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Dec 29, 2010
Thats my boy. Just like the wind. Here one second and gone the next
We are adopting the KISS principal
KISS principle?
can you shed some light al
Keep It Simple, Stupid
Ahhh now I feel really stupid
Not laughed this hard in a good while!
Thanks lads
Westy: WMI is something that's only realy of use to extract more power from a setup / lower intake temps from a heat pump.
In our current state of tune, the turbo produces very little heat, the manifold didn't even glow on power runs at AMD, and inlet temps are very low indeed.
Perhaps when it's got rods and the boost is turned up it might benefit from WMI, but to be honest I think even then it won't be needed to see a consistent 330bhp, only perhaps if we try to go above 330, which we won't be doing
Less to go wrong that way, and unlike your ME7.5, the extra timing has to be mapped in, it can't be dialed in on unisettings.
remember 300bhp in mine is the same power: weight as 400 in yours
I was only gaining a little bit so believe this!
I don't think that WMI is a particularly good day to day option, I destroyed tanks with not over the top nice fun drives and then when your driving around normally your constantly trying to not make the little green led come on. For full banzai-highest-state-of-tune for overtaking Porsches on the ring then yeah but have it switchable to that mode IMO.
but you destroy eveything dane
I would have to disagree
K04 cars should run wmi as std... they just run so so hot normally..
Hahahahahahahahahahahahahahahahahaha - so true!
In my view, its a bodge.
If they run hot, then you should be looking to fix the reasons WHY they're running hot rather than putting a sticking plaster over it!
I wouldnt want to use it on a daily driver, and i certainly wouldnt be mapping in timing for it, as thats just asking for melted pistons when it stops working.
Danes car is so stupidly quick it makes the world go backwards! haha.
Be interesting to see what you think of mine heat wise Bill, in it's low state of tune, at AMD on sunday, even after 6 back to back power runs, the manifold runners wern't even glowing, only the last 2'' of the collector started to glow a dull orange. I'm sure the turbo itself was glowing, but the manifold wasn't anything like Wellys 340bhp setup because it's just not being pushed hard at all in it's current form.
If it came down to having 325bhp without WMI or 345 bhp with WMI, I'd suffer the 20bhp loss and not run it I think, just seems like hassle and something else to keep on top of.
Can't wait for Sunday to see what she makes at Badger5, Just JKM left to try and I'll have had it on dynos north south east and west!
Dane, how did you used to use so much Meth? I top my tank up every week or so and I drive like a twat everywhere! lol
Which is precisely why care is key.
I don't run Meth for heat removal on bumble, Meth makes virtually nil difference to inlet temps as they are cold anyway.
Meth is used pretty much solely for octane increase in the fuel, and I can run with the meth turned off and still only pull 6's.
I think Dane's been drinking it!
Dane treats Meth like he treats clutch plates - it's there to be used!
Haha only 50:50 with water Westy
Welly: I dont really know mate, smaller tank perhaps so the tank empties quicker making it appear I used to use more?
Maybe.... or maybe you my friend are just an ANIMAL! lol
Who says its being mapped for it?
WMI keeps it happy and consistent.
You can wire in fail safes if running it out was a concern.
Its benefits are well proven.
Its not a bodge as you call it.
you a dyno slag now dude... lol
Well some cars are mapped for it, some arent. There was mention above of mapping the timing in or using unisettings to add it, hence my statement.
And ofcourse you can add failsafes for some faults like running out of fluid, but there are also faults you cant always detect, like pump failure or a leak or blocked nozzle. Or even a faulty check valve emptying the contents of the system into the intake tract when the engines off...
However, a correctly sized turbocharger for the power goals with a good intercooling system simply wont need it. Its only when your pushing things to the ragged edge, as per a K04 hybrid running 340hp, or a K04 making 285hp, does it start becoming required because everythings so far outside its comfort zone.
As such i view it as a bodge. The correct solution would be to install a turbocharger thats actually capable of making the desired power without being on the absolute ragged edge. Prawns example of his hybrid making 300hp is a perfect example of this. If you want 340hp, its far better in my mind to install a turbo that can happily and efficiently produce 340hp, while at the same time producing acceptable EGTs and not requring WM to be added to keep it safe.
your just a tight ****
Well i am scottish arent i?
Anyways, advocating spending MORE money on a proper turbo is hardly tight is it?
I suspect the big issue is that to spend eleventy billion quid on a hybrid turbo upgrade and only end up with a nice safe 310hp would leave a lot of people annoyed. So instead of realising that and buying the correct larger turbo in the first place like a GT2871 or whatever, they instead press on with fitting the wrong turbo and turn all the knobs up to 11 to try and get a power figure that justifies the money spend.
In all seriousness, wouldnt you rather see a customer install a nice 2871 or 3071 and get a safe, solid 350hp, that will be endlessly reliable, than install a K04 hybird, eeking out 342hp with 4 figure EGT's and needing water meth to keep it cool?
One way is 350hp done right, one isnt!
true Kev true, although I don't think the absolute safe limit for the hybrid has been reached yet. Wellys needed WMI at 338bhp, although Niki took mine to 329bhp on his dyno, and I got the impression from him that the turbo still had lots more to give and wasn't being pushed hard. that figure was made at around 18psi top end, with a 7100rpm rev limit.
Bill proved with Wellys that the turbo could hold 22psi beyond 7500rpm, so I think there's scope for 340bhp without massive EGT's. Whether the turbo could do more than 340 I don't know, but above that I'll admit WMI would probably be needed.
But that 10hp between 330 and 340 becomes more and more difficult to achieve as the exhaust restriction due to the turbine housing increases, and eventually you'll get to the point where you can add boost and dont actually get any more power.
I'm sure the compressor is capable of more, but i dont think the turbine side is. A simple comparison of the turbine housings on even a GT28RS to the K04 shows how restrictive it is!
350 from hybid is asking too much...... low 300's..... yea, they have their place..
and reality is a lot of folks turbos are at end of life now.. old cars.
if car was cheap to buy (relative) then budget for mods might stretch to bigger framed turbos.. Some folks want to evolve from their stock style setup, and hybrids fit into this category.
budget is the differentiator as well as power delivery...
we have one which runs 28psi >7krpm..
not that boost equates to power of course, just saying it can hold more when pushed
I have exhaust manifold pressure logs and egt's to confirm whats occuring..
hotside is'nt up to more.. without egt's going abscene
Just as well I won't want any more than 330 then I guess! I do see where you're coming from though, there has to come a point where it can't flow any more. I think on a built engine, 320-325bhp and some aggressive timing will give us more power than we will ever need
There does, and we did find it, hence why the boost came back down and WMI went in.
The hybrid got to the stage where additional boost gave nothing but heat, and thus reduced performance as you would expect. The upside to that being that with lower boost, and less EGTs, timing pull was less, and the power could be made up with safe timing advance on the large port.
Prawny, as we discussed, I think that the AGU large runner manifold really really help flow with your engine which is good, deffo for the win. I will be interested to see the difference in Bumble when I fit my manifold.
I run the FP Green without being on the ragged edge at 1.8 bar (Bill used to rum rape it 2.2 bar from memory) sustained across the rev band - and still use meth. Meth makes for a happier engine in my opinion.
I don't NEED to use it at all, but I do choose to because it will keep EGTs lower than they potentially would be, and it brings the octane level of the fuel up, and maybe just a little bit because makes big fat flames.
Higher octane, cooler charge air, cooler EGTs. All good things.
Today has been a good day for small things!
New gas struts arrived this morning for the bootlid, most breakers wanted £10 each for used struts which could die at any time, but BigAl managed to find them brand new on ebay for £20 delivered.
Fitted the new struts tonight, and the boot has never opened so nicely, so that's good news
Also has a new toy arrive today, which hopefully means more drive time and less time in the paddock changing wheels when it starts/stops raining!
word of warning, make sure you start all the bolts by hand before whizzing them up with that. My brother was in the habit of putting the loose wheelbolt into the end of the gun and whizzing it in, then going "dakdakdakdakdak" and calling that tight, until he went to fit his winters this year and noticed one of the bolts more or less fell out.
Looks like he'd cross threaded it and ripped all the threads off the bolt and it was more or less just sitting there with nothing more than friction. Luckily the hub itself was ok!
studs are the answer for frequent wheel changes.. aka track use
Studs are on the to-buy list Bill! and will be sourced through yourself I do believe
Hmmmm, I'd not considered studs. Sounds like a plan.
I think Bill does an array of stud sets, screw stud into hub with locktite, then fit wheels with nuts. Should make swaps MUCH easier!
Thats very good advice. Just a little add on, some years ago I had new tyres on my 3 series just before setting off on a 200 mile journey. Fifty miles or so later a front wheel seized on and the disc was glowing red. I later found out the garage had put the wheels on with an air gun and maybe 180/200 ft Lbs or more. I couldn't get the wheels off using a 6 ft extension to the torque wrench and had to go to a garage with an air gun to have them removed. There I also found out that the alloys had been twisted. Thanks garage. So the sequence should be, nut on by hand, air gun to take up the tension only and then torque them by hand, never by using the gun.
More wheels painted up for track use:
These came from Tufty, a bit battered and abused, but a little while with a grinder and some paint and they're more than good enough for track use
Separate names with a comma.


