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Running unmolested for the first in a grand prix this season, Ralf Schumacher was able to lead from start to finish and claim a maiden F1 victory at Imola.
With brother Michael having to retire before half-distance in front of his adoring Ferrari fans, Ralf upheld family honour with a drive very reminiscent of the world champion. Ahead for all but the first few hundred yards, the Williams driver dominated proceedings, and completed the 62 laps without the sort of drama that has dogged his first three appearances this year.
Despite starting 'only' third on the grid, Schumacher Jr wasted little time in making his move to the front, putting his left-hand wheels perilously close to the grass in order to catapult past polesitter David Coulthard on the run to Tamburello. The Scot appeared to get a little too much wheelspin away from the line, while team-mate Mika Hakkinen, starting alongside, suffered on the dirty side of the circuit and held up those starting behind him.
This allowed fifth place man Jarno Trulli to follow Schumacher up the inside, squeezing past the Finn's McLaren through the first chicane, and joining Ralf and Coulthard at the front of the field. Michael Schumacher, meanwhile, suffered behind Hakkinen, dropping to fifth, with Ferrari team-mate Rubens Barrichello faring even worse in dropping from sixth to eighth.
Trulli could not stay with either of the front two for long, as Ralf and Coulthard set a searing pace under the equally hot Italian sun. By the end of the opening lap, the gap was already approaching a second and, by the end of the third, it had jumped out to 5.5secs.
From then on, it was simply a case of how far - and how quickly - could the leaders extend their advantage in order to overcome the perceived penalty of having to make two stops on softer rubber. The tyre choice dilemma had been the talk of the paddock overnight, with Ferrari opting for harder compounds and a single-stop strategy against McLaren's softer option, and opening out a substantial margin over Schumacher and Barrichello would be vital for success.
The Ferrari opposition took an early blow on lap four, when Michael Schumacher slowed coming out of the Traguardo chicane at the end of the lap. The German later pointed to gear selection trouble as the cause, but the moment dropped him behind both Juan Montoya and Olivier Panis, and, later in the lap, behind his team-mate too.
It soon became clear that the front-running Williams and McLaren had the legs on the home favourites, as the gap between the two Schumacher brothers opened out to twenty seconds with the first pit-stop window looming. Although both leaders were circulating at around two seconds a lap faster than anyone else, Ralf also had the upper hand on DC, and quickly had a four-second cushion back to the McLaren.
Further back, there was greater drama, for Michael Schumacher slowed dramatically on the run from Tosa to Piratella. With Panis reclaiming one of the places he had earlier lost to the Ferraris, Schumacher began the slow crawl back to the pits with a front left puncture, careful not to let the deflated rubber cause any more damage than was necessary to the front of his car. By the time he stopped for attention, the leaders were already more than halfway around their 24th lap, and Michael would quickly call it a day when further problems were detected with the Ferrari.
Montoya, driving one of the cars with which the German was dicing, was, like the world champion, thought to have been on a one-stop strategy, such was his pace at the tail-end of the top six, but the Colombian scotched that theory with a pit-stop on lap 27. Remarkably, this was Montoya's first F1 stop, having not made it this far in the previous three events, and emphasised the true manner of his team-mate's pace at the front of the field, which led to a new lap record on the 26th tour.
Schumacher and Coulthard made their stops in short order after Montoya, both emerging from the pit-lane with their original positions intact. Lower down the order, McLaren managed to turn Hakkinen around in time to put him back ahead of Trulli, who had become something of a rolling roadblock for the Finn, while Ferrari waited to pull off perhaps the tactical move of the race, short-fuelling Barrichello in order to put him ahead of Hakkinen, but necessitating a switch from one to two stops for the Brazilian.
By this stage, the lower order had already seen several changes, with Fernando Alonso starting the ball rolling on only the sixth lap when an over-exuberant entry to Variante Alta saw the Minardi driver spearing off into the barriers on exit. Jos Verstappen wasted no time in joining the Spaniard on the sidelines, as his Arrows ground to a halt on the very next lap, while Kimi Raikkonen became the third casualty, the victim of an unexplained failure that pitched him into the wall on the hill to Piratella. Like Alonso, the Finn was unharmed in the impact, but no longer a part of a thrilling scrap for potential points with Panis.
Benetton's day had already been ruined, despite a flying start from Fisichella, which vaulted him ahead of Bernoldi and Verstappen. Team-mate Button made two pit-stops on successive laps as the team struggled with the refuelling equipment, and the Italian's good early work was undone as his B201 continued to be less than user-friendly. Fisichella would eventually retire back in the pits, while Button soldiered on to a lonely twelfth place finish.
Jacques Villeneuve never got to grips with either his BAR or team-mate Olivier Panis, and eventually succumbed to a big engine failure on lap 31, his displeasure evident as he thumped the steering wheel in frustration. Two laps earlier, the race had lost Gaston Mazzacane in smoky fashion, and would later do the same with Eddie Irvine.
The biggest disappointment to neutrals, however, was the demise of Juan Montoya, who found a box of the same just when he need gears and clutch the most. The Colombian was holding down a solid fifth place, with Hakkinen in his sights, when he was first alerted to a possible problem and, with delicious irony, this then manifested itself as he came in to make his second F1 pit-stop.
Wheels on and fuel in - albeit with a delay to the latter - Montoya went to restart but, with no drive, stalled on his marks. Attempts to restart the FW23 resulted in little, until the crew physically dropped a wheel-spinning Colombian off the jacks and down pit-road after an interminable one minute and eight seconds.. That was not the end of the problem, however, and Montoya could only limp back to the pits and another premature exit.
Throughout the middle section of the race, his team-mate held a comfortable ten-second advantage over second-placed Coulthard but, with the second round of stops approaching, the Scot began to nibble away at the gap. Knowing that his best chance of overhauling the powerful BMW-powered Williams was to out-fumble him in the pits, Coulthard put in successively quick laps on the countdown to his stop, but Schumacher responded, between bouts of traffic, to stabilise the margin.
Ultimately, Coulthard's ploy failed to pay off, as both drivers again exited the pits in the positions they had entered them, and the run to the final flag would only see McLaren edge closer to Williams. Despite having to dodge through the lower reaches of the top ten, Schumacher showed commendable composure and, even when the team showed him an 'oil pump' board, he reacted accordingly to ensure his success.
Swooping close to the pit-wall, the German showed his undoubted pleasure to representatives of Williams, BMW and Michelin, who had all waited a long time for the winning feeling to return. Coulthard was just four seconds adrift at this point, but no threat to the victor.
Barrichello and Hakkinen were similarly split, with the Brazilian getting the nod for the final podium position - something for the tifosi at least - while Trulli remained the last unlapped runner in fifth, ahead of team-mate Heinz-Harald Frentzen, who ran a largely unobtrusive race to take the final point.
This was Ralf's day, though, and, like Barrichello, Frentzen and Johnny Herbert before him, made every effort to enjoy breaking the establishment's hold on the silverware. No longer a target for his opponents, young Schumacher proved to be the hit of Imola.
Race Result:
1. Ralf Schumacher Germany Williams-BMW 62 laps 1hr 30mins 44.817secs 202.062kph
2. David Coulthard Britain McLaren-Mercedes +4.352secs
3. Rubens Barrichello Brazil Ferrari-Ferrari +34.766secs
4. Mika Hakkinen Finland McLaren-Mercedes +36.315secs
5. Jarno Trulli Italy Jordan-Honda +1min 25.580secs
6. Heinz-Harald Frentzen Germany Jordan-Honda +1 lap
7. Nick Heidfeld Germany Sauber-Petronas +1 lap
8. Olivier Panis France BAR-Honda +1 lap
9. Jean Alesi France Prost-Acer +1 lap
10. Enrique Bernoldi Brazil Arrows-Asiatech +2 laps
11. Luciano Burti Brazil Jaguar-Cosworth +2 laps
12. Jenson Button Britain Benetton-Renault +2 laps
Rtd Tarso Marques Brazil Minardi-European 50 laps completed
Rtd Juan Montoya Colombia Williams-BMW 48 laps completed
Rtd Eddie Irvine Britain Jaguar-Cosworth 42 laps completed
Rtd Giancarlo Fisichella Italy Benetton-Renault 31 laps completed
Rtd Jacques Villeneuve Canada BAR-Honda 30 laps completed
Rtd Gaston Mazzacane Argentina Prost-Acer 28 laps completed
Rtd Michael Schumacher Germany Ferrari-Ferrari 24 laps completed
Rtd Kimi Raikkonen Finland Sauber-Petronas 17 laps completed
Rtd Jos Verstappen Holland Arrows-Asiatech 6 laps completed
Rtd Fernando Alonso Spain Minardi-European 5 laps completed
Fastest lap: Ralf Schumacher Williams-BMW 1min 25.524secs


