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Updated: 2012-04-15T19:32:28.118-04:00
2005-10-25T15:53:24.960-05:00Last week Christina Kahrl (who I'm a huge fan of) got a couple of questions about the Mets first baseman or lack thereof in a chat she did on BP. She indicated that she thinks the Mets should give Victor Diaz the job. I like Diaz. I was a proponent of him as Major Leaguer before the season and I still am. However, I think she's giving his bat more credit than it deserves. He's got a very good bat for a second baseman, but he'd be overmatched as an everyday corner infielder.
2005-10-07T11:58:59.926-05:00John Danks, LHP, Texas Rangers
2005-10-05T10:47:01.766-05:00Kendry Morales, 1B, Anaheim Angels
2005-09-30T22:39:44.826-05:00I was looking at BA's Cal League Top Prospect List and I spotted their "5 Years Ago" window.
2005-09-16T11:40:14.246-05:00Rick Ankiel, OF/LHP?, St Louis Cardinals
2005-09-12T15:34:37.976-05:00With all due respect to Will Carroll, this report is powered by a brand new Dell.
2005-09-08T17:41:42.520-05:00J.J. Furmaniak, SS, Pittsburgh Pirates
2005-09-07T13:54:19.133-05:00A couple of interesting things have happened in the last few days and I'd like to talk about them.The first thing is the Pirates firing of Lloyd McClendon as manager. Actually, that's not the thing I find interesting. McClendon is a decent manager. He never struck me as either incompetent or gifted. He just fades into the background of managers who can do an adequate job, but aren't going to make a big difference. In fact almost every manager meets that description to me other than the ones who are needlessly destructive by means of running pitchers into the ground or by habitually overmanaging. The thing I'll miss about McClendon is the knowledge that once or twice a season he'll completely go off the deep end and make an ass of himself during an argument with an umpire. I'm not above saving these kinds of incidents on my PVR and rewatching them when I need a laugh. Right now I have the Frank Robinson staring contest saved.What I find interesting is a brief discussion yesterday on ESPNews between Michael Kim and I believe it was Brian Kenny. The discussion centered around the fact that the Pirates don't suck because of McClendon, but instead because of the fact that they don't retain the young talent they produce. I concede that the sorry state of affairs in Pittsburgh isn't McClendon's fault. But it isn't because of free agent defections either. Over the last decade, they've kept most of the good players they've found or produced. Jason Kendall and Brian Giles immediately come to mind. The problem is twofold.1. They've squandered the resources they have had by locking up both good players (Giles and Kendall) and bad players (Pat Meares and Kevin Young) for too long and for too much money.2. They haven't produced enough talent to begin with.Think about it for a second. What players have they really produced since Barry Bonds left? They found Brian Giles, getting him in a steal of a deal. Copy that with Kip Wells and Josh Fogg, both of whom are decent pitchers, but nothing that's going to blow your skirt up and are likely going to be pushed aside by the wave of pitching talent bubbling up through the system. Then you have Kendall, who is a pretty good player. The only guy I can come up with that they regrettably threw aside for monetary reasons was Aramis Ramirez. I guess you could count Jason Schmidt, but I tend to think that they just got unlucky with him as he was injury prone and mediocre in his time in Pittsburgh.Most of the blame for the last decade of futility falls on Cam Bonifay's inept shoulders. I know it is a running theme here to chant that it isn't money but brains that builds winning teams, but even teams on a shoestring budget can stumble into relevance once or twice a decade if they're run competently. If they're run by really good GM's and scouting departments, they can become fixtures in playoff races like the A's and Twins have. There is hope in Pittsburgh right now fed by the emergence of Jason Bay and Oliver Perez and the young talent on display in the form of Zach Duke, Ryan Doumit, Paul Maholm, Brad Eldred, Ronny Paulino, and Ian Snell. They have to shepherd these players into the lineup and rotation, hope that their early promise is a sign of things to come, and then surround them with good talent, but that's an ongoing concern everywhere that you have a young group of talented players. The big choices come in the form of Craig Wilson and Oliver Perez, both of whom have value either in trade or in being talent to add to the young guys. It remarkable how much this organization resembles that of the Brewers, who are facing a similar set of circumstances.The next thing is on a similar theme of competence vs incompetence. Vince Namoli is leaving the Rays after the season, and it's possible (maybe even likely) that Lou Pinella and Chuck LaMar are going with him. This organization is showing a pulse despite contin[...]
2005-08-28T08:57:26.580-05:00Yuniesky Betancourt, SS, Seattle Mariners
2005-08-23T13:31:28.770-05:00Starting out with Formula 1, this is interesting news. I'm not sure how good Scott Speed would be in F1 next year, but in general the idea is at least intriguing. Having an american driver in a Formula 1 cockpit would help next year's USGP attendance, but I'm afraid of getting him into the wrong team. I doubt there'd be much interest if he winds up in a Minardi or a Midlands seat since he'd have almost no chance of being relevant. I'd like to see him stay in GP2 and get into a heavy test schedule with Red Bull Racing. Get some time in F1 cars before jumping in. It would also give Red Bull a chance to sort out their driver situation and clear a spot for him.
2005-08-18T09:18:50.803-05:00I went to a day game between the Indy Indians and the Durham Bulls. I was hoping to watch BJ Upton and Delmon Young. 1 out of 2 ain't bad. Unfortunately Upton spent most of the afternoon as Durham's first base coach. He was on deck as a pinch hitter when Mark Corey got Jeff Deardorf to end the game on a groundout.Young did play and he looked like everything he was supposed to be. It is obvious why scouts have been falling all over themselves in praising him. He's tall with a muscular, athletic build like you see in Vlad Guerrero and Jermaine Dye. He looks like if he wasn't a baseball player he could be a wide receiver or a small forward. His swing looks good too, though not picturesque in a Griffey circa 1998 kind of way. He had little or no problem handling Chris Enochs, who was having his best game of the year. He went 3 for 4, smashing two doubles down the left field line and poking a solid single into center. He also scored Durham's only run on an Earl Snyder double down the line. The kid can run and he can hit. He needs to draw more walks to be an MVP candidate, but even if he doesn't he has the talent to be a solid starting right fielder.In the field, I didn't get much of a look at Young. He only fielded a couple of balls and didn't make any serious throws. The scouting reports give him good marks and given his athleticism and reports of classic right field arm strength, the Dye comparison crops up again. He has the talent to be a top notch player. He just needs to make some adjustments.The Bulls also featured Eric Munson, Josh Phelps, and Fernando Cortez. Former Major Leaguers Munson and Phelps are looking more and more like AAAA guys, though some of the better ones you'll see.Munson has that take and rake approach down to a science. He's also capable of launching majestic blasts. But his swing is a little long and looping. I saw him a couple years ago with Toledo and he looks a little more polished, but he still has the same strengths and weaknesses. At this point I think what you see is what you get.I saw Phelps a couple years ago too when he was with Syracuse. He's more of a mystery. A couple years ago he looked like the best player on the field because he WAS the best player on the field by a good margin. He looked like he was going to walk into the Skydome and take the Major Leagues by the scruff of the neck and show it who was boss. Yesterday he looked like just another guy. He's lost out there. His plate discipline has eroded and he looks like he's just guessing. He's putting up pretty decent numbers, but it's obvious why he wasn't making the grade in Tampa.Cortez is a second base prospect that I haven't talked about yet. I should do that soon. I like him but he's not a sure thing. He's struggling with his batting average and his walk rate. He looks good at the plate though and he didn't swing at bad pitches and he got good wood on everything he swung at. He's good defensively and he's a good baserunner as his 23 for 27 success rate in stealing bases can attest. He might stall in AAA or he might go on to become a solid player in bigs. It's too early to tell, though he has some work to do. If he makes it, think of him as Robinson Cano with speed.The Bulls had Kevin Cash on the bench, which is a shame. I've always liked him as a kind of poor man's Jason LaRue. With a day game following a night game, his absence was not unexpected.The two prospects on the Indians roster were Ronny Paulino and Ray Sadler. I like what I see in Paulino. The kid can play. Like Cash, he was resting following a night game where he caught. He did play though, as the DH. The Pirates like his defense though, so I wasn't going to gripe about the missed opportunity. At the plate, he looks more muscular than most catchers, especially with the batting stance he uses. He [...]
2005-08-16T13:16:40.493-05:00Gabby Martinez, 1B, Tampa Bay Devil Rays
2005-08-14T08:33:10.980-05:00How about a notes column? I have several things that may warrant their own posts, but I feel like knocking them out all in one fell swoop.-The sports world has been abuzz with the Terrell Owens controversy. My interest in the subject is limited. I'm conflicted about it for a couple of reasons. The first is that I really want him to play. I have him on my roster in a fantasy football league. He's a big gamble and my team will likely live or die with whether or not he plays. The other side of it is that I take pleasure in watching the NFL's chickens come home to roost. Say what you will about Scott Boras, but the guy is right. NFL contracts are a joke. A contract's integrity is tied to the ability of both parties to change or get out of the deal. It's incredibly easy for teams to get out the deal and it is commonplace for players to restructure their deals either for more money or to improve the team's salary cap flexibility. The team can drop the player at any point, so any notion of loyalty is implicitly a one way street. There are definite advantages to non-guaranteed contracts, especially for the owners. They get cost certainty in a sport where career-ending injuries are a fact of life. I'm surprised this kind of thing doesn't happen MORE often. Teams cut guys every year and shrug their shoulders passing it off as "just business."That being said, T.O. is acting like an insufferable prick and deserves every bit of negative press that is coming his way.-The other big controversy of the last few weeks is the Raffy Palmiero suspension. There's already been reams of articles written about this and I'll try to refrain from repeating anybody else's viewpoint.Here's my take on this. Raffy is incredibly stupid. He's monumentally stupid. This crap that he was taking has been around since the 60's. If he thought that he could get away with it, he deserves to be banned from the game just on the principle that he's too dumb to deserve money and fame. You're a goddamned millionaire for chrissakes. It's one thing for a 20 year old A-ball flunky living on $1000 a month to use the cheap stuff that shows up on every drug screening known to man. It's another thing entirely for a guy who makes that every day. According to just about every authority known to man, there are at least a dozen BALCO's out there (probably 2 to 3 times that) with a roster of undetectable (and more effective) steroids ready for consumption. All you have to do is pay more money and have some connections. Just go find a track star somewhere. He'll point you in the right direction. Unbelievable.-On a happier note, I was right, then I was wrong. This is one of the most amazing things to happen this year. The A's were beyond awful during the first couple months and I thought that even the most optimistic scenario ended with them getting back to .500 in the final month of the season and building towards relevance next year. Instead, they were over .500 within a month and are obviously very relevant this season. Barry Zito and Eric Chavez have straightened themselves out. The bullpen has recovered. The offense is smoking. And Dan Johnson has been great since being called up.What Billy Beane has done is very rare. He's remade his roster without falling into obscurity. This is something that many teams have failed to do. The only immediate example that comes to mind is John Schuerholtz and the Braves. In basketball, you have Donnie Walsh and the Indiana Pacers. This also means that those who doubt Beane is among the best GM's in the game should probably get out a bib because they'll be eating some crow. This is now undoubtedly Beane's team. There are very few holdovers from before he took over.-Last on the list of grievances is just a brief mention f[...]