text: I know it goes by area. BUT, if we could all stick together it would pay off for all of us in the long run. Keeping your Minimum prices the same at least $35.00. Who wants to cut grass for 20 0r even 25 Bucks anymore? Maybe when I was 10. So spread the word guys. Be Strong

subset: commoncrawl


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If so, what happened? Was everything 𝘳𝘶𝘪𝘯𝘦𝘥 𝘧𝘰𝘳𝘦𝘷𝘦𝘳?
Have an opinion?
Be the first guy to share an opinion
and earn 1 more Xper point!
No, but I was with a siblings friend... twice lol. The first time was kinda rough, the guy ended up cheating on me aND we ended things pretty ugly. My brother and I never talked again. The other guy I dated is still really close to my brother. We all got over it lol. Overall tho, I wouldn't recommend it. Was a bit weird and I promised my brother to never do it again haha.
You cannot undo this action. The opinion owner is going to be notified and earn 7 XPER points.


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Two years have passed since young apprentice magician Nathaniel became famous by foiling the ruthless Simon Lovelace. Now 14, Nathaniel is ambitiously climbing the ranks of the magicians' government. The Prime Minister himself has placed Nathaniel in charge of capturing the Resistance, a group of unruly commoners working to undermine the magicians' empire. But after several failed attempts, Nathaniel is forced to admit he can't do it alone.
"great fun"


text: Sorting type: Most visited Most visited Alphabetical | Pages in category "Pages with broken file links" Averii REIGN OF THE CHEESE: BEST CHARACTER R IN THE WORLD:BEGINNING OF THE DAWN OF THE REIGN OF CHEESE Zir Blog posts INVADER VEX/PICTURES (post two) Retrieved from "http://irkempire.wikia.com/wiki/Category:Pages_with_broken_file_links?oldid=12899" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Hidden categories Add category Cancel Save


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Here's something I've been trying to figure out for awhile now. Where is the best place for a guy to meet a woman? The obvious answer is at a bar, club, party, whatever. But at the same time, most women I meet at those kind of events, I'm not really looking for much, if you catch my drift.
Let's say you run in to a girl at the grocery store, fellas. You know that if you approach her, she's gonna be way too busy finding herself some comfort food from her last break up for her to dealing with your ass, at that moment.
Ooo! Or maybe we meet you at school. But then, you're probably stressing over the test you have the next day, and you really need to study, right?
Can you help us out, ladies and clue us in as to where y'all have been hiding?
Most Helpful Girl
The same women who go to grocery stores, libraries, etc also go to clubs
You could possibly find wifey At the club but she probably won't be the main one catching attention Bc she's not over there making a scene. But wifey material chicks also enjoy the nightlife too. They just may not be the main ones guys notice Bc they focus on the hoes10|10|0


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Hi Guys,
I finally got a test environment working regarding our DFS-R.
However, I have now created a "Replication Group Schedule" which is NOT working.
Basically, I have told it to NOT replicate during the hours of 11am to 14pm.
BUT it still keeps mirroring data.
I have left it for a good few hours now. We don't have a massive network. And it takes about 1 second to replicate a few files over.
Any ideas?
3 Replies
Sep 13, 2010 at 9:05 UTC
Hi, I don't have first hand knowledge of DFS, but I did find this interesting:
"Note that these schedules operate according to the schedule of the receiving member of a replication action over a replication connection i.e. DFS Replication is a pull process not a push process. "
Does this help?
Sep 14, 2010 at 2:33 UTC
Hi James
Just a quick question - did you set the schedule on all the servers in the replication group? You can have different schedules for different servers within the same group.
One other thing to try would be to create a new file on one of the servers and a different file on another - see if it is replicating both ways.
Hope this Helps
Sep 22, 2010 at 4:30 UTC
Hi guys, cheers for all your replies.
It turns out in the end, the replication did happen at the scheduled time.
It just took a long time for it to happen!
This discussion has been inactive for over a year.
You may get a better answer to your question by starting a new discussion.


text:
What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
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JotForm Support
If you want a user to select a date from 3 options, then you can simply use a Dropdown field so that they can pick a date for the meeting.
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Outside companies pay to advertise via these links when specific phrases and words are searched. Clicking on these links will open a new tab displaying that respective company's own website. The website you link to is not affiliated with or sponsored by Kohls.com