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Question: Two days ago our 5 year old male bichon got hit by a truck and we were forced to say good bye to him. Our 3 year old female border collie mix has not been herself since. Usually very active and playful, she's laying around and seems depressed. Should we get her a companion right away or just let her go through whatever it is she is going through? If a companion is appropriate, should it be an older or younger dog and male or female.
Answer: I'm so sorry about you losing your 5 year old. As far as your other dog is concerned, it is apparent how dogs are very emotional and need time to grieve as well. I think you are right in suggesting that she may want a playmate in the near future. Your 5 year old was not just a friend to her, but it was also a lifestyle for her to have a playmate. Dogs are very much used to routines, and when things change, this adds stress to their life. So I think she is depressed for 2 reasons: the loss of a lifelong friend, and the loss of routine in her life.
The important thing about getting a second dog is whether YOU are ready for it. I think in your case, you have been through it before....so go for it if you are ready. Remember though, it is a big commitment to get a new puppy! If you are not ready at this time, don't do it. She may eventually adapt to being the only dog and her depression should go away. If you decide that you are really not ready for another dog, you may have to be more committed to spending time with her to keep her stimulated and active.
Old dog versus puppy: It is usually easier to introduce a puppy versus an older dog. This is true unless you have found an older dog to adopt who has a history of being socialized with other dogs. I don't think male or female matters. Sometimes 2 males in the house may have problems, but you are not in that situation.
Good luck, and, again....my sincerest condolences.
Dr. Hersman
East Springfield Veterinary Clinic

subset: commoncrawl


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Choco dip, Chocolate Shake, Cold Coffee
Sundae, Badam Shake, Kulfi
Creamy Zone is an ice-cream parlour that has two outlets in Marathahalli, and the fact that both of them are crowded all day says a lot about the delicious desserts they serve. Vijay, from Chennai, is the owner of Cream n Spicee, a 12 years old well-known outlet Chennai. Bangalore's young population attracted him and he decided to open a couple of ice-cream joints here and that's how Creamy Zone came about in Marathahalli. Recently he opened one more outlet in Marathahalli itself near Kalamandir. Creamy Zone serves not just icecreams, milkshakes and desserts such as sundaes and kulfi.
- Choco Dip at Rs.30/- is a popular menu item.
- Milk Shakes are also available.
- Peak timing is from 4:30 PM to 7:30 PM.
Seating: Unavailable


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Bankruptcy Law
Bankruptcy Law Questions? Ask a Bankruptcy Lawyer.
I think what you are referring to is the federal "wild card" exemption that is an option for bankrupt debtors who have commenced a bankruptcy case filing. This federal wild card exemption is available throughout the US, if the debtor elects to use the federal exemptions to protect their personal assets rather than those exemptions offered by their respective State of residence.
The federal wild card exemption can be found at 11 U.S.C. Sec. 522(d)(5).
California also has a wild card exemption that can be used by bankrupt debtors who may choose to elect to use California State exemptions to protect their assets in a bankruptcy case filing. This can be found in the Code of Civil Procedure Section 703.140
I hope you founf this information helpful.


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NetWellness is a global, community service providing quality, unbiased health information from our partner university faculty. NetWellness is commercial-free and does not accept advertising.
Monday, September 25, 2017
Wellness Center
Dizziness/Blurred Vision
I had some ear pain about three weeks ago,that i thought was from water getting in my ear,then the going iout in the cold.it hurt for about 4days or so,the pain was sharp sometimes throbbing,but i did not go to a dr,and as of now it only comes and goes occasionally,about a week ago i had a fever of 100.00,for just a day that im aware,but since i just recently went into the hosp for dizziness and extreamly blurred vision,the dizziness and blurred vision does not go away,I have had it for about 9 days.it is really bad and most of the time it makes me feel as if im going to pass out,i had a number of blood draws,ekg ct scan chest xray, suger test,blood pressure,all supposedly came back ok,they also looked in my ears and said they were ok,but they wanted me to see a specialist called an ent,they said it could be an inner ear problem.they wanted to admit in the hosp,but do to work i am unable to get time off or i will be fired. is there a medication other than antivert i can take thats non drowsy?any other causes you may think of?how long can i expect this to last?thank you
Is there a medication other than antivert i can take that's non-drowsy? Astelin nasal spray up each side of the nose in AM and PM often clears in 7 days.Any other causes you may think of? Chronic eustachian tube dysfunction due to the gluten in your dietHow long can i expect this to last? Until you treat it properly
Glen F Aukerman, MD, DABFP
Professor of Family Medicine
College of Medicine
The Ohio State University


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- Home
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- Darice® 8oz Cotton Jersey Loom Bands
Darice® 8oz Cotton Jersey Loom Bands
Product ID: LOOP004
Take your loom loops projects to the next level with high quality cotton jersey loom bands! Weave together these loom bands to make extra soft pot holders, purses and more.
Make sure your supply stays stocked with this 8oz container that includes soft and subtle colors like:
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Color: Assorted
Material: Other
Product Type: Other
Shape: Other
Our Price: $3.47
8 ounces per package.