2005-08-08T08:46:21.263-05:00Yesterday I went to the Indianapolis Indians/Toledo Mudhens game that featured a number of interesting players. I was with my wife, my brother, and his girlfriend. I didn't take notes, this is all personal recollection combined with the box score. Nevertheless, here's my commentary.Mike Connolly started the game for Indy and was the star of the show. He kept Toledo's lineup off balance by doing his best Jamie Moyer impression all day. He threw a lot of off speed stuff. I mean a lot. It looked like he had a changeup in the low 70's, a slurvy breaking ball in the high 70's, and a fastball that worked mostly in the mid 80's. His location was good all day on all three pitches and he looked like he was toying with the batters. His defense also helped. All 4 infielders looked good.Speaking of Connolly's defense, Yurendell DeCaster looked outstanding at first base. It's a rare day when a first baseman looks like the best defensive player on the field, but this was one of them. DeCaster has played third in the other times I've seen him, and he looked comfortable there, making all the routine plays. He didn't stand out though. I don't remember him charging any ground balls or making any diving stops followed by a rocket across the diamond to just nail a streaking runner. Today though, he made at least 3 plays that just stood out. One was a diving stop right over the first base bag to start a double play. That was a very hard hit ball and his reactions were pretty impressive. He also smoked a couple of singles through the infield. He's now in his mid 20's and he looks like he's settling in as a good AAA regular with maybe a callup here and there to provide an extra body on somebody's bench. His ceiling probably looks like his teammate Ty Wigginton, only with a little more power.The Indians also had Bobby Hill and Ty Wigginton in the lineup and they looked just as you'd expect to look. They looked like the AAAA guys they are. Wigginton is the better player of the two, but Hill is a little younger. Still, I have more faith that Wiggy is more likely to see a Major League clubhouse again. Hill looks like he's on the career trajectory that has him out of baseball within 5 years and he isn't that great defensively at either 2B or 3B. Wigginton by comparison is a worse defensive second baseman, but is pretty good at the hot corner. He can be of some use to a team that needs a bench bat and a guy who can be a defensive replacement for their 3B.Graham Koonse looked good at the plate. He smashed a pretty majestic home run over the center field wall. That's a hard thing to do at Victory Field.Nate McLouth didn't do much, but I still like him.This was the first time I saw Ronny Paulino and I liked what I saw. His swing looked quick. He didn't chase any bad pitches. And he smoked what seemed like every pitch he saw that was over the plate. I'll have to watch him again to get a feel for his defense behind the plate. He really didn't have any plays that challenged him. He looked comfortable back there, but I couldn't tell you how well he throws or how fast his reactions are.On the other side was Kenny Baugh. Baugh had more velocity, but he wasn't nearly as sharp. He wasn't wild, but he didn't have command over his pitches, missing up and over the heart of the plate. His breaking stuff just sat there waiting to get hit. I'd like to know whether this was a bad day or if he's tiring towards the end of the season.The entire Toledo team looked listless. They looked apathetic. First among that crowd was Carlos Pena, who looked more like he was waiting for a bus than trying to play baseball. At the plate he looked mediocre. In the field he looked awful, exhibiting little range, bad hands, and a complete [...]
2005-07-12T17:19:40.260-05:00Nate Schierholtz, OF, San Francisco Giants
2005-06-27T08:54:26.613-05:00Sergio Mitre, RHP, Chicago Cubs
2005-06-21T23:47:09.756-05:00Adam Harben, RHP, Minnesota Twins
2005-06-21T23:01:55.063-05:00Fernando Cabrera, RHP, Cleveland Indians
2005-06-19T09:35:17.276-05:00This weekend is the Us Grand Prix here in Indy, and F1 racing is my OTHER great love in sports. Today will be the first time in 4 years that I haven't attended the race. I went to the practice and qualifying sessions yesterday and the day before. So pardon the non-baseball interlude. Here's a brief baseball fan's guide to F1.F1 has a lot of parallels with MLB. Both are among the more capitalistic organizations in sports. There are definitely the haves and the have-nots. Here's an easy guide for what team is what.Ferrari=YankeesThey're the richest teams in their sport, and the glamour team. They've also been dominant over the last decade, but they're both struggling a bit this season. The each have the highest paid athlete in the sport (Michael Schumacher and A-Rod) and an iconic uniform (pinstripes and the NY and Ferrari red with the prancing horse logo). If you like to root for the evil empire, you'll probably love to root for the guys from Maranello. Still, nothing epitomizes the glamour and excess of F1 quite like this team. One place where the comp breaks down is in the decision-making process. Ferrari is organized, disciplined, stable, and extremely competent. There is no George Steinbrenner looming over everybody like the Sword of Damocles.McLaren-Mercedes and Williams-BMW=Giants and DodgersThey are the traditional powers of F1, and also bitter rivals. They are also mega-rich and driven to succeed with big fanbases. Here in Indy, you're likely to see a lot of McLaren gear since Indy is annually dominated by Columbians, who root for their favorite son, Juan Pablo Montoya.Also note their rival German engine suppliers. This has surely upped the stakes of their rivalry over the last few years, but it won't be this way for much longer. BMW and Williams have been bickering at each other and will surely go their separate ways at the end of the season. The hot rumor is that BMW will buy the Sauber-Petronas team and make the engines AND cars. No word yet on who Williams would recruit to build their engines.Renault=TwinsRenault has risen to prominence over the last few years on the strength of their smarts. They've developed a car that has incredible stability and efficiency. And while they're still likely to spend piles and piles of cash, the emphasis is never on their budget but rather their ideas and their ability to develop great designs.Toyota=AngelsToyota just showed up a few years ago and have spent more than anybody besides Ferrari over that period of time. It's starting to pay dividends too. They had been milling around at the back of the pack until this year, and now they're in the fight for poles and race wins. Jarno Trulli won the pole yesterday. Like Arte Moreno, they have deep pockets and a deep desire to win.BAR Honda=PhilliesThey show flashes here and there of being a really, really fast team, but it always seems to fall short. Even last year when they finished 2nd in the constructors championship, they seem to have been overshadowed by Renault and the ever-present Ferrari.One BAR note, I remember a race weekend several years ago where they were blowing engines like they had an unending supply. And it isn't just that they were trashing motors, it's the way in which they were blowing them up, in explosive, smoky glory. It was like they were fogging for insects. I think they ended up going through half a dozen engines in 3 days with 2 cars. Unbelievable. When you're at 19,000 RPM, you don't get a check engine light and a funny smell.Sauber-Petronas=Blue JaysThey're the best of the perennial backmarkers. They run Ferrari engines[...]
2005-06-19T07:34:35.380-05:00Martin Prado, 2B, Atlanta Braves
2005-06-14T17:56:09.466-05:00J.P.Howell, LHP, Kansas City RoyalsDrafted 31st Overall, 2004 Draft, TexasBats L/Throws L22 YO, 6'0", 180 lbsI've been trying to write this report for a week and a half now. Part of the problem I've been having is that I tried to make it not just a prospect report, but also a status report on the Royals franchise. I almost had it completed, but I had some technical problems, some burnout, and the Royals got REALLY ambitious and promoted him to AAA Omaha and THEN to the majors, which I completely didn't see coming.Howell is a part of the hope that I carry around for my favorite team. He's a classic finesse lefty, but one with a lot of upside, courtesy of his sick breaking stuff. He doesn't have a ton of velocity. He maxes out just short of 90 MPH, and works a couple ticks below that on the gun most of the time, but he has uncanny control of both location and speed. And he varies between 2 and 4 seem grips. The two seam has a break inside the zone and the 4 seam has a sinking action. He also has really brutal breaking stuff with a curve that he can control for both location and break. Finally, he has a splitter that drops off the table.Howell elicits a lot of comparisons to Zach Greinke, and for good reason. He's the same kind of pitcher. He does a lot of the same kinds of things. It's reasonable to think that the scouting brass took a look at their most recent success story and tried to emulate it. Howell is one of 3 similar pitchers they took last year. Matt Campbell has lost his command and Bill Buckner is following right in Howell's footsteps. On the other hand, it isn't a completely fair comparison since Howell is actually older than Greinke already. Still, Howell is a breakout star in the minors who is rocketing up to the majors like he's wearing JATO's. Whether you do it through velocity or break, the big thing is to miss bats. Howell misses bats.2005 High Desert: 1.96 ERA, 48 K, 24 BB, 33 H, 2 HR, 46 IP2005 Wichita: 2.50 ERA, 23 K, 5 BB, 12 H, 2 HR, 18 IP2005 Omaha: 5.06 ERA, 2 K, 4 BB, 7 H, 0 HR, 5 IP2004 Idaho Falls: 2.77 ERA, 38 K, 12 BB, 16 H, 1 HR, 26 IPmL Career: 2.46 ERA, 111 K, 45 BB, 68 H, 5 HR, 95 IP He had a stunningly effective ML debut, striking out 8 in 5 innings while allowing only one run for the win. I honestly have no idea how he'll translate at this level for the rest of the season. Pushing a guy this far this fast is always a ticket to unpredictable results. Furthermore, for better or worse, I'm not particularly fond of the strategy. I'd rather see them give Howell at least a half season in Omaha before throwing him to the wolves. Then again, Allard Baird has done a lot of flaky things this season. I like Howell in the long term, but with the rapid ascent and resulting lack of good stats, it's really hard for me to isolate exactly HOW much I like him.ETA: Now, whether I like it or not4 StarsNote: I apologize for the lack of activity around here. As I mentioned before, I've had a touch of burnout that I'm trying to overcome. I won't abandon this blog, but I think that the pace of updates probably won't return to its previous levels until probably the offseason. Doing prospect reports is hard, time-consuming work. Check that, doing INFORMATIVE prospect reports is something that is hard and time-consuming. I strive to make these reports informative, entertaining, and well-written. As I continue to do this, I think I get progressively better at it, as my early stuff was little more than basic, one-paragraph blurbs. I'd also like to expand into more editorial cont[...]
2005-06-06T07:03:43.930-05:00I attended the Indianapolis Indians game yesterday afternoon. The player I wanted to see was pitcher Ian Snell. I also got another look at Nate McLouth and a first looks at Joe Borchard and Brian Anderson. I was hoping to see Brad Eldred, he didn't play, I presume because he was hit by a pitch on saturday.
2005-06-05T10:06:52.590-05:00Chad Orvella, RHP, Tampa Bays Devil Rays
2005-06-03T06:10:30.926-05:00Jose Bautista, 3B, Pittsburgh Pirates
2005-06-09T18:20:34.736-05:00Jason Botts, OF/1B, Texas Rangers


