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Cardinals nearly drafted Abdullah, not JohnsonPosted by on June 30, 2016 – 9:31 pm
There will be some interesting parts to the Cardinals' 2015 season revealed now that "All or Nothing" is now available to stream on Amazon video. One is there right at the outset of the first episode. The cameras take you into the Cardinals' draft room when they are on the clock in the second round, all set to select Nebraska running back Ameer Abdullah — VP of player personnel Terry McDonough is literally on the phone with Abdullah — when the Lions end up taking Abdullah the pick before Arizona. (The disappointment is palpable. It's a scene you have to watch play out.)
How much would've changed last season had the Abdullah pick been made? Without the ability to draft Abdullah, the Cardinals took outside linebacker Markus Golden in the second round. And then they went with running back David Johnson in the third round. Golden has already played his way into a probable starting job following a solid rookie season, while Johnson had 13 touchdowns as a rookie and is going to be the anchor for the Cards' running game in 2016.
Johnson, in fact, is a guy who the Cards' decision-makers feel can be a star in the NFL. Abdullah had a solid rookie year for the Lions too, but I'd guess the Cards would have no desire to flip Johnson for Abdullah right now. Johnson showed he can run the ball and his ability to catch is fantastic (Johnson made a grab on a wheel route during OTAs that had teammates marveling. In the offseason.)
Feels like this turned out pretty well for the Cardinals.
Tags: Ameer Abdullah, David Johnson, draft, Markus Golden, Terry McDonough
Posted in Blog | 21 Comments »
Rookies signed at warp speedPosted by on May 9, 2016 – 3:22 pm
It's not hard to remember, not if you have been following the Cardinals for any length of time, but signing draft picks used to be much, much more difficult. Yes, the ease in which picks are signed these days is rules-related — once the new collective bargaining agreement essentially slotted each pick's money and took the hardest part (money) out of the negotiating equation, things were going to speed up.
But to think the Cardinals already have all of their draft picks under contract on May 9 is impressive. The time frame to finish up since 2011, when the new CBA went into effect, has gotten earlier and earlier:
2011: Amid the chaos of so many signings as the CBA was ratified post-lockout just as training camp was starting, first-rounder Patrick Peterson and second-rounder Ryan Williams signed July 31.
2012: First-rounder Michael Floyd and third-rounder Jamell Fleming signed June 11.
2013: First-rounder Jonathan Cooper signed July 29.
2014: First-rounder Deone Bucannon signed June 5.
2015: First-rounder D.J. Humphries signed June 1.
2016: Sixth-rounder Harlan Miller, third-rounder Brandon Williams and fourth-rounder Evan Boehm sign May 9.
The Cardinals aren't unique — the Bears have been signing their entire draft class within a couple days of the draft the last couple of seasons, for instance — but to have all those deals done not only before the players break prior to camp but before OTAs have even begun is a good thing. The days of the Cards having their first-round pick sit out at least a few days of training camp — or more, Wendell Bryant — are long over.
Tags: Brandon Williams, CBA, contract, D.J. Humphries, Deone Bucannon, draft, Evan Boehm, Harlan Miller, Jamell Fleming, Jonathan Cooper, Michael Floyd, Patrick Peterson, Ryan Williams
Posted in Blog | 23 Comments »
No trades, no QB and draft aftermathPosted by on April 30, 2016 – 5:07 pm
The Cardinals made no more trades. And they didn't get a quarterback.
Those were the top two things on the possibilities list going into the draft, in part because of Paxton Lynch and his presence at the back half of the first round. If Lynch had been on the board for the Cardinals, it would have been intriguing — would a team tried to trade up for him with a sweet deal? Or might the Cardinals go ahead and take him as that long-awaited shot at a QB of the future? But it became moot when the Broncos traded up to 26 to get Lynch.
After that, the Cards didn't have the capital to trade up into the second round and didn't see a reason to move back. Meanwhile, if there were other quarterbacks around in whom the Cards had interest, they didn't excite them enough to pull the trigger. And frankly, once you get to the fourth or fifth round, those QBs left are likely backups at best.
Instead, the Cards went heavy on defense, and heavy on the secondary. You can say what you want about needs and best player available, but often for teams those things dovetail as they set their draft board and it's really not a surprise the Cards ended up with a potential starting center and depth in the secondary, in addition to an upgrade on special teams.
— All things considered, Robert Nkemdiche should be an excellent piece if he can go hard and stay away from any off-field issues. There's a reason someone so physically gifted was there at No. 29. The reality is he would have gone soon after if the Cards hadn't picked him, so the Cardinals didn't stretch to take him. But they need something out of him this season, and he he needs to become that guy on the defensive line as that position evolves over the next couple of seasons.
— All three of the defensive backs taken are in the same mold: Brandon Williams, Marqui Christian and Harlan Miller have speed, can significantly help on special teams, and aren't ready to drop in and play a major role on defense yet. The Cards have had success in this area with Justin Bethel, but in truth they still need Bethel to become a better cornerback and not just a Pro Bowl special teams guy.
— I like that Christian won the Cliff Harris award for the nation's best defensive player in small college (Divisions II, III and NAIA) and I like that Adrian Wilson was impressed by him at a college all-star game. Wilson has a talent for scouting — Keim wouldn't have given him this job if he didn't believe that — and we will see if he has forecasted correctly.
— Would the Cardinals have liked Ryan Kelly at center? I'm sure. But I think the pick of Evan Boehm makes so much sense. He's got the credentials, even as a fourth-rounder, and he's got the mentality that not only fits Bruce Arians but Harold Goodwin. Lyle Sendlein started for many years as an undrafted rookie. It's easy to picture Boehm doing the same.
— Does the youth at cornerback mean the Cardinals bring back Jerraud Powers? Arians said they don't need to add any vets. If he did come back, do they keep five cornerbacks (Peterson, Bethel, Powers and the two draftees)? Last year they only had three cornerbacks on the roster because they kept five safeties.
— Among the positions I'd expect the Cards to hit in the undrafted rookie market: long snapper, quarterback, wide receiver. All three things weren't hit in the draft. They will need another arm behind center and they certainly need a long snapper.
— That's it. We'll see how this draft class truly pans out around the 2019 season. In the meantime, rookie minicamp is next weekend.
Tags: Adrian Wilson, Brandon Williams, Broncos, draft, Evan Boehm, Harlan Miller, Jerraud Powers, Marqui Christian, Paxton Lynch, Robert Nkemdiche, Ryan Kelly
Posted in Blog | 55 Comments »
Wednesday before the 2016 draftPosted by on April 27, 2016 – 4:57 pm
The draft, thank goodness, is close.
There are many who love the run-up to the draft each year. I'm not really one of them. Let me know who the new Cardinals will be and we'll go from there. It's a little different when this franchise was picking top 10, but 29th (or 30th, we'll get to that in a second)? There's just so much that can happen that changes the dynamic whenever it is the Cards actually make a pick. Still, I wanted to put out some thoughts as we head into the 2016 selection process.
— I won't be surprised if the Cardinals trade down Thursday night. Yes, Steve Keim said it'll be harder for picks to make the team, but if they can spin the late first-rounder into an early second-rounder and maybe an early fourth, those guys are far enough up the food chain to be near-locks. So much of it has to do with who is available when the Cards are on the clock. That seems obvious but it's also true. You figure the quarterbacks available — and teams trying to move up to get one — would influence that the most.
— The Cardinals (without a trade) will pick the 29th player but the NFL is still listing them with the 30th pick. No. 29 was supposed to be the Patriots, who lost it in DeflateGate, so if you are curious to know why the league's draft tracker has a difference, that's it.
— If I had to guess, I'd say the Cardinals do draft a QB at some point but it'll be Saturday.
— It's hard to argue with those who think the Cards would take center Ryan Kelly in the first round if he's there. I don't think he will be. I think it'll most likely be defense — a cornerback if one is there, a defensive lineman if not. Wouldn't rule out linebacker/pass rusher, but I'd lean toward an up-front guy.
— I don't do mock drafts these days — I know, a crushing disappointment — but we do have a mock coming from the Cardinals, straight from the mind of safety Tony Jefferson. He has the Cards taking Clemson safety-or-corner T.J. Green. Maybe Jefferson eventually follows in the footsteps of one-time Cardinals defensive back Corey Chavous, who was a draft guru even when he was playing and continues working in that role these days.
(Cohort Kyle Odegard will have a full mock draft roundup of all the picks made across the internet for the Cardinals tomorrow.)
— The Cardinals currently have 73 players on the roster, so room for 17 right now. With six draft picks, that means 11 undrafted free agents. I think there will be more than 11 undrafted rookies signed, so I expect some cuts, and that doesn't include the possibility of adding picks.
Even if the Cards don't make a pick tomorrow, it'll be an interesting night all the way around. See you then.