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Step 2: The Preliminary Test
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Will '3-gatsu no Lion' Return for Season 2?
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Actually, we estimate the odds on renewal as quite possible, taking into account a brilliant reception of the anime series. Let's take a look at some figures. Currently, according to MyAnimeList, "3-gatsu no Lion" has a score of 7.79 out of 10 based on about 5,500 user votes. At the same time, according to Crunchyroll the sports comedy series has a score of 5 stars out of 5 based on 4 reviews and 6 user votes.
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Know what Jahlil Beats uses?
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The producer is seen using this throughout the whole video more
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Height 5'4 130 lb and had a breast aug. 4 yrs ago. Just last week I have noticed a deflation and went back to my surgeon. I am having both redone due to wanting to go fuller. I was an A cup before first surgery and now a C cup(370 cc) using a saline. I want a full D and he suggested a 500cc to 540cc hp. saline Im looking for a fuller breast with less sagging. When I come out of surgery I want to see a big difference in my breast size and concerned that it wouldn't be enough. Got any advise?
4 Years Post Op, Exchanging For Larger Implants. Will They Meet My Expectations? (photo)
Doctor Answers 14
Breast Implant Revision?
Thank you for the question and pictures.
It is impossible to say whether the 502 to 540 mL implants will meet your goals.
Prior to proceeding with the revisionary breast augmentation surgery it will be very important to communicate your size goals with your surgeon. In my practice I find the use of goal pictures to be very helpful. I have found that the use of words such as "natural" or "D cup" or "fake looking" or "top heavy" means different things to different people and therefore prove unhelpful. Also, as you know, cup size varies depending on who makes the bra; therefore, discussing desired cup size may also be inaccurate.
I use intraoperative sizers and place the patient in the upright position to evaluate breast size. Use of these sizers also allow me to select the breast implant profile (low, moderate, moderate plus, high-profile) that would most likely achieve the patient's goals. The patient's goal pictures are hanging on the wall, and allow for direct comparison. I have found that this system is very helpful in improving the chances of achieving the patient's goals as consistently as possible.
Best wishes.
Learn more: http://www.poustiplasticsurgery.com/Procedures/procedure_breastrevision.htm
Bigger---Yes. Less Sagging---No.
Dear Jacquieg, With the increase in size you are considering, you will be larger in size; that is a given. Unfortunately because of your body build and your breast tissue's characteristics, with the larger implant and its increased weight, you probably will sag even more than now. This will not be immediately apparent after your surgery but as the tissues stretch under the increased weight, the breasts will again sag.
Have you considered a silicone implant instead of a saline filled device? While silicone implants will not halt the problem of sagging, they may be less likely to ripple and wrinkle than saline implants.
Hope this helps.
May Benefit from a Lift or Mesh with Implant Revision
It is certainly possible to #increase your implant size with a #revision. However, the #pocket will need adjustment and a lift may be necessary; to better #support the new implant. Additionally, a mesh for further support may be helpful depending on the #implant size and skin #elasticity.
With both implant types there are choices when it comes to size, shape, and profile. The criteria best to suit you will be discussed in full detail at your breast augmentation consultation. Any cosmetic #revision has risks of unhappy outcome or other complications. Also, the right implant for the revision is contingient on shape of body and your desired outcome. Your procedure should always be performed by a #PlasticSurgeon who is board-certified and has a great deal of experience specializing in cosmetic #surgery. You will then greatly improve your chances of getting the result you desire, and, without the need for another revision surgery. It is suggested that you look at before and after photos of the surgeons actual patients, and read patient #reviews. Gathering all of this information will help you make a well-informed decision.
Learn more: http://www.horowitzmd.com/plastic-surgery-procedures-newport-beach/breast-revision/
You might also like...
Caution going to larger implants
In general, larger implants mean bigger problems in the long run, including such things as bottoming out, visible ripples, and malposition. This is more likely when there is poor tissue coverage as in thin patients such as yourself. Consider silicone implants for less rippling, and you may benefit from an acellular dermal matrix graft such as Strattice for an internal bra.
Re-augmentation/replacement of breast implants
I would disagree with a number of issues mentioned in the answers here and stress a few things not mentioned directly. Breast implants do not lift breasts and larger implants do not lift them more. Your breasts are off-axis (point off to the side), wide apart, and look completely filled by the width of the existing implants. I don't think a larger implant will fit well and will not look at all natural, particularly if it is a high profile (off-axis, widely spaced, somewhat ptotic breasts do not look good with a lot of forward projection).
I don't think (although I can't prove it) that implants cause breasts to sag, larger implants cause breasts to sag more or faster, and silicone-gel filled implants cause less sagging than saline-filled. If you already have properly filled saline-filled implants, a larger saline-filled implant that is also properly filled will not ripple more or have additional problems the first didn't. Breast implants are like a pillow rather than a weight and if your breast is going to lose tissue tone and sag it is going to do it regardless of the size/weight/type of implant.
In many cases for a replacement procedure (starting with middle profile implants), the width and forward projection of the implant can be increased by about a half cup size each but in your case I wouldn't advise it as I think you will look rather unnatural. I do think you can stay with saline if you're doing okay with the feel but I wouldn't increase the forward profile and I wouldn't increase the width of the implant more than a cm or so because of the characteristics of your breast.
Saline implants and large imlants will increase sagging
Thank you for sending the photos, it is very helpful. From your photos you can see that you are sagging now. Although all imlants can lead to sagging, saline implants tend to cause more sagging compared to silicone. This is because they are both heavier and less compressible. Larger sized implants, no matter what the fill, are also more prone to sagging. Your tissues can only withstand so much. If you convert to larger, high profile, saline implants now, you may have a temporary "lift". This will be temporary and your tissues will start to stretch, leading to more sagging, due to the extra weight and lack of compressibility of the implant. You can think of it as putting in a tissue expander, like we do when we need to stretch the skin after mastectomy, in order to have enough skin to put in an implant. Just so you understand the power of saline implants to stretch the skin; we use saline tissue expanders when we want to stretch the skin to put in a breast implant for breast reconstruction as well as in other reconstructive procedures. If you were my patient, I would advise you switch to either the gel or form stable silicone implants. This will help minimize how much stretch your tissues will undergo, but it will not eliminate it. Also, it is possible that you will need a lift sometime in the future to maintain the aesthetic result that you like. Hope this helps.
Tracy M. Pfeifer, MD
4 Years Post Op, Exchanging For Larger Implants. Will They Meet My Expectations? (photo)
Even with your posted photos very hard to be definitive in our advise. Larger implants will add to the downward decent. so you may need a lifting also. Best to have a few in person evaluations with boarded PSs in your area.
Sagging with breast implants
Jacquie, I hope you are seeing what all these other experts are saying. Gravity can't be beaten. If you go with bigger implants you are adding weight and more weight pushing against the lower skin of the breast will just stretch it out more. It is very common for patients to come to me with your contour wanting bigger implants because they want more fullness in the upper breast. We talk awhile and then I ask them to tell me how they can pour water into a bucket and make it sit at the top of the bucket. They laugh and say "You can't". Then I tell them neither can I add volume to their breast and keep it from going to the bottom.
Larger implants, fuller yes, less sagging no
The larger implant will get you fuller, though you might have further thinning of the tissue and a bit more sag over time. We would favor a gel as the implant size reaches 550cc, and a moderate profile to keep the implant from appearing too round. The 'big difference' would probably be the 600cc.
Best of luck, peterejohnsonmd.com
Learn more: http://www.peterejohnsonmd.com
Breast implants exchange
With the implants you have now, you are already sagging. Remember larger implants are also heavier and put more strain on the skin to hold them up. The likely scenario is that they will sag again.
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.


text:
Melbourne Confidential
Reporter: Chris Masters
Broadcast: 14/03/2005
One Saturday last May, career criminal Terence Hodson and his wife Christine settled in for a quiet drink, a smoke and a night of TV at their home in Melbournes middle class Kew.
Someone, somehow, gained access that night to their heavily fortified house past the surveillance cameras, the steel window grilles, the security doors and the two German shepherd guard dogs.
Terence and Christine Hodson were kneeling side by side as each was shot twice in the back of the head. They became victims number 26 and 27 in Melbournes relentless cycle of gangland killings.
Terence Hodson had known his life was in peril. "My Dad told me he was a dead man walking," his daughter Nikki tells Four Corners.
Hodson had been living dangerously as a registered police informer for about three years. He refused to go into witness protection, chancing life at home with his family. But from the moment he was exposed by internal police documents that were leaked widely throughout the underworld, he was a marked man.
Gangsters knew that Hodson had "lagged" on them. According to one underworld kingpin who speaks to Four Corners, he was "fair game".
Hodson had also been due to testify against two detectives over an alleged attempted theft of more than $1 million worth of drugs. Three weeks after Terence and Christine Hodsons murders, the charges against one of those detectives were dropped.
The police investigation into the Hodson murders continues, overseen by Victorias new Office of Police Integrity. A reward of $100,000 awaits anyone who dares to nail the killer, or killers.
Victoria Police have long insisted that no firm links can be drawn between the parallel scandals of the gangland killings and the entrenched corruption that has plagued parts of the Victoria Police.
But Four Corners can reveal new evidence that supports this connection evidence that Terence Hodson took to his grave.
Reporter Chris Masters profiles the murdered Terence Hodson, a British migrant, devoted father and grandfather, who opportunistically turned his hand to anything that would turn a dollar drugs, guns, stolen goods, cars, antiques.
Masters pieces together the events leading up to and immediately following the execution of Terence and Christine Hodson. Through candid interviews with underworld figures, family members, investigators and corruption-fighters, he paints a chilling picture of the criminal sub-culture that thrives beneath Melbournes respectable surface and has infected some of its police.
"Melbourne Confidential" Four Corners, 8.30 pm Monday 14 March, ABC TV.
This program will be repeated 11pm Wednesday 16 March.
NB: For legal reasons, two versions of this program will be screened one in Victoria, the other throughout the rest of Australia.


