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Having read about anti-aliasing I came to realise that I could render my scene 8X times the original size of the screen and then shrink it to render it on my original screen to improve the effect that I have rendered on the screen. Could someone help me on how to achieve this and is shaders the only way to achieve this?
Um, why don't you just use multisampling like everyone else? Even if you're using deferred rendering, there are ways to use multisampling in tandem with that.
Multisampling covers triangle edge aliasing, while anisotropic filtering covers texture aliasing. Between those two, you pretty much have all the antialiasing techniques you need. Unless you're procedurally generating textures, of course.
The modern technique is to render your scene to one or several framebuffer objects of the desired size, then use these framebuffer objects as textures and render them to the screen. Basic usage means setting the texture to
Another way is to use the accumulation buffer (tutorial here). This will make advanced usage such as gamma correction more difficult to implement, but the basic idea is very simple. It doesn't require shaders either.
If you're using D3D there's no need for shaders to implement this. Just create your extra large render target, render your scene to that, and at the end of the frame call StretchRect() to do the resizing of the big render target to the back buffer.
Depending on where the aliasing is coming from, this may not look any better than MSAA, and MSAA is much quicker because it only runs the pixel shader once for each output pixel, and not eight times.
Note that even when using the fixed function pipeline any modern card will convert those settings into pixel shaders in the driver.
You should also make sure you're using the right texture filter settings, and that your textures have mip maps, as both of those are cheap to fix and can cause some nasty aliasing if they aren't right.


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Free For Haul Friday, Volume #002
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subset: commoncrawl


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Find hotels in Leesburg using the list and search tools below. Search for the cheapest discounted hotel and motel rates in or near Leesburg, FL for your upcoming personal or group travel. We list the best Leesburg, Florida hotel and motel rooms. Browse the Leesburg area hotels to find the perfect lodging! Please use the provided map of the Leesburg hotels. Booking 5+ Rooms? Find Leesburg Group Hotel Rates
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The Dock Side restaurant was very nice. And Sonny's Barbeque was awesome, food and price!


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Hmmmm wonder whats going to come out of this. I'm sure they have a little unwritten rule to not do it still. But with all the hardball being played in the Smartphone and tablet market things could get ugly real fast.
Justice Department orders Apple, Google, others to end ban on cross-hiring
Looks like Apple, Google and others will have to put a stop to their handshake deals over not hiring each others employees, thanks to the US Justice Department:
According to the complaint, the six companies entered into agreements that restrained competition between them for highly skilled employees. The agreements between Apple and Google, Apple and Adobe, Apple and Pixar and Google and Intel prevented the companies from directly soliciting each other's employees. An agreement between Google and Intuit prevented Google from directly soliciting Intuit employees.
"The agreements challenged here restrained competition for affected employees without any procompetitive justification and distorted the competitive process," said Molly S. Boast, Deputy Assistant Attorney General in the Department of Justice's Antitrust Division. "The proposed settlement resolves the department's antitrust concerns with regard to these no solicitation agreements."
The government was concerned that the deals prevented employees at the companies involved from getting competitive salary and job offers via "cold calls" aka poaching or active solicitations.
The proposed settlement between the DOJ and the companies prevents them entering into any no-poaching agreements, or any agreements against cross-hiring, for 5 years.
So we pretty much figure the iOS teams' phones are going to be ringing off the hook from now until 2015, right?
[DOJ, thanks to everyone who sent this in]
Have something to say about this story? Leave a comment! Need help with something else? Ask in our forums!
Reader comments
Justice Department orders Apple, Google, others to end ban on cross-hiring
Who is john galt?
@Wayne .. they are not controlling hiring... they are actually making it better for the employees... Imagine if your employer's competitor can't hire because of some deals that they made between each other..
YOU END UP WITH NO LEVERAGE... that's actually an anti-socialism ruling right there...
Anyway my only problem with this is .. why is it 5 years.. why not forever..
When is the last time the government stepped in and actually helped somebody? Social Security? Medicare/Medicade? Katrina? I could list more but the obvious answer is NEVER. Anything the government touches, they make worse. Anytime the government tells a private business how much they an make and who they can and cannot hire, it is a closer step towards socialism. If fact, it is the very definition of socialism. Besides, where in The Constitution does it give the federal government the power to do this sort of thing? Answer: NOWHERE!
"So we pretty much figure the iOS teams' phones are going to be ringing off the hook from now until 2015, right?"
Nah, probably Apple's marketing team.


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|82 posts found
Novice Member
Joined: 11/30/11
While i can agree that this follows the most traditional methodology of MMO's i cant say it fits in with all of them.
TSW is the best example here.
I've been running nightmares for probubly 5 or 6 weeks now. Sure its possible to To run instances for gear. However doing so would be shooting yourself in the foot. The best gear ive gotten has come from the items i have purchased and upgraded myself. PVP works the same way for progression and both can actually be quite effective in the other aspect. Alot of these fights actually do come from being better. Successfully Impairing to interrupt, Keeping active afflictions on the boss so that your team mate may capitalize on the situation. Making sure you are running the right buffs and dont blow them with poor timing. Having a build that actually works with all the abilities so your not boosting your strike attacks but not using any. Understand where im coming from.
Thats part 1. Part 2 is the Boss fights themselves. I have run Raids in plenty of games, TSW NM runs have been while somewhat Simple, MUCH more difficult. Ask a TSW player why we entered a NM run and we wont say. There is a +5 sword in there that will make all the other fights simpler. You may hear, We are in need of Currency so that we can enhance our gear. Or you may hear and i feel this is much more Common "We havent beaten it yet"
The difference in Drops for anything above QL10 is Stat Alocation. A drop from the first Nightmare instance may have 445 Attack Rating, 130 Crit chance and 40 Crit Power where as a drop from the Last Nightmare run would have something along the lines of 445 Attack Rating, 130 Crit Power and 40 Crit rating.
Also if it is the idea of attaining Gear that is stronger or somehow different thatn your previous gear. then your in the Wrong Genre, RPG's all play this way and they all SHOULD play this way. Having a sword that acts just like a sword has its own Genre its called Hack and Slash.
Because i can.
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Joined: 3/03/12
OP cmon.
Since the early days of pen and paper rpgs were founded on progression.. wtf? Yeah we played D&D and the likes for fun, but we wanted to progress our character. We wanted levels, skills, and gear.... wtf? sorry.. it's late here.
pen and paper gave birth to mmorpgs. in case you did not know /roll, or RNG (Random Number Gernerator/tion) they come form 1d3s 1d4, 1d6, 1d8, 1d10, 1d12s......1d100s. Those are die, that's plural for dice just incase.
This is like asking fellow football players "Do you think we are trained to gain yards?"
Funny :) but i think you mix the two characters. In the anime Tom is no match for Jerry's brains and wits, so for me it should be Tom that doesnt understand Jerry and not the opposite. :)
Novice Member
Joined: 2/27/08
Originally posted by Rohn
Yes, but in a good PnP RPG, progression isn't just being handed shiny things, it's improving the character, but by improving their stats and by knowing how to better utilize the character. Of the two, the second is the most important. In an MMO though, progression is usually so mind-numbingly simplistic, you get new armor that looks the same as your old armor, a new sword that looks the same as your old sword so you can go out and fight new, stronger enemies that look just like your old enemies. Progression is done so badly in most MMOs, it's laughable.
Played: UO, EQ, WoW, DDO, SWG, AO, CoH, EvE, TR, AoC, GW, GA, Aion, Allods, lots more
Originally posted by Silok
Which is where it gets into the "Doubling Plus Factor" - so to speak, and makes it pretty tough on devs.
Say you start off with a standard Fantasy MMORPG. Somebody wants a Sci-Fi MMORPG. You're now at two games. Somebody wants faster leveling and more focus on endgame. Not everybody does though. So now you have two Fantasy games and two Sci-Fi games. Somebody wants more action orientated combat. Not everybody does though. But still, now you're at four Fantasy games and four Sci-Fi games. Somebody wants a Superhero game. Tada, you've got four Superhero games. Somebody wants another genre, bam - four of them. Then you get into features that folks want and others do not want - BAM - for each game, you've got two. Somebody wants dungeon finder - somebody doesn't - you're at 8 Fantasy, 8 Sci-Fi, and 8 Superhero games. Somebody wants Post Apocalyptic - bam - wait, Post Apocalyptic means different things... who knows how many games you'll end up with there? Heh, throw in Sandbox versions of those games and....
...sometimes we have to settle. Or we just walk away.
I believe it's one of the reasons that so many folks are always looking for the next game - they're looking for the game that does not exist. It's version #248 of 3257. It may or may never exist.
I miss the MMORPG genre. Will a developer ever make one again?
Explorer: 87%, Killer: 67%, Achiever: 27%, Socializer: 20%
Advanced Member
Joined: 12/17/06
Progression is not bad - it may inspire to grow for a long and long. Finished Ice Monk - ok, go for Fire Hunter, finished Fire Hunter - go for Slug Warrior etc etc etc...untill all 99 classes are up to top (and each class is harder and harder to master).