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Registration is now closed
Entry and Awards Applications must be submitted no later than June 15th, 2017.
Ashley for the Arts provides artists and crafters an opportunity to win cash rewards. In order to be eligible to win one of these awards, artists and crafters are required to submit 4 images (by email or regular mail) representing the piece of art or craft that you want to be judged on to Ashley for the Arts (email: firstname.lastname@example.com or mail to: One Ashley Way / Arcadia, WI 54612) by June 15, 2017. No more than 2 pieces can be submitted for review. Images and storage devices will not be returned. Pieces are reviewed and judged by a panel of professionals. Awards are based on originality, execution of design, technique and craftsmanship, creative use of materials, aesthetic qualities, and diversity of media.
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Booth Fee: $50* (Artists and crafters must provide their own 10′ x 10′ tent)
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subset: commoncrawl


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Average Rating: 5/5 stars (18 reviews)
100% would recommend it to a friend.
I can't believe they came out with these. I noticed them in the US magazines but had never seen them in Canada, but finally we have them. I will say though you do have to watch. Do not cheap out on them and buy the ol' dollar store one. I was doing that and it was actually cutting my paper. I now buy a good one and it is so worth it. At the same time I grab a couple refills and I am good to go for awhile. I find I try not to use them on easy quick little jobs I will use my squares or maybe the dots in a box, but if I go scrapping somewhere I will take that or if I am scrapping on the road I will take 1 or 2 of these. This definately is a must have in my books. Saves, time and money and fighting with the dots and squares that get stuck together!!! Good luck on whatever you decide.
I've been buying Glue Dots in the box for years. I seen this dispenser type at the store a couple weeks ago. At first I didn't want to buy it it because it's a little more expensive than the Glue Dots in the box. I also wasn't sure about buying it because I didn't like the fact that the dispenser was not refillable. I'm trying to cut down on throwing trash in the landfill. Well, this unit was on sale so I bought one. I used it to apply Glue Dots to some little sequin jewels. It was so much more easy than the kind in the box that you have to peel off by hand and then try to place on the craft item.
I would totally recommend these to any paper crafter.
Great new way to use glue dots. You have to be careful when applying to make sure you get the dot exactly where you want it when you are working with a small area. The best way is to manually advance the tape so that the dot is at the very tip. Then press it down and you have it in the perfect spot. Very easy to apply and great for taking to a crop or class. Glue dots have done it again!
Zots stink. Glue Dots Dot N Go rollers are GREAT! They're easy to place and lasts a long time. These are my go-to adhesives for heavy embellishments or just anything that doesn't require insurance to stay put. The only bad thing about these is that they are not refillable.
I can't live without glue dots. These little guys are perfect for everything: ribbon, buttons, skittles, bling, etc. They are easy to use & have such a strong bond. Be sure & have a couple on hand, one for you scraproom & one for you crop bag.
I have yet to use this dispenser personally but I was watching a craftsy class and the instructor had one and I knew I had to have one! It was a great price and easy to locate on scrapbook.com! Scary to be so excited by a mini glue dot dispenser!
I was making honeycomb Christmas ornament & they were coming apart after just a short time. I tried glue dots, glue, it was way too tedious holding till the glue dried, hot glue, worked, but is lumpy, the I saw these dots & they do hold!!
I recently picked up one of the mini glue dot dispensers at Michael's after friends here at Scrapbook.com recommended these. They're perfect for scrapbook adhesive needs. the dispenser couldn't work better, I love using it!
I love, Love, Love, these glue dots dispensers! This is one of four that i own! They work perfect on my projects and they don't get stuck in the dispenser unit like the other ones I've had! Happy Scraping!
Finally a dispenser for Glue Dots! Now you can put them where you want them -- not on stuck on your fingers or other tools. This product is a must-have for scrapbookers! Thank you Glue Dots!
I've always loved glue dots, but I'm really going to like using the dispenser. No more paper all over the place, or little plastic squares to deal with.
This new dispenser is great! Makes paper crafting a breeze. Why didn't they think of this sooner?
LOVE this product.
So easy to apply the dot right where it is needed with no fuss or muss.
Best @#$%* little product there ever was!!! These little dots are amazing
I use this adhesive for accents, flowers, etc. It works well for me.
great product, works just like the sheets
So easy to use!!!!!
Ever fought with a roll of glue dots? It is so aggravating when they stick where you don't want them to - the table, your arm, etc. This dispenser is a life saver! It makes it so much easier to apply the glue dot whereever you want it. I only wish that it was refillable. The convenience is worth the extra cost in my book though!
Used in this layout: "Y" Yo Ho Yo Ho A Pirate's Life For Me


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North Dakota - Casselton
Sales Tax Calculator of Casselton for 2017
Calculation of the general sales taxes of the city Casselton, North Dakota for 2017
How 2017 Sales taxes are calculated in Casselton
The Casselton, North Dakota, general sales tax rate is 5%. The sales tax rate is always 7.5%
Every 2017 combined rates mentioned above are the results of North Dakota state rate (5%), the county rate (0.5%), the North Dakota cities rate (2%). There is no special rate for Casselton.
The Casselton's tax rate may change depending of the type of purchase.
Please refer to the North Dakota website for more sales taxes information.
Casselton city rate(s)
7.5% is the smallest possible tax rate (58012, Casselton, North Dakota)
The average combined rate of every zip code in Casselton, North Dakota is 7.5%
Other 2017 sales tax fact for CasseltonThere is 1 out of 1 zip code in Casselton that are beeing charged city sales tax for a ratio of 100%.
Last sales taxes rates update
The last rates update has been made on October 2017.


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Mercury Computer Systems, Inc. (NASDAQ: MRCY), a leading provider of specialized, high-performance computing solutions for complex applications, unveiled its smallest embedded system at an exclusive event in conjunction with the Critical Embedded Systems (CES) MediaFest 2008, which commences at the Hilton Scottsdale Resort and Villas in Scottsdale, AZ.
The PowerBlock(tm) 50 system from Mercury Computer Systems is a high-performance, ultra-compact embedded computer designed for maximum performance in a minimal footprint, for small platforms in the 6- to 10-pound range. Optimized for real-time image, sensor, and signal processing and ruggedized for harsh environments, it is fully integrated and programmable, with state-of-the-art liquid cooling. The PowerBlock 50 extends Mercury's robust offering of computing solutions available in very small to large form factors to suit a broad range of customer applications.
The system's modular architecture allows for flexible configurations of multiple processors, delivering well over 100 GFLOPS of processing power in a small, lightweight package. A fully configured PowerBlock 50 weighs less than 10 pounds, measuring approximately 4″ x 5″ x 6″ – and can be held comfortably in one hand.
"The PowerBlock 50 was specifically designed to help our customer base pursue 6- to 10-pound payloads, and revolutionizes the ability to perform extreme computing in space- and weight-constrained applications," said Brian Hoerl, Vice President of Sales for Advanced Computing Solutions at Mercury Computer Systems. "With groundbreaking processing density and a flexible development environment, the PowerBlock 50 extends Mercury's strategy of enabling new levels of computing power for systems embedded in small platforms."
The system is available now as the PowerBlock 50 EDK (Engineering Development Kit), which is a complete software development platform. The EDK includes a PowerBlock 50 system, Linux BSP development environment, and a desktop heat rejection unit (HRU) to support the PowerBlock 50′s cooling requirements. As the first in a series of small form factor platforms, the PowerBlock 50 EDK is designed for desktop use in a laboratory or software development environment, for development and optimization of runtime software deployable on PowerBlock 50 systems.
The PowerBlock 50 EDK is customizable into configurations that include PowerQUICC(tm), Virtex(tm)-4, and Intel processors, and SATA storage. Each configuration includes Gigabit Ethernet and RS-232 I/O interfaces.
The PowerBlock 50 EDK is available today. For more information, visit Mercury at CES May 5-6 at the Hilton Scottsdale Resort and Villas in Scottsdale, AZ; contact Mercury at (866) 627-6951.


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Add the Munchkin 5.5 in. extension to your Munchkin Auto-Close Metal gate and Munchkin Easy-Close Metal Gate to accommodate wider openings. This 2.75 in. wide and 29.5 in. tall extension is constructed of steel for lasting durability and strength. The extension easily attaches to your gate without the use of tools.
- Extensions can be combined to span a variety of openings sizes up to 54 in. wide
- No tools required
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- Easy extension installation video available at www.infantgates.com


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Contact Martin Collins
03/05/2016 10:03:02
"I chose Ecotrack for my indoor school because it really works. It is hard wearing, and excellent for the horses for both jumping and Dressage"
Read More
22/01/2016 13:41:14
"I'm very impressed with the new Martin Collins surfaces at Jackdaws. They give a lovely feel and the horses really stretch out to give the best of themselves."
The Martin Collins Ecotrack arena surface installed at Olympia's 2015 London International Horse Show received praise from riders and commentators alike.
21/01/2016 13:54:00
"Martin Collins have done a great job with the new surfaces at Jackdaws, they allow me to work the horses precisely as I like to , regardless of the weather and to get the best out of every one from start to finish."
03/05/2016 10:10:21
The Charles family were full of praise for the new Martin Collins arena surface at the Wales & West showground in April 2016
21/01/2016 13:51:00
"Jonjo has built his career around doing everything possible to get the horses at Jackdaws to relax and develop to the best of their ability. It's no surprise to see the new Martin Collins surfaces. They will help them do the very best for their owners."
Sarah Hosmer discusses the new racing surface from Martin Collins talking to Jonjo and Edward Gillespie OBE who acts as consultant to Jackdaws.
Registered Ecotrack Logo for EU


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We invite you to join our efforts to enrich community life through music. You can be linked with our vibrant tradition and exciting future by:
We are a Section 501(c)(3) charitable fine arts organization. We offer both general-donation and designated-sponsorship giving opportunities. Contact us for more information.
Because we keep our ticket prices low, we reply on monetary donations to cover half of the cost of producing concerts. You can give in a number of ways:
General donations
Gifts of any amount are deeply appreciated and used where most needed. We recognize donors in our concert programs, at eight levels of giving:
|Virtuoso $5,000 +
|Benefactor $500 +
|Sponsor $50 +
|Guardian $2,500 +
|Patron $250 +
|Supporter $25 +
Angel $1,000 +
Sustainer $100 +
Sponsors of concerts, artists and masterpieces are widely recognized in print and digital promotions for our concerts, and in our concert programs.
Sponsor a concert. One sponsorship is available for each concert: $4000 per concert.
Sponsor an artist. These sponsorships are available:
Sponsor a masterpiece. These sponsorships are available:
Program advertising sponsorships
We offer opportunities to support the production of our printed concert programs, with recognition in an ad that appears in those programs. See this form for details or contact us with any questions.