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He was a little bit off there. What a shame!
Have you been watching any of the 2012 Olympics from London? We've watched some of the NBC live broadcasts during the afternoon and some of the NBC unlive broadcasts on at night.
I've enjoyed several sports, but especially gymnastics. I've been intrigued by the commentators covering the gymnastics events. I understand that the judges are looking for perfection and the announcers have to help the audience, but, to be honest, I usually can't see the mistakes that the judges see and commentators point out. Instead, I see artistry and athleticism that is unmatched by 99.9% (+) of the world's population.
You know what I'm talking about, right? One hand moved to the side by half an inch too much, or a small step after flipping 10-20 times through the air with a few twists? These are errors… devastating… dream-breaking. Of course, if I tried to do even part of that routine… well, you know how that would turn out.
I wonder if we're like that among our brothers and sisters in Christ too often. We expect perfection when it comes to almost anything, especially when we are gathered together. One small misstep or one small word misspoken is a huge mistake… devastating… heretical maybe.
So, slowly, this develops into this idea that God demands "excellence"… excellence in speaking ability… excellence in serving… excellence in leadership… excellence in singing… excellence in everything.
And we make God unapproachable for everyone who is not "excellent" (however we define "excellence").
Interestingly, from reading the New Testament, it seems that God calls and uses the broken… the imperfect… the ones who recognize that they are not excellent and accept others in the un-excellent state.
It seems that every group has their definition of what is expected from others. And if anyone can't provide that, then they should remain on the sidelines.
I've learned something very important over the last several years. Sometimes God speaks loudest through the quietest voice. Sometimes he speaks clearest through some who can barely put a sentence together. Sometimes God serves more powerfully through the one who stumbles along. Sometimes he serves most consistently through some who make mistakes.
And, perhaps I should change "sometimes" above to "often."
But, what happens when those who are not "excellent" are not allowed to speak or to serve? What happens when only those who are "excellent" speak and serve?
I believe the answer is the same in both cases: the church is less healthy and the growth (maturity) of the church is hindered.
6 Comments
Comments are closed. If you would like to discuss this post, send an email to alan [at] alanknox [dot] net.
I LOVE the NLT version of Eph 4:2 (speaking of Ephesians!)-
"Be patient with each other, making allowance for one another's faults because of your love." Can you imagine what the church would look like if the believers obeyed that verse?!
Good post. Interestingly enough, those who set the standards for excellence in the church often fail to see their own shortcomings.
I always appreciated the humility reflected in Dr. David Martyn Lloyd-Jones statement that he would not bother to cross the street to hear himself preach.
We need more leaders like the apostle Paul who said his adequacy or competency was from God (2 Cor. 3:5). This same apostle was also very big on the church functioning as a body with many members who contribute to the church meeting by participating in a variety of ways "for the common good" (1 Cor. 12:7).
God brings glory to himself by working through the entire body of Christ made up of imperfect people and using humble methods (1 Cor. 1:26-31). More thoughts here: http://www.lambblood.com/no-going-back.html
Our Father gives us the freedom to fail. It is almost as much of a sober responsibility than the freedom to succeed. (almost) I also quite liked MamaT's Ephesians reference. A common saying around my House is "Do not be harder on yourself than our Father is on you." It works wonders.
I did notice something today, Alan, that I'd like to ask you. Why don't you capitalize 'he' when referring to The Lord? Or the church? (as in The Church)
Simply something I have noticed in the years of my Salvation, of course. Some folks capitalize Him, some do not. Curious as to why or why not, Alan. What say you?
I have seen the scripture which says that Daniel had an "excellent spirit" (Daniel 6:3) mistakenly turned around to say that God wants us to have "a spirit of excellence." The difference is subtle, but significant. Our "spirit of excellence" often sidelines or quarantines that which God wants to use, be it things or people, which are "the weak", "the foolish" and "the things that are not." (1 Cor.1:27,28 )We especially see this in those who are perfecting "platform ministry" and the crafted experience of "church". This ultimately weakens and deprives the church of the riches of Christ's inheritance that is IN the saints. All of them! "Excellent" post! 🙂
If we mentor the saved into becoming true disciples of Jesus, this sort of debate becomes very empty. As I learn to focus more and more on the one who was perfect in the flesh, the more I realize that "but by the grace of God, there go I".
At the same time, I will do my best for Him. And one day if He says "that was excellent, Jon" then I will say "Thank you Sir" Until then….


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My exam didn't start until 5:30, and I really hadn't eaten anything all day because I was so nervous. (This is typical for exams, but even more pronounced for this board exam.) Then, each time you check into the exam or leave to go to the bathroom, you are photographed, fingerprinted and asked to sign your name- just a little more pressure added to the pressure cooker.
The exam is 5.5 hours long, it took me a little more than 4 hours to take it. I'll be the first to admit that I'm not a great test-taker. I can talk myself out of or into any variety of answers. However, I think the hardest part of this test was simply its length- staring at a computer screen for that long takes its toll.
I wasn't sure if I wanted to know my results or not- I walked out of the exam feeling like such a failure. There were a lot of difficult questions with no clear correct answer. I was tired and hungry through most of the exam which made concentrating difficult. I was fairly convinced that I would have to take the exam over, and I was embarrassed just thinking about explaining it to my family and my employer.
As it turns out, I couldn't wait to see my results. The next morning I logged onto the FSBPT website and paid $57 to get my individual score report. I PASSED!