I think it is the MMORPG that should offer something extra - and once again, I will refer to Istaria. My toon has finished several fighting schools and several crafting schools as well. I could grind for experience, turning in trophies or power-levelling...but instead, I craft day and night, gaining no xp.
Why? Just because I do want to help other people with their plots and buildings. I craft tier 1 or tier 2 stuff, add it to structures and enjoy seing how structure appears out of scaffold. Or sometimes I just go to starting area, asking new players if they need fire support / tools / weapons. It is now and it would be when I will reach end-game (level 100 in all schools).
And please notice, I am progression fan, I do love to see how level numbers increase, be it fighting or crafting. I just saw another aspect of the game: fun without xp. I go near couple animals and cast some funny spell on them: it has no result, but just looks nice. I go to aid structures - and owner will never know it was I that helped. Or I just go to help some newbie: be it Dragon who wants more treasure for hoard or some biped in need to kill that terrible lvl.10 grulet.
In short: players should see some other "side" purpose. Istaria has plots and everyone may help other person's buildings. The world is large and there are so many buildings waiting to be completed.
Originally posted by Cephus404
It's the meatier mob with a beefier bat mentality. I think STO does it the worst because of their replayablity of missions. You can literally fight level 50 versions of the level 1 mobs. I mean - the stats are boosted of course - but it's the same mob...same look, same name, etc...just meatier and beefier.
Many games will at least change the model and the name, but in the end - it's still the meatier mob with the beefier bat. That level 100 boss that rules a kingdom is no smarter than the level 10 boss that sleeps in a tent in a cave. There are as many "guys" defending the tent guy as the kingdom guy. They just have more health and do more damage. Meh...
I miss the MMORPG genre. Will a developer ever make one again?
Explorer: 87%, Killer: 67%, Achiever: 27%, Socializer: 20%
Originally posted by Cephus404
Dont forget that modern mmo ( i dont dare put the rpg) are not for rpg fans, they are for fast action solo gamers now. Thy why we dont have real character progression and the long journey who come with it.
Originally posted by VirusDancer
You are mixing things here. I dont talk about themes, fantasy or sci-fi has nothing to do about the fact that all major mmo have the same kind of progression. Solo fast and easy.
Fast action combat or slow tab targeting doesnt matter to me, if the game offers me some real character progression, with a lots of thing to do and yeah i want time sink features.
In FFXI i used to do fishing for hours to get money or cook to get my kebab. I was breeding chocobos to get one with a different colors than yellow. I could spent days playing without going get some lvl.
After month of playing my highest job level was 43. I did played more than 4 hours a days. I didnt even scrath the surface.
I cant do this in modern mmo. After somes weeks all the maps are reveal, you are max lvl and you grind gears...or i heard now it's cosmetics o well. Game over i think.
Hard Core Member
Joined: 12/25/03
Someone outside of the gaming generation would look at us and ask, "Are these guys are being trained to be happy playing games instead of real life?"
No one is being trained to do anything, people simply do things that stimulate the brain, releasing the chemicals that make you feel satisfied (can't remember the name) when someone becomes "addicted" to a style or specific action that satisfies them it's hard and sometimes impossible to become satisfied any other way. We're not being "trained", its just natural. Unfortunately.
professional web programming and design.
Originally posted by Silok
It's not a mixing thing. I was just looking beyond you. You're an example though - you're looking for version #26 of 3257. You want a game with a certain set of features. There is going to be somebody else that wants something else. There are going to be people where the theme matters - so again - there would need to be countless games to handle everything that everybody wants.
So we generally have to compromise, we have to settle, or we have to walk away.
Maybe Game X has 60% of what you want - which is more than Game Y or Game Z. So you play Game X, but you're never really happy with Game X. Perhaps Game R once did it for you, but that was ten years ago and Game R still looks like a ten year old game. You want Game U, which is Game R with an updated graphics engine - but that's mostly Game R still. Odds are though, that Game U is not going to exist.
It's a case not of looking for the best game...but the best game. Not the perfect game, but the game that comes closest.
Folks tend to get pretty pissy when they hear about a new game, focus on what they think it might include, get hyped about certain features...only to find out that those features are a small part of the game. It's more painful than not having any games having some of the features you want.
It's like telling somebody - hey, I've got a great piece of cake here - want a piece? You say sure and as you reach for it, they hit you with a baseball bat. You exclaim WTF!?!?!? They say that each piece of cake comes with a free whack of a baseball bat to the head. Then on top of that, you have to finish the cake (including getting hit with the baseball bat) - for the chance of getting a glass that may or may not have some milk in it. That's how MMOs feel to me these days.
But oddly enough, I feel worse about single player games...meh, sometimes I wish I had kept my old computers as well as my old games. Sure, the graphics might look like Hell compared to what we have today - but nobody's going to make those games with today's graphics. I'd rather have to deal with the crappy graphics for games that I can enjoy hours on end... than to continue risking reaching for that piece of cake only to get hit by a baseball bat.
I miss the MMORPG genre. Will a developer ever make one again?
Explorer: 87%, Killer: 67%, Achiever: 27%, Socializer: 20%
Originally posted by Kilrain
You know, you actually make a great case for why folks are trained rather than they are not trained. I mean, you've basically described a Pavlovian response for the release of Serotonin and Dopamine with the understanding of the tolerance issues involved in the addiction.
So while one can make the case that the underlying process is natural, one cannot make that same case for the overall events that have transpired - it completely ignores the artificial means by which we've reached this point.
The drug dealer and drug addict analogy comes to mind. Some people in MMOs...well, they had a low tolerance. So they needed it bigger and they needed it faster. Then bigger. Then faster.
The developers know this - they're not stupid. They've looked around at how things are changing overall. They're furthering the process instead of fighting against it...it's a way for them to make money. Hell, it's one of the reasons that F2P makes so much money - working off of that same addiction.
Some people are being trained...in the sense they're being taught that in order to get that good feeling - bigger and faster, they need to follow a certain path...
I miss the MMORPG genre. Will a developer ever make one again?
Explorer: 87%, Killer: 67%, Achiever: 27%, Socializer: 20%
Originally posted by VirusDancer
You know you write all this text to say almost nothing, all you do is to shift the discussion so the real subject here is lost.
First let rewind to the begin, you said in a earlier reply '' People should be happy that there are multiple types of MMOs to play now, but as you can see, they aren't'' and i replyed to you that (in short) all modern mmo offer the same things this is why im not happy.
And you you reply with all this mumbo jumbo who mean nothing about game X and game B, that im looking for version 245 or whatever.. Seriously where do you want to go with this?
I think i was clear enough about my opinion on the real subject of this thread. Now i dont think this discution is going no where.
Apprentice Member
Joined: 12/03/11
Why bother with 99% of your thread when you could of just wrote: how can we force the MMO community to like GW2 because i like it.
You can't.
Originally posted by Silok
Um, I did not say "People should be happy that there are multiple types of MMOs to play now, but as you can see, they aren't"
Since you cannot even follow who said what, I honestly am not suprised that you cannot follow what I've bene saying. Even though it's the simplest thing to grasp... not everybody wants the same thing. You're obviously not happy with where the majority of the games have gone. In order for those games to appeal to you, they would need to create an additional copy of the game - tada, doubling. Two people want different things, then you need two different games. You add a third person that might want some of what the first does and some of what the second does, you're looking at a third game - tada, doubling plus.
That you could point out where certain games are a certain and then say you want something else...without being able to comprehend that it would require two games to satisfy both yourself and those that like it the way it is...is mind boggling.
It's very unlikely that there's going to be a perfect game for anybody - people go with what come's the closest. If there's nothing close enough, then they will take a break from the genre. While McDonald's might not be a person's first choice for chicken, if it's on the way home and the chicken place is out of the way - they may just make that compromise. Now if they're looking to get a steak, mashed potatoes, and a beer - they're likely to go somewhere else.
How can you not get that?
I miss the MMORPG genre. Will a developer ever make one again?
Explorer: 87%, Killer: 67%, Achiever: 27%, Socializer: 20%
Originally posted by Sylvarii
It might be a matter of perspective, but I felt the OP was asking more on how to get folks not to complain about it - than about liking it. The OP found something they like...and there are folks complaining about it - trying to change it. I saw it as a defensive post rather than a marketing post.
I miss the MMORPG genre. Will a developer ever make one again?
Explorer: 87%, Killer: 67%, Achiever: 27%, Socializer: 20%
Advanced Member
Joined: 10/02/04
I have not read the entire thread but i got this to say..
Progression should be part of the fun, it always has been for me.
In all the MMORPGs I have played even Darkfall I have enjoyed my character progression infact i would say character progression is one of my favourite things about MMORPGs... tho less so with recent themepark games as characte progression is way too fast..
Hard Core Member
Joined: 7/29/10
Magic Propels my Rolly Chair.