Tags: Corey Chavous, draft, Patriots, Ryan Kelly, Steve Keim, T.J. Green, Tony Jefferson
Posted in Blog | 44 Comments »
Center may be college non-centerPosted by on April 19, 2016 – 4:51 pm
Lyle Sendlein and Ted Larsen are gone. And while A.Q. Shipley remains and the Cardinals have signed a couple of other street free agents in Taylor Boggs and Valerian Ume-Ezeoke, it's pretty clear the Cardinals are on course to draft a center at some point. Maybe it's the first round, a guy like Alabama's Ryan Kelly (who has been a favorite for mock drafters to scribble next to the Cardinals at 29th overall.) But it won't be a surprise, even though the Cards don't have a second-round pick, if they wait. After listening to both Steve Keim and Bruce Arians Tuesday, it shouldn't even be a surprise if one comes later — and isn't even technically a center. Not yet.
"In this draft, there are several opportunities to draft centers in all rounds," Keim said. "Some of those guys are projections. There are some guys in the second, third, fourth rounds, who are going to be guys who played left tackle or they played guard at the collegiate level, who we worked out at center or they played center previously in their career that we think has the skill set. There are going to be opportunities to address that position if we feel necessary."
Arians noted a couple of very good NFL centers like Jeff Hartings of the Steelers and Tim Grunhard of the Chiefs (Grunhard played guard in college, Hartings started his NFL career at guard before moving to center) that made the move. "When you say a college center, there might be three college centers, but there are 15 potential centers," Arians said.
Options obviously open up a lot of possibilities for that first pick. Waiting on a center makes it easier to take a cornerback. Or a defensive lineman. Whatever Keim might want.
Tags: A.Q. Shipley, Bruce Arians, draft, Jeff Hartings, Lyle Sendlein, Steve Keim, Ted Larsen, Tim Grunhard
Posted in Blog | 22 Comments »
Draft (i.e. QB) trade changes NFC WestPosted by on April 14, 2016 – 8:06 am
The draft was changed significantly Thursday morning, and with it, so was the NFC West. The Rams, now in Los Angeles, completed a huge trade with the Tennessee Titans to acquire the No. 1 overall pick. It will be a quarterback, either Carson Wentz or Jared Goff (the conventional wisdom seems to be Wentz.) The Rams were picking 15th overall, so the price to move up 14 spots was hefty: The Titans get back not only L.A.'s first-round pick but also two second-round picks and a third-rounder this season, as well as the Rams' 2017 first-round pick (which if the rookie QB struggles, could be pretty high.)
The Titans did add in a fourth- and sixth-rounder in the 2016 draft back to the Rams.
It's a reverse of what the Rams did in 2012 when they shipped the No. 2 pick to the Redskins so Washington could take QB Robert Griffin III. RGIII flamed out after an excellent rookie year, but the Rams didn't really benefit much from the trade either — they have yet to make the playoffs since then. Now coach Jeff Fisher and GM Les Snead have come to the point where they need to make a push or get pushed out of their jobs, so they pushed all their chips in for a QB. Neither Wentz or Goff have the same kind of buzz around them like a Cam Newton or Andrew Luck or Jameis Winston. Its a risk.
Meanwhile, you figure a No. 1 overall pick would play right away, meaning the Cardinals will be seeing a rookie QB twice this season. The Rams have two very good part in place to help a rookie QB — a running back who looks like he will be great in Todd Gurley, and a very good defense. If the QB pans out, the Rams will be in good shape over the next few years. If not, their roster will take a hit from giving up so many high picks. But like Cardinals GM Steve Keim says often, most of the time the QBs that become the "QB of the future" can only be found at the top of the draft. The Rams made sure they made it to that mountaintop, regardless of the price.
Tags: Carson Wentz, draft, Jared Goff, Jeff Fisher, Les Snead, NFC West, Rams
Posted in Blog | 43 Comments »
The Cardinals' exact draft picksPosted by on March 29, 2016 – 8:02 am
With the draft about a month away, the official draft order was announced Tuesday of all seven rounds. The Cardinals currently have six picks: One each in rounds one, three, four and six, two in the fifth, and none in the second or seventh. That could change if GM Steve Keim decides to wheel and deal at some point. The picks in the grand scheme of the draft:
— First (29th overall)
— Third (92nd)
— Fourth (128th)
— Fifth (167th)
— Fifth (170th)
— Sixth (205th)
The draft's first round will be held April 28th beginning at 5 p.m. Arizona time (8 p.m. ET). The second and third round are April 29th starting at 4 p.m., and the final four rounds are Saturday starting at 9 a.m.
Tags: draft
Posted in Blog | 28 Comments »
Watching those #Cardsdraft gemsPosted by on March 28, 2016 – 9:42 am
The draft is near. It's one month away today, actually, and as part of the countdown azcardinals.com will have six videos to mark the time to this year's selections. The #CardsDraft Gems will feature one player who was found after the first two rounds who has shown he can perform past the limits some of the draft analysts gave him when he was coming out of college.
The series starts with running back Andre Ellington — a 2013 sixth-round pick — today. Two weeks out from the draft (April 14) will be 2015 fourth-round defensive lineman Rodney Gunter. One week out from the draft (April 21) will be 2015 fifth-round wide receiver J.J. Nelson. Three days before the draft (April 25) it will be third-round wide receiver John "Smokey" Brown. Two days out (April 26), it will be third-round safety Tyrann Mathieu, and the day before (April 27) it will be third-round running back David Johnson.
Tags: Andre Ellington, David Johnson, draft, J.J. Nelson, John Brown, Rodney Gunter, Tyrann Mathieu
Posted in Blog | 23 Comments »
Cardinals will draft a QB – unless they don'tPosted by on February 26, 2016 – 7:50 am
Is there an urgency for the Cardinals to develop a young quarterback, given that starter Carson Palmer is 36 years old? That's not even a question that needs to be asked at this point. It's not like the Cards haven't been talking and thinking about this since Steve Keim and Bruce Arians came into power, though. There was a reason they drafted Logan Thomas in 2014.
So Thomas didn't work out, and the team traded for Matt Barkley, and at this point, Barkley too is mostly an unknown. He didn't get any significant practice time in the Cardinals' offense, and they haven't seen him in a preseason game. Pinning their hopes on his development — at least, pinning them only on his development — wouldn't be prudent. The Cardinals probably need to draft a quarterback, and as I sit here in Indianapolis for the current version of the Scouting combine, long before the Cards have had any draft meetings, I will guess they will take one at some point in April.
But it's not a guarantee. Both Keim and Arians acknowledge the need and importance to obtain a young QB. But both left the door cracked that the Cardinals might not. Keim insists he does not want to force a pick, especially at quarterback. The Cards will scour the background of these second-tier QB hopefuls — like Michigan State's Connor Cook (pictured below) — knowing the top guys will be gone by the time they draft, and see if one makes sense. If you don't feel a guy has a legitimate chance to play in the league, it doesn't make much sense to draft one.
But the search is important. Someone has to play QB when Palmer is done. You'd rather make that decision pro-actively, rather than having it made for you when the time comes.
Tags: Bruce Arians, Carson Palmer, Connor Cook, draft, Logan Thomas, Matt Barkley, Steve Keim
Posted in Blog | 37 Comments »
How Mathieu impacted Keim's draft philosophyPosted by on February 16, 2016 – 8:13 am
Safety Tyrann Mathieu at some point is going to get a new contract from the Cardinals. He's been perfect for the franchise, both on the field and off it, even with all the questions about him coming out of college. General Manager Steve Keim, in fact, acknowledged Tuesday that Mathieu — who was Keim's third-round pick in Keim's first draft as a GM — actually has had an impact on Keim's draft philosophy.
"Going into my first draft as a GM, there's no way I thought a player like Tyrann Mathieu should get a second chance," Keim said during the "Doug and Wolf" show on Arizona Sports 98.7. "Now that we gave Tyrann that chance and he's become the player and the person that is is, he's changed my thinking on that a little bit that some — some — players deserve second chances."
It's a pretty significant acknowledgment. But it's also worth noting that Keim emphasized that only "some" should get a second chance in his eyes. There are things to figure out from a player who is about to be drafted and those frequently intangible things are what would sway Keim one way or the other.
Keim has to see a player who is "genuinely embarrassed" for whatever mistake might have been made. Keim also needs to believe in a player's passion for the game, which is something he is searching for from every single one of his draft picks anyway. Mathieu had that passion (which is easily seen daily now) and a love, and Keim was certain that Mathieu understood the Cardinals would be his last chance.
There are a lot of parts of the Mathieu story that helped get him drafted (the Patrick Peterson connection perhaps the most important) but that Mathieu's impact reached all the way to Keim's core beliefs is just another reason why Mathieu has been so important to this franchise.
Oh, and when asked about Mathieu's potential contract extension and whether his two ACL tears could push the Cards to do a shorter deal, Keim made it clear — the Cardinals want to work out a long-term deal with the Honey Badger.
Tags: draft, Steve Keim, Tyrann Mathieu
Posted in Blog | 23 Comments »