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- Watery
- Watery Wa"ter*y, a. [AS. w[ae]terig.]
[1913 Webster]
1. Of or pertaining to water; consisting of water. ``The
watery god.'' --Dryden. ``Fish within their watery
residence.'' --Milton.
[1913 Webster]
2. Abounding with water; wet; hence, tearful. [1913 Webster]
3. Resembling water; thin or transparent, as a liquid; as, watery humors. [1913 Webster]
The oily and watery parts of the aliment. --Arbuthnot. [1913 Webster]
4. Hence, abounding in thin, tasteless, or insipid fluid; tasteless; insipid; vapid; spiritless. [1913 Webster]
The Collaborative International Dictionary of English. 2000.


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Stiri Concerte Bilete Poze Artisti Tabs & Chords Versuri Radio Online Liste Magazin de Muzica
Versuri Smashing Pumpkins - Shades of Black
Album: Smashing Pumpkins - Zeitgeist
I'm on the street yeah
I want you
I'm looking for myself
I'm gonna make it
I'll take it
Like everybody else
Belle of the fawning
I'm yawning
Sister can't you spell
Above suspicion
Hey listen !
I'm digging my own hell
'Cause I want you bad, ah
'Cause I want you bad
And without peer
And without fear
I'm without anyone at all
I'm torn apart, decrying
How unjust you are
For busting
My black heart
'Cause you don't want me no more
But just you worry
'Cause when they scratch-scratch my door
You'll hurry
Ah 1, 2, 3
This gun is loaded, devoted
You postulate the rest
Riding the seesaw
There's no law
That I have ever met
I'm just a flat punk
On dead junk
Riding a vanguard
Cut from the vaunted
I'm haunted, till death do us part
'Cause I want you bad, ah
'Cause I want you bad
Fall in hate with me with one trick
You will want it all
The yeah-yeah tears
The now and here
The without anyone at all
I'm torn without
I'm crying out for doom
'Cause you don't want me no more
But babe don't worry
'Cause when you scratch-scratch my door
I'll show you, either or?
We are the lurking
The panzers
The black as coal as night
Stealing the stealthy
And stellar
Until we get it right
Notice the yearlings
The dead things
The pretty as you please
I am the regent, the marquis
Sowing my bad seeds
'Cause I want you bad, ah
'Cause I want you bad
Fall in hate with me with one trick
You will want it all
As St. Patrick pipes on!
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Koby Altman became the unlikely general manager of the Cleveland Cavaliers last month. His first big move: trading Kyrie Irving.
The National League has a rare opportunity to declare offensive supremacy in a way unseen in decades.
Italy's third-largest city is packed with shrines to a retired Argentine soccer star with a history of spectacular cheating, controversial politics and a drug ban. 'He's a little crazy.'
Subscriber Content Read Preview
Pro football may rule big-screen TVs in the U.S., but it's the small screens of smartphones where the National Football League hopes to make its play in China.
Alabama coach Nick Saban said by watching the Weather Channel, he already knows what to expect during the solar eclipse.
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Pro golf's youth movement, led by Jordan Spieth, stems from a sophisticated junior program that has grown even as overall participation in the game has declined.
This year's field is decimated by injuries, raising hopes that the two superstars could meet in New York for the first time
Former Ole Miss football coach Hugh Freeze resigned in July after the school confronted him with its findings about a "pattern of misconduct." Flight records place Freeze in the same city as an escort service called on university phone. The school says other incidents also raised red flags.
As leagues see more players over 70, they're making allowances for those who take a while to reach first base. The Antiques take on the Geezers.
It appears that Giancarlo Stanton has figured out that he doesn't have to swing wildly from his heels to send baseballs soaring into the stratosphere.
Michigan football coach Jim Harbaugh is the counterintuitive outlier in a sport that breeds conservative thinkers. In that way his unlikely embrace of soccer is perfectly Harbaughian.
There is hope that the Pyeongchang Games will promote harmony between South and North Korea but recent events are causing concern.
The Kansas City Royals have exceeded the expectation of every prominent computer projection over the past five years.
The U.S. Open announced that Maria Sharapova has been given a wild card into the women's singles tournament.
Justin Thomas won the PGA Championship on Sunday, cementing the 24-year-old's place as one of golf's brightest young stars.
Arsenal's Olivier Giroud is the rare soccer player whose most dangerous position is starting every game on the bench.
Former New York Yankees captain Derek Jeter plans be a limited partner in the group led by venture capitalist Bruce Sherman, who will be the controlling owner.
The NFL suspended Dallas Cowboys running back Ezekiel Elliott six games for violating the league's personal conduct policy—after a long investigation into multiple alleged domestic violence incidents from last year.
There is a simple formula to winning games in the NFL: Keep your quarterback upright.
Rickie Fowler has won more than $26 million on the PGA Tour and is one of golf's most recognizable faces, but a major title still eludes him.
As the Premier League kicks off its season, it's worth remembering one truth of English soccer: the average Premier League manager lasts less than 18 months.
The Los Angeles Dodgers have baseball's highest payroll but they haven't just used their financial muscle to load up on stars. They assembled a powerhouse by focusing on the fringes of the roster.
Rory McIlroy appeared poised to dominate golf, but after going three years without winning a major title, it feels like something is missing.
The PGA Championship will move to May starting in 2019, golf's governing bodies announced.
One year after suffering a severe concussion and three broken vertebrae in a crash at the Rio Olympics, Dutch cyclist Annemiek van Vleuten is back on the bike—and winning.
After blowing a 28-3 lead to the Patriots in the Super Bowl, Atlanta is trying to use the memory as motivation this season
Jay Cutler's return to the NFL is good news for fans who enjoy watching quarterbacks fling passes deep downfield.
The Miami Dolphins agreed to sign quarterback Jay Cutler, who just three months ago called it quits, according to multiple reports.
The Seattle Mariners acquired All-Star first baseman Yonder Alonso from the Oakland Athletics for rookie outfielder Boog Powell on Sunday.
Eight-time Olympic champion Usain Bolt finished third in the men's 100-meter world championship final in London, behind Americans Justin Gatlin and Christian Coleman.
More golf courses are experimenting with offerings that are shorter and cheaper than the traditional 18-hole round.
Brevin White could've chosen to play football at almost any college he wanted. He chose Princeton.
The New York Yankees are quite possibly better equipped than any other team in baseball for the pressure-cooker format of the playoffs. But first, they actually have to make the playoffs.
Usain Bolt is set to contest one last 100-meter sprint on Saturday night at the world championships in London, his final individual event before a long-planned retirement.
Paris Saint-Germain will have to pay a record transfer fee of $262 million to pry Neymar from Barcelona. It's all part of the plan to reorganize the European game by brute force.
A combination of Legends Hospitality and NFL On Location would potentially provide travel and ticket services for the world's biggest sporting events
The average return to playoff teams during the last two months of the pennant race has been less than one win.
Tennis star Stan Wawrinka said he will miss two U.S. Open warm-up events, putting his U.S. Open status in doubt.
The Rockets signing P.J. Tucker—yes, P.J. Tucker—was the most revealing move of the league's crazy summer
Caeleb Dressel just won seven golds at swimming's world championships, but the lineup for the 2020 Tokyo Games isn't as favorable.
The Los Angeles Dodgers acquired pitcher Yu Darvish from the Texas Rangers, while the New York Yankees traded for Oakland A's pitcher Sonny Gray.
The team granted Bartman a ring, leading him to say he hoped the gesture leads to "healing and reconciliation"
Officials in Los Angeles and leaders of the International Olympic Committee have reached a deal to bring the Summer Games to Southern California in 2028.
NFL commissioner Roger Goodell says the culture around head injuries in football has changed. His comments came in response to a recent study that showed the effects of head trauma on former football players.
Six months after discovering a natural talent for racing, Besnik Sokoli trains in a boiler room hoping to compete for his native Kosovo.
A majority of fans in the Los Angeles area can't watch Dodgers games on television due to a cable-TV contract feud that has lasted for nearly four seasons.
Jordan Spieth's impromptu decision to chew gum during the British Open has sparked an unlikely debate.
The polarizing quarterback, who created a firestorm with his national-anthem protests last year, still hasn't been signed despite playing decent as a starter last year
The NFL's salary cap for this season is a record $167 million per team—but many teams are hoarding the extra cash.
Caeleb Dressel became the first swimmer ever to win three gold medals on a single night at either the world championships or the Olympics.
The Chicago White Sox have embarked on a scorched-earth rebuild that could set a new standard for how to repair a struggling franchise.
Since 1913, there have only been seven instances of a player going through a calendar month with at least 100 plate appearances and a .500 batting average. Jose Altuve could join that exclusive club with a few more good games.
Derek Jeter joins a deal to buy the Miami Marlins. Here's some free advice for the new sports owner.
Another round of anthem protests has Jason Gay ready to walk away from the game. Or...maybe not.
Jason Gay: A depressing report from Rio underlines the economic and moral hazard of the Olympics.
The first two games of the NBA Finals were statistically the fastest playoff games in history. The Warriors are better when they're playing faster.
Mike Trout is a two-time AL MVP and was in the midst of another stellar season, before he suffered a torn thumb ligament. But don't count him out of this year's MVP race just yet.
Although many of the NFL's most famous touchdown celebrations last less than 15 seconds, analysis reveals that Green Bay's Lambeau Leaps take a bit longer.
Red Sox ace Chris Sale has now reached double-digit strikeouts in seven consecutive outings and needs one more to tie his own major-league record.
The NBA draft lottery is designed to help the league achieve competitive balance. But no system can protect the Brooklyn Nets from themselves. As a result, the Boston Celtics will be the best team to have at least a top-four pick in more than 30 years.
Over the past seven years, Real Madrid's domestic results have bounced up and down, but in Europe, it remains a model of consistency.
Teams have shown more of a willingness to put their players on the shelf since the league implemented the 10-day DL.
The Hall of Fame coach says it's key that certain players get paired with coaches who have enjoyed success with similar athletes in the past
History shows college quarterbacks with losing records usually struggle in the NFL
The Cleveland Browns are widely expected to select Myles Garrett first overall in Thursday's NFL draft. History indicates, however, that Garrett has virtually no chance to be this draft's best player.
Oakland's Adam Rosales isn't a speedster, but has recorded eight of the 10 fastest home-run trots, since 2015.
Houston Rockets guard Patrick Beverley is great at pestering the Thunder's star player.
As the NHL playoffs begin on Wednesday, momentum is critical to Stanley Cup success. Rare is the team that limps into the postseason and catches fire to become champions.
The Cardinals catcher doesn't drive in many runs—but he earns his sizable new paycheck by elevating the St. Louis staff
The Minnesota Timberwolves have the most kicked-ball violations in the league—and that's more strategic than you might think.
Kentucky takes over the top ranking in our annual valuations of NCAA teams
Where all 30 MLB teams rank in terms of players taken in fantasy drafts this season
The defending World Series champs built their roster by stockpiling young prospects. Their neighbors on Chicago's South Side are trying to do the same
Mets pitcher Noah Syndergaard has had an average fastball velocity of 97.5 miles per hour in the past two seasons. Can his elbow withstand the stress created by such velocity?
Some of baseball's top aces, including Clayton Kershaw, Madison Bumgarner and Noah Syndergaard, opted not to take the ball for Team USA. Limited data shows it might be a wise decision.
There is one pitcher leading baseball's seemingly endless quest to shorten the length of games: Houston Astros reliever Chris Devenski.
A statistical model for predicting upsets has identified three worthy underdogs: Middle Tennessee, Xavier and Princeton.
As the power surge takes over baseball, fewer and fewer players are consistently hitting for a high average.
Teams might want to not overeact to John Ross's eye-popping 40-yard dash time, because recent history hasn't been kind to combine speedsters once they reach the NFL.
The Boston Red Rox traded two top prospects this offseason for left-hander Chris Sale, but the five-time all-star risks becoming the latest southpaw to struggle at Fenway
After 12 trades last winter, general manager Jerry Dipoto has made 14 this off-season—the most in at least two decades.