Lets take a step back, If you played and enjoyed Rpg's prior to switching to mmorpgs then you would appreciate how much progression and stat building is staple.
However, It's my belief that most people that want 'fun casual games' didn't, or don't like rpg's in the first place.
Apprentice Member
Joined: 12/03/11
The OP talks like their is no progression in GW2 lol,like the game is all about just having fun and not worrying about better items/armour.
So OP are you telling me that you are still running around in your level 1 armour not caring about getting better stats because you are having to much fun.Are you telling me that you would play GW2 even if it gave you no rewards or better items as you progress.
GW2 is like any other MMO,it's a tredmill of proggression to get better shinny items,have you even reach level 80 lol.
You like GW2 and bully for you but don't assume that anyone who dosent share your views is not having fun.
Novice Member
Joined: 4/27/12
The opinion of a penguin.
Why are they seperate? Progression for me is enjoyment.
To use a real world analogy: I could stay home and enjoy myself all day by playing games, kicking back and relaxing. But there comes a time when it gets dull, sooner rather than later. If I'm constantly out developing and changing then life is always exciting, despite any hardships. Same plays out, to an extent, with MMOs (for me at least).
GW2 doesn't have an illusion of any meaningful progression what so ever to me, therefore, imo it's worthless.
Ah needz mah progressions in RPGs, otherwise... you just got the same thing as an FPS. And FPSs are always more fun than a tab targeting MMO.


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Top Definition
Attracted to all sexes in a romantic way, but not necessarily in a sexual way. Used by asexuals instead biromantic to disregard the idea that there are only two sexes.
"I don't get it. Bretta is totally hot, and she'll date anything, but she's still a virgin."
"That's because she's panromantic asexual."
"That's because she's panromantic asexual."
додав theflying_clubcup 24 Січень 2009
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Able to be attracted to all genders in a romantic way, but not necessarily in a sexual way. Used by people that feel this romantic attraction applies to them, regardless of their sexual orientation.
"I'm a panromantic lesbian. It's when a girl is attracted romantically to people regardless of their gender, but she is only sexually attracted to other girls."
додав AlinaKarib 6 Листопад 2014


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These breezy designer inspired cz sterling silver palm tree stud earrings almost bring the air of tropical beaches to the senses as they hang from the ear. The soothing design is washed with shimmering cubic zirconias to enchant the piece to remind one of relaxing freedom. The earrings measure 5/8 inches long and weighs 1.3 grams a piece to make these cz sterling silver palm tree stud earrings a great piece for the summer.
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Drop dead gorgeous models & pornstars lured into sleazy motel rooms with promises of fame and fortune only to have their bouncing bare bottoms spanked red raw because they're bad, bad, baaaad girls. This is the real deal. This is Bun Beating FUN !
Categories: Reality
Pornstars: Aaralyn Barra
Submited: 3 years old


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Important Professional Development Information:
Final Flex Hours Reported for 2014-2015
Useful Flex Week Information:
Individual Activity
Attends, participates in or presents an activity such as a speech, demonstration, skills lab, seminar, lecture, conference, course (not to be used for salary advancement), or similar activity. The subject of the activity must relate to staff, student, or instructional improvement. This form does not require pre-approval.
After attending the activity and before June 30, report your attendance on the Individual Activity Report Form.
Form for reporting participation in an individual activity:
To submit via email: Open and complete the form. Please type your name where it asks for signature. It is suggested that you add your last name to the file name when you save the document e.g., IndividActivHorlings.docx. Lastly, email the form to your Division Rep who will sign and forward to the flex office with a cc to you. It's not required to send by email, but saves paper and time! Thank you!
Professional Development Week Forms for Faculty and Division Admins
If you would like to present an activity such as a speech, workshop, demonstration, lecture, meeting, seminar, etc. during fall or spring Professional Development Week please email Jane Horlings or the Academic Senate Office. Presenters receive 3 flex credits for each hour of the presentation. No additional credit for preparation time is allowed. This format does not require pre-approval.
Forms for Presentations to be given during Professional Development Week:
- Professional Development Week Presenter Form (Fall 2015 deadline is April 3, 2015)
- Professional Development Week Division/Department Meeting Form (Fall 2015 deadline is April 10, 2015)
(Please note: This form is used to schedule meetings, not to report attendance/flex hours)


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I have always wanted a 1919, so I sold a bike to fund a beltfed.
Should I build? I have built 2 AK's succesfully (and building more) with the forums help but these belt feds look tricky and I know nothing about them.....
Should I buy? I am a working class slave on a budget but I dont want to buy a lesser product since I will keep it to pass on.
Who makes the best quality, authentic semi-auto 1919?
Original 30.06 cal or 308?
Could I get a 1919 with tripod with traverse and elevation for around $1,750.00?
How well does the emory crankfire work? I really want the F/A version but dont have $18,000.00.................


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Who needs a vending machine filled with candy, when you can have a vending machine full of skincare!!
I love that there are self serve kiosks at the airports filled with ProActive skincare. I have been recommending ProActiv to my younger clients, or friends who battle with acne for quite some time now. The ProActiv kit works wonderfully to treat severe acne, and heal outbreaks.
The two products that I always tell everyone are must buys are the Green Tea Moisturizer and the Refining Mask. I have personally gone through tubes of both. Tubes! I know that a product is good when I go through it and can't imagine not having it in my cabinet.
I keep the Green Tea and the Mask with me for travel, since my skin tends to be fickle when I fly or bounce around from different cities.


text: Prev | Next Purchase this photo Billy Summers/The Putnam Herald Vendors and shoppers enjoy the 12th Annual PTO Crafts Fair at West Teays Elementary School on Saturday, Dec. 1, 2012. Gallery: Putnam in Pictures, Friday, Dec. 7 Dec. 07, 2012 @ 01:39 PM 2012/The Herald-Dispatch Did you miss something in Putnam County this week? Chances are, one of our photographers was there. ()


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Beneficiario di un regalo CRÉATION? Beneficiario di un forfait LYS?
"Unique in the world:golf on the hotel's driving range and its pitch & putt."Diego Resusta, Maître de Maison, presents his property:
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- Cell culture (1)
- Endometriosis (1)
- Ovary (1)
- RNA sequencing (1)
- Real-time semi-quantitative PCR (1)
- Three-dimensional in vitro modeling (1)
- Biowissenschaften (5)
- Informatik (1)
- Prediction of extracellular proteases of the human pathogen Helicobacter pylori reveals proteolytic activity of the Hp1018/19 protein HtrA (2008)
- Exported proteases of Helicobacter pylori (H. pylori) are potentially involved in pathogen-associated disorders leading to gastric inflammation and neoplasia. By comprehensive sequence screening of the H. pylori proteome for predicted secreted proteases, we retrieved several candidate genes. We detected caseinolytic activities of several such proteases, which are released independently from the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI). Among these, we found the predicted serine protease HtrA (Hp1019), which was previously identified in the bacterial secretome of H. pylori. Importantly, we further found that the H. pylori genes hp1018 and hp1019 represent a single gene likely coding for an exported protein. Here, we directly verified proteolytic activity of HtrA in vitro and identified the HtrA protease in zymograms by mass spectrometry. Overexpressed and purified HtrA exhibited pronounced proteolytic activity, which is inactivated after mutation of Ser205 to alanine in the predicted active center of HtrA. These data demonstrate that H. pylori secretes HtrA as an active protease, which might represent a novel candidate target for therapeutic intervention strategies.
- Domain organization of long signal peptides of single-pass integral membrane proteins reveals multiple functional capacity (2008)
- Targeting signals direct proteins to their extra- or intracellular destination such as the plasma membrane or cellular organelles. Here we investigated the structure and function of exceptionally long signal peptides encompassing at least 40 amino acid residues. We discovered a two-domain organization ("NtraC model") in many long signals from vertebrate precursor proteins. Accordingly, long signal peptides may contain an N-terminal domain (N-domain) and a C-terminal domain (C-domain) with different signal or targeting capabilities, separable by a presumably turn-rich transition area (tra). Individual domain functions were probed by cellular targeting experiments with fusion proteins containing parts of the long signal peptide of human membrane protein shrew-1 and secreted alkaline phosphatase as a reporter protein. As predicted, the N-domain of the fusion protein alone was shown to act as a mitochondrial targeting signal, whereas the C-domain alone functions as an export signal. Selective disruption of the transition area in the signal peptide impairs the export efficiency of the reporter protein. Altogether, the results of cellular targeting studies provide a proof-of-principle for our NtraC model and highlight the particular functional importance of the predicted transition area, which critically affects the rate of protein export. In conclusion, the NtraC approach enables the systematic detection and prediction of cryptic targeting signals present in one coherent sequence, and provides a structurally motivated basis for decoding the functional complexity of long protein targeting signals.