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The Dixon-Rhyne Project
Reinvention, the new album and experiment from Rob Dixon and Melvin Rhyne, is a melding of the bebop jazz organ quartet with world music and jam. Though jazz has always been steeped in improvisation, it has had periods where its intricacies have been ingrained into composition on the page with little room for individual color or influence. This album has touches of the San Francisco cool jazz scene and free bop where a jazz combo moves with a melody like a patch of wild mint around a garden, finding new soil and nutrients for its growth. It's an organic thing, and Dixon and Rhyne are showing that age (whether young or old) isn't any barrier to creating something called jazz.
Rob Dixon, who is comfortable with tenor and alto saxophones, is 37 years old. Born in Georgia, he studied jazz at Indiana University and then went on to New York to work as a side man with The Count Basie Orchestra, The Ellington Band, Rufus Reid, Tony Bennett, and Ray Charles. When he returned to Indianapolis, he formed a trio with drummer Kenny Phelps and organist Brad Whitely. They combined straight jazz with funk influences from Soulive and released an album, "What Things May Be," in 2006.
It was around this time that Dixon met Melvin Rhyne, who plays Hammond B3 organ and Mini Moog. Over three decades Dixon's senior, Rhyne had a history in jazz. Though he was a self-taught jazz pianist, he found work with up-and-coming jazz groups. In the mid 50s, he played with the reed multi-instrumentalist Rahsaan Roland Kirk and switched to organ at that time. Rhyne collaborated with jazz guitar legend Wes Montgomery in the early 60s. Soon after, Rhyne moved to Wisconsin and became active in the local music scene. In 1990, he returned to recording and did a record with guitarist Herb Ellis and trumpeter Brian Lynch. He even did a quartet session with Joshua Redman. When he moved back to his hometown of Indianapolis, he and Dixon seemed fated to work together. Now, 71 years old, Rhyne is taking his hard-bop organ and adding his velvet touches to this new project.
Dixon asked his trio drummer, Kenny Phelps, to join the group. His solid drumming has made him a popular session player. Finally filling out the quartet is an unexpected player. Fareed Haque, the sensational guitarist and sitar player with Garage Mahal, came aboard to add color with several guitars.
For Rhyne, this might have been the biggest stretch, to come into a jam-rich environment with the likes of Haque, but Rhyne clearly shines in this new album, putting a mark of jazz authority to the project. His organ work is varied, lively, and inventive. The improvisation that Dixon calls forth from his saxophones sets a benchmark for the rest of the quartet, and Haque, in particular, excels in meeting that level of creativity. And Kenny Phelps keeps it all on track.
The quartet is joined by Salar Nader on tablas on "Shadow and Light" and "Tomorrow Sierra." These two tunes are perhaps the most risk-taking for a jazz ensemble (but not for a jam group with strong jazz roots). "Shadow and Light" is reminiscent of the work of San Francisco percussionist Babatunde Lea and his quartet featuring saxophonist Richard Howell. Though the tablas add an Eastern feel, rather than Afro-Cuban as in Lea's work, they are not as pronounced as in "Tomorrow Sierra." "Shadow and Light" is more jazz whereas "Tomorrow Sierra" has a pronounced world sound with a trippy edge to the jazz.
All of the tunes, except one, on this CD are written by Dixon but enhanced by the quartet. The only cover, "Chit'lins Con Carne" is a classic gleaned from jazz guitarist Kenny Burrell's 1967 recording, Midnight Blue. It's a soul jazz tune where Phelps' gospel backbeat carries the quartet along, allowing Haque to explore this old chestnut.
Throughout the entire album, the sax, organ, and guitar all take turns at soloing, without overstepping anyone's place in the group. No one outshines anyone else. They work as a cohesive whole, creating a real conversation between musicians and producing some of the best jazz I've heard in a long time.
Reinvention is an album to sit and savor. If you're a seasoned jazz enthusiast, you'll love the freshness in this album. If you're knowledge of jazz comes from jam, this will be one to add to your collection. It is one of the best new albums out that combines the long legacy of jazz with the richness of new innovators.
The Dixon-Rhyne Project is something to try to catch live. They are playing at the Jazz Kitchen in Indianapolis on July 9 and continue to play in the city when they can.
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Reviews // 2 Articles
Don't Feel Doomed: An Interview With the Moondoggies
30 May 2011 // 6:00 PM
"It's very natural to be overwhelmed or consumed by negative things," Kevin Murphy says. "This record is about trying to be constructive, about not wanting to feel doomed."
The Moondoggies: Adiós I'm a Ghost
15 Aug 2013 // 6:04 PM
The third album from "Seattle's premier urban-rustic folk-rock act" has its share of beard-rock moments.
The Moondoggies: Don't Be a Stranger
16 Oct 2008 // 6:00 PM
There's nothing slack in this Southern rock. This album is infused with a snake-handling zeal, a volatile combination of cut-loose freedom and deep-in-the-bones fear that make it impossible to ignore.


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Nicole Richie undoubtedly turned heads at a trunk show for friend Simone Camille! The mother of two showed off her lean frame in a hot pink knit crop top and matching pleated skirt by what appears to be Azzedine Alaia:
I'll admit it: I'm actually not sure Nicole's outfit is by Mr. Alaia. The notoriously elusive designer barely has an online presence, hasn't released runway images since the Fall 2011 couture season, and sells online sparingly.
That said, he is known to craft a chic knit flippy skirt, and his crop top and skirt combos are beloved by everyone from Mariah Carey to Rihanna.
The closest I could find to Nicole's ensemble is this framboise colored cocktail that looks like it could be the dress version of Ms. Richie's two piece:
All that to say, I'm not sure, and since Alaia doesn't sell a ton online, the look for less will have to do! Get her skirt look for a steal with this $52 Halston Heritage Pleated Skirt from Saks:
Complete with these pieces:
What do you think of her ensemble?
Images: Wireimage/Pacific Coast News


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Tim, one of our club members has built this new Helicoptor.
Here's a quick explanation of what I've done, unfortunately I didn't take any pics as I went along. The majority of the work is in detailing to get it looking less toy like. even so I've still spent about 30 hours in total but I am quite slow.
I started by sorting out all the wiring for the lighting which was a pain. To get the tail beacon and port and starboard nav lights meant de-soldering the LED's and threading the wiring through the tail and horizontal stabs. I used these lights (www.giantshark.co.uk/night-flying-lights-p-405040.html) but swapped the red and green nav light for these 2mm LEDs which are more to scale (www.maplin.co.uk/standard-2mm-ceramic-leds-10381)
The landing skids came black with no foot rail or bear paws (platforms at the back). the rails are simply balsa cut to strips and shaped each end and the 'paws' are cut from 0.5mm styrene sheet. this was then given 4 coats of the appropriate grey paint (Humbrol 126) I have still to make the front skid extensions and add them on.
Inserting the mechanics is pretty straight forward and here I only added foam pads at the fixing points to reduce vibrations. I also made up a new battery tray and forward support so the battery can be pushed as far forward as poss. This needs doing in order to get the CoG correct and even with a 190g pack I still needed to add about 90g of ballast to the nose.
I then sourced what decals I could and drew up the rest. These can be found attached if any one wishes to use them, just print onto printable white and clear self adhesive A4 sheet. I can email them as a word doc which may be easier to print and modify and also will be a better resolution, cant upload Word Doc's here.
The supplied aerial's etc.. are all black so some will need painting white.
|You can't tell me this looks anything else than a real machine. Thanks to Tim for the description and really good pics.