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This is the August 31, 2012 news archive. View today's Brewers rumors and news.
Milwaukee Brewers
Milwaukee Brewers News and Rumors
D-backs claim Ransom off waivers from BrewersMLB.com Aug 31, 2012The D-backs claimed Cody Ransom off waivers on Friday and plan to activate the infielder when rosters expand Saturday.Share Tweet
Karstens exits in first with right hip flexor strainMLB.com Aug 31, 2012Jeff Karstens' attempt to pitch his way past the strained left groin that had shortened his previous start was brief -- and costly. Karstens was pulled from his Friday night start against the Brewers with one out in the first inning.Share Tweet
Brewers dedicate Uecker statue at Miller ParkA statue of popular Brewers broadcaster Bob Uecker was dedicated outside Miller Park on Friday, and those in attendance recalled it was all made possible because of some spilled mashed potatoes and gravy.Share Tweet
Uecker Honored Before Brewers' WinAug 31Brewers unveil statue of Bob Uecker before 9-3 win over Pirates.

subset: commoncrawl


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Literally No One Has Actually Built Any Houses Under This Government Scheme To Build More Houses
Ministers said in 2012 that the policy would "completely change" the way communities planned developments.
A £17 million programme to encourage local communities to build more houses has yet to result in a single house being built.
The Community Right to Build was launched as a "radical" new policy in 2012 with the promise that it would enable communities who want new housing to hold a referendum on any development and bypass their local council's planning department.
But not one such referendum has been held since the policy was rolled out two years ago, a freedom of information request shows. As a result, no houses or other projects have been completed under the scheme.
Ministers put aside £17 million of funding for the policy at its launch, with costs including maintaining a website and advisers for prospective bidders. The communities department said it was possible that houses would eventually be built under the scheme since two local groups have submitted five proposals, although they have to be put to a vote.
"For too long communities have had to use their energy fighting development they didn't want rather then putting it to use bringing about the homes, shops and facilities they did," he said. "The Community Right to Build completely changes that and puts communities in the driving seat."
Advice on the scheme's website says the new power encourages development "without having to go through a lengthy and cumbersome planning process", which some have blamed for preventing housebuilding.
A communities department spokesperson did not deny the scheme has yet to result in a single house being built: "The Community Right to Build is one of a range of powers giving local people more say over the future of their area," they said. "To date there have been over 2000 uses of Community Rights, including five ongoing Community Right to Build Orders granted Government funding, well over 1,000 areas creating neighbourhood plans, and 28 neighbourhood plans have passed referendums."
The policy is not to be confused with the government's Right to Build, announced this year, which deals with the selling off council land for housebuilding, and has a similar name.


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It would be pretty great to have Emma (or you, Erika) or anyone who wants to, add to the playlist I created based upon your article. Collaborate here:
I couldn't agree more with the opening sentence of this review ("John Prine should be one of the four faces on songwriting's Mount Rushmore, cheek by jowl with Lucinda Williams, Bob Dylan and Bruce Springsteen."). He's way under-rated. But I think the list should include Kris Kristofferson, and make it FIVE faces.
Great review. I agree, Blue & Lonesome is a great raw and authentic album from the greatest Rock n Roll Band.
dude....like the previous post.MF DOom has been around a lot longer then Snoop. Peep the artists wiki page or do some research before you post such drivel.
Kanye is a substandard artist? Would like to see the grading scale that produced this conclusion.
DOOM has been in the game for quite sometime. Some would argue even longer than Snoop. MF DOOM started with KMD. He was Zev Love X then. They had decent rotation on MTV back then. Them with the likes 3rd Base. I remember seeing them on YO! MTV raps. Please do not lump him in with the likes of a substandard artist such as Kanye. Thanks.
nice Hated name-check in 2016
ya ya ya
Great descriptive article; cool photo-wish they were connected with their instruments; and very talented and entertaining music makers that always compel head bobbing and hip shaking.
Thanks, Greg. We made the correction.
Little know fact: Minor Threat drummer Jeff Nelson's nephew just graduated from the U of Montana.
FYI - Absolute Loser isn't a Sub Pop release - it's from Easy Sound Recording Company.
Great writeup! They will also be performing with Snailmate (from AZ), Wormwood, Krillhead and Mr. Soap at the Real Lounge on Monday the 11th
Yay! They are absolutely my favorite local band, I'm glad they are getting some recognition for all their hard work!
6 months ago, Bry played a show the day after she broke her ankle (with only ibuprofen for the pain) because she hates to cancel when people count on her. She loves her band mates, and she cries at almost every practice, especially when they sing with her.
When Kyle first joined, he learned 12 songs in a week so they wouldn't have to play a show without a bassist. He's a decade younger than everyone else in the band, but his youthful exuberance makes up for his relative lack of experience.
Gavin's only been with the band a few months, but he's transformed the way they think about their music. His years of more formal training means he can help put words to the techniques and sounds that the others can play but sometimes struggle to explain.
Brady is the drummer of the band both literally and metaphorically. He is steady, reliable, and supportive. He and Bry are the two founding members that still play with the band, and I can't imagine them not playing together. Brady helps make merch for the band, knitting hats and making pins. He's a good band dad.
I'm dating/related to half of the band, so I get to be the head of their fan club.
great band! they will also be at the Palace on the 30th for June Cavalcade
You need to listen to him if you haven't! Dan said it right when he said OT has heart. Proud to have him representing Montana!
It seems this reviewer has a chip on his shoulder or something.
These band of brothers share not only their musical blood, but that of true brotherly love & respect for each other. They often will acknowledge their fans from the stage, especially laOnda, their close fan club, of which I am proud to say I am a ten year member of. Their music is a mix of unique, heartfelt & dynamic lyrics combined with their musical talent in both their instruments & soulful voices that have each known deep pain in their lives as well as happy times...all reflected in their Texican lyrics. If you haven't been lucky (or smart) enough to go see them perform live, trust me you will not be disappointed!!! I've only seen them 106 times (much fewer than many !) in 19 states, but am eagerly awaiting their much overdue trip back to New England. Sadly, and understandably, they had to cancel last year, because of the sudden death of their beloved Mom. It'll be 15 months since I've seen them, but I know I'll be right there singing every word quietly to myself, snapping pictures when I know that special pose is just about there, with my laOnda Sistas I have come to be so close to and love! I'll be in my musical Heaven and be so grateful that I have these three incredibly talented brothers to thank for making all this s very special healing part of my life! Yes they are worth seeing for sure!!!
I love you too joey, and I love you too Larry. I'd like to go out fishing, or even just BBQ up at the house with you any time big guy!!
-Myk Miller


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Yoshi! Time again for a new profile! ahem.....-long pause- Erm......-even longer pause- so.... yeah nevermind. (Is a terrible profile maker). But with that out of the way, I bid you farewell and apologize for the lack of profilelyness. ;)
2,492 total episodes
Ah, I know what you mean. Been under some stress a few months ago, all kinds of things happening together (lots of deadlines at school, moving, suddenly taking care of my own bills :P), had no desire to watch any anime for a good while. Anyhow, take care, and have fun with the horror ^^
*throws confetti in the air*
Woo, welcome back! :P
Alright, I'll go right to the recommendations.
There you go, I hope it helped you a bit :P Make sure to stick around this time!
Ey, welcome back! For as far as you're actually back ^_^
Good to hear you're liking Bartender, not something that will appeal to everyone, but the slow pace is soo nice if you're looking for a calming series
I've been having a bit of a harder time aswell lately, with exams coming up, moving house and such :P Not -as much- free as I used to have these days :P
Anyways, let me know what you thought of Bartender once you've finished it!
Well, first cca 10 minutes are great and would make a perfect OVA. Unfortunately it is a full-length movie and the rest of it is not good at all. If you are bored (are you often bored? ^^) go for it, otherwise just watch those 10 minutes!
Hmm? http://img195.imageshack.us/img195/5191/recnd.png 0_o


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3,4-Diaminobenzoic acid undergoes cyclocondensations to form, for example, quinoxalines1 and benzimidazoles. It acts as a redox label for electrochemical detection of single base mismatches.
S Ram; D S Wise; L L Wotring; J W McCall; L B Townsend. Synthesis and biological activity of certain alkyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates and related derivatives: a new class of potential antineoplastic and antifilarial agents. Journal of Medicinal Chemistry.1992, 35 (3), 539-547.
Laleh Enayati Ahangar; Masoud A. Mehrgardi. 3,4-Diaminobenzoic acid (DABA) as a redox label for electrochemical detection of single base mismatches. Electrochimica Acta.2011, 56 10264-10269.
Gefahrenhinweise (EU): H315-H319-H335
Causes skin irritation. Causes serious eye irritation. May cause respiratory irritation.
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Avoid breathing dust/fume/gas/mist/vapours/spray. Wear protective gloves/protective clothing/eye protection/face protection. IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. IF INHALED: Remove to fresh air and keep at rest in a position comfortable for breathing. Take off contaminated clothing and wash before reuse. Call a POISON CENTER or doctor/physician if you feel unwell. Specific treatment (see label). Store locked up. Store in a well-ventilated place. Keep container tightly closed. Dispose of contents/container in accordance with local/regional/national/international regulations.


