1.
Alternatively, FAA treated mice received increasing doses of rIL2 ranging from 10 U to 100,000 U, as shown in FIG. 2. The control group in FIG. 2, represented by the dotted line, received no FAA or rIL2. Mice were then monitored for survival and statistical analyses were performed by the X2 test.
Since 250 mg.kg of FAA markedly enhanced NK activity both in lymphoid and in nonlymphoid sites, as shown in Tables 1 and 2, and NK cells constitute a major precursor for lymphokine-activated killer activity (LAK) generated by rIL2, experiments were performed to determine whether FAA and rIL2 could have additive or synergistic antitumor activity when used in combination.
FIG. 1 shows that a single bicompartmental administration of FAA alone (125 mg/kg intravenously plus 125 mg/kg intraperitoneally) or multiple daily intraperitoneal administrations of either 10,000 U or 100,000 U of rIL2 alone only slightly prolonged the survival of Renca-bearing mice.
In contrast, the combination of FAA and 10,000 U of rIL2 rendered 80% of the tumor-bearing mice free of grossly visual disease through 120 days. Moreover, when FAA-treated mice were tested with a range of daily doses of rIL2, long-term survivors were obtained with as little as 100--100 U rIL2 per day (5/19 survivors), as shown in FIG. 2.
The survival curve is statistically significantly improved over the control curve at doses of rIL2≧1000 U/mouse. Significantly improved long-term survival was observed for 1000 U (P<0.05). 10,000 U (P<0.05), 30,000 U (P<0.005), and 100,000 U (P<0.005).
Overall, these results demonstrate that the use of FAA in association with moderate doses of rIL2 affords appreciably improved long-term survival of mice bearing murine renal cancer as compared to treatment with either FAA or rIL2 alone.
The intravenous and/or intraperitoneal administration of therapeutic c=doses of FAA, ranging from about 110 mk/kg of body weight to about 500 mg/kg of body weight, resulted in potent augmentation of the rIL2 in the spleen or liver. Peak levels of NK-mediated lysis were generally achieved by 24 hour post injection, with levels of NK activity decreasing to background by about day 6.
According to the present invention, the administration of FAA in association with moderate doses of rIL2 appears to be a more useful approach to the treatment of cancers having cells susceptible to an interleukin-2 activated natural killer cell mediated anti-cancer effect than administration of high doses of rIL2 alone. Recent studies have also shown that the combination of FAA and rIL2 is also effective in eradiating established experimental hepatic metastases, and that the inclusion of adoptive immunotherapy in the treatment regimen does not further increase survival.
The mechanism by which FAA and rIL2 complement each other in the treatment of cancers susceptible to treatment therewith is not known. The augmentation of NK activity by FAA is an indirect effect, since this agent does not boost NK activity in mice or humans in vitro. Thus, it appears likely that the induction of NK activity, and perhaps the therapeutic effects thereof, are mediated by metabolites of FAA or by cytokines induced by FAA.
The FAA and rIL2 can conveniently be administered intravenously or intraperitoneally, in a suitable carrier.
Carriers which can be used in the present invention include suitable pharmaceutically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Solutions for administration intraperitoneally or intravenously contain from about 0.1 to about 99.5 percent by weight, and preferably from about 25-85 percent by weight, of active ingredient, together with the excipient.
Suitable formulations for parenteral, intraperitoneal, or intravenous administration of the active compounds may include suspensions of the active ingredients as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils, for example sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension such as sodium carboxymethylcellulose, sorbitol, or dextran.
The FAA is preferentially administered by bolus injection, continuous infusion, or delivery from an osmotic pump in close proximity to the administration if rIL2 by any of the above routes. The optimal dose of rIL2 required for use with FAA is in the range of about 5,000 to 50,000 U/day, along with about 100 to about 500 mg/kg body weight of FAA.
The FAA can be administered in advance of the administration of the rIL2 by about one day. The rIL2 can be administered one time per day for at least four days beginning after the FAA treatment.
While the invention is described above in relation to certain specific embodiments, it will be understood that many variations are possible, and that alternative materials and reagents can be used without departing from the invention. In some cases such variations and substitutions may require some experimentation, but such will only involve routine testing.
The foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and therefore such adaptations and modifications are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation.
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Montreal Canadiens (13-4-4) at Boston Bruins (14-2-2), 7:30 p.m.
(Sports Network) - The Montreal Canadiens have notched a point in 10 straight
games, while the Boston Bruins are riding a season-long six-game winning
It's no surprise then that the two clubs share the top spot in the Northeast
Division, but one team will grab sole possession on Sunday night when the two
rivals meet in Boston.
The Canadiens and Bruins both come into this meeting with an Eastern
Conference-high 30 points, though Boston has played three fewer games and has
one more victory. That has the Bruins atop the conference standings, with the
Canadiens fourth overall.
Boston is 14-2-2 on the season, its best 18-game start in franchise history
since the 1929-30 club was 16-2-0.
The Bruins haven't lost since a road setback in Buffalo on Feb. 15 and are
looking to win seven straight for the first time since Dec. 10-28 of last
Montreal, meanwhile, seemed to hit a low point with a 6-0 home loss at the
hands of the Toronto Maple Leafs on Feb. 9. That was the club's third straight
defeat at the time, but the Habs have since gone 7-0-3, winning their first
five after the blowout to the Leafs.
The Canadiens avenged the loss to the Maple Leafs on Monday with a 5-2 road
win and saw their offense stay hot on Saturday against the Pittsburgh
Penguins. However, the defense wasn't as sharp and Montreal lost a 7-6
decision in overtime.
The clubs combined for six goals in the second period of a back-and-forth
contest and Brian Gionta's second goal of the game tied things up with 9:06
remaining in the third period. The Pens, though, scored just 52 seconds into
the bonus frame.
"Crazy game. Exciting for the fans. That's one of the reasons we've got
coaches that start to get gray hair," said Canadiens coach Michel Therrien.
"But we're making comebacks and we found a way to get a point."
Brandon Prust, David Desharnais, Max Pacioretty and P.K. Subban all scored,
while Carey Price ended up allowing seven goals on 36 shots. Brandon
Gallagher, Tomas Kaberle, Alexei Emelin and Lars Eller each had two assists
for Montreal.
"It was one of those games, with momentum shifting back and forth a couple of
times, but we have to be better than that," said Pacioretty, whose club begins
a five-game road trip tonight.
The Bruins were engaged in a less-exciting contest on Saturday, but they came
out on the positive end thanks to a 3-2 win over the Tampa Bay Lightning.
Tyler Seguin and Rich Peverley scored in the second period to erase a two-goal
deficit and Brad Marchand put home the game-winner with 2:16 to play while on
the power play.
Marchand's goal was his team-leading 11th of the season, while Seguin and
Peverley notched their fourth and third goals of the campaign, respectively.
"Our guys that haven't scored much are starting to come around," said
Peverley. "Hopefully this will lead to them getting more."
Backup Anton Khudobin gave No. 1 Tuukka Rask the night off and made 20 saves.
The Bruins notched a 2-1 victory in Montreal on Feb. 6, their fifth straight
victory in this series, and it featured a goal and an assist by Seguin and 20
saves from Rask.
Price stopped 21 shots and Subban had a goal for the Canadiens, who have lost
two straight and four of their last five in Boston.
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