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In Parkinson disease, the second most common neurodegenerative disorder in humans, increased alpha-synuclein (SNCA) levels are pathogenic, as evidenced by gene copy number mutations and increased alpha-synuclein levels detected in some familial and sporadic PD cases, respectively. Gene expression can be regulated at the post-transcriptional level by elements in the 3′ untranslated region (3′UTR) of mRNAs. The goal of this study was to determine whether the 3′UTR of human SNCA can affect gene expression. Comparative sequence analysis revealed very high conservation across the entire 3′UTR of human SNCA over millions of years, suggesting the presence of multiple functionally important domains. EST and RT-PCR analyses showed that four different polyadenylation events occur in the 3′UTR of human SNCA. Finally, using luciferase assays, we examined the effect of the minor allele of five naturally occurring single nucleotide polymorphisms (SNPs) in the 3′UTR of SNCA on gene expression. The minor allele of SNP rs17016074 increased luciferase expression by 32% in a transient transfection assay in SHSY5Y neuroblastoma cells. Understanding the role of the 3′UTR of human SNCA and identifying functionally important naturally occurring SNPs using reporter assays can complement disease association studies in humans, uncovering potential susceptibility or protective polymorphisms in Parkinson disease. Our findings demonstrate that the 3′UTR of human SNCA, as a whole, and rs17016074, in particular, are loci of potential clinical importance for Parkinson disease.
Parkinson disease (PD) is the second most common neurodegenerative disorder in humans. Approximately 90% of all PD cases are sporadic, with the remaining ~10% being familial. In the vast majority of PD cases, the exact etiology of the disease is not known [10]. In addition to the point mutations that cause some cases of familial PD, two lines of evidence suggest that, in the absence of point mutations, increased levels of wild-type alpha-synuclein are also pathogenic. First, in some sporadic PD cases, SNCA mRNA levels in the brain are increased [3, 9, 21, 25]. Second, eight familial PD cases carrying multiple copies of SNCA have been identified [2, 6, 11, 12, 19, 24]. Due to the absence of point mutations in any of the copies of SNCA in these patients, the cause of PD appears to be the mere increase in alpha-synuclein levels. Moreover, in support of a dosage effect, PD patients from families with two extra copies of SNCA have a more severe phenotype than PD patients with only one extra copy [6, 12, 22]. The pathogenicity of multiple SNCA gene copies and the apparent dosage effect of alpha-synuclein levels in both sporadic and familial PD highlight the clinical significance of the regulation of SNCA gene expression.
Regulation of gene expression can take place at the level of transcription, by controlling mRNA synthesis, as well as post-transcriptionally, by controlling mRNA stability and translation. Studies on the transcriptional regulation of SNCA have been primarily centered on the NACP repeat, which is believed to affect SNCA transcription [4]. Numerous association studies have established a link between increased risk of PD and NACP alleles that increase SNCA expression [13].
Increased SNCA expression could also result from misregulation of its post-transcriptional control. Post-transcriptional control of gene expression can be mediated by several elements, many of which are located in the 3′UTR of mRNAs [1, 15, 26]. Despite a series of studies that report an association of polymorphisms at the 3′ end of SNCA with sporadic PD [16-18, 23, 27], the precise function (and mature sequence) of the 3′UTR of human SNCA mRNA is not known.
The goal of this study was to determine whether the 3′UTR of human SNCA can affect gene expression. To find evidence of important regulatory elements, we first examined the degree of sequence conservation of the 3′UTR of SNCA across multiple species. We then performed experiments that were designed to identify the sequence that constitutes the functional 3′UTR of the human SNCA message. Finally, using luciferase reporter assays, we identified a single nucleotide polymorphism in the 3′UTR of human SNCA that has a significant impact on gene expression.
NM_000345 is the human SNCA mRNA sequence used as a reference throughout this study. The 3′UTRs of SNCA orthologs (Fig. 1) were obtained from the following NCBI entries L33860 (canary), NM_204673.1 (chicken), XM_001496904 (horse), XM_855879 (dog), NM_000345 (human), XM_1162591 (chimpanzee), XM_001095402 (rhesus monkey), NM_001034041.1 (cow), NM_001037145.1 (pig), NM_009221.2 (mouse), NM_019169.2 (rat), NM_001087154.1 (Xenopus laevis). Mutliple sequence alignments were performed using ClustalW2 (http://www.ebi.ac.uk/Tools/clustalw2) with the gap extension penalty set to 0.05 and the gap distance penalty was set to 1. Sequence similarities were visualized using the BOXSHADE program (http://www.ch.embnet.org/software/BOX_form.html). The last 337 nucleotides shown in Fig. 2 were obtained from contig NT_016354 (NCBI). RepeatMasker (http://www.repeatmasker.org) identified repeats in the 3′UTR of SNCA.
Global sequence alignments of chicken-human ortholog pairs were performed using a version of FASTA (GRASTA: ktup = 3, opt cutoff = 100) on sequences previously identified [20]. Sequence pairs were used if the 3′UTRs of both orthologs were longer than 50 nucleotides in length after the trimming of terminal adenosine residues; The final data set consisted of 426 ortholog pairs. For local sequence alignments, chicken-human ortholog pairs from HomoloGene (NCBI) were identified by text matching of gene symbols. We obtained 2653 pairs of orthologs for which both species had unambiguously associated, experimentally verified RefSeq mRNA records and where both of the paired sequences had trimmed 3′UTRs greater than 50 nucleotides in length. The sequences were subjected to pairwise BLAST alignment (bl2seq version 2.2.19); all masking and low-complexity filtering options off. Only non-overlapping, plus-strand alignments with E-values < 1 × 10−6 were accepted.
All expressed sequence tags (ESTs) were obtained from the Unigene cluster Hs271771 (NCBI). ESTs that did not align with fully-spliced SNCA mRNAs and did not contain a polyA tail were excluded.
RT-PCR analysis (Amersham Pharmacia, 27-9261-01) was performed on RNA extracted from the brain of [Tg(SNCAWT); Snca-/-] [8] mice. These mice are deleted for the murine Snca gene and contain a P1 artificial chromosome (PAC) that carries the entire SNCA including several kb of upstream and downstream genomic sequence. The mice were sacrificed following NIH guidelines (protocol number G-98-13). RNA was extracted from 14 days old mouse brain using Trizol (Invitrogen, 15596-026). Oligo(dT)18-NotI was used for first-strand synthesis (Amersham Pharmacia 27-9261-01) and appropriate samples were treated with DNaseI (Gibco, 18068-015). PCR amplification was carried out using anchored oligo(dT)20 (Invitrogen 12577-011) or TTAAGGAACCAGTGCATACCAAAACACA (R1) and one of the following forward primers: CTACGAACCTGAAGCCTAAGAAAT (F1) or ATTTTATTTTTATCCCATCTCACT (F2).
The first 574 nucleotides of the 3′UTR of human SNCA was amplified using the primers TCTAGAGAAATATCTTTGCTCCCAGTTT and GGATCCTAAAGTGAGATGGGATAAAAATAAAAT from DNA extracted from human fibroblasts using standard protocols. The full length 3′UTR was cloned into the pGL3-Promoter (Promega E1761), after XbaI/BamHI excision of the SV40 late polyA signal. The open reading frame (ORF) of luciferase of the pGL3-Promoter was replaced with the ORF of Luc2CP obtained from pGL4.16 (Promega E6711).
All SNPs in the 3′UTR of human SNCA were obtained from dnSNP (NCBI). Haplotypes and linkage disequilibrium information across the 3′UTR of human SNCA were retrieved from the HapMap Genome Browser (www.hapmap.org) and the NIEHS Environnmental Genome Project Web site (http://egp.gs.washington.edu/). The minor alleles of all SNPs were introduced into luciferase constructs using the QuikChange Multi Site-Directed Mutagenesis kit (Stratagene 200515). The mutagenesis primers used are shown below: ATCAGCAGTGATGGAAGTATCTG TACCT (for rs10024743), TATGAAATTTTACCATTTTGTGATGTG (for rs17016074), TCCCTTTCACTGAAGCGAATACAT GGTAGCAGG (for rs34825021), TCCCTTTCACTGAAGTGAATACATAGTAGCAGG (for rs35716318) and TTATAAGATTTTTAGGTGTTTTTTAATGATACTGTC (for rs35733299).