- Die Gene sind nicht alleine schuld : wie wir durch unser Lebensumfeld die Gene prägen können (2009)
- »Das sind meine Gene – deswegen kann ich daran nichts ändern!« Wie oft hört man solche oder ähnliche Äußerungen von Menschen mit Fettsucht oder anderen Malaisen. Aber unterliegen Fettsucht oder komplexe Erkrankungen tatsächlich weitgehend unabänderlichen Naturgesetzen, oder sind sie doch beeinfl ussbar? Vor einigen Jahren noch hätten selbst gewiefte Genetiker keine oder wenigstens keine gute Antwort auf solche Fragen geben können. Mit dem Fortschreiten der Molekularbiologie in den vergangenen drei Jahrzehnten konnte sich jedoch ein Wissenschaftszweig, die bereits in den 1940er Jahren von Conrad Waddington definierte Epigenetik, zur Blüte entwickeln, der die Genetik und ihre (Aus-)Prägung durch Lebensumstände und die Umwelt zusammenbringt.
- Ein erfolgreiches Wissenschaftsmodell für die Zukunft : das fachbereichsübergreifende Center for Membrane Proteomics (2004)
- Novel three-dimensional in vitro models of ovarian endometriosis (2014)
- Background: Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity. It affects 1 in 10 women of reproductive age. This chronic condition commonly leads to consequences such as pelvic pain, dysmenorrhea, infertility and an elevated risk of epithelial ovarian cancer. Despite the prevalence of endometriosis and its impact on women's lives, there are relatively few in vitro and in vivo models available for studying the complex disease biology, pathophysiology, and for use in the preclinical development of novel therapies. The goal of this study was to develop a novel three-dimensional (3D) cell culture model of ovarian endometriosis and to test whether it is more reflective of endometriosis biology than traditional two dimensional (2D) monolayer cultures. Methods: A novel ovarian endometriosis epithelial cell line (EEC16) was isolated from a 34-year old female with severe endometriosis. After characterization of cells using in vitro assays, western blotting and RNA-sequencing, this cell line and a second, already well characterized endometriosis cell line, EEC12Z, were established as in vitro 3D spheroid models. We compared biological features of 3D spheroids to 2D cultures and human endometriosis lesions using immunohistochemistry and real-time semi-quantitative PCR. Results: In comparison to normal ovarian epithelial cells, EEC16 displayed features of neoplastic transformation in in vitro assays. When cultured in 3D, EEC16 and EEC12Z showed differential expression of endometriosis-associated genes compared to 2D monolayer cultures, and more closely mimicked the molecular and histological features of human endometriosis lesions. Conclusions: To our knowledge, this represents the first report of an in vitro spheroid model of endometriosis. 3D endometriosis models represent valuable experimental tools for studying EEC biology and the development of novel therapeutic approaches.


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iOS 5 feature: over the air (OTA) automatic daily backups
If you're tired of consistently having to sync your device to iTunes in order to back it up (I know I am), get ready for a big change. iOS 5 is bringing automatic OTA backups! The backups will be available over Wifi and will back up each day.
Backups will include -
- Your purchased music (what about stuff in our iTunes that isn't iTunes purchased?)
- Media (books, photos, videos)
- Device settings and app data.
What does this mean for end users? It means gone are the days of having to worry about losing your data if your device gets stolen or damaged.
Get a new one, sign in with your Apple ID and there's all your data. Just the way you left it.
Excited yet?
[Image via Engadget]
Have something to say about this story? Leave a comment! Need help with something else? Ask in our forums!
Reader comments
iOS 5 feature: over the air (OTA) automatic daily backups
What about contacts and calendar info?
This is the big question... save game files from games (just as any app-specific files) will be backed up, no doubt, but will they be deleted when we delete the app in question?
That was one of the most peculiar ideas Apple ever had. Let's hope they've finally understood the idiocy of it.
so no widgets or siri :( , seems like a catchup iteration as opposed to anything I can get excited about.
Ya, I was excited about this... 2 years ago when I got my palm pre and has this feature built in, it works great, I've factory reset my pre, then re-synced my phone and all my settings and apps were right there where I left off, it's great. Once again, apple imitates and people drool over them. This should have been something that Apple did a long time ago, syncing to itunes is the biggest problem with apple products today imo, I hate having to hook my ipad to my pc to sync/backup/update etc. Watch, next they will copy webos notifications and people will think it's the best ever! Granted, it's palm/HP's fault for letting people catch up when they had a 2yr lead on the competition.
I see 'text & sms messages' in that screenshot!! I sure hope we can backup them up and do a restore as new now and get to keep our texts!!!!
So we get all our bought iTunes music from the past


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Scarface: Fuck you, fuck you, fuck you, you're cool, and fuck you, I'm out!
"I don't call the fighting in my films 'violent', I call it 'action'. An action film borders between fantasy and reality. If I were to be completely realistic in my films, you would call me a violent, bloody man. I would simply destroy my opponent by tearing his guts out. I wouldn't do it so artistically." ~Bruce Lee
I would bet the farm on the fact that Joey used whatever he did for weight cutting purposes.
Not saying it's right but I don't see a big deal with PED's to begin with.
There are many paths to freedom, not all are peaceful
Does it help with weight cutting and putting on muscle leading up to the fight, of course. But when it comes down to the actual fight with both guys in the cage i honestly think the best fighter is the one can put it all together and i dont think PEDs help that.
Got a lot of soul searching to do. Sorry to everyone I've let down
Two more dents in the integrity of the sport, and more ammunition for the Culinary Workers Union.
Favourite Fighters: A. Silva, Velasquez, Swanson, Bisping, W. Silva, Barnett, Faber, Dos Santos, Manuwa, McCall, Pickett & Poirier
Least-Favourite Fighters: Story, Sylvia, Browne & Lentz
0-1 on sig bets.
Very surprised to see Beltran was using but not so much about Palhares.
Those who do not appreciate life, do not deserve life.
Joey Beltran: 'I Did Not Inject Nandrolone Into My Body' - FightLine.com
joey beltran✔
I can say without a shadow of a doubt I did not inject Nandrolone into my body. I am sorry to my family and friends for the shame this...
10 Jan 13joey beltran✔
Brought to any of you. I promise soon the whole story will be told and I will go through whatever is necessary to find the reason for this..joey beltran✔
Positive test. I am at fault for taking a supplement or perhaps combination of something that caused my test result. My team and I will ...joey beltran✔
Seek the truth. I am sorry once again and truly apologize to the people that matter the most to me.- Joey Beltran
Nandrolone (19-nortestosterone) is an anabolic steroid that may be present naturally in the human body, albeit in minute quantities of less than 0.4 ng/ml.[The positive effects of the drug include muscle growth, appetite stimulation and increased red blood cell production and bone density.
Last edited by Cat--Smasher; 01-11-2013 at 05:09 PM.
And if you want beef, then bring the ruckus
Where should the line be drawn?
At weight-cutting?
If users have to use a substance to get to a particular weight, perhaps they should be fighting at the next highest bracket instead.
Weight-cutting is a ridiculous and outdated system and I'd rather see it go then allow athletes to harm themselves with PEDs.
I think for me the biggest problem with PED use being accepted is that it forces the guys that don't want to use it to feel like they have to because everyone else does. Long term health effects being a risk is not something anyone should have to risk for entertainment to the masses.
And just for arguments sake what happens in a fight where both guys are equally skilled but one is using PED's and the other isn't ?
Got a lot of soul searching to do. Sorry to everyone I've let down
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A method and apparatus for transmural ablation using an instrument containing two electrodes or cryogenic probes. A clamping force is exerted on the two electrodes or probes such that the tissue of the hollow organ is clamped therebetween. Bipolar RF energy is then applied between the two electrodes, or the probes are cryogenically cooled, thus ablating the tissue therebetween. A monitoring device measures a suitable parameter, such as impedance or temperature, and indicates when the tissue between the electrodes has been fully ablated.
1. A device for clamping and ablating cardiac tissue comprising:
a first handle member;
a second handle member pivotally connected to the first handle member;
first and second jaw members associated with the first and second handle members, respectively, the jaw members each having a distal tip and being movable by the handle members between a first open position and a second clamped position, the jaw members having insulated outer surfaces with convex, opposed clamping surfaces, each clamping surface having a central peak, the central peak of the first jaw being aligned with the central peak of the second jaw;
a first elongated ablation electrode extending along the central peak of the first jaw member;
a second elongated ablation electrode extending along the central peak of the second jaw member;
the first and second ablation electrodes being adapted to be connected to an RF energy source; and
one of said first and second jaw members including a pair of EKG monitoring sensors on the tip spaced distally from its associated ablation electrode for contacting cardiac tissue and being adapted to be connected to an EKG monitor, so that when cardiac tissue is grasped between the first and second jaws, the EKG sensors contact the cardiac tissue and transmit the signals generated by the tissue to the EKG monitor.