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The players exchanged a break of serve in the opening set, but it was 19-year-old Zverev who gained the upper hand in the tie-break.
By forcing Zverev to hit several forehand errors, Gasquet managed to get the service break back later in the set for 2-all.
Grigor Dimitrov won his second title of the season by beating David Goffin 7-5 6-4 in the final of the Sofia Open in Bulgaria. Zverev would later team up with brother Mischa to win the doubles title, becoming the first player since Lleyton Hewitt in 2014 to win the singles and doubles at the same event.
How Facebook Is Stepping Up Its Efforts to Thwart Discriminatory Advertising
Additionally, it is testing an automated system that uses machine learning technology to identify potentially controversial ads. Facebook has announced that it has taken significant steps towards prohibiting discriminatory advertising in its site.
Alexander Zverev won his second career ATP Tour title with a 7-6 (4), 6-3 win over three-time defending champion Richard Gasquet in the finals of the Open Sud de France.
Gasquet faced two break points while serving down 3-4.
"It was a hard match", said Gasquet. "It was close during the first set".
Jones begins mind games, opts for open roof in Wales
England survived another scare when scrum-half Rhys dived over a ruck and fell inches short of a try. It's a fair judgement to compare them to the All Blacks right now - that's how good they are.
The third-seeded Gasquet needed two hours, 16 minutes to finish off De Schepper and move closer to his bid for a third straight tournament title.
Defeat ended world number 22 Gasquet's 10-match winning streak in Montpellier.
"I'm very happy to win my first title of the year", said Zverev. "The recipe for my success here will be revealed when I retire [laughing], but for sure I'll come back here next year".
George Clooney's mum gushes about his new babies
The notoriously private couple kept tight-lipped about pregnancy rumors when they first arose last month. Oscar-winning George Clooney is one of Hollywood's top A-list actors and box office draws.
Krajicek said the presence of highly-rated German teenager Zverev and Bulgarian Dimitrov was a stroke of fortune.


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Q&A: 'Divergent' Music Supervisor, Randall Poster Talks About The Influence of 'Yeezus' & Ellie Goulding On Film's SoundtrackPoster talked to Radio.com about how he recreated the 'Divergent' team's musical vision of a dystopian future.
Listen to M83's New Song 'I Need You' Off the 'Divergent' SoundtrackM83's new song "I Need You" off the Divergent soundtrack is a cross between Bon Iver and Kenny G. And if that description doesn't strike your fancy, we're not sure what will.
Paramore Hopes fun. Sweep The GRAMMYs
Watch: Skrillex Teaches Richard Branson How To DJEverybody wants to be a DJ, even celebrity billionaires like Richard Branson. Watch as EDM superstar Skrillex shows him the ropes of rocking the ones and twos.
Bill Clinton Plays M83's "Midnight City:" Surfer Stephen's Viral Video Of The Day
Top 10 Reasons Katy Perry And Russell Brand Should Not Get Back Together
Coachella in Pictures
Thursday 30: Digidal Gets Your Coachella Weekend Started With Today's Mix!
Midnight Lights - Super Bowl Dubstep: Surfer Stephen's Viral Video Of The Day
Jay-Z, Adele, & M83 Wait For Their Moment On The Daly Download!
Top Hip-Hop, Dance, & Pop Artists Playing At Coachella
New Music From Rihanna, Flo Rida, Big Sean, & M83 On AMP Radio!


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My Nonprofit Reviews
Review for Sojourner Center, Phoenix, AZ, USA
Acceptance, understanding and empowerment are the three best adjectives I can use to describe what I feel when I walk through the gates at any of Sojourner Center's campuses. I have been a Vanguard (volunteer) at SC going on four years and have seen many transformations, including my own. I appreciate the level of commitment that is consistent throughout the staff, participants and Vanguards. Everyone from the director to the woman who just walked through the gates for the first time are all on a level playing field and I see this as a key element to Sojourner Center's success as an organization. Another key element Sojourner Center embraces is that they offer constant opportunities for choice as part of their empowerment model. Whatever a woman may choose as a path for for herself and her children, she is never judged. I am proud to support Sojourner Center and play an active role in overcoming the impact of domestic violence, one life at a time throughout our community.
More Feedback
I've personally experienced the results of this organization in...
I found myself in an abusive marriage shortly after I became a Vanguard, and successfully ended the relationship with him and got my life back on track utilizing tools and support that SC offered.
If I had to make changes to this organization, I would...
I don't believe that i would change anything. Sojourner Center does need more funding, however, to be able to continue working as a well oiled machine and offer the services that the survivors of domestic violence in our community need.
Would you volunteer for this group again?
For the time you spent, how much of an impact did you feel your work or activity had?
A lot
Did the organization use your time wisely?
Very Well
Would you recommend this group to a friend?
Did your volunteer experience have an effect on you? (teaching you a new skill, or introducing new friends, etc.)
i learn something new about myself and about the organization every time I step foot on campus - it never ceases to amaze me!
How did this volunteer experience make you feel?
It made me feel strong and confident. I felt like i was feeding my soul. Upon leaving I felt compelled to do more for the families utilizing SC's services as well as introducing others to SC's services.
When was your last experience with this nonprofit?


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| Approved Homepage | owned by ~rugk
This add-on integrates the secure instant-messaging app Threema into the forum software XenForo. Using the Threema Gateway it offers three new two-step authentication (also called two-factor authentication) modes for users and admins.
📝 Source code
🔵 XenForo
🔽 Download
Three 2FA modes offer you and your users a flexible and secure 🔐 way for easily securing their account.
Multiple settings allow server admins to configure and/or restrict any aspect of the add-on and one can always extend this add-on to do other things with the Threema Gateway.
The add-on is built with security, flexibility and user choice in mind and is straightforward to use.
It is aimed at all XenForo admins, who want to increase the security of their forum by allowing users to secure their login with a solid, well-tested, famous crypto-messenger app as an alternative to the existing 2FA options in XenForo. When you enable all the three completely new Threema 2FA modes, users have a diverse choice and can do anything from not enabling a single mode to enabling all of them.
So let's allow users to keep their accounts under their control and make the world a little safer!