SHSY5Y cells (ATCC CRL-2266) were transfected with 1 ug of luciferase construct and 100 ng of Renilla plasmid (Promega E2231) using FuGENE (Roche 11-814-443-001). Cell lysates were analyzed using the dual luciferase assay kit (Promega E1910) and the semi-automatic luminometer Lumat LB 9507 (EG&G Berthold).
To gain an understanding of the overall functional significance of the 3′UTR of SNCA, we examined its degree of conservation throughout evolution. Alignment of the 3′UTR of SNCA from twelve species revealed sequence blocks that have remained unchanged over millions of years (Fig. 1).
To quantify the degree of SNCA 3′UTR conservation seen across species, we subjected the 3′UTRs of 426 chicken-human ortholog pairs to global sequence alignment. We determined that the 3′UTR of SNCA was the 24th most highly conserved 3′UTR of the sequences analyzed, yielding a 610-nucleotide alignment with 71.6% identity. To extend this analysis, we performed local sequence alignments on a larger set of ortholog pairs to delineate regions of unusually strong 3′UTR conservation between chicken and human. About 25% of 2653 orthologous pairs yielded one or more local alignments of 80% identity or greater, indicating that conservation between chicken and human orthologs in limited regions of the 3′UTR is not a rare occurrence. However, the SNCA 3′UTR sequences displayed an atypically high level of conservation, with three significantly scoring local alignments: 88.7% identity (106 nucleotides), 86.2% identity (87 nucleotides), and 91.2% identity (34 nucleotides). We considered alignment quality (E-value) and relative coverage of length in evaluating the local alignment results, and SNCA ranked in the top 10% of chicken-human orthologs analyzed with respect to both criteria. These results suggest that human SNCA contains several functional elements that are distributed throughout its 3′UTR.
To determine the pattern of alternative polyadenylation in the 3′UTR of human SNCA, we identified all putative polyA signals present in the 3′UTR of human SNCA (Fig. 2). Of the eight polyA signals predicted, three are detected in a short stretch of 25 nucleotides and are referred to herein as the "polyA triplet". The eighth polyA signal is located downstream of a LINE element that is also present in the 3′UTR of some human SNCA transcripts (Fig. 2).
Alignment of all ESTs of human SNCA obtained from various tissues revealed that the eight putative polyA signals mediate four polyadenylation events (Fig. 3). EST analyses showed that the 3′UTRs of 95% of SNCA mRNAs are up to 574 nucleotides long (Fig. 3 and Table 1). This suggests that the first 574 nucleotides of the 3′UTR of SNCA are the most relevant for human physiology.
RT-PCR analyses using total mouse brain RNA confirmed the polyadenylation pattern shown in Fig.3 (data not shown). RT-PCR analyses additionally confirmed a much higher abundance of SNCA mRNAs that are 574 nt long (data not shown).
Table 1 summarizes the polyA signal usage in the 3′UTR of human SNCA and includes information on predicted GU-rich elements. GU-rich elements located downstream of polyA signals are known as downstream sequence elements (DSE) and can affect polyadenylation efficiency [5, 7, 14].
Due to the clinical importance of increased alpha-synuclein expression in Parkinson disease, we retrieved all single nucleotide polymorphisms (SNPs) present in the first 574 nucleotides of the 3′UTR of human SNCA (Fig. 4a) and examined their effect on luciferase expression in neuroblastoma SHSY5Y cells. Of the five SNPs examined, only rs17016074 resulted in an increase in luciferase expression over numerous experiments performed under diverse conditions (Fig. 4b). The average increase in luciferase activity caused by the presence of the minor allele of rs17016074 is 32.8% (Fig. 4b). A single nucleotide change at the polymorphic locus rs17016074 can therefore affect reporter gene expression in neuroblastoma SHSY5Y cells.
If rs17016074 can affect expression of endogenous SNCA in humans, it could also affect susceptibility to Parkinson disease. Due to an apparent lack of recombination events, the low frequency of the minor alleles of most of these five SNPs and their differing frequency in various human populations (data available through NCBI, HapMap, and the NIEHS Environmental Genome Project Web sites), haplotypes containing the minor allele of rs17016074 with more than one minor allele of the four other SNPs are not found. We conclude, therefore, that combinations of minor alleles at the other four SNPs are unlikely to affect SNCA expression in vivo in humans.
In this study, we have shown that human SNCA mRNA molecules have any of four different 3′UTR sequences. We have also shown that the first 574 nucleotides of the 3′UTR of human SNCA are highly conserved and included in 95% of its mRNAs. Finally, we have identified a single nucleotide polymorphism, rs17016074, that can increase reporter gene expression in neuroblastoma SHSY5Y cells. The presence of a functional SNP in the 3′UTR of human SNCA qualifies the SNP and the entire SNCA 3′UTR as potential susceptibility loci for Parkinson disease.
Rs17016074 is located between the two most frequently used polyA sites in the 3′UTR of human SNCA (Fig. 4a). Rs17016074 is located immediately upstream of (but not in) a downstream sequence element, which could affect polyadenylation efficiency at the immediately upstream polyA signal (Table 1). The effect on reporter gene expression of rs17016074 suggests that a functionally important element is located between nucleotides 473 and 528 of the 3′UTR of human SNCA. Therefore, it contains elements that can indeed affect gene expression, a finding that is consistent with the biological importance suggested by the high conservation of the 3′UTR of SNCA over millions of years.
Knowing the 3′UTR sequence of SNCA mRNAs lays the framework for understanding the importance of genetic variation at the 3′ end of SNCA in Parkinson disease. Several studies have reported an association of the 3′end of human SNCA with sporadic PD [16-18, 23, 27]. To date, the molecular details of these association studies were not clear, because the entire 3′UTR sequence of SNCA mRNAs in both cases and controls was not known. Of all the polymorphisms that are reported to be associated with sporadic PD in these studies, only rs356165 is actually present in the 3′UTR of SNCA mRNAs. Rs356165 is located in the LINE element of the 3′UTR of human SNCA (Fig. 2 and Fig. 3) and is therefore included in only 5% of SNCA mRNAs (Fig. 3). The minor allele of rs356165 could, therefore, have a direct effect on SNCA expression only by affecting a small minority (about 5%) of SNCA mRNAs in which it is present. Alternatively, it is possible that the association between rs356165 and sporadic PD is driven by other SNPs in SNCA that are functionally important and in linkage disequilibrium with rs356165. The minor allele of rs17016074 is unlikely to be such a polymorphism, since none of the published association studies included PD patients of African descent, where the minor allele of rs17016074 is detected. It is noteworthy that Parkinson disease is inadequately studied in people of African descent (African Americans and sub-Saharan Africans). Rs17016074 is therefore a novel, clinically important polymorphism identified as a result of our studies.
In summary, we have determined the sequence of the 3′UTR present in SNCA mRNAs in humans and identified a single nucleotide polymorphism that is of potential clinical importance for Parkinson disease. Identifying polymorphisms that can increase alpha-synuclein expression may lead to an understanding of the etiology of sporadic Parkinson disease, which constitutes ~90% of all PD cases. As the total number of sporadic PD patients increases due to increase of the human lifespan, polymorphisms that stimulate alpha-synuclein expression become even more clinically significant.
We would like to thank Yien-Ming Kuo for help throughout this project and critical review of this manuscript and Lowell Umayam, Gabriel Renaud, and Anh-Dao Nguyen for bioinformatics support. This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health and by the Department of Medicine, UCSF School of Medicine.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