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1.20.17 Tour de Ski; Heavy Medal
12.13.16 Christmas Season in Davos
12.5.16 Starting with a Bang
3.28.16 Over and Out
This is your last blog post from me…because the World Cup season is now finished! It was a big year and I got to race over 40 times in 9 different countries! These are all the countries I trained and raced in, although I went to some of them more than once: Sweden, Finland, Norway, Switzerland, Italy, Germany, Czech Republic, Canada, USA. I had some great races and got 5 World Cup podiums, but I also had some races that weren't so great and I learned a lot of lessons from them. Having bad races and then learning from them is what made me faster for the next ones! Overall, I'm very happy with how the year went, and I had a lot of fun traveling and racing with my teammates. We work hard to be good teammates to each other and it makes the long season a lot more fun when you are friends with the people you live with!
2.23.16 Last Weeks in Europe
This past week we've had three very exciting races in Sweden! We first flew to Stockholm for a city sprint, like the one I told you about in Drammen, Norway. They closed off streets and laid down snow, with banners and fences all along the side of the course. But what made the Stockholm sprint extra special was that it went around the Royal Palace! We got to race right in front of the palace, then they spread snow up and over the steps to form a hill so we went up one side, back down and around the palace, and then up the other side in a "U" shape. There were royal guards in uniform guarding the course, and the King himself handed out medals to the winners. That's a pretty cool race, and I wish we had a race like this back home. Can you imagine if we raced around the White House and the President of the United States came to watch and hand out the medals at the end? That's what it was like for the Swedish skiers racing in their home country.
2.11.16 City Sprints
The past two weeks, I have been training, traveling and racing in Norway. The first week I was just training, because we had a weekend off from World Cup racing. I drove with my teammates to Sjusjøen, which is where part of the Norwegian Birkiebeiner trails are. You might have heard of the American Birkie (and I bet your parents probably have!) but the Norwegian Birkie race is where it all started. There are hundreds of kilometers of groomed ski trails in Sjusjøen, and I only skied a fraction of them in the week that I stayed there.
2.1.16 Relay Hugs
Hi MYSL friends!
This week I'll be answering some questions you've been asking about racing on the World Cup. But first, a short update on the last weekend of racing! After our recovery week and training camp in Italy after the Tour de Ski, we traveled to Nove Mesto, which is a small town that's very into cross country skiing, biathlon and bike racing in the Czech Republic. We raced an individual 10km skate, and a 4x5km relay, and it was a huge weekend for team USA! In the skate race, we had four girls score points. To score a World Cup point for your country, you have to finish in the top 30 people. In that skate race I finished 3rd, so I got to be on the podium for the second time in a World Cup! It was really exciting and I was so happy to have another good race.
1.16.16 Reflections on a Big Win
Hey there MYSL skiers!
Since I last wrote to you, some very exciting things have happened! I finished the Tour de Ski in 10th place, and 6 of my teammates also completed every stage race and finished the Tour. Sophie Caldwell and I both won stages of the tour; Sophie won a classic sprint, and I won an individual start 5km skate race. It was such an exciting tour for our team. I'm going to walk you through the day and what it felt like to be the first American woman to win a modern day distance World Cup!


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- bel·le·trist, noun bel-ˈle-trist
belles-let·tres, French bel-le-truh - plural noun
1. the writer of belles lettres
1. literature regarded as a fine art, especially as having a purely aesthetic function; elegant literature, especially that which is refined.
Call me Pax. I am the proud owner of two advanced literate roleplays, and a long-running graphics shop. These are my heart and home on Gaiaonline. I am a grad student with a love for literature and philosophy. I am ambitious, reasonable, intelligent, witty, forthright and empathetic. I have been on Gaia for a total of seven years. I am lucky enough to have met so many incredible people, tender friends, and loyal companions here. And in case you were wondering, yes, I made my own profile! Finally, my comrades - never lose your loyalty, never forget a good deed done, and always have the courage to be someone you can respect.
Non ducor, duco.
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You've had a hand in molding me,
Into what I've managed to grow to be,
But let's just keep the "what" between u and me.
You've steered me through almost every storm,
You were always there to help pick out the thorns,
And light up the world in the aftermath with a glow,
Like a beautiful full moon gently smiling through.
It's always there wherever I go.
Your words play softly like a classic guitar,
In that most calming sound amid the char,
Stopping my head from spinning and guiding my feet back to the ground.
You've managed to turn so many tears into laughter,
And many more fears into crowns.
Those words I'll be carrying with me,
Through every ride still in store for me;
No matter how long it all may be,
I'll be carrying you around indefinitely,
Even at times when it's all a little ghastly.
You'll always be in my heart and mind,
As for my life; well I most certainly plead that you stick around!
Since I'll be missing you,
Every minute of every day, and all year round.
You're my confidant and my best real friend,
And that's what you'll always find in me,
For all of eternity and until the end of time.
Although at times it may seem to be,
That life may try to get in between you and me,
Or maybe time, even some snow or land or seas.
It won't really matter to me,
'Cause what you've engraved in me,
Is so undeniably sincere,
That only the grave may just try to take it away from me.
© Copyright 2017 Moons. All rights reserved.
Status: Finished
Genre: Poetry
This was beautiful and full of emotion:)!
I loved it!
Well written by a very talented person!
so special, very heartwarming!! This certainly is a precious keepsake, love it love it!
Oh wow that was so nice, i love the way you use words! I love it!
I really enjoyed the poem. Straight from the heart like all good poetry should come from!
Poem / Poetry
Poem / Poetry
Paste the link to picture in the entry below:
Paste the link to Youtube video in the following entry:
Cannot annotate a non-flat selection. Make sure your selection starts and ends within the same node.
An annotation cannot contain another annotation.
There was an error uploading your file.


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Politicians, trade unions and business leaders will join hundreds of postal workers at a rally in Westminster today to protest against the Government's plans to privatise Royal Mail.
The Communication Workers Union (CWU) said the event was aimed at giving MPs a "clear message of dissatisfaction" with the Postal Service Bill which paves the way for the privatisation.
The Bill is currently in committee stage and the union said it believed it contained "huge loopholes" which put at risk the universal pricing of deliveries and the post office network.
Billy Hayes, CWU general secretary, said: "If people think the weather has been bad for deliveries, you've not seen anything if the Government gets its way."Reuse content


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It's Hair Loss Support At Its Best
Hello Vancouverites! Connecting is one of the best ways to feel happier and become more informed! Come as you are, whether you are shy or outgoing. This is a genuine and fun group where all of us - new to alopecia or experienced, hair-wearer or au natural, seeking treatment or not - all come together and be supportive, informative, and positive for one another. After 4+ years of running this group, I can say for sure that you'll feel better after a meetup! :)
Come to our monthly meetups, or, start by joining this group and be in the loop of upcoming meetups! Sometimes I include alopecia news / remedy / stories too.
If your kid / teen has alopecia, please contact us and we'll put you in touch with other parents! It'll be, I believe, quite awesome for your child :)
Location: Vancouver
Members: 75
Latest Activity: Feb 11
This group gets together monthly at one of the members' homes - a cozy, positive, and fun environment, for those with alopecia. We are here to support one another, and every meetup has been amazingly mood-lifting.
Join us here and we'll send next meeting details to you in a group email!
You can always get a hold of us via AW messaging or at alopecia.vancouver[at]gmail.com
We are affiliated with CANAAF (Canadian Alopecia Areata Foundation).
Next meet up: We meet about once a month. Please email Tanya at the emil address above!
Started by Tanya. Last reply by Sher Nov 6, 2015. 20 Replies 0 Likes
Started by Tanya. Last reply by Tanya Aug 15, 2015. 6 Replies 0 Likes
Started by Tanya. Last reply by lookswow Oct 18, 2014. 3 Replies 0 Likes
Started by Tanya. Last reply by Tanya Jul 13, 2012. 3 Replies 0 Likes
Hi Manhhuy,
Ah, I was born in Taiwan :)
When contacting NAAF, I recommend that you have your lawyer write the letter.
There are many English errors in your sale pitch below. That's understandable, since English is not your first language. However, you need to come across as trustworthy and reputable, if you want your future patients to have trust in you.
You wouldn't trust a doctor who makes a lot of spelling mistakes, right? What if they made a spelling mistake in the prescriptions? So, please write carefully, and have a professional write your letters when you can.
Best of luck!
Hi Tanya,
I am Chinese was born in Vietnam.
I speak little Mandarin, Cantonese, Vietnamese and English.
Thank you for suggestion. Sure, i will contact NAAF.
Dear Manhhuy,
Thank you for reaching us :)
We are a support group, so we focus on supporting each other. For discussing your service, I suggest that you contact NAAF. If we have members interested, I'll be sure to contact you.
Also, may I ask where you are from?
Hi Tanya.
My name is Manhhuy Ly.
I live in Vancouver. I am an Esthetician and Hair restoration.
Last year, in early April 2015, my sister had the Telogen effluvium
problem, her hair had shedding on the floor everywhere she gone.
She asked me for help. I did the research.What is there, why is there, how to treat it.
I started treating her hair early in April, by the end of the month the vellus had arrived, after 3 months of treatment, her hair grew so rapidly and gone back normal stage. She always has short hair cut.
Then my friend Mr Shaw who saw the whole procedure, and asked me for help. I started treating him in August, He had Telogen effluivum and Frontal fibrosing .In September, his hair grew so rapidly and said to me (why do not do this as business).
In that time, i did not realize that hair loss Which has no cure the moment.There is big population in the world who suffer from Alopecia areate.
I have been treating hair loss as volunteer for over a a year. At first, whenever i told people that i could treat hair loss. Everyone who are my good friend laughed at me, they said how could you do it while the hair loss researches could not do it. In January, 2016 . I hired the Wardell International business adviser and Oyen Wiggs green & Mutala llp Intellectual property Lawyers. my lawyer name is Stephanie A. Melnychuk. B.sc.(Biochemistry).M.Sc (Chemistry)J.D. My clients suggeted me. to join in (VAASG).I have been treating Alopecia totalis. Frontal fibrosing alopecia.
Scarring alopecia. Telogen effluvium. Traction alopecia.Trichotillomaina. But I do not treat for Alopecia unversalis and hair loss due to medical reasons
Yes for sure Lea, above this wall is a forum area where we post hairstylists, wigs, hats info. Everyone, if you have new places / sources, add to it! <3
haha, yes maybe good to do a double check. I just realize how depend i am on and that memory isn't so good when couldn't even remember your apt # right. Lol But so you know your bldg does have tuff security Tanya! thank you~ & Deeann too!
Oh was curious if people wanted to share hairstylist they like, shops, websites for wigs, plus non like scarfs, hats too. Been curious about and wanting good & new.
Lovely to see everyone, as usual. Oh no Lea. We drove off without your phone? It was great to meet Carla and to connect in a way we all understand. Please know we are here to support you on the days that are more challenging. I hope to see you again soon. The coffee and conversation was great, and I look forward to our next meet up. Thank you for all your kind words about the book. It was hard work that was motivated by all of you, and it's nice to hear all the nice things people are saying about it. It means I hit on the things that matter.
Thanks everyone for coming! Omg I laughed so hard. Such a great turn out and so awesome to catch up with everyone :) And nice to welcome new member Carla!
Thanks for bringing the delish coffee Lea! Such a long drive for you and Deeann from the US...extra long drive for you for getting your cell phone back lol. We'll do a checklist before you leave next time ;)