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TEL AVIV (Sep. 19)
A number of anti-Semitic incidents in Minsk, one of them involving a relative of one of the Israeli Olympic athletes killed in Munich, were reported today by Jewish sources in the Soviet Union. The sources said that Daniel Slavin, 14-year-old nephew of slain Olympic wrestler Mark Slavin, was attacked by hooligans who threw acid on his face. He suffered burns but his eyes were saved.
The sources said that many Minsk Jews have received leaflets in the mail warning them to go to Israel "or we shall kill you." The leaflets were signed "Black September," the Arab terrorist group responsible for the Munich outrage. But they are believed to be the work of local hoodlums, the sources said.


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Exposure Vol. 2
4K , 1 x 80′
What makes a climbing mecca? The Scene takes a comprehensive look into four major epicenters of hard climbing and training, and the characters who define them by their relentless commitment to the sport. Featuring groundbreaking first ascents in bouldering, trad, and sport climbing, including Chris Sharma's Fight or Flight (5.15b) in Oliana, Spain. Filmed in stunning 4K Ultra High Definition, join an international cast of characters as they give us a glimpse into the impossible.
Check availability in your territory.
|Inquire Now


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Energy is typically the second largest overhead cost in the production of greenhouse crops in Michigan and other northern states. This MSU Extension bulletin, developed by Erik Runkle, MSU floriculture Extension specialist, and A.J. Both, agricultural engineer at Rutgers University, presents 13 production strategies and technologies that greenhouse growers can use to reduce energy consumption and improve production efficiency.
Some of the practices discussed include:
•Installing efficient photoperiodic lighting when growing long-day plants.
•Managing greenhouse temperature based on the crop and finish date.
•Installing and maintaining retractable curtains.
•Installing infrared anti-condensate polyethylene film.
•Replacing an inefficient heating system with a more efficient one.
This 16-page document, in PDF format, can be downloaded free at the MSU Greenhouse Energy Cost Reduction Strategies website. It also includes links to resources for more information on the different topics. The target audience of his document is greenhouse producers of floriculture crops located in temperate climates, although many of the concepts can apply to other greenhouse-grown crops.
This publication was funded by the Michigan Floriculture Growers Council, who received a Michigan Department of Agriculture and Rural Development grant through the USDA Agriculture Marketing Service Specialty Crop Block Grant Program-Farm Bill.
Erik Runkle's work is funded in part by MSU's AgBioResearch.
Download the guide here: http://www.flor.hrt.msu.edu/energy