text:
Restricted Items
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text:
One Year Ago...Edit
[We see a sign called 1 year ago]
And Now...Edit
Jo and the Nanny 911 crewEdit
Jo: "I visited the Jenkins Family a year ago and tried to help them take back control of their daughter Alexandra's behavior. However, Alexandra disrespected me so badly that I had to end up leaving the house. Steve and Nora were so upset that they begged me to come back in the future. I kept my promise, but this time I brought a little surprise with me."
Deb: "Hello, my name is Deborah Carroll. I have over 29 years experience of being a nanny and I believe in the "tough-love" approach. When I heard about Alexandra's behavior, I knew I had to help Jo."
Stella: "I'm Stella Reid. I've been a nanny for 22 years and have helped families across England. When I heard about the family's rebellious daughter who sneaks out at night to do drugs with her boyfriend, I knew I also had to help Jo."
Yvonne: "I'm Yvonne Shove. I've been a nanny for 22 years and I like to help families doing it tough."
Jo and Mike RugglesEdit
Mike: Hi, I'm Mike Ruggles, and I'm a Chicago developmental therapist who has been helping families in crisis for over 15 years. When I heard about the Jenkins family's rebellious daughter, that's then I decided to give a lending hand."
[airplane lands and Mike steps off]
Jo: "Hi."
Mike: "You must be Jo Frost. I'm Mike Ruggles, developmental therapist."
Jo Returns to the Jenkins HouseEdit
[Nanny Jo, Mike Ruggles, Nanny Stella, Nanny Yvonne and Nanny Deb arrive at the Jenkins residence]
[Jo knocks]
Jo: "It's me, Jo Frost."
Nora: "Hello Jo. Who are these people with you?"
Mike: "Hi, I'm Mike Ruggles. I've been a developmental therapist helping American families in crisis for 15 years."
Stella: "I am Stella Reid. I've been a nanny helping families across England for over 22 years."
Yvonne: "I am Yvonne Shove. As a nanny, I've been helping families for over 22 years."
Deb: "And I am Deborah Carroll. I've been a nanny for 29 years and I believe in the 'tough-love' approach."
Nora: "Alexandra's been arrested for possession of illegal drugs by the police. They found marijuana and cocaine in her bag."
[We see a brief shot of Alexandra's mugshot]
Steve: "In addition to that, she has also been expelled from school."
Nora: "Yes, she was expelled from St. Margaret's School for Girls for computer hacking and for the hazing incident."
Jo: "I couldn't believe what I just heard. Alexandra doing drugs, yet again! Poor Nora."
Nora: "She's also started smoking and drinking."
Deb: "When Alexandra got home, we seriously needed to talk to her."
Yvonne: "What about Liam? How is he?"
Steve: "Liam's doing fine."
[knock on the door]
[Nora answers it, and it is a police officer with Alexandra]
Jo: "Sure enough, a policeman arrived at the door with Alexandra. She was caught using drugs."
Nora: "Thank you, officer."
[The policeman leaves]
Nora: "Alexandra Jeanette Jenkins! I have had it!"
Deb: "Young lady, we need to have a serious talk with you!"
Yvonne: "We heard that you have been sneaking out at night to do drugs!"
Stella: "And not to mention smoking and drinking."
Alexandra: "Who the (bleep) are you three?"
Deb: "We are the nannies from Nanny 911. I am Nanny Deborah."
Yvonne: "and I am Nanny Yvonne,"
Stella: "and I am Nanny Stella."
Alexandra: "And who's this gorgeous gentleman next to HER? (referring to Jo)"
Jo: "That is Mike Ruggles, he is a developmental therapist."
Alexandra: "Hi."
[Liam comes out of his bedroom with his Nintendo 3DS]
Steve: "These people are here to help Jo help us so we can be a happier family."
Announcer: "Coming up on Supernanny...Yvonne, Stella, Jo, Mike and Deb lay down the law."
Deb: "No drinking alcohol."
Mike: "Let your folks where you're going and when you'll be back."
Stella: "No more drugs."
Announcer: "But will three more nannies plus a therapist be enough to bring Alexandra down?"
Yvonne: "No smoking."
Announcer: "When Supernanny returns."
Laying Down The LawEdit
Alexandra escapes from homeEdit
[Time: Approximately 10:50 PM]
[Alexandra runs away from her parents, Liam, Yvonne, Stella, Deb, Mike, and Jo who are all chasing after her as she is trying to visit a local video arcade to hang out with her friends at night]
Stella: "Young lady, you need to come back here right this minute!"
Mike: "Stella is right. If you do not return home, you will lose your Facebook privileges for the rest of the week!"
Alexandra: "Stay away from me! Don't you freakin' dare gang up on me when I am going to the video arcade!"
Steve: "It's bedtime, Alexandra, and it's after curfew!"
Alexandra: "(bleep) OFF! WHY DON'T YOU ALL GET A (bleep)ING LIFE AND LEAVE ME THE (bleep) ALONE!!!"
[Alexandra's friends surround Yvonne, Stella, Deb, Mike and Jo]
Jo: "Who are you, young people?"