2. The device of
3. The device of
4. The device of
5. A cardiac tissue grasping apparatus comprising:
first and second grasping jaws, the grasping jaws each having a distal tip and being relatively moveable between open and closed positions; each jaw including a raised electrode and a receding clamping surface in face-to-face relation with the electrode and clamping surface of the other jaw; the clamping surfaces of the jaws comprising an insulating material and the raised, face-to-face electrodes connectible to an electrical power source;
whereby when tissue is grasped between said clamping surfaces, the electrodes are substantially entirely contacted by the tissue; and
one of said first and second grasping jaws including a pair of EKG monitoring sensors on the tip spaced distally from its associated electrode for contacting cardiac tissue and being adapted to be connected to an EKG monitor, so that when cardiac tissue is grasped between the first and second grasping jaws, the EKG sensors contact the cardiac tissue and transmit the signals generated by the tissue to the EKG monitor.
6. The apparatus of
7. The apparatus of
8. The apparatus of
9. The apparatus of
10. A device for clamping and ablating cardiac tissue comprising:
a first handle member;
a second handle member;
first and second jaw members associated with the first and second handle members, respectively, the jaw members each having a distal tip and being movable by the handle members between a first open position and a second clamped position;
a first elongated ablation electrode extending along the first jaw member;
a second elongated ablation electrode extending along the second jaw member;
the first and second ablation electrodes being adapted to be connected to an RF energy source; and
one of said first and second jaw members including a pair of EKG monitoring sensors on the tip spaced distally from its associated ablation electrode for contacting cardiac tissue and being adapted to be connected to an EKG monitor, so that when cardiac tissue is grasped between the first and second jaws, the EKG sensors contact the cardiac tissue and transmit the signals generated by the tissue to the EKG monitor.
11. The device of
12. The device of
13. The device of
14. A cardiac tissue grasping apparatus comprising:
first and second grasping jaws, the grasping jaws each having a distal tip and being relatively moveable between open and closed positions; each jaw including an elongated electrode and a clamping surface in face-to-face relation with the electrode and clamping surface of the other jaw; the clamping surfaces of the jaws comprising an insulating material and the face-to-face electrodes being connectible to a power source; and
one of said first and second grasping jaws including a pair of EKG monitoring sensors on the tip spaced distally from its associated electrode for contacting cardiac tissue and being adapted to be connected to an EKG monitor, so that when cardiac tissue is grasped between the first and second grasping jaws, the EKG sensors contact the cardiac tissue and transmit the signals generated by the tissue to the EKG monitor.
15. The apparatus of
16. The apparatus of
17. The apparatus of
18. The apparatus of
This application is a continuation-in-part of application Ser. No. 09/844,225 filed Apr. 27, 2001, now issued U.S. Pat. No. 6,517,536, which is a continuation in part of application Ser. No. 09/747,609 Dec. 22, 2000, now issued U.S. Pat. 6,546,935, which claims the benefit of provisional application Ser. No. 60/200,072, filed Apr. 27, 2000.
Atrial fibrillation is the most common heart arrhythmia in the world, affecting over 2.5 million people in the United States alone. Ablation of cardiac tissue, in order to create scar tissue that poses an interruption in the path of the errant electrical impulses in the heart tissue, is a commonly performed procedure to treat cardiac arrhythmias. Such ablation may range from the ablation of a small area of heart tissue to a series of ablations forming a strategic placement of incisions in both atria to stop the conduction and formation of errant impulses.
Ablation has been achieved or suggested using a variety of techniques, such as freezing via cryogenic probe, heating via RF energy, surgical cutting and other techniques. As used here, "ablation" means the removal or destruction of the function of a body part, such as cardiac tissue, regardless of the apparatus or process used to carry out the ablation. Also, as used herein, "transmural" means through the wall or thickness, such as through the wall or thickness of a hollow organ or vessel.
Ablation of cardiac tissue may be carried out in an open surgical procedure, where the breastbone is divided and the surgeon has direct access to the heart, or through a minimally invasive route, such as between the ribs or via catheter that is introduced through a vein, and into the heart.
Prior to any ablation, the heart typically is electronically mapped to locate the point or points of tissue which are causing the arrhythmia. With minimally invasive procedures such as via a catheter, the catheter is directed to the aberrant tissue, and an electrode or cryogenic probe is placed in contact with the endocardial tissue. RF energy is delivered from the electrode to the tissue to heat and ablate the tissue (or the tissue may be frozen by the cryogenic probe), thus eliminating the source of the arrhythmia.
Common problems encountered in this procedure are difficulty in precisely locating the aberrant tissue, and complications related to the ablation of the tissue. Locating the area of tissue causing the arrhythmia often involves several hours of electrically "mapping" the inner surface of the heart using a variety of mapping catheters, and once the aberrant tissue is located, it is often difficult to position the catheter and the associated electrode or probe so that it is in contact with the desired tissue.
The application of either RF energy or ultra-low temperature freezing to the inside of the heart chamber also carries several risks and difficulties. It is very difficult to determine how much of the catheter electrode or cryogenic probe surface is in contact with the tissue since catheter electrodes and probes are cylindrical and the heart tissue cannot be visualized clearly with existing fluoroscopic technology. Further, because of the cylindrical shape, some of the exposed electrode or probe area will almost always be in contact with blood circulating in the heart, giving rise to a risk of clot formation.
Clot formation is almost always associated with RF energy or cryogenic delivery inside the heart because it is difficult to prevent the blood from being exposed to the electrode or probe surface. Some of the RF current flows through the blood between the electrode and the heart tissue and this blood is coagulated, or frozen when a cryogenic probe is used, possibly resulting in clot formation. When RF energy is applied, the temperature of the electrode is typically monitored so as to not exceed a preset level, but temperatures necessary to achieve tissue ablation almost always result in blood coagulum forming on the electrode.
Overheating or overcooling of tissue is also a major complication, because the temperature monitoring only gives the temperature of the electrode or probe, which is, respectively, being cooled or warmed on the outside by blood flow. The actual temperature of the tissue being ablated by the electrode or probe is usually considerably higher or lower than the electrode or probe temperature, and this can result in overheating, or even charring, of the tissue in the case of an RF electrode, or freezing of too much tissue by a cryogenic probe. Overheated or charred tissue can act as a locus for thrombus and clot formation, and over freezing can destroy more tissue than necessary.
It is also very difficult to achieve ablation of tissue deep within the heart wall. A recent study reported that to achieve a depth of ablation of 5 mm, it was necessary to ablate an area almost 8 mm wide in the endocardium. See, "Mechanism, Localization, and Cure of Atrial Arrhythmias Occurring After a New Intraoperative Endocardial Radiofrequency Ablation Procedure for Atrial Fibrillation," Thomas, et al., J. Am. Coll. Cardiology, Vol. 35, No. 2, 2000. As the depth of penetration increases, the time, power, and temperature requirements increase, thus increasing the risk of thrombus formation.
In certain applications, it is desired to obtain a continuous line of ablated tissue in the endocardium. Using a discrete or point electrode or probe, the catheter must be "dragged" from point to point to create a line, and frequently the line is not continuous. Multielectrode catheters have been developed which can be left in place, but continuity can still be difficult to achieve, and the lesions created can be quite wide.
Because of the risks of char and thrombus formation, RF energy, or any form of endocardial ablation, is rarely used on the left side of the heart, where a clot could cause a serious problem (e.g., stroke). Because of the physiology of the heart, it is also difficult to access certain areas of the left atrium via an endocardial, catheter-based approach.
Recently, epicardial ablation devices have been developed which apply RF energy to the outer wall of the heart to ablate tissue. These devices do not have the same risks concerning thrombus formation. However, it is still difficult to create long, continuous lesions, and it is difficult to achieve good depth of penetration without creating a large area of ablated tissue.
As noted above, other forms of energy have been used in ablation procedures, including ultrasound, cryogenic ablation, and microwave technology. When used from an endocardial approach, the limitations of all energy-based ablation technologies to date are the difficulty in achieving continuous transmural lesions, and minimizing unnecessary damage to endocardial tissue. Ultrasonic and RF energy endocardial balloon technology has been developed to create circumferential lesions around the individual pulmonary veins. See e.g., U.S. Pat. No. 6,024,740 to Lesh et al. and U.S. Pat. Nos. 5,938,660 and 5,814,028 to Swartz et al. However, this technology creates rather wide (greater than 5 mm) lesions which could lead to stenosis (narrowing) of the pulmonary veins. See, "Pulmonary Vein Stenosis after Catheter Ablation of Atrial Fibrillation," Robbins, et al., Circulation, Vol. 98, pages 1769-1775, 1998. The large lesion area can also act as a locus point for thrombus formation. Additionally, there is no feedback to determine when full transmural ablation has been achieved. Cryogenic ablation has been attempted both endocardially and epicardially (see e.g., U.S. Pat. No. 5,733,280 to Avitall, U.S Pat. No. 5,147,355 to Friedman et al., and U.S Pat. No. 5,423,807 to Milder, and WO 98/17187, the latter disclosing an angled cryogenic probe, one arm of which is inserted into the interior of the heart through an opening in the heart wall that is hemostatically sealed around the arm by means of a suture or staples), but because of the time required to freeze tissue, and the delivery systems used, it is difficult to create a continuous line, and uniform transmurality is difficult to verify.