text:
|Publication number
|Publication type
|Application number
|Publication date
|Jul 3, 2007
|Filing date
|Oct 26, 2005
|Priority date
|Jan 28, 2004
|Fee status
|Also published as
|Publication number
|Naishu Wang, David F. Zhou
|Original Assignee
|Dnt Scientific Research, Llc
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (12), Referenced by (11), Classifications (39), Legal Events (4)
|External Links: USPTO, USPTO Assignment, Espacenet
This is a continuation-in-part of co-pending U.S. patent application Ser. No. 11/090,463 filed Mar. 25, 2005 which is a continuation-in-part of U.S. patent application Ser. No. 10/767,897 filed Jan. 28, 2004.
This invention relates to rapid confirmatory testing apparatuses for analyzing body fluids and other fluids using immunochromatography, and more particularly to fluid test apparatuses for detecting antibodies or antigens in a near-patient setting, such as at the point-of-care, and/or in a clinical laboratory setting conducting large scale rapid, confirmatory examination.
Over past decades, the prior art has offered several types of rapid diagnostic testing techniques primarily for body fluids such as whole blood, serum, plasma, urine, spinal fluid, amniotic fluid, mucous, saliva, and the like for the presence of infection or other conditions such as pregnancy, abused drugs and cardiovascular disorders such as acute myocardial infarction (AMI).
The first of these tests were the Latex Particle Agglutination tests, then the Flow Through tests leading to the current Lateral Flow Single Step test. Such tests typically utilize well known sandwich-type immunoassay techniques. In such tests a fluid specimen is supplied from a subject which could carry at least one analyte, such as an antibody, which is specific to the condition being tested. The fluid specimen is exposed to a conjugate having at least one mobilizable binding member, such as an antigen (or antibody in some cases), which has immuno-determinant(s) (or specific binding sites for the immuno-determinant(s) in certain cases) of the analyte in question. The binding member is conjugated to a visibly detectable label such as colloidal gold. During exposure of the specimen to the conjugate, an immuno-chemical reaction occurs wherein the analyte in question binds to the binding member to form the first affinity binding labeled analyte complex.
The fluid containing the labeled analyte complex is then directed to flow into a reaction membrane having a zone coated with at least one immobilized capture binding member which is similarly immuno-determinant of the analyte in question. As the fluid passes through the membrane, a second immuno-chemical reaction occurs wherein the labeled analyte complex binds to the capture binding member to form the second affinity binding immuno-sandwich complex. The accumulation of the secondly bound immuno-sandwich complex beyond a threshold amount in the zone creates a colored test line, the so-called "T-line". The reaction membrane typically has a second zone located further downstream from the T-line as an internal system control line, the so-called "C-line". The control line is used as an internal indicator of functional validity.
Unfortunately, depending on the type of condition being detected, these tests provide a typical accuracy of between 85% and 99%, falling short of the 99.5% or above accuracy generally considered to be necessary for a confirmatory test. The reasons for the insufficient accuracy are primarily due to the lack of overall higher sensitivity and specificity of the apparatus. Different samples may contain chemicals or particles which interfere with or inhibit the fluid flow or otherwise interfere with one or both of the affinity binding reactions. Prior apparatuses have attempted to enhance sensitivity or specificity by pretreating various parts of the apparatus with reaction or flow enhancing reagents, pH conditioning chemicals, or even non-specific adhesive blocking molecules which will "block-out" non-analyte molecules which might cause non-specific adhesion, or otherwise compete with the analyte in question for specific binding members, especially on the reaction membrane. These attempts have met with limited success in some types of testing, but do not provide the desired accuracy in many others. Also, pretreatment with two or more of the above pretreatments exacerbates the difficulties in obtaining uniform manufacturing due to potential incompatibilities between the pretreatment chemicals. For example, the pH conditioner might disrupt the effectiveness of the non-specific blocking member molecules. Or, the manufacturing step of pretreating with the second pretreatment chemical can dislodge some of the first pretreatment chemical.
Further, lot-to-lot variation in the manufacture of the test apparatuses can often lead to ambiguous results, such as false negatives as well as weak false positives, so-called "ghost lines" or "phantom lines". False negatives typically occur when non-specific molecules interfere with the first and/or second affinity binding actions. It has been found that non-analyte molecules can clump together in fluid samples that are not well mixed so that they temporarily prevent access between analytes and binding members. Even temporary interference can prevent an adequate number of labeled analyte complexes and/or ultimately immuno-sandwich complexes from forming. In this way, if a non-analyte molecule or clump of molecules blocks access between analytes and binding members for only a few seconds, it may be enough to induce a false negative result. Further, clumps of non-analyte molecules can carry an overabundance of the labeled mobilizable binding members to the second affinity binding site to generate a false positive.
Chemically non-uniform flows can result in flows having non-uniform first affinity binding by the time they reach the reaction membrane leading to inaccuracies. Such non-uniform flows can be caused by a number of factors. First, some portions of the fluid may flow faster than others from time to time. In those tests having deposits of dried reagent, faster flows tend to reach the dried reagent first. These flows tend to exhibit a greater degree of first affinity binding per unit fluid or at least uptake of mobilizable labeled binding members, and can potentially carry a greater concentration of clumps of non-analyte molecules which can carry away labeled mobilized binding members. Further, the deposit of dried reagent itself can exhibit portions of higher concentration than others resulting in similar chemical nonuniformity in the flow. Other flows having a lower than average concentration of analyte molecules, and/or having a greater concentration of non-clumped, non-analyte molecules which merely inhibit analyte binding but do not carry away mobilizable labeled binding members, exhibit less apparent first affinity binding. These flow and concentration dis-uniformities are responsible for many of the unsatisfactory results discussed above.
Therefore, although these prior devices provide a convenient, quick, economic, and simplified way to conduct such testing without requiring sophisticated instrumentation or trained professionals, in many settings these rapid tests are useful only for preliminary screening purposes, not as a confirmatory test. To this day, for example, the Western Blot Analytical Assay is the only one reliably used for the confirmatory detection of HIV infection in a clinical laboratory setting worldwide. Due to its multi-step manipulation and verification phases, completion of this type of assay takes days, if not weeks. Such a delay can unfortunately lead to further propagation of infectious pathogens such as HIV or other serious results, such as the metastasis of cancers. There is virtually no generally accepted practical or economical confirmatory rapid diagnostic testing technique for use in a point-of-care setting to rapidly detect serious diseases such as HIV infection and AMI, available in the market place today.
Therefore, there is a need to refine the accuracy and expedite the performance of prior immunoassay chromatographic rapid testing apparatuses to a higher and new level for use in the speedy and early detection and confirmation of the presence of pathogens or pathogenic conditions such as occurs with HIV infection, cancers and other disorders.
The instant embodiments provide an apparatus capable of rapidly conducting a confirmatory immunoassay test for an analyte (or analytes) in question. These instant embodiments may also provide an apparatus that can be used, for example, in a point-of-care setting.