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…reminded of the crimes, which the Jews have committed for centuries on men… ritual murder. … History points out hundreds of cases, in which non-Jewish children were tortured to death. They were also given the same incision through the throat, as is found on slaughtered animals….
germanvictims: the purpose of the slow, torturous death is to create adrenalin from the stress and terror in the blood which the Jews believe enhances the blood and the Jews drink that or put into Matzo balls for strength. ~gv
Julius Streicher in American captivity. His last words before his hanging:
"Purim Fest 1946!"
By Dr. Harrell Rhome
This article is a chapter in my unpublished 2012 manuscript entitled Opening The Memory Hole, Reviewing Some Ignored But Important Historical Events And Personalities. To find out more about this book, email me at email@example.com.
This chapter, re-edited, is from Blood Ritual, An Investigative Report Examining A Certain Series Of Cultic Murder Cases by Harrell Rhome, writing as Philip de Vier, National Vanguard Books, 2001. What follows is excerpted from a timeline of publications and key events related to ritual murder crimes. To order a hardcopy or eBook edition, email as per above.
Streicher is shown in his Nuremburg cell.
Publisher Acquitted of Criminal Libel Charges.
Julius Streicher of Der Sturmer newspaper, was acquitted of libel in a noted court case. Streicher even managed to read sections of The Talmud into the court records that, among other things, revealed the verses permitting the cheating and even deaths of the goyim, the court also ruling that his quotations were essentially accurate.
Der Sturmer newspaper, Special Edition of May 1934.
Julius Streicher, an early member of the National Socialist Party, was the editor and publisher. Dubbed "the Jew Baiter of Nuremberg" for his radical opposition to the Jews, he was certainly a colorful and notorious figure of the politically volatile twenties and thirties. For his early work with the party, he was named Gauleiter (district governor) over the Nuremberg area. He proved to be, however, too corrupt in his business practices, and was removed from his post early in the war. Nonetheless, with great perseverance and persistence, he published Der Sturmer until the end of the war and his capture by the Allies. The Special Edition of May 1934 was a hot seller, soon going into several reprints. But it was too hot for some circles, especially the Church (both Catholic and Protestant) as Streicher said some defamatory and uncomplimentary things about Holy Communion and its sacrificial origins. These passages do not appear in the only known English translation.
This issue also contained illustrations that his critics called obscene. In truth, the offending material was straight out of old court records and books. The pictures were of old paintings and woodcuts depicting ritual murders. This was not the only issue that featured stories about Jewish ritual murder. Such a story appeared every few issues, but the 1934 Special Edition packed many accusations into one big issue. The howls of the Jews and their supporters spread over the world, accompanied by requests to the German government to suppress any further distribution of the issue. It is of interest to the serious researcher as it compiles and condenses material from many famous cases such as that of St. Simon of Trent (1475). Without commenting on or endorsing Julius Streicher's political views, we can certainly benefit from a study of the material he published in that famed May 1934 issue. Translated into English, it still circulates.
DER STURMER, No. 28, Vol. 16, p. 5. Issue of July 1938. The May 1934 issue was not the only time Julius Streicher featured prominent ritual murder stories in his newspaper, which appeared on a rather regular basis.
Ritual Murder_Blood Pass Over Best Translation_Ariel Toaff-pdf
Some of the more lurid and allegedly libelous issues were translated into English for Streicher's trial at Nuremberg. In some instances, these appear to be the only English translations ever made of this material. In the following passage, the paper drew a parallel between kosher animal slaughters (regarded as cruelty to animals) and the ritual slaughter of humans.
"The ritual murder Jews slaughter (schaechten) men. Whoever had the occasion to be an eyewitness during the slaughtering of animals or to see at least a truthful film on the slaughtering, will never forget this horrible experience — it is atrocious. And unwillingly, he is reminded of the crimes, which the Jews have committed for centuries on men. He will be reminded of the ritual murder. … History points out hundreds of cases, in which non-Jewish children were tortured to death. They were also given the same incision through the throat, as is found on slaughtered animals. They also were slowly bled to death while fully conscious." From the Records of the International Military Tribunal (I.M.T.), partial translation of the document designated as 2700-PS.
This forensic speculation is evidently quite dangerous and deadly. For such "genocidal" acts, the publisher was tortured and hanged in 1946 during the Nuremberg atrocities.
Nuremberg, Germany.
The trial, torture and execution of Julius Streicher, who was a newspaper journalist, cartoonist and publisher.
In 1946, the International War Crimes Tribunal heard the cases against the major National Socialist figures, a group that included Streicher. Let's be straight about this. The Jews universally revile him as a modern-day Haman, right out of the Book of Esther. As investigators, we decided to do a little more background checking into this infamous and supposedly vile figure. Briefly, here is what we found. Contrary to popular belief, perhaps because of his party uniform worn in most photographs, he was never a soldier, policeman or any type of armed combatant. Before he became a full-time publisher and NSDAP organizer, he was a schoolteacher. Although proud and aggressive, he never seriously hurt anyone. Moreover, Streicher never commanded or guarded a concentration camp. He was a financially corrupt official in an era that somewhat tolerated and encouraged it. For his practices he was deposed from his post of Gauleiter of Franconia. After this he was totally out of the loop as far as having any role in government decisions or personal influence on his leader. He was unarguably arrogant, boastful, and overbearing as well as being hateful and spiteful in his writings. These, however, are not capital crimes in a civilized nation. Or were they? As we see, the controversial author and publisher spoke plainly.
"[We] relentlessly fight the shady mixing of religion and Jewish party politics, and fight to keep religion pure, as did the Lord when he threw the hagglers and usurers out of the Temple." Kulturkampf!, Flugblatt, 10 March 1924, Munich.
During the Nuremberg trials, he was asked about his role in the Nuremberg Race laws of 1935.
"Yes, I believe I had a part in it insofar as for years I have written that any further mixture of German blood with Jewish blood must be avoided. I have written such articles again and again; and in my articles I have repeatedly emphasized the fact that the Jews should serve as an example to every race, for they created the racial law for themselves — the law of Moses, which says, "If you come into a foreign land you shall not take unto yourself foreign women." And that, Gentlemen, is of tremendous importance in judging the Nuremberg Laws. These laws of the Jews were taken as a model for these laws. When after centuries, the Jewish lawgiver Ezra demonstrated that notwithstanding many Jews had married non-Jewish women, these marriages were dissolved. That was the beginning of Jewry which, because it introduced these racial laws, has survived throughout the centuries, while all other races and civilizations have perished." Trial, International Military Tribunal, Nuremberg, 1945, Vol. 12.
Julius Streicher's real "crime" might be described as a crime of persistence. He doggedly, determinedly and stubbornly published Der Sturmer until the bitter end. The main goal of the newspaper was complete and unequivocal opposition to what he, and many others, saw as a menacing international conspiracy. This is what convicted him at the Nuremberg international court of Jewish revenge. For this work against the Jews he was hanged at Nuremberg in 1946. Reportedly, the depleted and weakened Streicher, already repeatedly beaten and tortured, raised his voice and said "Purim Fest 1946!" just as his executioners released the trapdoor.
Records of the International Military Tribunal at Nuremberg show that Julius Streicher, although barred from introducing any testimony as to the truthfulness of his ritual murder allegations, was able to declare that he was not the actual author of the infamous Ritualmord edition! When asked who was the author, he replied: "My collaborator, the Editor-in-Chief at the time, Karl Holz, who is now dead. But I assume the responsibility." IMT Records, 29 April 1946, Vol. 12, p. 336.
Apparently one of the main arguments against the ritual murder issue was not its truth or falsity, but its bad taste and anti-Semitism. It is, as we know, "anti-Semitic" to say anything remotely critical of the Hebrew people or their history. But, is it deserving of torture and death? Regardless of your feelings about the Second World War, a close look will reveal that the Nuremberg trials were anything but fair. Most Americans would be appalled at the almost total lack of judicial due process. Streicher was repeatedly refused permission to introduce any evidence about the truth of his ritual murder allegations. His court-appointed Jewish attorney also refused him permission to testify. Truth was not important. Streicher must suffer as an example of what happens to a Haman in any age. The following excerpt from Streicher's testimony not only illustrates the shocking lack of fairness, but also shows how the defendant cunningly got some statements in the record.
[Dr. Marx, the court-appointed attorney speaks.] "The Prosecution accuses you, in connection with this ritual murder affair, of having treated the matter without documentary proof, by referring to a story from the Middle Ages. What, in brief, was your source? [Streicher replies.] The sources were given in that issue. Nothing was written without the sources being given at the same time. There was a reference to a book written in Greek by a former Rabbi who had been converted to Christianity. [Teofito] There was a reference made to a publication of a high clergyman in Milan, a book which has appeared in Germany for the last 50 years. Not even under the democratic government did the Jews raise objections to that book. That ritual murder issue refers to court files which are located in Rome, it refers to files which are in court. There are pictures in it which show that in 23 cases the Church itself has dealt with the question. The Church has canonized 23 non-Jews killed by ritual murder. Pictures of sculptures, that is, of stone monuments were shown as illustrations; everywhere the source was pointed out; even a case in England was mentioned, and one in Kiev, Russia. But in this connection I should like to say, as I said to a Jewish author here, that we never wanted to assert that all Jewry was ready now to commit ritual murders.
But it is a fact that within Jewry there is a sect which engaged in these murders, and has done so up until the present. I have asked my counsel to submit to the Court a file from Pisek in Czechoslovakia, very recent proceedings. A court of appeal has confirmed a case of ritual murder. Thus in conclusion I must say…." [Justice Jackson interjects.] "I object to this statement, your Honor. After his counsel has refused to submit it, he insists on stating here the contents of a court record. Now this is not an orderly way to make charges against the Jewish people. [We have never seen an "orderly" method described!] Streicher says he is asking counsel to submit. His counsel apparently has refused; whereupon he starts to give evidence of what he knows, in any case, is a résumé of the matters which his counsel has declined to submit here. It seems to me that, having appointed counsel to conduct his case, he has shown repeatedly that he is not willing to conduct his case in an orderly manner and he ought to be returned to his cell [What a good democratic example!] and any further statements he wishes to make to this court be transmitted through his counsel in writing. This is entirely unfair and in contempt of court." [The Presiding Judge speaks.] "Dr. Marx, I think you had better continue." [Dr. Marks.] "I should like to say that that closes this affair. The essential thing is whether one can say that he treated the case with documentary truth." From records of the Intl. Military Tribunal, I.M.T. Documents of 29 April 1946, Vol. 12, p. 337.
The story of Julius Streicher and his newspaper show the incredible power this remarkable accusation of human sacrifice holds over the Jews. No holds were barred when it came to stanching the flow from this bloody wound. In Streicher's case, it cost him his life. The accusations from the various Der Sturmer issues doubtless still shock and polarize readers. A reading of the court records clearly reflects that his publishing of the infamous Der Sturmer ritualmord issues, rather than alleged war crimes, was the real reason for his indictment. His execution was an act of punishment and revenge, a judicial Jewish ritual murder in the true Talmudic tradition of torture and terrorism. The botched and gruesome hangings of Saddam Hussein and later butchery of Muammar Gaddafi reflect the same perverted psychopathic paradigm.
©2012 Harrell Rhome d.b.a. Eagle Publishing Company All Rights Reserved.
Streicher's Cartoons – For his Cartoons he was condemmned to death at the Nuremberg court, claiming he incited the Germans to "kill Millions of Jew."


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Before we dive right into this countdown of the absolute worst things you could ever eat on public transport, let's take a minute to appreciate that 'nothing' is a perfectly reasonable answer.
FYI, We have done zero research to back up our thoughts and you're likely to disagree with most of what we're about to say.
People who realise that hot food in confined, busy spaces is just as bad as microwaving fish pie in the office will understand the struggle is real. As delicious as your chicken katsu curry pot might be, realise that everybody is looking down and nuzzling their scarves for the faint whiff of perfume or aftershave, as well as silently judging you.
Often, the windows are totally sealed, the air con almost never works and you get serious side eye for even turning the pages of your newspaper too loudly. Of course, nobody ever says anything. Welcome to Great Britain, the place where we bottle up our aggression during awkward social situations, encouraging the veins in our foreheads to pop, but at least we'll be ready to vent our frustrations to an unsuspecting friend later… over a nice cup of tea.
For us, hot meals and foods loaded with pungent aromas are by far the worst culprits, closely followed by anything loaded with garlic, onions, ketchup or fish.
Having said this, it's not only smells that cause passive aggressive feelings among passengers on buses and trains. Yep, we're talking about sounds. The audible 'crunch' of an apple, the 'slurp' of a juicy peach or the 'rustle' of a pesky bag or packet is enough to send some people 'round the bend.
Okay, let's compromise. Opening up a cheese sandwich or a cereal bar isn't doing anybody any harm, provided you follow the following public transport food rules…
- Always pick up your rubbish or put it in the bin provided.
- Don't chew, chop or crunch unnecessarily loudly.
- Don't eat in a way that might cause you to transfer crumbs onto the person beside you.
- Use an antibacterial hand gel to clean your hands after you've eaten. Touching poles and handles with food on your hands isn't doing anybody any favours.
- Realise that both the bacon butty and Egg McMuffin may both be breakfast items but they REALLY aren't the same as a granola bar.
Are you ready for this countdown? Tell us what you think in the comments.
10. Burgers from fast food places
The pungent whiff of reformed meat, sour ketchup and processed cheese is a throat-itching combo that fills buses and train carriages is the WORST. Everybody knows that anything that requires two hands to eat is not suitable for public transport.
You smell it before you even hear it. It's the feint rustling of a brown paper bag, tearing off the burger wrapper with reckless abandonment and a slobbery, carefree chew. Please don't be that person.
9. Any flavour of Monster Munch
The lingering whiff of flamin' hot, pickled onion and roast beef doesn't sit well with us. P.S. Don't put them on your fingers and nibble off each individual toe one by one. It's not cute.