text:
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Charitable giving
Each year a Charity of the Year is selected. The charity Wedlake Bell supports is selected by our charity committee from a set of candidates nominated by members of staff and has a personal connection to a member of staff. This year our Charity of the Year is The National Brain Appeal. Last year we supported Cardiac Risk in the Young (CRY).
About The National Brain Appeal
The National Brain Appeal is the charity dedicated to raising vital funds for The National Hospital for Neurology and Neurosurgery, Queen Square, London. Since the charity began in 1984, they have raised over £40m for state-of-the-art equipment, major building programmes and life-saving research. Its vision is to improve the outcome and quality of life for all those affected by a neurological condition.
For further information please visit www.nationalbrainappeal.org. (Registered Charity No. 290173)


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TRAVERSE CITY, MI – Chrysler Group still is backlogged on orders for the Dodge Charger and Chrysler 300, while the Dodge Magnum is holding to forecast demand.
But with the Magna Steyr Fahrzeugtechnik AG & Co. KG plant in Graz, Austria, ramping up production of the rear-drive family, there are no immediate plans to look for additional capacity, Frank Ewasyshyn, Chrysler executive vice president-manufacturing, says at the Management Briefing Seminars here.
DaimlerChrysler AG and Magna invested $38.6 million to launch the 300C sedan and Touring models in June. (See related story: Magna Steyr Launches Chrysler 300C)
Chrysler 300 Touring is sold in Europe.
"We're happy with where we are," Ewasyshyn tells Ward's. Full order books are desirable, but the auto maker also is pleased that, for now, there does not seem to be a need to invest in additional capacity.
The manufacturing chief laughs as he admits he would rather see the investment go toward new product.


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Black tops are always a trend. Women look beautiful in black and can wear it on any occasion. So the Orchid top is surely going to be a favorite among women. The fashionable black top is made using knit cotton spandex and nylon spandex net which makes it extremely comfortable to wear and the sheer panel at the shoulders and the 3/4th sleeves makes it stylish as well.
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London, Dec. 30 (Reuters): Oil prices charged higher again on Monday as traders bet on a US attack against Iraq early next year and as supplies from Opec nation Venezuela stayed choked off by a strike now in its fifth week.
US light crude futures in electronic trade set a new two-year high of $ 33.17 a barrel and by 1200 GMT were up 37 cents from Friday at $ 33.09. London Brent crude added 51 cents to $ 30.67 a barrel, a 15-month high.
Oil and politics are a volatile combination and we have two separate issues confronting the oil market at the moment, said Peter Gignoux, head of the London energy desk at Schroder Salomon Smith Barney.
Oil has risen more than $ 5 in December and prices are now more than $ 10 higher than at the start of 2002. Concerns are growing that costly energy bills could stifle global economic recovery.
Washington at the weekend ordered more US troops, aircraft and ships to head to the Gulf from January in preparation for a possible war against Baghdad.
US secretary of state Colin Powell said Washington had not yet decided whether to attack Iraq to force it to disarm weapons of mass destruction, but was taking prudent action in readiness.
Dealers think an attack could start soon after January 27 when the chief UN weapons inspector Hans Blix delivers a report to the Security Council on the progress of his inspection teams.


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|"Robert Muir (JIRA)" <j...@apache.org>
|[jira] Commented: (LUCENE-1606) Automaton Query/Filter (scalable regex)
|Tue, 21 Apr 2009 20:49:47 GMT
[ https://issues.apache.org/jira/browse/LUCENE-1606?page=com.atlassian.jira.plugin.system.issuetabpanels:comment-tabpanel&focusedCommentId=12701261#action_12701261 ] Robert Muir commented on LUCENE-1606: ------------------------------------- found this interesting article applicable to this query: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.16.652 "We show how to compute, for any fixed bound n and any input word W, a deterministic Levenshtein-automaton of degree n for W in time linear in the length of W." > Automaton Query/Filter (scalable regex) > --------------------------------------- > > Key: LUCENE-1606 > URL: https://issues.apache.org/jira/browse/LUCENE-1606 > Project: Lucene - Java > Issue Type: New Feature > Components: contrib/* > Reporter: Robert Muir > Priority: Minor > Fix For: 2.9 > > Attachments: automaton.patch, automatonMultiQuery.patch, automatonmultiqueryfuzzy.patch, automatonMultiQuerySmart.patch, automatonWithWildCard.patch, automatonWithWildCard2.patch > > > Attached is a patch for an AutomatonQuery/Filter (name can change if its not suitable). > Whereas the out-of-box contrib RegexQuery is nice, I have some very large indexes (100M+ unique tokens) where queries are quite slow, 2 minutes, etc. Additionally all of the existing RegexQuery implementations in Lucene are really slow if there is no constant prefix. This implementation does not depend upon constant prefix, and runs the same query in 640ms. > Some use cases I envision: > 1. lexicography/etc on large text corpora > 2. looking for things such as urls where the prefix is not constant (http:// or ftp://) > The Filter uses the BRICS package (http://www.brics.dk/automaton/) to convert regular expressions into a DFA. Then, the filter "enumerates" terms in a special way, by using the underlying state machine. Here is my short description from the comments: > The algorithm here is pretty basic. Enumerate terms but instead of a binary accept/reject do: > > 1. Look at the portion that is OK (did not enter a reject state in the DFA) > 2. Generate the next possible String and seek to that. > the Query simply wraps the filter with ConstantScoreQuery. > I did not include the automaton.jar inside the patch but it can be downloaded from http://www.brics.dk/automaton/ and is BSD-licensed. -- This message is automatically generated by JIRA. - You can reply to this email to add a comment to the issue online. --------------------------------------------------------------------- To unsubscribe, e-mail: firstname.lastname@example.com For additional commands, e-mail: email@example.com
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