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Win a ticket to the Time Out silent disco and trial the new Nike+ FuelBand SE
Your chance to earn a new Nike+ FuelBand SE and help us determine which of Time Out's Top 100 Party Songs burns the most energy
In the coming weeks, we'll be asking our writers to use the Nike+ FuelBand SE as they go out and about. From DJing to shopping to simply commuting, we want to find out what gets Londoners earning NikeFuel. We want you to be part of the NikeFuel challenge, starting with our Silent Disco in Covent Garden this Friday at 6.30pm. We're launching the ultimate good-time playlist, Time Out London's Top 100 Party Songs, lovingly compiled by our music writers, who'll be spinning the tunes.
We're looking for 50 volunteers to try the Nike+ FuelBand SE on the night. Yes, by home time we'll all know which boogie classic gives you the best workout. The event is sold out, but 50 lucky winners will receive a ticket and a Nike+ FuelBand SE in this draw. It closes at noon on Wednesday, so don't delay.
For your chance to win, just fill in your details below.
Terms and conditions apply. By entering this competition you agree to receive relevant communications from Time Out including news, events, offers and competitions. This competition will close at 12pm on Wednesday November 6 2013.


text:
Hi Everyone,
I am curious about who has and has not received the Winter Geraniums Around The World in the mail. I have not, but know of other that have. Know my address is correct in the records, and just wonder if maybe it is the area.
Sandy in Grass Valley


text:
Adult Sunday School
ADULT BIBLE STUDY Lifepoint offers a variety of adult and young adult Bible Study classes for every age and every walk of life. Our curriculum is designed so that our entire church is studying the same Bible passages. This helps connect all of our members and allows for extended discussion on Bible study topics […]Continue Reading


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House of Commons Journal Volume 1: 21 November 1606 (2nd scribe)
Journal of the House of Commons: Volume 1, 1547-1629
Smyth, Mr. Yaxley,Mr. Lieutenant, Mr. Oldsworth, Mr. Pettus, Sir Walter Cope, Sir Tho. Crompton, Sir Geo. Somers, Mr. Hoskins, Mr. Durdent, SirView result
Parishes: Denham
A History of the County of Buckingham: Volume 3
was the tenant in 1166. 89 Another member of the family, Walter Durdent ... and was succeeded by Thomas Durdent, whose son and heir Walter had inherited Denham ... are fine...View result
House of Commons Journal Volume 1: 08 May 1606
Journal of the House of Commons: Volume 1, 1547-1629
to consider of the Provisoes presently. Mr. Durdent, - in die Bill ... Heale, Sir Gam. Capell, Sir Fr. Knollys, Mr. Durdent, Sir Rich. Spencer, ... Chock, Sir Walter Vaughan, Sir Fr. Goodwyn -...View result
Fines for divers and other counties: Edward III
A Calendar To the Feet of Fines For London and Middlesex: Volume 1, Richard I - Richard III
Durdent. The manor of Denham Durdent, in the county of Buckingham, and land ... Walyngford, citizen and skinner of London, and Walter, son of John Meu, ... and John Imaigne, chaplain, and Philip...View result
Cartulary of Trentham Priory: Miscellaneous charters (2)
Staffordshire Historical Collections, Vol. 11
Roger de Clinton, 11291148. Bishops. Walter Durdent, 11491161. Bishops. ... Durdent de Thurvaston, salutem in domino, Noveritis me concecisse...View result
House of Commons Journal Volume 1: 19 June 1604 (2nd scribe)
Journal of the House of Commons: Volume 1, 1547-1629
James, Sir Tho. Hobby, Sir Jo. Heigham, Sir Fr. Eure, Sir Walter Cope, Sir ... Durdent, Sir Geo. Moore, Mr. Brock, Sir Valentyne Knightley, Mr. Noye, SirView result
House of Commons Journal Volume 1: 05 April 1606
Journal of the House of Commons: Volume 1, 1547-1629
Rainscroft, Sir H. Poole, Mr. Durdent, Mr. Wentworth, Sir Rob. Johnson, Sir Fr. ... Holt, Sir Geo. Smith, Sir Walter Cope, Sir John Hobart, Sir Wm. Herrick,View result
Close Rolls, Edward II: March 1326
Calendar of Close Rolls, Edward II: Volume 4, 1323-1327
16. Lichfield. Master Walter de Itlesp ( sic), clerk, acknowledges ... March 10. Merevale. Walter, abbot of Suleby, acknowledges, ... Eustace de Folevill, Robert de Folevill and Walter his...View result
Close Rolls, Edward I: October 1273
Calendar of Close Rolls, Edward I: Volume 1, 1272-1279
Westminster. Walter de Kanc[ia] attorney of the queen, came into chancery, ... And for this he found the following pledges, to wit Philip Durdent and Ralph Buzun of co. ... if the abbot cannot be present in...View result
Houses of Benedictine nuns: Priory of Henwood
A History of the County of Warwick: Volume 2
Houses of Benedictine nuns Priory of Henwood 5. THE PRIORY OF HENWOOD In the beginning of the reign of Henry II, when Walter Durdent was bishop of Chester (1149-1161), Ketelberne de Langdon founded a prioryView result


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It's not every day a homeless man gets to sleep on a cushy white mattress atop a firm box spring. And, when he does, there's a catch: It's sitting out of doors on Mission and Bosworth, and nearby employees arrange for a city wake-up call.
The incongruity of a man slumbering beneath a starry-skies-patterned blanket on a mattress and box springs on the sidewalk beneath the not-exactly starry skies is jarring, and your humble narrator stopped to inquire just as the police pulled up.
A trio of officers exited the cruiser. One lifted the blue blanket, revealing a pink-faced man blinking at the not-quite 9 a.m. sun. "Good morning," the officer said.
The supine man replied in kind, adding that he was deeply embarrassed he didn't wake up at an earlier hour. "I can't believe I slept in like this. I meant to be places."
"What's your name, brother?" asked another cop. "Dustin," replied the man.
The interaction was cordial. Wisps of conversation were audible over the Mission Street traffic: "Warrants? ... Misdemeanor ... Baseball bat in the park." The officers' radio crackled. Clearly Dustin was not Charlie Manson or any lesser personage necessary to trouble further. All they required of him was he gather his possessions and move along.
Dustin pulled on his boots and bundled the clothes and shoes that were sitting atop the mattress. He leaned a faded blue Schwinn on a laundromat wall and left the starry blanket atop a trash can. He propped the mattress and box spring next to his bike.
"You found the mattress there?" queried an officer. Dustin nodded. Left unsaid was that toting around a queen-sized bed is inconvenient for a man with a bicycle and little else.
"You have a great day, officers," he said, wheeling his bike down Mission. Clothes fell onto the ground. Asked where he'd go next, Dustin smiled and replied he wasn't sure.
He rubbed his jaw and said that sleep has been hard to come by, as he has a toothache. But then he smiled. "Those mattresses sure kicked ass, though."