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Subscribe to this topic via RSS or ATOM Topic - Jetstar Airways
Jetstar Airways is an Australian low-cost airline headquartered in Melbourne, Australia. It is a subsidiary of Qantas, created in response to the threat posed by low-cost airline Virgin Blue (now known as Virgin Australia). The airline operates an extensive domestic network as well as regional and international services from its main base at Melbourne Airport, using a mixed fleet of narrow- and wide-body aircraft. Parent company Qantas also has stakes in sister companies Jetstar Asia Airways and Valuair in Singapore (via its stake in Orange Star); and Jetstar Pacific Airlines in Vietnam. - Source: Wikipedia


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Similar to:
- Labor Brings Success
- Value of Labor
- Labor and Its Importance
Introduction: Man is destined to earn his living by the sweat of his brow so labour is a sacred charge and there is a great dignity in it. Nothing can be achieved in the world without labour. We cannot get the bare necessities of life if we do not undergo labour. We cannot fulfill a high ambition without labour and perseverance. The value of labour was felt in the past, is felt at present and will be felt in future. Work has been said to be a part of worship and has been given the highest place in human life. In fact labour is life and life is labour.
Importance of labour: Labour is essential for life. Absence of labour means starvation and death. For the very existence on earth man has to undergo hard labour. For greater progress and more comfort he has to labour more and more. It is human labour which has set up beautiful cities in places where there were dense forests. By his labour man has made deserts fertile and fruitful. By his labour man bas discovered the forces of Nature and employed them to his own service. So labour is the most important force behind all progress.
Usefulness of labour: Labour is really sacred and honorable. Those who do not labour to earn their living have either to steal or to beg. This makes them objects of hatred in the long run. If cultivator refuses to plough land and produce crops sufferings will surely come upon him as well as upon the entire society. It a labourer refuses to work in a mill or factory it will prove fatal both for him and for the sake of others.
Conclusion: The dignity of labour should be fully realized by, all. Labour should by given due respect. We should not feel shy to do any work by ourselves. No labour is mean. We should always remember that there is nobleness and even sacredness in work. So servants, sweepers, shoe makers and similar other people should not be looked down upon by us.


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MOVIE SYNOPSIS [ General Audiences ] Starred by Tyler Mane (see full cast), this film directed by Anthony J. Rickert-Epstein was premiered in TV or cinema in 2013. The feature film "Compound Fracture" was produced in USA. You can watch Compound Fracture online on TV cable or theaters with original audio in English at different dates. This film premiered in theaters in 2013.
Rating: 5 by 468 users./
Runtime: 90 minutes
Tyler Mane, Muse Watson, Derek Mears, Leslie Easterbrook, Renae Geerlings, Alex Saxon, Susan Angelo, Jelly Howie, Daniel Roebuck, Todd Farmer and Aaron Epstein.
Terror, Thriller.
90-minute film (full movie) directed by Anthony J. Rickert-Epstein.
The original audio of Compound Fracture has dialogues in Dolby Digital, it was produced in USA.
It premiered in cinemas or television in 2013.
Screenplay written by Renae Geerlings and Tyler Mane.
Anthony J. Rickert-Epstein.
John Saunders, Robert Ziglar, Anthony J. Rickert-Epstein, Tyler Mane and Renae Geerlings.
This film was produced and / or financed by Mane Entertainment.
Composed by Joel J. Richard.
Peacock Films and Level 33 Entertainment.
Without commercial breaks, the full movie Compound Fracture has a duration of 90 minutes; the official trailer can be watched in streaming on the Internet. You can watch this full movie free in EnglishDolby Digital in movie TV channels, renting the DVD or with VoD services (Video On Demand player, Hulu) and PPV (Pay Per View, Netflix).
See the page of this full movie, Compound Fracture in FULLTV Movies.


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Signature Approved Centre
Accredited Courses
Easy Payment Plans
Make a Payment
- Resources
- Affordable room hire
- Range of information leaflets
- Reading room containing books, journals, magazines, and DVDs on a range of topics relating to the Deaf Community
Useful Links
Electronic Notetaking
Record your meeting, consultation session, lecture, etc. Realtime almost verbatum electronic noteaking is a convenient way to record the content of business meetings, think tanks, planning meetings, and can prove a most useful record of lecture notes, minutes of meetings, etc.
This service may be used in conjunction with sign language interpretation, which facilitates interactive communication during live meetings, lectures, interviews, etc.
Electronic Notetaking may be the preferred communication mode for people who have a hearing loss, but for whom English is a first and preferred language. People who may be hard of hearing, have attended mainstream school and have not learned sign language.
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text: In Year 7, students learn new skills, in Year 8, they develop skills and in Year 9 they independently use and build on these skills to develop and progress in art and design. Students need to visit art galleries and museums and develop their ideas through investigations informed by contextual and other sources, demonstrating analytical and cultural understanding. Students need to write about artists and art movements and see art in its raw state. All the skills and techniques are transferable to KS4 and 5 and allow students to make an educated decision when selecting their GCSE options. Links to the art design industry foster enthusiasm for ADT and encourage career aspiration.