Published PCT applications WO 99/56644 and WO 99/56648 disclose an endocardial ablation catheter with a reference plate located on the epicardium to act as an indifferent electrode or backplate that is maintained at the reference level of the generator. Current flows either between the electrodes located on the catheter, or between the electrodes and the reference plate. It is important to note that this reference plate is essentially a monopolar reference pad. Consequently, there is no energy delivered at the backplate/tissue interface intended to ablate tissue. Instead, the energy is delivered at the electrode/tissue interface within the endocardium, and travels through the heart tissue either to another endocardial electrode, or to the backplate. Tissue ablation proceeds from the electrodes in contact with the endocardium outward to the epicardium. Other references disclose epicardial multielectrode devices that deliver either monopolar or bipolar energy to the outside surface of the heart.
It is important to note that all endocardial ablation devices that attempt to ablate tissue through the full thickness of the cardiac wall have a risk associated with damaging structures within or on the outer surface of the cardiac wall. As an example, if a catheter is delivering energy from the inside of the atrium to the outside, and a coronary artery, the esophagus, or other critical structure is in contact with the atrial wall, the structure can be damaged by the transfer of energy from within the heart to the structure. The coronary arteries, esophagus, aorta, pulmonary veins, and pulmonary artery are all structures that are in contact with the outer wall of the atrium, and could be damaged by energy transmitted through the atrial wall.
Accordingly, it is the object of the present invention to provide an improved method and device for making transmural ablations to heart tissue.
It is a related object to provide a method and device for making transmural ablation in heart tissue that minimizes unnecessary damage to the heart tissue.
It is a further object to provide a method and device for making transmural ablation in heart tissue that creates continuous lesions in a single step.
It is still a further object to provide a method and device for monitoring the electrical conductivity of the tissue in the transmural lesion simultaneously with the creation of the lesion.
It is also an object to provide a method and device for measuring the temperature of the tissue forming the lesion simultaneously with its creation.
These objects, and others which will become apparent upon reference to the following detailed description and attached drawings, are achieved by the use of a clamping and ablating device for use in treating cardiac arrhythmia having first and second handle members, with first and second mating parallel jaw members associated with the first and second handle members, respectively. The jaw members are preferably curved and are movable by the handle members between a first open position and a second clamped position, and the jaw members have insulated outer surfaces which may have convex, opposed mating surfaces. Each mating surface has a central region, with the central region of the first jaw being aligned with the central region of the second jaw. A first elongated electrode extends along the central region of the first jaw and a second elongated electrode extends along the central region of the second jaw. The first and second electrodes are adapted to be connected to an RF energy source so that, when activated, the electrodes are of opposite polarity. In a preferred embodiment, the electrodes are made of gold-plated copper and measure between approximately 3 to 8 cm in length and approximately 0.12 to 0.6 mm in width. By the use of such a device a clamping zone is created that is approximately at least three times wider than the contact zone of the electrodes with the tissue. This permits the ablation to be performed with a minimum of contact between the electrodes and any blood cells, thus greatly reducing the likelihood of thrombus. The design also allows for a minimum distance between the electrodes, further encouraging complete, transmural ablation that creates a continuous lesion in a single step.
With reference to the present invention, the compression of the atrial tissue is important because it insures that the exposed electrode surface or cryogenic probe is not in contact with any tissue or blood except the clamped tissue to be ablated. Specifically, the clamping of the tissue between the electrodes or cryogenic probes insures that the conductive or cooled area is only in contact with the clamped tissue. The compressed tissue acts to isolate the electrically active or cryogenically cooled surface, and prevents inadvertent energy delivery to other parts of the heart or blood. The outside temperature of the electrode can easily be monitored to insure that the temperature of the insulation in contact with blood remains below a critical temperature (40� C., for example).
In one form of the invention, transmural ablation using RF energy is accomplished by providing an atrial ablation device having a lower "j" clamp/electrode element and placing it on the atrial tissue below the pulmonary veins.
Once the pulmonary veins have been isolated, an upper clamp/electrode element is introduced, and the clamp assembly "J" is worked back onto the epicardial atrial tissue. Once the jaws are positioned below the ostia of the pulmonary veins, the tissue is partially clamped, allowing continued flow from the pulmonary veins to the left atrium. Once the clamps are safely away from the pulmonary vein tissue, and onto atrial tissue, the clamps are closed together to compress the tissue. Once the tissue is compressed, bipolar RF energy is used to ablate the clamped atrial tissue. The clamps are then removed, the lesion having been created. Lesions may also be created by inserting one clamp/electrode element through an incision in the heart so as to permit contact with endocardial tissue. This incision may be created with a separate instrument. Alternatively, the tip of one of the jaws may have a piercing structure associated therewith for making the entry incision. Once the clamps are properly located, the tissue is compressed and RF energy is applied.
Turning now to the figures of the drawings, a method embodying the present invention is shown schematically in
The wider zone of clamped tissue serves several purposes. When the clamping members are closed onto tissue, any blood in the clamped zone is squeezed or expressed out. Further, the distance between the electrodes is minimized, so that the ablation zone remains narrow. It is important to isolate the blood from the ablation zone to avoid creating thrombus. Accordingly, a clamped zone that isolates the ablation zone from the blood minimizes the temperature at the periphery of the ablation zone and will reduce the likelihood of the formation of thrombus by the blood in contact with the clamped zone.
Once tissue has been fully ablated with the clamp in the position shown in
This "clamping" method and device for creating transmural lesions has a number of advantages. First, using a two step method as shown allows for clamping and ablation of atrial tissue without stopping the blood flow from the pulmonary vein. Secondly, by clamping both walls together, and delivering energy through the clamped tissue, the atrial tissue is not penetrated. Because the atrial tissue is not penetrated, a larger jaw can be used, and the clamping force can be much higher because of the increased stiffness of the jaw. Also, there is no concern of bleeding from an atrial puncture.
Another advantage of this method and device is that ablation of tissue within the pulmonary veins is avoided, as recent articles have shown that ablation of tissue within the pulmonary veins can cause pulmonary hypertension and stenosis. Specifically referring to
Turning to
The grasper is made of a rigid material, such as stainless steel, and is substantially encased in a durable insulating material, such as ABS plastic. With reference to
In keeping with the invention, the grasper jaws have raised or convex, opposed tissue clamping surfaces, 90, 92, respectively, with each clamping surface, 90, 92 centrally supporting an electrode 94, 96, respectively, of opposite polarity. RF energy of opposite polarity is supplied to the electrodes 94, 96 through conductors 98, 100, which are connected to an RF generator. As with the previously-described jaw members, this electrode/clamp configuration provides a clamped zone of tissue that is significantly wider than the zone of ablated tissue created by the opposed electrodes. This causes for any blood in the clamp zone to be squeezed or expressed out of the ablation zone, thus reducing the likelihood of thrombus formation, as well as minimizing the distance between the electrodes, so that the ablation zone remains narrow. The clamping also eliminates the cooling effect of circulating blood.
With reference to
In keeping with a further aspect of the invention, the graspers may provide feedback that permits the user to gauge the completeness (i.e., degree of transmurality) of the ablation. Specifically, a transmural lesion blocks electrical signals because it is non-conductive scar tissue. Because impedance is simply the inverse of conductivity, the ability of the lesion to block electrical signals is accurately indicated by its impedance, which can be measured simultaneously with the creation of the lesion. During RF energy application to the tissue to be ablated, the current and voltage applied to the tissue are measured, and the impedance calculated and stored. Based upon a function of the impedance (e.g., its value, the change in value, or the rate of change in value) it is determined whether ablation is complete and transmural. See e.g., U.S. Pat. No. 5,403,312, which is incorporated by reference herein. Indicator lights or other types of signals (e.g., audible) may be associated with the grasper to correspond to the degree of ablation determined by the impedance feedback system. For example, once the impedance reaches a certain level for a certain period of time, a red light may be activated to signal that ablation is complete.
In keeping with another aspect of the invention, a feedback system for determining the temperature of the ablated tissue is also provided. To this end, the jaws include a series of thermocouples 102 that are supported in the insulating member 84 remote from the associated electrode 94 near the edge of the jaw 78. The thermocouples 102 protrude slightly through the surface of the insulating member 84 so as to engage any tissue clamped between the jaws 72, 74. Wires 104 are attached to the thermocouples 102 to transmit the information received to a remote location. Again, a visual or other indicator may be provided to alert the user that a certain pre-determined critical temperature (e.g., 40� C.) has been reached, thus permitting the user to avoid undesired thermal spread.
Turning to
The drive jaw assembly 118 comprises a drive electrode 126, a drive insulator 128, and a drive jaw cap 130. The drive electrode 126 provides a second electrical pathway adjacent the tissue to be ablated and is located on the inside of the drive jaw assembly 118 ("inside" being defined as the side contacting the tissue to be ablated) . The drive insulator 128 surrounds the drive electrode 126 and forms the inside of the drive jaw assembly 118. The drive jaw cap 130 forms the backside of the drive jaw assembly 118 ("backside" being defined as the surface opposite the drive electrode 126).