text:
We have previously reported that varying stimulus intensity produces qualitatively different types of synaptic plasticity in area CA1 of hippocampal slices: brief low-intensity (LI) theta-burst (TB) stimuli induce long-term potentiation (LTP), but if the stimulus intensity is increased (to mimic conditions that may exist during seizures), LTP is not induced; instead, high-intensity (HI) TB stimuli erase previously induced LTP ("TB depotentiation"). We now have explored the mechanisms underlying TB depotentiation using extracellular field recordings with pharmacological manipulations. We found that TB depotentiation was blocked by okadaic acid and calyculin A (inhibitors of serine/threonine protein phosphatases PP1 and PP2A), FK506 (a specific blocker of calcineurin, a Ca2+/calmodulin (CaM) protein phosphatase), and 8-Br-cAMP (an activator of protein kinase A) with 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor). These results suggest that protein phosphatase pathways are involved in the TB depotentiation similar to other type of down-regulating synaptic plasticity such as low-frequency stimulation (LFS)-induced long-term depression (LTD) and depotentiation in the rat hippocampus. However, TB depotentiation and LFS depotentiation could have differential functional significance.
In hippocampal area CA1, synaptic strength was shown to be up- or down-regulated by previous synaptic activities. Brief high-frequency stimulation (HFS) produces a long-lasting increase in synaptic strength, i.e., long-term potentiation (LTP), while prolonged low-frequency stimulation (LFS) leads to a long-lasting decrease in synaptic strength, i.e., long-term depression (LTD) (for review see Bear and Malenka 1994;Bliss and Collingridge 1993; Linden 1994). We previously observed that the same theta-burst (TB) stimulation produced different synaptic plasticity depending on the stimulus intensity: low-intensity theta-burst (LI TB) stimulation produced LTP (in agreement with Larson et al. 1986;Staubli and Lynch 1987), but high-intensity theta-burst (HI TB) stimulation induced lasting depotentiation of recently potentiated responses, without any changes in the synaptic responses at naive synapses.
The mechanisms underlying LTP and LTD have been studied extensively in area CA1 of rat hippocampal slices. The suggested mechanisms are depicted in Fig. 1. Both types of synaptic plasticity require postsynaptic calcium influx through activation of postsynapticN-methyl-d-aspartic acid (NMDA) receptors (Malenka and Nicoll 1993; Mulkey and Malenka 1992; Perkel et al. 1993). The difference between up- and down-regulation of synaptic plasticity (i.e., potentiation or depression) may depend on the magnitude of increases in intracellular calcium concentrations ([Ca2+]i) (Cormier et al. 2001; Hansel et al. 1997; Lisman 1989; Yang et al. 1999).
The small elevations in [Ca2+]i that occur during LTD induction may preferentially activate calcineurin, the Ca2+/calmodulin (CaM)-dependent protein phosphatase (Fig. 1, dotted line). Calcineurin then can inactivate inhibitor protein 1 (I-1), the endogenous inhibitor of serine/threonine protein phosphatase-1 (PP1); this allows the activation of PP1 (Oliver and Shenolikar 1998). PP1 dephosphorylates Ca2+/CaM protein kinase II (CaMKII) and other proteins, including glutamate receptors (Shenolikar and Nairn 1991; Shields et al. 1985), to promote LTD.
LTP-inducing stimuli are associated with somewhat larger increases in [Ca2+]i. This can activate CaMKII, which plays a key role in LTP induction through phosphorylation of the GluR1 subunit of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (among other substrates; Fig. 1, straight line) (Barria et al. 1997). In addition, moderate elevations of [Ca2+]i (Fig. 1, middle pathway), can activate PKA. PKA can phosphorylate and activate I-1, which then can inhibit PP1 (Blitzer et al. 1998). Thus PKA may have a gating role in LTP induction (Blitzer et al. 1998) and may also prevent LTD induction (Mulkey et al. 1994).
We previously reported that HI TB depotentiation requires NMDA receptor activation, similar to other forms of synaptic plasticity in area CA1 (Barr et al. 1995). Here, we found that phosphatases (PP1/PP2A and PP2B), which play critical roles in LFS-induced down-regulation of synaptic strength, are also involved in HI TB depotentiation.
Slice preparation
Hippocampal slices were prepared from 19- to 22-day-old male Sprague-Dawley rats. Rats were decapitated under halothane anesthesia and whole brains were rapidly removed and incubated in chilled artificial cerebrospinal fluid (ACSF) for 4 min. Transverse slices (500 or 625 μm) including hippocampus were cut from the removed brain at 4°C using a Vibratome (Campden, Berlin, Germany). Prior to use, slices were maintained for ≥1 h at room temperature in oxygenated (95% O2-5% CO2) ACSF, containing (in mM) 120 NaCl, 3.3 KCl, 1.23 NaH2PO4, 25 NaHCO3, 2 CaCl2, 0.9 MgSO4, and 10 glucose. All recordings were performed at 29–32°C on slices submerged in ACSF in the recording chamber. The ACSF was perfused at a rate of approximately 2–2.5 ml/min.
Stimulation and recording protocols
Extracellular recordings were made using 150 mM NaCl-filled electrodes (2–3 MΩ). Recording electrodes were positioned in the stratum radiatum of area CA1 in hippocampal slices to record the field excitatory postsynaptic potentials (fEPSPs). Synaptic responses were evoked using monopolar tungsten stimulating electrodes (A-M systems, Carlsborg, WA). Stimuli were square wave current pulses (0.1–0.2 ms duration) delivered at 1–2 stimuli/min. The stimulating electrodes were placed in the s. radiatum to activate the Schaffer Collateral pathway projecting to CA1. The basal synaptic response was chosen to be at 20–30% of the maximum rising slope of fEPSP from each slice, which fell within stimulus intensities of 40–80 μA. Tetanic stimulation was delivered by a TB stimulation pattern composed of 10 minitrains (TB-10) given at 200-ms intervals; each minitrain consisted of 4 pulses given at 100 Hz. LTP was elicited by TB stimuli at the stimulus intensity that gave the basal synaptic response (LI TB), while depotentiation was induced by TB stimuli at 10 times the basal stimulus intensity (HI TB). In some cases, depotentiation was induced by five minitrains of TB stimulation (TB-5). This shorter (TB-5) stimulus was used to produce a lower magnitude of depotentiation that might be more sensitive to modulation by drugs. In some experiments, the HI TB stimuli were applied twice at 20-min intervals to monitor accumulative depotentiation.
Drug application
Stock (1–10 mM) solutions of okadaic acid, calyculin A (LC Laboratories, Woburn, MA), and rapamycin (Sigma, St. Louis, MO) were dissolved in dimethyl sulfoxide (DMSO; final concentration of DMSO between 0.075% and 0.1%). FK506 (Fujisawa Pharmaceuticals, Deerfield, IL) in an intravenous injection solution form (6 mM in 80% vol/vol ethanol) was used (final concentration of ethanol 0.66%). Stock solutions were kept as frozen aliquots, and each aliquot was thawed immediately before use. Slices were preincubated for 90–180 min in okadaic acid (1 μM), calyculin A (0.75 μM), FK506 (50 μM), or rapamycin (1 μM) before transferring to the recording chamber, after which slices were perfused with ACSF. 8-Br-cAMP (BioMol Research Laboratories, Plymouth Meeting, PA) was directly dissolved in ACSF at 300 μM and applied by bath-perfusion 35 min before HI-TB stimulation and throughout the experiments. 8-Br-cAMP was also applied together with 3-isobutyl-l-methylxanthine (IBMX, Sigma), a phosphodiesterase inhibitor, based on a previous report that 8-Br-cAMP blocked LTD when applied with IBMX (Mulkey et al. 1994). 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, Sigma), an A1 adenosine receptor antagonist, was included in control and test solution to avoid any confounding effect of IBMX on adenosine receptors. The stock solutions of IBMX (20 mM) and DPCPX (1 mM) were prepared by dissolving them in either DMSO (final concentration of DMSO 0.25%) or 0.1% NaOH, respectively. In control experiments, which were conducted in an interleaved manner, slices were exposed to the vehicle solvents (e.g., DMSO or ethanol) at the same concentration used during drug application.
Data acquisition and analysis
Field potentials were sequentially amplified by an Axoclamp-2A amplifier (Axon Instruments, Foster City, CA) and a DC amplifier (Warner Instrument, Hamden, CT) and digitized at 10 kHz by Lab PC+ (National Instruments, Austin, TX). Data were acquired and analyzed by programs designed by Dr. Jeffery L. Calton (Dartmouth College) using Labview software package (National Instruments). fEPSPs were quantified by measuring the slope at ±300 μs from the half-peak time of the rising response. The slope was determined by dividing the voltage difference between these two time points by 600 μs (Fig.2 A). Since the response at this time window gives near-linear rising phase, this measure is close to the true value of the rising slope of fEPSP. To make sure that any change in response was attributed to synaptic plasticity, we measured the fiber volley. The fiber volleys were quantified by measuring their amplitude relative to the baseline before the stimulus. We observed some changes in the magnitude of the fiber volley through these experiments, but the direction of changes did not depend on stimulation types or recording times. When the fiber volley amplitude changed more than 10%, the resulting data were excluded from our data analysis. When we examined the time-dependent decay of LTP, we observed that the LTP magnitude declined during the first 10 min after LTP induction and then was maintained ≤60 min without further decay (Fig.2 B). The LTP magnitudes at 20, 40, and 60 min after LTP induction were 95.6 ± 7.76%, 92.4 ± 8.50%, and 90.51 ± 6.91%, respectively (n = 5). There were no significant differences among these time points. Therefore the magnitude of depotentiation was measured by comparing the magnitudes of LTP between 20 min after LTP induction and 20 min after depotentiation induction (equivalent to the 40 min after LTP induction) from each slice. LTP and depotentiation were measured as follows: % potentiation = fEPSP slope after LTP stimulation × 100/fEPSP slope before LTP stimulation: % depotentiation = (% potentiation before depotentiation stimulation − % potentiation after depotentiation stimulation) × 100/% potentiation before depotentiation stimulation
Statistical analysis
Statistical comparisons were made using paired or independent Student's t-test with the level P < 0.05 considered to be significant (SPSS, Chicago, IL). In some cases, two-way ANOVA with repeated measures was used for statistical comparisons. Numerical and graphed data (Origin, OriginLab, Northampton, MA) are presented as a mean ± SE.
Effect of PP1/PP2A inhibition on TB depotentiation
To test whether PP1 or PP2A activity is involved in the induction of TB depotentiation, we studied the effect of okadaic acid and calyculin A (PP1/PP2A inhibitors) on TB depotentiation. When HI TB-10 stimulation was applied, depotentiation was induced in control slices pretreated with solvent (0.1% DMSO; Fig.3, A and B). The magnitude of depotentiation was 70.4 ± 5.92% (P< 0.001) 20 min after the first TB-10 stimulus and 86.6 ± 6.07% (P < 0.001) 20 min after the second TB-10 stimulus (n = 5). In slices pretreated with okadaic acid (1 μM, 2–3 h), the magnitude of depotentiation was 25.5 ± 3.97% (P < 0.001) and 38.1 ± 6.23% (P= 0.001) 20 min after the first and second TB-10 stimulation, respectively (n = 8; Fig. 3, A andB). The magnitude of TB depotentiation was significantly different between control slices and okadaic acid-pretreated slices (P < 0.001 for both the first and the second TB depotentiation; Fig. 3 B).
HI TB-5 stimulation induced smaller, but still significant, depotentiation in the control slices (pretreated with solvent 0.075% DMSO) compared with HI TB-10 stimulation (Fig.4, A and B). The magnitude of depotentiation was 20.5 ± 5.52% (P= 0.008) and 45.9 ± 10.82% (P = 0.002) 20 min after the first and second TB stimulation, respectively (n = 5). In slices pretreated with calyculin A (0.75 μM, 2–3 h), depotentiation by HI TB-5 stimulation was completely blocked (Fig. 4, A and B). Depotentiation 20 min after the first and second TB stimulation was not statistically significant: 4.3 ± 4.66% depotentiation (P = 0.713) and 12.0 ± 5.09% depotentiation (P = 0.200), respectively (n = 6). This result suggests that the activity of PP1/2A is involved in the induction of TB depotentiation.
A previous study reported that in the presence of PP1/PP2A inhibitors, LFS enhanced synaptic transmission through presynaptic mechanisms (Herron and Malenka 1994). To test whether similar presynaptic changes were induced when HI TBS was delivered in the presence of PP1/PP2A inhibitors, we examined the effect of HI TBS in naive (not previously potentiated) synapses. Slices were pretreated with okadaic acid and were also exposed to APV (to block NMDA receptor effects) during the experiment. We found that HI TBS in the presence of PP1/PP2A inhibitors did not enhanced synaptic transmission (data not shown). Therefore this result supports the proposal that PP1/PP2A inhibitors block TB depotentiation rather than mask depotentiation via enhancement of synaptic transmission.