In one embodiment there is provided a self-contained, multi-stage, programmed, interrupted downward flow, rapid confirmatory immunological test ("RCIT") apparatus contained in a single molded enclosure. The immunoassay test can be performed in either a sandwich and/or competitive assay format. The apparatus can carry one or more chromatographic test strips in an inclined downward orientation forming "down-flow" test strips. The primary exposure of a fluid specimen to a specific antibody or antigen (or to a group thereof) conjugated to a label such as colloidal gold, or other type of label such as colloidal carbon, latex beads, or magnetic beads, etc. (hereinafter "conjugate") in a volume measured, reactive, buffered solution occurs in a first premix chamber before flowing on to contact the strips in a second chamber. A holding reservoir located on a fluid path between the first and second chambers interrupts the flow of the mixture to allow a short period of mixing incubation before proceeding with the secondary specific immunological binding reaction in the reaction membranes of the strips. The incubation period allows for further mixing of the fluid resulting in a greater degree of proper first affinity binding compared to prior rapid test technology.
In some embodiments, the down-flow strips are not of the type used by prior lateral flow testing methods in that they are not directly connected with any conjugate pad, but rather provide a reaction membrane which links with the outflow of the reservoir at the strip's top end. The down-flow strips can include a single layer of uniformly dispersed porous matrix material such as uniformly porous polyethylene commercially available from Porex Corporation of Fairburn, Ga.
In some embodiments, a supply of aqueous mix buffer solution is held in a sealed tank until the sample specimen has been introduced into the apparatus and its cap closed. A prong in the undersurface of the cap punctures a membrane sealing the upper opening of the tank allowing the buffer solution to be dispensed into a first chamber under atmospheric pressure. A pad at the bottom of a second chamber in contact with a lower part of at least one down-flow strip absorbs the excess wash buffer that has not been retained by the strip. The strip or strips can be held in an inclined rather than straight vertical position in order to reduce the height of the apparatus. The flow out of the incubation reservoir and into the strip is prompted by a combination of siphoning, gravity and capillarity action forces.
In still other embodiments, the enclosure is shaped to orient the test strips on an incline from horizontal. A first measured supply of aqueous mix buffer solution is held in an openable tank until the sample specimen has been introduced through an inlet into the first chamber containing a pad impregnated with an amount of lyophilized conjugate utilizing colloidal gold or other label. Under the push of a manipulable member, the tank seal is opened, causing the mix buffer to flow into and mix with the sample and conjugate. A porous dam interrupts the flow out of the first chamber to incubate the mixture. Further, the flow through the porous dam causes improved mixing of the fluid to provide a more uniformly high degree of first affinity binding. The mixed and incubated fluid then flows out of the first chamber into a second chamber containing one or more downward-flow oriented chromatographic strips.
The flow through the dam and down-flow strips is prompted by a combination of siphoning, surface tension and gravity forces. After waiting for an adequate amount of time for the mixture to flow through the strips, a second tank containing an amount of wash buffer solution is opened under the push of another manipulable member to wash down the remaining mixture through the first chamber and the strips and end the reaction at the signal zones on the strips. The lower pad absorbs the wash buffer and, along with the angled orientation of the strips, discourages reverse flow of fluid back up into the strips. Both of the manipulable members are movable, built-in components of the apparatus.
The instant apparatus has many unique and advantageous features, including a self-contained measured volume mix and wash buffer tanks, a simplified program for successively opening these tanks during processing, interrupted flow from the first chamber to the second chamber, and diffusive action of the porous dam having numerous fluid furcations and convergences that provide more uniform mixing which improves accuracy and makes the apparatus well suited to rapid diagnostic point-of-care and/or near-patient testing.
Some of the instant embodiments provide, a flow immunoassay testing apparatus for testing a fluid specimen for the presence of an analyte, said apparatus comprises: a first chamber shaped and dimensioned to accept said specimen and be subjectable to a supply of mix buffer solution and a source of labeled conjugate specific to said analyte; a second chamber holding at least one test result signal generator responsive to an amount of said analyte bonded to said labeled conjugate; and a flow-interrupting dam located on a fluid path between said first and second chambers.
In some embodiments said dam has a first porous portion. In some embodiments said first portion has a first pretreatment condition. In some embodiments said first pretreatment condition is selected from the group consisting of: being pretreated with a surfactant; being pretreated with a pH conditioner, being pretreated with a non-specific adhesive blocking molecule; and, having no pretreatment. In some embodiments said surfactant comprises a non-ionic detergent. In some embodiments said dam is a first dam and said apparatus further comprises a second dam spaced a distance apart from said first dam, wherein said second dam has a second porous portion. In some embodiments said first portion has a first pretreatment condition and said second portion has a second pretreatment condition, and said first pretreatment condition is different from said second pretreatment condition. In some embodiments said first portion comprises a material having a plurality of intersecting surface structures, wherein a junction between first and second of said structures is not substantially parallel. In some embodiments said first portion comprises a material selected from the group consisting of: fiberglass, cellulose and fibrous plastic and the like. In some embodiments said generator comprises a chromatographic test strip including a zone held on a membrane in an oblique, downward flow orientation. In some embodiments said membrane comprises a plurality of test zones adapted to provide a measurable basis for a quantitative result display. In some embodiments said membrane comprises a plurality of test zones adapted to provide a measurable basis for a qualitative result display. In some embodiments said strip is formed without a source of mobilizable labeled binding members. In some embodiments said strip further comprises a diffusive pad upstream from said zone. In some embodiments said second chamber comprises a plurality of chromatographic test strips adapted to provide a measurable basis for a quantitative result display. In some embodiments said signal generator is adapted to provide a measurable basis for a quantitative result display. In some embodiments said conjugate source comprises a lyophilized amount carried on a structure within said first chamber. In some embodiments said mix buffer solution is preformulated to carry an amount of said conjugate source in suspension. In some embodiments the apparatus further comprises means for triggering a dispensing of said supply into said first chamber. In some embodiments a volume of said supply of mix buffer solution is adjusted to create a minor outflow through said dam. In some embodiments the apparatus further comprises an openable tank shaped and dimensioned to releasably hold an amount of a wash buffer, wherein said tank in an open condition is in fluid communication with said dam. In some embodiments said supply of mix buffer solution has a volume between about 200 microliters and about 300 microliters. In some embodiments the apparatus further comprises a second supply of wash buffer solution having a volume between about 2.5 milliliters and about 3 milliliters.
In some embodiments it is provided that in an immunoassay flow testing apparatus wherein a fluid specimen in a buffered solution is first contacted with a colloidal conjugate in a first part of said apparatus, then applied to a chromatographic testing strip in a second part of said apparatus, an improvement which comprises a porous, flow interrupting and diffusing dam between said first and said second parts.
In some embodiments it is provided that in an immunoassay testing apparatus wherein a specimen is contacted with a reactive solution, the resulting mixture is applied to at least one chromatographic test strip, and said strip is contacted by a wash solution, an improvement which comprises: a first built-in manipulable member for releasing said reactive solution onto said specimen; and, a second, built-in manipulable member for releasing said wash solution onto said strip.