Each of the electrodes 120, 126 is attached to an electrically conductive means, such as a wire, that runs the length of the extension shaft and through the conductor cord 112 for coupling to the RF generator 114.
Each jaw assembly 116, 118 is supported by a two piece extension shaft comprising a right fixed member 132 and left fixed member 134 (for the fixed jaw) and a right drive member 136 and left drive member 138 (for the drive jaw 118). A shaft cap 139 covers the coextensive portions of the fixed members 132, 134 and the drive members 136, 138 (when the jaws are in the open position as seen in FIG. 34). The right fixed member 132 and left fixed member 134 combine to form a structure that extends from a handle 140, through the shaft cap 139, and then terminating at the distal end of the instrument 110 in the fixed jaw assembly 116 on the right and left sides, respectively, of the instrument. Similarly, the right drive member 136 and left drive member 138 extend from the handle 140, through the shaft cap 139, and then terminate in the drive jaw assembly 118 on the right and left sides, respectively, of the instrument. The portions of the fixed members 132, 134 co-extensive with the fixed jaw assembly 116 are joined by a fixed bridge 142 along the length of the jaw. Similarly, the portions of the drive members 136, 138 co-extensive with the drive jaw assembly 118 are joined together by a drive bridge 144 along the length the drive jaw 118.
The handle 140 comprises two mating halves 140 a, 140 b for encapsulating the actuation and force control mechanisms for the grasper, as well as providing for grounding of the shaft components by means of a conductive shaft pin 141. In order to move the drive jaw assembly 118 between its open and closed positions, the handle 140 includes a lever comprising a pair of lever plates 146 and a lever shroud 148. The lever is pivotally mounted on a support member 150 extending between the two halves 140 a, 140 b of the handle 140, with a lever spring 151 biasing the lever to its open position (FIG. 34). The lever plates 146 are coupled by a lever pin 152 to a carriage 154 that captures the proximal ends of the drive members 136, 138, so as to provide translational motion to these members.
The carriage 154 includes a lost motion assembly comprising a carriage spring 156 for controlling the minimum and maximum loads that can be applied to tissues that are to be captured between the jaw assemblies 116, 118. As can be readily appreciated, the thicker the tissue that is grasped between the jaws, the greater the compression of the spring 156, and the greater the compression force exerted by the jaws on the tissue. (The range of tissue thickness is expected to be between about 1-15 mm.) Adjustment of the compression force is accomplished by pre-loading the carriage spring 156 with a load adjustment screw 158. The lost motion assembly also includes a thumb latch 160 for releasing the clamping pressure and for providing a mechanical stop for the spring-loaded carriage 154. The thumb latch 160 is pivotally mounted on a latch pin 162 to secure the thumb latch to the handle 140. Additionally, a latch spring 164 is provided for biasing the thumb latch 160 to its locked position. A latching step on the carriage 154 interfaces with the tip of the thumb latch 160 to provide for the mechanical stop.
When the lever is pivoted with respect to the handle 140, the drive jaw assembly 118 and its drive members 136, 138 slide along the longitudinal direction of the shaft to bring the two jaw assemblies 116, 118 into contact with the tissue intended to be grasped.
In order to ablate a narrow, long region of biological tissue with the instrument 110, the tissue is first placed between the open instrument jaws 116, 118. The user then grasps the actuation lever comprising the lever plates 146 and lever shroud 148 to apply the force required to drive the drive members 136, 138 and drive jaw assembly 118 distally, thus compressing the tissue and automatically engaging the thumb latch 160. The thumb latch 160 locks the position of the drive members 136, 138 and the drive jaw assembly 118 with respect to the handle 140 and the fixed jaw assembly 116. The amount of jaw force on the tissue is controlled by the lost motion assembly between the lever and the drive members 136, 138.
With the jaws closed on the tissue, the operator activates the RF generator 114. RF energy passes through the tissue between the electrodes 120, 126, thus ablating the tissue between these electrodes. After completion of the ablation cycle, the operator releases the clamping of the tissue by depressing the thumb latch 160, thus releasing the carriage 154. With the carriage 154 released, the lever spring 151 drives the drive members 136, 138 and the drive jaw assembly 118 proximally to their open positions. The actuation lever, since it is directly coupled to the carriage 154, also returns to the open position.
Turning to
With reference to
With reference to
With reference to
With reference to
With reference to
With reference to
With reference to
With reference to
With reference to
A further embodiment of a grasper according to the present invention is shown in
The jaws 252, 254 also include a lost motion connection including a spring to bias the jaws toward the closed position. With reference again to FIG. 65A and
With reference to
Lesion 4 connects the lesion 1, which surrounds the right pulmonary veins, to the mitral valve annulus (MVA). It may be made through the same incision and purse-string suture used for making lesion 3. With reference again to
When making lesion 4, care must be exercised in locating the grasper jaws so that the electrodes, when RF energy is applied, do not damage the mitral valve leaflets. It is known that the electrical signals generated by atrial tissue differ from the electrical signals generated by ventricular tissue. Consequently, the distal tip of one of the jaw members of the grasper includes an EKG sensor so that the EKG of the tissue contacted by the tip of the grasper can be monitored.
As best seen in
It may also be desirable to make a lesion between the superior vena cava (SVC) and the inferior (IVC). This may be created in two steps, in which lesions 5 and 6 are made. With reference to
A lesion 8 is made between the right atrial appendage and the tricuspid valve annulus (TVA) utilizing an incision and purse-string suture made in the RAA, as illustrated in FIG. 52H. Lesion 8 is made on the opposite side of the right atrium as lesion 7, and thus is shown in dotted line in
A final lesion 11 is illustrated that connects lesion 10 circumscribing the left atrial appendage with lesion 2 that circumscribes the left pulmonary veins. As illustrated, the lesion 11 is made utilizing an incision and purse string suture through which the grasper jaw is introduced, the incision being located in the left atrial appendage beyond the lesion 10.
In a further embodiment, the present device consists of two long, linear, wire-type electrodes, which are in parallel relationship to each other, each approximately 1 mm in diameter, and 50 mm long. The electrodes are insulated along their entire surface with a thin layer of high dielectric material such as polyamide, except for a thin strip of electrically conductive material that runs along the length of each electrode, in face-to-face relationship with each other. The electrodes are comprised of a high modulus material, such as tungsten or carbon fiber.
One of the electrodes is designed to be introduced into the interior of a hollow organ through a small puncture wound in the wall of the organ. The second electrode is introduced on the opposite side of the hollow organ wall. The device incorporates a mechanism for advancing each electrode individually, or both simultaneously, in parallel relation with each other. The device also includes a clamping mechanism that brings the two electrodes together so that their exposed conductive surfaces are in face-to-face relation and the electrodes exert sufficient pressure to clamp the tissue. Once both electrodes have been advanced to their desired positions, the clamping mechanism is activated which brings the two wires together, and clamps the tissue between the two exposed electrode surfaces. RF energy is then applied between the two electrodes, and the tissue is ablated in a long, continuous, transmural line. A monitoring device measures the voltage, current, impedance, and/or temperature between the two electrodes, and an algorithm determines whether the tissue is fully ablated.
This device provides a way to achieve and verify a fully transmural and continuous line of tissue ablation by locating the atrial tissue between two bipolar wire electrodes, and clamping the tissue. The forceps consist of two electrode pads of opposite polarity designed to grasp and clamp tissue. A well-known method of determining the status of the tissue between the electrode pads is to monitor the current, voltage, and impedance of the tissue, as done using the Richard Wolf generator for bipolar forceps. It is well known in the art that the ablative status of tissue clamped between two bipolar electrodes can easily be determined by monitoring the increase in tissue impedance as the tissue dessicates.
This device is to be used with an RF generator that monitors current, voltage, and impedance to determine the state of tissue ablation of the tissue compressed between the inner and outer electrodes. The RF generator will be equipped with an indicator which informs the user of the status of the clamped tissue, and when ablation is complete (i.e., transmural along the entire length of the electrodes).
This device provides the capability of creating long, transmural lesions through atrial wall tissue of varying thickness because it employs an active bipolar electrode on each side of the atrial wall, and the ablation proceeds from both the inside and outside of the atrial wall. The device is also unique in that the electrodes are used to compress the tissue to be ablated. This compression is critical because the inside and outside surfaces of the atrium can have irregularities, and a high clamping pressure insures that both electrodes are making good contact with tissue along the full length of each electrode. Clamping the tissue also reduces the distance between the electrodes, and makes the ablation more efficient because the electrical energy is more concentrated. Because of this higher concentration of energy, lower powers and temperatures can be used to achieve complete ablation, and the process is considerably faster.