On the other hand, we found that LTP in the presence of calyculin A was significantly decreased compared with control (66.8 ± 6.02% vs. 100.5 ± 11.76%, P = 0.0248). Considering that LTP in slices pretreated with okadaic acid is comparable to the control, this decrease in LTP in slices pretreated with calyculin A may not be attributed to the inhibition of PP1/2A. In fact, inhibition of PP1/2A is expected to positively modulate LTP induction (Blitzer et al. 1998), even though disinhibition of PP1/2A through I-1 knockout did not affect the LTP induction in Shaffer collateral CA 1 synapses (Allen et al. 2000). Further studies may be required to understand this effect of calyculin A.
Effect of calcineurin inhibition on TB depotentiation
Since synaptic activation of PP1 may be mediated indirectly through the activation of calcineurin (the Ca2+/CaM-dependent protein phosphatase that dephosphorylates and inactivates I-1) (Oliver and Shenolikar 1998), we tested whether calcineurin was involved in TB depotentiation using FK506, a specific calcineurin inhibitor. Prior studies have reported complex effects of FK506 on LTP—including developmental differences. In hippocampal slices from adult animals, FK506 caused LTP induction, whereas in hippocampal slices from young animals, FK506 prevented LTP induction (Wang and Kelly 1997; Wang and Stelzer 1994). However, in other studies using hippocampal slices from young animals, LTP induction was not prevented in FK506-treated slices (Mulkey et al. 1994). In our experiments using young animals, pretreatment of rat hippocampal slices with FK506 did not interfere with LTP induction, in agreement with Mulkey et al. (1994) (Fig.5, A and B). In the slices pretreated with FK506 for 2–3 h, HI TB-10 stimulation did not induce depotentiation, but induced a slight enhancement, which was not statistically significant (−7.3 ± 8.60% depotentiation,P = 0.677, n = 9; Fig. 5, Aand B). On the other hand, there was significant depotentiation in the control slice pretreated with solvent (0.66% ethanol) following the same HI TB-10 stimulation (49.7 ± 9.04% depotentiation, P = 0.007, n = 6; Fig.5, A and B).
In some cases, fEPSPs were followed by population spikes after LTP induction. Even though we selectively analyzed the fEPSP by measuring the slope in the rising phase of the responses, one may argue that the drug effect could be affected by the development of population spikes. Therefore in a separate set of experiments, we analyzed the effect of FK 506 on depotentiation at different stimulus intensities. The fEPSP slopes were plotted as a function of the fiber volley amplitudes (Fig.5 C). When the magnitudes of depotentiation were compared among different stimulation intensities, there was no significant difference [F(5,18) = 0.483, P = 0.784], while there is significant difference in the depotentiation magnitude between control and FK506-treated slices [F(1,18) = 67.237, P < 0.001].
To ensure specific effects of FK506 on calcineurin rather than on a calcineurin-independent pathway, we studied the effect of rapamycin on HI TB-10 depotentiation. Rapamycin is known to bind to the FK506 binding protein and act through FK506-calcineurin-independent mechanisms. In this study, we found that HI TB-10 stimulation induced significant depotentiation (52.6 ± 13.9%, P = 0.02, n = 4) in slices pretreated with rapamycin (1 μM). The magnitude of depotentiation in slices pretreated with rapamycin was not significantly different from the magnitude of depotentiation in control slices pretreated with solvent (DMSO 0.1%), which was 46.0 ± 9.4% (P = 0.012,n = 4; P = 0.708 between control and rapamycin). This suggests that calcineurin activity is also required for the induction of TB depotentiation.
Effect of PKA activation on TB depotentiation
Since PKA can also result in PP1 inactivation by phosphorylating endogenous I-1 (Blitzer et al. 1998;Oliver and Shenolikar 1998), we tested the effect of PKA activation on TB depotentiation. We used 8-Br-cAMP (300 μM) and phosphodiesterase inhibitor IBMX (50 μM) based on the report that 8-Br-cAMP blocked LTD when applied in conjunction with IBMX (Mulkey et al. 1994). In addition, DPCPX (1 μM), an A1 adenosine receptor antagonist, was included in both the control and test solution to avoid any confounding effect of IBMX on adenosine receptors (Mulkey et al. 1994). Under this condition, as noted by Mulkey et al. (1994), LTD induced by LFS was blocked (data not shown).
HI TB-10 stimulation induced significantly smaller depotentiation in the presence of 8-Br-cAMP and IBMX (P = 0.003). The magnitude of depotentiation in the presence of 8-Br-cAMP and IBMX was 27.1 ± 2.60% (P = 0.016, n = 4), whereas the magnitude of depotentiation in the control solution (0.25% DMSO and DPCPX, 1 μM) was 52.2 ± 5.58% (P = 0.0073, n = 4; Fig. 6,A and B). DPCPX alone prevented the posttetanic depression, but did not affect TB depotentiation. This result suggests that TB depotentiation was partially inhibited by PKA activation.
In this study we showed that inhibitors of PP1/2A and calcineurin block the induction of TB depotentiation, as does PKA activation using 8-Br-cAMP and IBMX. These results are consistent with the well-accepted role of protein phosphatases in the down-regulation of synaptic strength (Mulkey et al. 1993, 1994) and the involvement of PKA in negatively modulating protein phosphatase activity (Blitzer et al. 1998; Mulkey et al. 1994;Oliver and Shenolikar 1998).
What determines whether phosphatases or kinases predominate to regulate synaptic strength? It has been proposed that weak stimulation (like LFS) induces LTD by producing a modest rise in [Ca2+]i, which in turn, activates a protein phosphatase pathway. This level of [Ca2+]i may be below the threshold for activating protein kinases such as CaMKII. Stronger stimulation (like HFS) induces LTP by producing a higher level of [Ca2+]i, and thus activates protein kinases, including CaMKII (Cormier et al. 2001; Hansel et al. 1997; Lisman 1989; Yang et al. 1999).
Given these relationships, how does strong stimulation (HI TBS) activate the protein phosphatases pathway? One possibility is that HI TBS deactivates or desensitizes NMDA receptors during stimulation, leading to only a small elevation of [Ca2+]i. In a preliminary study we observed even higher elevation of [Ca2+]i in the hippocampal proximal dendrites during HI TBS than during LTP-inducing stimulation (Kang et al. 1998). However, we did not visualize spines in that study, so it is conceivable that the [Ca2+]i increase in spines (which is primarily NMDA receptor-dependent) might be smaller during HI TBS than during LTP-inducing stimulation. In other words, HI TBS would increase [Ca2+]i in spines to a low level, similar to LFS. This would activate a common pathway for the down-regulation of synaptic strength, namely, the activation of protein phosphatases. This possibility is currently under investigation.
On the other hand, if HI TBS increases [Ca2+]i in dendritic spines to levels higher than LTP-inducing stimulation (as observed in the proximal dendrites), then we must conclude that protein phosphatase pathways can be predominantly activated not only by small elevations of [Ca2+]i but also by large elevation of [Ca2+]i, whereas intermediate levels of [Ca2+]i represent the optimal conditions for activating protein kinases.
How might high levels of [Ca2+]i activate the protein phosphatases? We speculate that the following mechanism is involved. Moderate elevations of [Ca2+]i as seen during LTP induction activate protein kinases such as CaMKII and also suppress phosphatase activity by the concomitant activation of PKA (Blitzer et al. 1995, 1998; Makhinson et al. 1999). PKA, which negatively regulates PP1 activity by phosphorylating the endogenous PP1 inhibitor, I-1, responds to the activation by Ca2+/CaM-dependent adenylyl cyclases (AC) present in CA1 neurons (Ahlijanian and Cooper 1988; Piascik et al. 1980; Potter et al. 1980). These forms of AC show a bell-shaped activity curve relative to increasing calcium concentrations (Ahlijanian and Cooper 1988; Piascik et al. 1980; Potter et al. 1980). Therefore AC activity may be decreased by large elevations of [Ca2+]iinduced by HI TB stimuli. In addition, PKA activity can be decreased by Ca-dependent activation of phosphodiesterase (PDE). The resulting low PKA activity is accompanied by a disinhibition of PP1, which dephosphorylates CaMKII (Shenolikar and Narin 1991; Shields et al. 1985), NMDAR (Westphal et al. 1999), and glutamate receptor type 1 (GluR1) subunit of AMPA receptors (Lee et al. 2000) to promote depotentiation.
If HI TB stimulation favors phosphatases, why then does HI TB stimulation not produce LTD in naive synapses, as seen with LFS (Barr et al. 1995)? This suggests that LTD and depotentiation are mechanistically distinct. Growing experimental evidence supports this viewpoint. For example, Lee et al. (2000) reported that identical stimulation conditions recruit different signal-transduction pathways depending on prior synaptic history. In naive synapses, LTD induction results from the preferential dephosphorylation of GluR1 at PKA sites. In contrast, depotentiation in previously potentiated synapses results from the dephosphorylation of GluR1 at CaMKII sites (Lee et al. 2000). There is also evidence from gene disruption studies that the specific calcineurin isoforms (i.e., calcineurin Aα) mediate depotentiation, but not LTD, even though both LFS-induced LTD and depotentiation can be blocked by pharmacological inhibition of calcineurin (Huang et al. 1999; O'Dell and Kandel 1994; Zhuo et al., 1999). In a similar manner, HI-TB stimulation may selectively depotentiate signals mediated by CaMKII (but not PKA), or may utilize specific phosphatase isoforms to transduce signals at postsynaptic sites. Clearly, other mechanisms could be postulated, but further work analyzing second messengers and postsynaptic signaling pathways will be required to resolve this issue.
What is the functional significance of depotentiation? LTP is studied as the molecular mechanism that underlie learning and memory, and the disruption of LTP such as depotentiation may subserve the mechanism underlying memory loss, i.e., amnesia. In support of this point of view, the protein phosphatase pathways that mediate depotentiation, was shown to mediate amnesic effects (Genoux et al. 2002). Depotentiation produced by HI TB stimuli may have functional consequences that differ from depotentiation induced by other means. For example, in LFS-induced depotentiation, the stimuli are relatively low in intensity and resemble some naturally occurring neuronal firing patterns. As such, LFS-induced depotentiation may be relevant to normal physiological processes such as desaturation of potentiated pathway or natural decay of memory. In contrast, HI TB stimuli are, by definition, of pathologically high intensity, and the stimuli are given as theta bursts—a specific pattern that enhances neuronal responsiveness. These two factors work together; the net result of which is that HI-TB stimuli activate many afferent fibers and evoke neuronal responses that include robust population spikes. These burst-like responses resemble activity recorded during seizures. In fact, in vitro studies showed that seizure activity or seizure-like extracellular conditions induced depotentiation (Harrison and Alger 1993; Hesse and Teyler 1976; Moore et al. 1993).
In humans, seizure activity is commonly associated with memory impairment or amnesia (Halgren and Wilson 1985;Squire 1986; Thompson 1991). Patients with epilepsy have episodes of memory loss such as difficulty remembering past events (retrograde amnesia) and retaining newly learned information (anterograde amnesia). The degree of memory loss in epilepsy patients has generally been correlated with the frequency and/or severity of seizure. The consequences of seizures on memory are also well documented in patients who undergo electroconvulsive therapy (ECT), which involves electrical induction of a seizure to produce a therapeutic change in mood (Squire 1986). As is the case for epilepsy patients, both anterograde and retrograde memory loss are associated with ECT, and the degree of memory loss is positively correlated with the number of seizures administered, as well as seizure duration. Such memory impairment was observed not only in adults but also children with epilepsy (Stores 1981). Therefore TB depotentiation examined in young rats in this study may model seizure-induced amnesia, and further studies on TB depotentiation could help to develop treatments that ameliorate memory disorders in patients suffering from epilepsy or trauma.
In summary, HI TB depotentiation is mediated by a complex protein phosphatase cascade that is inhibited by PKA. These results support the hypothesis that the protein phosphatase pathways play a critical role in the down-regulation of synaptic strength in the plasticity under both physiological and pathological conditions.
This study was funded by a Veterans Affairs Grant to W. A. Wilson, National Alliance for Research on Schizophrenia and Depression Young Investigator Award to S. D. Moore, and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-52054 to S. Shenolikar.
Address for reprint requests: W. A. Wilson, 508 Fulton St., Veterans Administration Medical Center, Neurology Research Bldg. 16, Rm. 25, Durham, NC 27705 (E-mail.Wilkie.wilson{at}duke.edu).
- Copyright © 2003 The American Physiological Society