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Human immunodeficiency virus (HIV)-1 has been demonstrated to contribute to the pathogenesis of HIV-associated nephropathy. In renal biopsy studies, podocytes have been reported to be infected by HIV-1. However, the mechanism involved in HIV-1 internalization into podocytes is not clear. In the present study, we evaluated the occurrence of HIV-1 internalization into conditionally immortalized human podocytes and the mechanism involved. Human podocytes rapidly internalized R5 and X4 HIV-1 primary strains via an endocytosis-dependent pathway, without establishing a productive infection. The HIV-1 internalization was dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) receptor mediated. The role of DC-SIGN was confirmed by using specific blocking antibodies and transfection with small interfering (si) RNA/DC-SIGN. Since podocyte HIV-1 trafficking was not altered by pH-modulating agents, it appeared that HIV-1 routing occurred through nonacid vesicular compartments. Interestingly, transfection of podocytes with neither siRNA/caveolin-1 nor siRNA/clathrin heavy chain inhibited podocyte viral accumulation. Thus it appears that clathrin-coated vesicles and caveosomes may not be contributing to HIV-1-associated membrane traffic.
- HIV-1 receptor
- HIV-associated nephropathy
visceral epithelial cells (podocytes) are highly specialized and differentiated cells which support the glomerular capillaries, synthesis of glomerular basement membrane, and regulation of glomerular permselectivity (31). The study of podocytes in culture had been controversial because of its terminally differentiated phenotype. However, this problem was taken care of by the development of a constitutively immortalized human podocyte cell line by transfection with the temperature-sensitive simian virus 40 (SV40)-T gene (50). These cells exhibit a regular, cobblestone-like polygonal phenotype and express podocyte-specific O-acetylated ganglioside, WT-1 protein, nephrin, and CD2AP, providing a suitable phenotype for studying pathways involved in human renal disorders including HIV-associated nephropathy (HIVAN).
Many studies confirmed the central role of podocytes in the pathogenesis of HIVAN (29, 66, 67), which undergo characteristic phenotypic alteration-dysregulated phenotype, re-entry of the cell cycle, and proliferation (2). Podocyte dysfunction appears to be the result of the combination of the direct effect of viral gene product expression (66, 68), the specific host, and genetic factors (26, 28, 30, 44). However, much of our understanding of the effect of HIV-1 on podocytes is related to the rodent models, which allow only the study of the postentry phase of the HIV-1 life cycle; therefore, little is known about the interaction between HIV-1 and human podocytes in general, and the mechanism involved in podocyte HIV-1 entry in particular.
In general, HIV-1 enters susceptible cells by fusion of its envelope with the plasma membrane after binding to the CD4 molecule (11) and interaction with the chemokine coreceptors CCR5 or CXCR4 (54). Nevertheless, HIV-1 entry into CD4-negative human cells has been widely reported (1, 5, 15, 57, 59). In the majority of instances, HIV-1 entry into CD4-negative cells has been reported to occur through the endocytic pathways (35, 38, 62, 63) and at times, resulted in the productive infection (13, 63).
Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is an endocytic receptor, which belongs to the C-type lectin family. This large group of proteins [such as the macrophage mannose receptor (MMR) and DEC-205] are specialized in the recognition of carbohydrate structures present on cellular and viral proteins and are implicated in several biological processes, including cell adhesion and antigen presentation (17, 53). The role of C-type lectins in HIV-1 pathogenesis has been highlighted by studies demonstrating their capability to bind HIV-1 in a CD4-independent manner (10, 23, 41, 58, 65), which may further increase viral transmission to permissive cells (19). DC-SIGN is highly expressed in dendritic cells (56, 60) and was originally cloned for its ability to bind and internalize heavily glycosylated HIV-1 gp120 protein (10). Interestingly, the expression of DC-SIGN has also been demonstrated in other cells, including macrophages (53) and platelets (9).
In the present study, we have shown that human podocytes express the DC-SIGN receptor, which efficiently captures HIV-1. Specific antibody-blocking studies inhibited entry of the virus in podocytes transfected with siRNA/DC-SIGN as well as podocyte transfer of HIV-1 to T cells confirmed the functionality of DC-SIGN in these cells. The interaction between HIV-1 and human podocytes resulted in the activation of podocyte HIV-1 trafficking and degradation. Our results provide insights into the role of the attachment factors on human podocytes involved in HIV-1 internalization that appears to involve the DC-SIGN-dependent endocytic pathway.
Chloroquine (CLQ), ammonium chloride (NH4Cl), bafilomycin A1, and aldrithiol-2 (AT-2) were purchased from Sigma-Aldrich (St. Louis, MO). T-20 (Roche, Indianapolis, IN) was obtained from NIH AIDS Research and Reference Reagent Program, (cat. no. 9845). Clathrin heavy chain (HC) siRNA (h), caveolin-1 siRNA (h), clathrin HC (TD.1) mouse monoclonal antibody, and caveolin-1 (N20) rabbit polyclonal antibody were obtained from Santa Cruz Biotechnology (Santa Cruz CA).
Cells and viruses.
Immortalized human podocytes were developed from primary human podocytes by transfection with the temperature-sensitive SV40-T gene and were characterized by their expression of WT-1 and nephrin (50). Human peripheral blood mononuclear cells (PBMCs) were prepared from peripheral blood mononuclear cells of HIV-1-negative donors as described previously (23). PBMCs were isolated from blood obtained from the New York Blood Bank (unidentified donors). Monocytes were obtained from PBMCs that adhered to plastic plates and cultured for 6 days in medium containing 100 U/ml GM-CSF (Sigma-Aldrich) and 10 ng/ml IL-4 (PeproTech, Rocky Hill, NY) to generate immature dendritic cells (IDCs). Several strains of HIV-1 were used, including R5 HIV-192US660 and X4 HIV-192HT599. Viral inoculums were adjusted according to reverse transcriptase (RT) activity to 20 × 104 cpm/ml. In cocultivation studies, lymphocytes activated with phytohemagglutinin (PHA; 5 μg/ml, Sigma) were added to podocytes in a ratio of 2:1 in a medium supplemented with 20 U/ml of IL-2 (Roche). In blocking studies, cells were pretreated with specific antibodies: anti-DEC-205 (MG38; Serotec, Raleigh, NC); anti-CXCR4 (NIH AIDS Research and Reference Reagent Program, cat. no. 4083), anti-MMR (15-2; Santa Cruz Biotechnology); anti-DC-SIGN (ab13487; Abcam, Cambridge, MA); or a matching isotype control (Serotec) for 30 min before HIV-1 treatment. For inactivation with AT-2, a viral stock solution was treated with 1 mM AT-2 in DMSO or DMSO alone for 1 h at 37°C. Treatment agents were removed by ultrafiltration with a centricon centrifugal filter device with a YM-100 MW membrane (Millipore, Bedford, MA). A control virus preparation was processed in parallel with inactivated samples. Human podocytes were transfected with specific siRNA against DC-SIGN (Invitrogen), clathrin HC (Santa Cruz Biotechnology), caveolin-1 (Santa Cruz Biotechnology), or control siRNA at concentration of 40 nM, using as a transfection reagent Lipofectamine 2000 (Invitrogen). After 6 h of transfection, the cells were grown for another 48 h and then used for Western blot analysis or treatment with HIV-1. 293T cells were transfected with pcDNA3-DC-SIGN-expressing plasmid (NIH AIDS Research and Reference Reagent Program) or control plasmid (Clontech) using FuGENE (Roche) transfection reagent for 3 days.
Detection of HIV-1-specific DNA by PCR.
Before pulsing, viral stocks were treated (1 h at room temperature) with 200 U/ml of RNase-free DNase (Roche). Before preparation of cell lysates, control and HIV-pulsed cells were washed once with PBS, then treated with 0.05% trypsin at 37°C for 10 min to eliminate noninternalized virus, and subsequently washed four times with PBS. Cell lysates were subjected to PCR analysis using HIV-1-specific primers amplifying early transcript LTR RU5, as well as late pol and gag transcripts as described previously (23). Amplified DNA was analyzed by Southern blot hybridization using 32P-labeled probes. Amplification of the β-tubulin gene was used to control the amount of DNA in each sample. Serial dilutions of 8E5/LAI cells, containing one HIV-1 genome per cell, were included in each amplification reaction to standardize the results. In each set, the number of experiments was carried out in duplicate.
HIV-1 p24 Ag detection.
HIV-1 p24 Ag concentrations in the culture supernatants were determined by ELISA (41). In brief, cell-free culture supernatants were lysed with Empigen BB followed by p24 capture by an immobilized anti-p24 Ag polyclonal antibody (D7320; Aalto Bio Reagents, Dublin, Ireland). Bound p24 Ag was then detected using an alkaline phosphatase-conjugated anti-p24 Ag monoclonal antibody (BC 1071-AP; Aalto Bio Reagents) and the AMPAK ELISA amplification system (DAKO, Glostrup, Denmark).
Real-time RT-PCR.
Total RNA was isolated using an RNeasy Kit (Qiagen, Valencia, CA). To eliminate DNA contamination, extracted RNA was subjected to digestion using RNase-free DNase. Reverse transcription was performed with 1 μg of RNA using Moloney murine leukemia virus reverse transcriptase (MMLV-RT; Life Technologies BRL, Carlsbad, CA) in a reaction mix that contained 5 mM MgCl2, 50 mM KCl, 10 mM Tris·HCl, 1 mM dNTP, 2.5 μM random hexamers, and 2.5 U/μl MMLV-RT. Quantitative RT-PCR was carried out in an ABI Prism 7900HT sequence detection system using the primers shown in Table 1. SYBR green was used as the detector and ROX as the passive reference gene. The data were analyzed using the comparative Ct method (ΔCt method). All data were controlled for quantity of RNA input by performing measurements on an endogenous reference gene, GAPDH. In each set, the number of experiments was carried out in duplicate.
Electron microscopy.
Podocytes were pulsed with HIV-1 for 1 h, then washed and fixed with 2% glutaraldehyde, buffered with 0.05 M Na cacodylate (pH 7.3). The cell pellet was postfixed in osmium tetroxide and prepared for electron microscopy (EM) studies by routine procedures.
Western blotting and immunoprecipitation.
Cells were lysed in RIPA buffer (50 mM Tris·HCl, pH 8, 1% Triton X-100, 100 mM NaCl, 1 mM MgCl2). The protein fraction was analyzed on SDS-PAGE, followed by transfer to a nitrocellulose membrane (Bio-Rad, Hercules, CA), and immunoblotted with specific antibodies [anti-DEC-205 (H-250), anti-CXCR4 (C-20; Santa Cruz Biotechnology), and anti-DC-SIGN (ab5716; Abcam)]. Blots were developed with horseradish peroxidase-conjugated appropriate secondary antibody (Santa Cruz Biotechnology) followed by enhanced chemiluminescence (PerkinElmer, Boston, MA). DC-SIGN immunoprecipitation was done with anti-DC-SIGN (120507; Abcam).
Flow cytometric analysis.
Podocytes were washed with PBS and blocked with PBS containing 20% human serum. Afterward, cells were stained with specific antibodies [anti-DEC-205-FITC (MG38; eBiosciences, San Diego, CA); anti-DC-SIGN-FITC (DCN46; BD Pharmingen, San Jose, CA); and anti-CXCR4 (C-20; Santa Cruz Biotechnology) and corresponding isotype antibody (BD Pharmingen)]. After washing, cells were stained with appropriate secondary FITC-conjugated antibody (BD Pharmingen) and then fixed with 4% buffered formalin. Staining was analyzed with FACS Calibur (Becton Dickinson, San Jose, CA) using Cell Quest software.
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay.
Cell viability in the presence of used drug concentrations was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT; Sigma) assay as described previously (39).
Statistical analysis.
Student's t-test was used to calculate P values.
HIV-1 entry into human podocytes.
Human podocytes were exposed to primary strains of HIV-1 with different coreceptor usage, R5 HIV-192US660 and X4 HIV-192HT599. There was no difference in viability of cells treated under control and experimental conditions (data not shown). As shown in Fig. 1A, human podocytes exposed to either R5 or X4 viral strains were positive for the specific HIV-1 strong-stop DNA (LTR RU5), the HIV-1 early reverse transcript. The adequacy of washing was tested on HIV-1-nonpermissive 293T cells, transfected with either control or DC-SIGN plasmid. Both control (mock) and cells expressing control-plasmid were negative for LTR RU5, whereas, 293T cells expressing DC-SIGN were positive for LTR RU5 (Fig. 1B). The time course effect on podocyte HIV-1-LTR RU5 content was studied by incubating human podocytes with the primary HIV-192US660 for variable time periods. HIV-1 strong-stop DNA was detected in podocytes within 30 min, whereas, podocyte viral load peaked at 2 h and decreased by 24 h (Fig. 1C).
Intracellular viral localization by EM studies.
To confirm HIV-1 internalization, EM studies were carried out. Podocytes showed the presence of intracellular viral-like particles in the vacuoles located in close proximity to endoplasmic reticulum (ER) (Fig. 2).
Noninfectious entry of HIV-1 into human podocytes.