As an example, to fully ablate a 5 mm deep lesion, 30 cm long can take several minutes with an endocardial catheter electrode array, and the temperatures can be as high as 80 to 90 degrees centigrade at the tissue surface with the generator power as high as 40 to 50 watts. In benchtop testing of the present invention in animal hearts, a fully transmural 30 mm line through 5 mm of tissue was achieved in 5 seconds at 20 watts.
With reference to
The operation of the device begins by advancing the inner electrode wire 201 by advancing the slider button 203. Once the inner electrode 201 is advanced to the desired length, the outer electrode 202 is advanced by advancing slider button 204. Note that further advancement of slider button 204 also advances slider button 203, so that both electrodes 201 and 202 advance simultaneously. Because of the bend 202 a in the electrode wire 202, and the notch 205 a in the slider tube assembly 205, the slider tube advances along with the outer electrode 202. Once both electrodes are advanced to the desired length, the slider tube 205 is advanced so that the end 205 b of the slider tube 205 contacts the arcuate wire segment 202 b of electrode wire 202. Further advancement of slider tube 205 acts to compress the electrode wires 201 and 202 together along the entire effective length L.
The compression of the tissue is important because it insures that the exposed electrode surface is not in contact with any tissue or blood except the clamped tissue to be ablated. Referring to
In another embodiment of the invention, a penetrating compressive/tensile electrode is used. Once the jaws are positioned below the ostia of the pulmonary veins, the tissue is partially clamped, allowing continued flow from the pulmonary veins to the left atrium. An electrode needle is introduced which enters the left side of the atrial tissue and exits on the right side into a tip securing point on the lower jaw. This point will prevent the tip from moving axially when a needle is pushed. The lower atrial tissue can be compressed by "pushing" on the needle with a force that compresses tissue between the needle electrode and the lower jaw electrode. Bipolar RF energy is then applied between the needle and lower jaw electrodes to ablate a line of tissue from the needle entry to exit point.
Once the lower atrial tissue has been ablated, the upper jaw is moved down to contact the tip of the lower jaw. Note that this still provides an open lumen for blood flow from the pulmonary veins to the left atrium. The needle is rotated 180 degrees on its axis so that the electrode surface faces up. The needle is then "pulled" to create tension, and exert a compressive force that compresses tissue between the needle electrode and the upper jaw. Bipolar RF energy is then applied between the needle electrode and upper jaw to ablate the tissue. Note that the partial closing of the upper jaw to contact the tip of the lower jaw could be done prior to compressing the lower atrial tissue.
With reference to
Thus, it can be seen that a transmural ablation device and method have been provided that overcome the limitations of the prior art. First, current technology involves ablation devices deliver ablation energy to either the inside (endocardium) or outside (epicardium) of the heart. Using these techniques, the tissue ablation proceeds from one wall of the heart through the tissue to the opposite wall. To date, there has been no reliable way to consistently achieve lesions that penetrate the full thickness of the atrial wall (transmural lesions), and there has been no way to determine either continuity or transmurality of these lesions. If the lesion does not penetrate through enough of the atrial wall, conduction can still occur, and the lesion does not fully block the electrical signals that are causing the arrhythmia. Using an endocardial approach, if the lesion penetrates too far through the wall, critical structures such as coronary arteries, veins, or the esophagus can be damaged on the outside of the heart. Using an epicardial approach, if the lesion penetrates too far, blood can be coagulated, or critical structures such as valves, nodes, or connective tissue can be damaged on the inside of the heart.
There has also been no reliable and consistent way to safely achieve fully continuous, long (greater than 1 cm) lesions in the atrial wall without a high risk of thrombus, damage to critical structures, or extensive damage to the atrial tissue.
The present invention overcomes these shortcomings because the conductive area of each electrode is very narrow compared to the width of the clamped area. As a result, the thermal damage to the tissue is minimal. In contrast, current technology uses catheter electrodes which are typically 1 or 2 mm diameter requiring a lesion width of almost 8 mm to achieve a depth of 5 mm. Using the present invention, a lesion depth of 5 mm with a width of less than 2 mm can be achieved. This aspect of the invention allows for longer linear lesions with less power delivery because less tissue is being heated. There is, therefore, considerably less damage to healthy atrial tissue for a lesion of a given depth and length. Recent efforts in creating linear lesions using endocardial electrodes resulted in ablation of over 20% of the atrial endocardium, and a commensurate decrease in atrial contractility.
Another advantage of this device is that ablation can be done on a beating heart. Using a high modulus material such as tungsten or carbon fiber would allow a minimum diameter, and a maximum clamping pressure for a given clamping length. Once the device is clamped onto the atrial wall, the position of the electrodes can be verified by visually inspecting the position of the outer electrode before delivery of RF energy. If the clamping pressure is higher than the atrial pressure, then clamping over a coronary artery would cut off blood flow, and the resulting change in the EKG would act as a warning to the user prior to applying RF energy. The clamping will prevent any movement of the electrodes relative to the heart wall, and RF energy can be applied with confidence that the ablated tissue will be contained completely between the two electrodes.
Another important feature of this device is that the energy transfer is limited to the tissue clamped between the two electrodes. The insulated electrodes protect structures on the outside of the heart from being exposed to RF energy. Because of this limitation of current flow, damage to critical structures can be avoided.
Another advantage of this device is that it can easily be adapted to a minimally invasive thoracoscopic approach. The device shown has been reduced to a 5 mm diameter device, and can probably be reduced to 3 mm or less. Using video thoracoscopy, the device could be introduced through a small intracostal incision, and used to create fully transmural linear lesions on a beating heart, possibly under local anesthesia on an anesthetized patient.
Accordingly, a device for performing transmural ablation has been provided that meets all the objects of the present invention. While the invention has been described in terms of certain preferred embodiments, there is no intent to limit the invention to the same. Instead it is to be defined by the scope of the appended claims.
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Professional Fighter
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Style: Tai Chi & TKD--
For your viewing pleasure....
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What made me snort with incredulation was this:
Until I realised what it actually meant...Mr Politically Correct GIJoe6186:
Fat people disgust me in every way imaginable. I was at Freindly's with my girl tonight and saw a bunch of fat fuckers. I felt sorry for the pavement they were killing and the people who had to see them. .
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Heaven Gates!!!
Oh ****, I'm sorry. BHAHWHWHWHHAHAHAHAHAHAA. Oh God...
... man, I couldn't stop laughing when I went to the homepage, with all those quite flying starts, with the chubby pimp-Mastah smiling and ****. For a second I though I was looking at Marshall Applewhite's "Heaven Gates" website.
Honest to God, for some reasons, the following pictures scream of "Chuck'N'Cheese':
My d43dl3y belly... It's too sexy for my love, too sexy for my love, love, love... look at my glitterry pimp paraphernalia
Ugh, I gotta block that incoming chi blast...
BWHAAAAGGGG!!! Stop and gimme that chocolate-glazed donut!!!!
****, everybody has a belly... and I can't find my wee wee.
Read this for flexibility and injury prevention, this, this and this for supplementation, this on grip conditioning, and this on staph. New: On strenght standards, relationships and structural balance. Shoulder problems? Read this.
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**** you math class
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Find accommodations in Lafayette with the hotel list provided below. Find cheap and/or discounted hotel rates in or near Lafayette, OR for your personal leisure or group travel. We list the best Lafayette, Oregon motel and hotel rooms. Browse the Lafayette area hotels to find the perfect lodging! Please use the provided map of the Lafayette hotels.The Lafayette center point is about 4 miles from Evergreen Wings & Waves Educational Waterpark and 4 miles from Downtown McMinnville.
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Status: Out of Print
weight: 12.56 lbs
in inches: 12 x 19 x 23
Learn to Play the Easy Way
Prof. Easy
*note: There are copies without outside packaging, no Red Box.
Product Info
- Ages: 10+
- Players: 3-4
- Playing Time: 60 minutes
- Designer: Klaus Teuber
- Art: Tanja Donner & Franz Vohwinkel & Stephen Graham Walsh
- Made in: Germany
10th Anniversary Settlers of Catan 3-D Special Edition Treasure Chest Set™
Commemorating this momentous and joyous event, a special edition has been offered. This special edition includes all the components needed to play Settlers of Catan, and Cities & Knights for 3-4 players.
This edition features three dimensional hand painted tiles made of heavyweight resin and a complete interlocking border. Each player has a complete set of hand painted settlements, cities, metropolises, city walls, knights and roads. The Merchant marker, Barbarian Ship and the three Robbers are also sculpted in fine resin and hand painted. The special wood case is designed to keep your set safe and will feature a special slotted level with slots to hold each hex.
Resource, development and commodity cards are finely crafted in full color casino stock and stored in three small plastic trays. With finely crafted Hex number markers formed of clear plastic disks, view of the beautiful terrain is unobstructed. Limited in production and available only while supplies last... Order yours now!
Look for other games in these categories:
Series: Settlers of Catan Format: Tile Laying
Educational Resources: Cooperation, Economics, Math, Probabilities, Resource Management, Strategic Thinking, Trading/Negotiation
LITKO Officially Licensed Catan Dice Tower
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