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Your safety is guaranteed during this excursion into Amsterdam's darker side, as a reliable and trustworthy guide will be accompanying you.
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Amsterdam Walking Tour of The Red Light District
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Carleen Brice is author of ORANGE MINT AND HONEY, an Essence "Recommended Read" and a Target "Bookmarked Breakout Book," and the best-selling CHILDREN OF THE WATERS. In February 2010, ORANGE MINT AND HONEY premiered on the Lifetime Movie Network as SINS OF THE MOTHER, starring Jill Scott. It was the second-highest rated original movie in LMN's history and received two 2011 NAACP Image Awards. Brice is the recipient of the 2009 First Novelist Award from the Black Caucus of the American Library Association and the 2008 Break Out Author Award at the African American Literary Awards Show. She was recently named one of the 25 most influential black fiction writers on Twitter.


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Virtual Reality: Barter and Restructuring in Russian Industry
A general consensus in the transition economies literature links the existence of enterprise restructuring with the pace of the transition process and the potential for economic growth. The existing literature is less clear, however, about whether the lack of economic growth is caused by the lack of enterprise restructuring. Complicating the debate in Russia is the confusion regarding the role of barter transactions in enterprise restructuring. Much of the confusion is generated by proponents of a "virtual economy" interpretation of how the Russian economy and Russian enterprise managers operate. This paper dispels much of the confusion about the existence of enterprise restructuring and the corresponding role of barter by demonstrating why the virtual economy model fails to accurately depict economic actions or outcomes in Russia. We develop the argument that barter is closely related to an absence of liquidity in the Russian economy, using both macro-level and micro-level data to document the consequences of "structural illiquidity." Our results are unambiguous: both the incidence and volume of barter transactions are inversely related to liquidity. We conclude that analyses using barter transactions as evidence of the lack of enterprise restructuring in Russia stem from: (1) the lack of clear consensus about what constitutes enterprise restructuring in transition economies and how it varies with the stage of the transition process; (2) errant assumptions about managers' objective functions; (3) the relative mix of formal and informal restructuring mechanisms; (4) the lack of attention to industry variation and, within industry, to managerial characteristics; and (5) the Texan complex (if it ain't big, it ain't ...) which causes analysts to ignore changes in enterprise operations unless they occur on a grandiose scale.
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The Department of Energy and Babcock & Wilcox have signed a deal for the funding of the company's small modular reactor development project. Under the terms, B&W's mPower technology will get $79 million in the first year. About $150 million will be available over a five-year period, according to department estimates.
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Google's Jsonnet Language Generates JSON
Google has produced a new data templating language called Jsonnet, a portmanteau of JSON and sonnet, that generates JSON.Google recently introduced a new open-source configuration language for generating JSON known as Jsonnet. Google quietly released Jsonnet a few months ago as a programming language for specifying data. The Jsonnet Website calls Jsonnet a data templating language. Jsonnet doesn't just generate JSON: It is also an extension of JSON, said Dave Cunningham, a member of Google's New York Technical Infrastructure team, in a blog post about the new language. "By adding new constructs between the gaps of existing JSON syntax, Jsonnet adds useful features without breaking backwards compatibility," Cunningham said. "Any valid JSON is also a valid Jsonnet program that simply emits that JSON unchanged, and existing systems that consume JSON (or its cousin YAML) can be easily modified to accept data in the full Jsonnet language. As such, Jsonnet is an example of a templating language, but one specifically designed for JSON data and less error-prone than other techniques."
Cunningham also noted that many systems can be configured with JSON, but writing it by hand can be difficult. "Jsonnet is packed with useful data-specification features that expand into JSON for other systems to act upon," he said.
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