Since we did not detect the HIV-1 late reverse transcripts (pol, gag) (Fig. 1C) and because the nascent synthesis of HIV-1 strong-stop DNA has been reported to occur also within a viral particle (64), we wanted to ascertain whether the presence of LTR RU5 was the result of reverse transcription that occurred in the host cell or whether it was a part of the incorporated viral particle. In these studies, HIV-1 was inactivated with AT-2, which eliminates infectivity but preserves conformational and functional integrity of viral surface protein (49). AT-2-treated virions bound comparably to native virions (to target cells) but showed arrest of the progression of viral life cycle. Since there was no difference in strong-stop DNA content between AT-2-HIV-1 vs. native-HIV-1-treated podocytes, it appeared that the proviral DNA was part of the virions (Fig. 3).
Because cell-free HIV-1 transcytosis has been proposed as a potential mechanism for viral crossing to several tissue-specific cells (3, 4, 21, 33), we studied whether the cell-free HIV-1 could cross human podocytes and escape (without the establishment of productive infection). After treatment with HIV-1 (2 h), podocytes were trypsinized, washed, and seeded onto Transwells (0.4-μm membrane separating podocytes from primary human activated PBMCs). During 14 days of cocultivation, no HIV-1 p24 antigen was detected (data not shown). Similarly, the cell-free supernatants harvested at 24 and 48 h (after the cells were exposed to HIV-1 and washed) were not able to establish the productive infection in activated PBMCs (data not shown). These findings indicate that the internalization of captured HIV-1 by human podocytes results in the intracellular hijacking and degradation of viral particles.
Expression of HIV-1 receptors in human podocytes.
The primers used for gene amplification of HIV-1 receptors in CIHPs are described in Table 1. We did not find any detectable levels of gene expression for CD4 and CCR5 receptors (Table 2). Consistent with the published data (25), we found very low CXCR4 gene expression. Moreover, podocytes showed mRNA expression of C-type lectins, including DEC-205 and DC-SIGN, and no expression of MMR. Data on podocytes and PBMCs (RT-PCR) are shown in Fig. 4A. Percentages of human podocytes showing surface expression of different receptors were as follows: DEC-205 (25%), DC-SIGN (3%), and CXCR4 (0%) (Fig. 4B), whereas Western blot analysis showed relatively high expression of DC-SIGN protein, very low expression of DEC-205 protein, and no expression of CXCR4 (Fig. 4C). Because other homologs of DC-SIGN protein, l-SIGN (also called DC-SIGNR) (53), have been reported to be able to bind HIV-1 (48), we also verified its expression by real-time PCR; however, as shown Table 2, we did not detect the expression of l-SIGN transcripts in CIHPs.
DC-SIGN-dependent endocytosis of HIV-1 into human podocytes.
To rule out podocyte HIV-1 entry through fusion (conventional HIV-1 receptors), we evaluated the effect of the T-20, a known HIV-1 fusion inhibitor, on podocyte viral entry. Although T-20 completely inhibited the infection of primary R5 and X4 HIV-1 strains in T cells, it had no effect on the internalization of the same primary R5 and X4 HIV-1 strains in podocytes (data not shown). In addition, pretreatment of podocytes with an anti-CXCR4-specific antibody before HIV-1 exposure did not decrease the HIV-1 strong-stop DNA concentration (Fig. 5A). These findings suggest that podocyte viral entry is not dependent on classic fusion-mediated entry.
To determine the role of endocytosis, we evaluated the effect of hypertonic media (a nonspecific inhibitor of endocytosis) (12, 24) on podocyte HIV-1 entry. As shown in Fig. 6, there was complete inhibition of HIV-1 entry in podocytes in the media containing 0.45 M sucrose. Because C-type lectins are bound to the high-mannose-containing carbohydrates (16), we evaluated the effect of yeast mannan on podocyte HIV-1 entry. As shown in Fig. 6, mannan (5 mg/ml) blocked the internalization of virus by 80%. These findings supported the role of mannose in podocyte HIV-1 entry.
To identify the role of the specific lectin involved in podocyte HIV-1 entry, we carried out blocking studies. Podocytes were pretreated with specific antibodies against DEC-205 and DC-SIGN before incubation with HIV-1. As shown in Fig. 5A, preincubation with an anti-DC-SIGN antibody markedly decreased HIV-1 entry in human podocytes. In contrast, no inhibition of podocyte HIV-1 entry was observed with pretreatment with anti-DEC-205 or a correspondent isotype. The effect of the anti-DC-SIGN antibody was dose dependent (with the saturation of inhibition at a concentration of 10 μg/ml) (Fig. 5B). In addition, transfection with specific siRNA/DC-SIGN significantly inhibited the entry of virus in human podocytes compared with the control siRNA (Fig. 7).
Human podocytes express DEC-205/DCL-1 fusion mRNA transcripts.
Since anti-DEC-205 did not inhibit HIV-1 entry into podocytes, we hypothesized that the podocytes may not be expressing classic (wild-type) DEC-205 receptors. Recently, a novel DEC-205/DCL-1 fusion protein has been demonstrated in a Hodgkin's lymphoma cell line and in human dendritic cells (6, 27). The DEC-205/DCL-1 fusion protein is a splice variant of DEC-205 and a novel C-type lectin, DCL-1, that carries the extracellular domains of DEC-205 and a transmembrane and cytoplasmic domain derived from DCL-1 (Fig. 8B). To detect mRNA for DEC-205 (between CTLD10 and the cytoplasmic domain) and DCL-1 (CTLD and the cytoplasmic domain), we have used specific primers for the cytoplasmic tail (6). The DEC-205/DCL-1 fusion transcripts were detected by combining the DEC-205 forward primer and the DCL-1 reverse primer. A very small amount of the wild-type DEC-205 mRNA transcripts was detected with the primers specific for the cytoplasmic tails of this receptor compared with the wild-type of the DCL-1 receptor and DEC-205/DCL-1 fusion transcripts (Fig. 8A). Upon sequence analysis of the DEC-205/DCL-1 fusion protein and wild-type DCL-1, using primers shown in Fig. 8C, the transcripts were found to correspond to the DEC-205/DCL-1 fusion protein variant (Ref. AY184222) and DCL-1 (Ref. AY314007).
DC-SIGN is a functional receptor for HIV-1 entry into human podocytes.
It has been reported that in dendritic cells, DC-SIGN not only captures HIV-1 but also contributes to cytoplasmic viral sequestration before viral transfer to T cells (18, 32). Moreover, stably DC-SIGN-transfected cells were not only capable of retaining HIV-1 for 3–6 days in culture but were also able to transmit HIV-1 to target cells (T cells) (18, 32). To determinate whether the DC-SIGN receptor expressed in human podocytes is a functional receptor for viral sequestration and/or viral transmission to the target cells, we cocultivated HIV-1-pulsed podocytes with activated PBMCs. HIV-1 could establish productive infection in lymphocytes for up to 6 days (Fig. 9), indicating that DC-SIGN expressed on human podocytes has the potential for viral sequestration. Since we could detect the HIV-1 strong-stop DNA (by PCR) only up to 72 h, it appeared that DC-SIGN could sequester only a minimal (undetectable) number of infectious viral particles in podocytes for a longer time.
HIV-1 trafficking in human podocytes.
To gain insight into viral traffic, we evaluated the effect of vesicular pH-modulating agents on podocyte HIV-1 strong-stop DNA content. Cells were pretreated with CLQ and NH4Cl, the agents known to block vesicle acidification as well as the endo-lysosomal degradation system. CLQ and NH4Cl did not alter podocyte HIV-1 accumulation (Fig. 10A). To confirm this further, cells were pretreated with bafilomycin A followed by evaluation for podocyte viral accumulation. As shown in Fig. 10B, bafilomycin A did not modulate podocyte viral accumulation. These findings indicate that podocyte viral trafficking might have occurred through pH-neutral vesicles.
Since clathrin-coated vesicles and caveosomes also contribute to the endocytic pathway (34, 47), we studied the role of clathrin-coated vesicles and caveosomes on HIV-1 membrane traffic in podocytes. Podocytes were transfected with the specific siRNA/clathrin HC or siRNA/caveolin-1 or control siRNA, followed by viral entry protocol. As shown in Fig. 11A, cells transfected with siRNA/caveolin-1 showed diminished expression of caveolin compared with cells transfected with control siRNA and cells transfected with siRNA/clathrin HC. Similarly, cells transfected with siRNA/clathrin HC displayed diminished expression of clathrin compared with control and cells transfected with siRNA/caveolin-1 (Fig. 11B). Cells transfected with either siRNA/caveolin-1 or siRNA/clathrin HC did not modulate viral accumulation in podocytes (Fig. 11C).
Human podocytes rapidly internalized R5 and X4 HIV-1 primary strains via an endocytosis-dependent pathway. Human podocytes expressed DC-SIGN receptors, which mediated capture of R5 and X4 HIV-1 primary strains. Since the internalized virus did not undergo reverse transcription and the amount of viral components decreased with time, it appears that HIV-1 particles in human podocytes are directed for degradation. Interestingly, a small fraction of the captured replication-competent viral particles survived inside the podocytes and could establish viral replication after transmission to target cells. These results are consistent with previously published studies showing that DC-SIGN not only captured and internalized HIV-1 particles but also enhanced trans-infection to T cells (18, 32).
We have previously reported that DEC-205 mediated HIV-1 entry in renal tubular cells (23, 39). Interestingly, podocytes also expressed DEC-205 receptors. Therefore, we expected a potential role of DEC-205 in podocyte HIV-1 entry. However, the blocking study with the specific anti-DEC-205 antibody did not support this notion. In addition, pH-modulating agents (contrary to renal tubular cells) did not show any effect on virus trafficking in podocytes. These findings indicated that pH-dependent endocytic compartments involved in renal tubular cell HIV-1 trafficking are not involved in podocyte HIV-1 trafficking. Further investigation revealed podocyte-expressed DEC-205/DCL-1 fusion protein instead of wild-type DEC-205 receptors. This hybrid protein carries the outer domain of DEC-205 and transmembrane and cytoplasmic domain of DCL-1 (6). These findings provided an explanation for nonfunctional DEC-205. At present, the role of DCL-1 and the functional significance of DEC-205/DCL-1 fusion protein are not known. However, expression of this protein in dendritic cells was associated with the abrogation of endocytic activity (6). We propose that podocyte expression of DEC-205/DCL-1 may be contributing to the lack of endocytic HIV-1 entry in podocytes.
We have recently demonstrated that HIV-1 entry into human podocytes was inhibited by disruption of specific membrane microdomains by cholesterol depletion (39). However, we did not evaluate any selective pathway in these studies. In dendritic cells, a significant portion of DC-SIGN resides in cellular membrane microdomains (7). Moreover, HIV-1 binding and uptake in IDCs have been reported to occur through a cholesterol-sensitive pathway (20). Many viruses, including HIV-1, target lipid rafts during both cellular entry and viral assembly (14, 37, 55). Recently, new data on the postendocytic trafficking of raft markers have provided insights into postendocytic trafficking. Interestingly, one of the better known lipid raft-mediated trafficking pathways discovered for SV40 involved pH-neutral vesicles (46).
The phagocytic pathway of the DC-SIGN receptor remains controversial. DC-SIGN binding has been shown to many pathogens (8, 51, 56, 64); however, several studies indicate that the internalization pathway of DC-SIGN in dendritic cells is dependent on the type of ligand. The antigen Lewis X and mycobacterial ManLAM are efficiently captured and internalized through DC-SIGN and are targeted to lysosomes (19). On the other hand, DC-SIGN-mediated HIV-1 entry was routed to nonlysosomal compartments and it was associated with sustained virulence in dendritic cells (32). Similarly, the hepatitis C virus entered via DC-SIGN/l-SIGN escape lysosomal degradation (36). Our study in human podocytes suggest the involvement of the neutral pH-compartment in the trafficking pathway of HIV-1; however, further studies are required to delineate the exact route.
In the present study, HIV-1 could establish productive infection in lymphocytes for up to 6 days, indicating that DC-SIGN expressed on human podocytes has the potential for viral sequestration. Since we could detect the HIV-1 strong-stop DNA (by PCR) only up to 72 h, it appeared that DC-SIGN could sequester only a minimal (undetectable) number of infectious viral particles in podocytes for a longer time. An alternative possibility can be considered that a smaller number of viral particles might have persisted by being attached to the cellular surface in the trypsin-resistant compartments. However, EM studies did not show any presence of HIV-1 particles on the surface of the human podocytes. Moreover, EM studies showed the presence of HIV-1 particles inside the cells. Thus it appears that there may be two possible sources for viral transfer to the immune cells.
We conclude that human podocytes have the capability to capture and internalize HIV-1 through a pH-independent endocytic pathway, which utilizes DC-SIGN receptors.
This work was supported by NIDDK Grant RO1 DK 083931. The reagents and viral strains were obtained through the National Institutes of Health (NIH) AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH included T-20 (fusion inhibitor from Roche; no. 9845), pcDNA3-DC-SIGN-expressing plasmid, anti-CXCR4 Ab (no. 4083), and all viral strains.
No conflicts of interest, financial or otherwise, are declared by the authors.
- Copyright © 2010 the American Physiological Society
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