In some embodiments there is provided a method for premixing a measured buffer solution with a fluid specimen to form a mixture for dispensing to a chromatographic test strip, said method comprises: preloading said solution within an openable tank; placing a fluid specimen in a premix chamber; opening a passageway between said tank and said premix chamber, thereby dispensing said solution onto said specimen to create a mixture of said solution and said specimen; and, flowing said mixture from said chamber to said strip; and wherein said method further comprises delaying said flowing for an incubation period. In some embodiments the method further comprises washing said strip after passage of a time period after said flowing.
In some embodiments where it is provided that in an immunoassay apparatus comprising a conjugate source adapted to carry a mobilizable binding member molecule specific to a particular analyte and a reaction membrane carrying a capture binding member molecule, an improvement comprises: a first porous interrupting, diffusive dam located on a fluid flow path between a portion of said conjugate source and a portion of said reaction membrane, thereby creating a plurality of convergent fluid paths between said conjugate source and said membrane.
In some embodiments there is provided a method for conducting a fluid flow immunoassay wherein said method comprises: diffusing a fluid mixture comprising a specimen, a mix buffer and a conjugate through a diffusive dam before said mixture reaches at least one chromatographic test strip.
The instant apparatus is useful to rapidly and confirmatorily determine the presence of analyte in a sample. The sample can include, for example, body fluids such as whole blood, serum, plasma, urine, spinal fluid, amniotic fluid, mucous, saliva, and the like.
Analyte, as used herein, refers to a compound or composition to be measured. The analyte can be any substance (antigen or ligand) for which there exists a naturally or genetically occurring specific binding member such as a binding molecule (e.g., an antibody or receptor).
Analyte also includes any antigenic substances, haptens, antibodies, and combinations thereof. The analyte can include a protein, a peptide, an amino acid, a ligand, a hormone, a steroid, a vitamin, a drug including those administered for therapeutic purposes as well as those administered for illicit purposes, a bacterium, a virus, and metabolites of or antibodies to any of the above substances. The analyte can also comprise an antigenic marker or antibody or receptor for single or multiple pathogenic conditions.
Representative analytes include steroids such as estrone, estradiol, cortisol, testosterone, progesterone, chenodeoxycholic acid, digoxin, cholic acid, digitoxin, deoxycholic acid, lithocholic acids and the ester and amide derivatives thereof; vitamins such as B-12, folic acid, thyroxine, triiodothyronine, histamine, serotonin, prostaglandins such as PGE, PGF, PGA; antiasthmatic drugs such as theophylline, antineoplastic drugs such as doxorubicin and methotrexate; antiarrhythmic drugs such as disopyramide, lidocaine, procainamide, propranolol, quinidine, N-acetylprocainamide; anticonvulsant drugs such as phenobarbital, phenytoin, primidone, valproic acid, carbamazepine and ethosuximide; antibiotics such as penicillins, cephalosporins, erythromycin, vancomycin, gentamicin, amikacin, chloramphenicol, streptomycin and tobramycin; antiarthritic drugs such as salicylate; antidepressant drugs including tricyclics such as nortriptyline, amitriptyline, imipramine and desipramine; as well as metabolites thereof. Additional therapeutic drugs include, for example, carbamazepine, free carbamazepine, cyclosporine, digoxin, FK778, lithium, N-acetylprocainamide, tacrolimus, free valproic acid, and the like, as well as the metabolites thereof.
Representative analytes also include drugs of abuse, and their metabolities, including amphetamines, methamphetamines, barbiturates, benzodiazepines (BZD), cannabinoids, cocaine (benzoylecgonine), opiates, phencyclidine (PCP), tricyclic antidepressants (TCA), methadone, propoxyphene (PPX), marijuana (THC), methylenedioxymethamphetamine (MDMA, or Ecstasy, or XTC), morphine, oxycodone, and bupromorphine. Representative drugs of abuse further include ethanol, heroin, hydromophone, oxymorphone, metapon, codeine, hydrocodone, dihydrocodiene, dihydrohydroxy codeinone, pholcodine, dextromethorphan, phenazocine and deonin.
Hepatic analytes include, for example, albumin bromocresol green (BCG) or purple (BCP), alkaline phosphatase, hepatitis B core antigen/antibody (anti-HBc), hepatitis B e antigen/antibody (anti-HBe), hepatitis B surface antigen/antibody (anti-HBsAg), hepatitis C virus (HCV), anti-HCV, direct bilirubin, gamma-glutamyl transpeptidase (GGT), antibody to Hepatitis A virus (HAVAb-IgG, HAVAb-IgM), hepatitis B surface antigen (HBsAg), lactate dehydrogenase (LD), neonatal bilirubin, prealbumin, total bilirubin, total protein, and the like.
Analytes related to pregnancy and fertility include, for example, human chorionic gonadotropin (hCG), beta-hCG, total beta-hCG, luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), estradiol, free estriol, total estriol, progesterone, prolactin, sex hormone binding globulin (SHBG), testosterone, and the like.
Analytes to determine blood disorders include, for example, B12, ferritin, folate, haptoglobin, and transferrin.
Analytes used to determine cardiac disorders include, for example, C-reactive protein (CRP), highly sensitive C-reactive protein (hsCRP), creatine kinase (CK), CK-MB, myoglobin, troponin, B-type natriuretic peptide (BNP), apolipoprotein A1, apolipoprotein B, and high density lipoprotein (HDL).
Cancer analytes include, for example, prostate specific antigen (PSA), free PSA, total PSA, fecal occult blood (FOB), acid phosphatase, alpha-fetoprotein (AFP), beta-2 microglobulin, CA 125™, CA 15-3™, CA 19-9™, carcinoembryonic antigen (CEA), PAP, pepsinogen, sqaumous cell carcinomas (SCC), and the like.
Analytes associated with inflammation and immunology include, for example, C3, C4, CRP, IgA, IgG, IgM, RF, and the like.
Analytes used to determine exposure to disease causative organisms include, for instance, rubella IgG, rubella IgM, toxoplasmosis IgG and IgM, cytomeglovirus (CMV) IgG and IgM, HTLV III, Anti-EBNA, mononucleosis, HAA, herpes, and anti-Streptolysin O.
Infectious disease analytes include microorganisms such as Streptococcus pyogenes, Staphylococcus aureous A, Endotoxin, Chlamydia, Syphillis, Gonococcus, Helicobactor pylori (H. pylori). Additionally, disease analytes include viral organisms such as hepatitis (HBV, HBsAg, HCV, HAA), hepatitis A virus, hepatitis B virus, hepatitis Non A-Non B, IgE, cytomeglovirus (CMV), herpes viruses, rubella viruses and the like. Further included, are, for example, toxoplasmosis, anti HTLV-I/HTLV-II, BSE, chagas antibody, CMV AB, CMV IgG, CMV IgM, CSF glucose, CSF protein, HIV AB, HIV-1/HIV-2 (rDNA), rotazyme II, and the like.
Analytes pertaining to endocrinology include, for example, thyroglobulin autoantibodies (anti-Tg), thyroid peroxidase autoantibodies (anti-TPO), C-Peptide, cortisol, HbA1c (hemoglobin fraction), PTH, triiodothyronine (T3), free T3, total T3, thyroid hormone, thyroxine (T4), free T4, total T4, thyroid stimulating hormone (TSH), and the like.
Pancreatic analytes include, for example, amylase, lipase, and the like.
Veterinary analytes include, for example, Heartworm Ag, E. canis Ab, Lyme Ab, Giardia, parvovirus, FIV, FeLV, and the like.
Analytes can also include, for example, insulin, gamma globins, allergens, cystic fibrosis antigens, toxins, such as those associated with tetanus and animal venoms, and insecticides.
The precise nature of a number of analytes together with a number of examples thereof are disclosed in Litman, et al., U.S. Pat. No. 4,299,916, issued Nov. 10, 1981; and Tom, et al., U.S. Pat. No. 4,366,241, issued Dec. 28, 1982, each of which is hereby incorporated by reference in its entirety.
The signal provided to the user of the apparatus is provided by accumulation of a binding member such as a specific antibody and/or antigen; ligand and/or receptor ("binding molecule") conjugated to a label. In the instant embodiments, labels that produce a readily detectable signal are used. Thus, the instant embodiments provide colored labels which permit visible detection of the assay results without the addition of further substances and/or without the aid of instrumentation.
Examples of labels that can readily detected include, for example, dye sols, metal sols, nonmetal sols, colored latex particles, color indicators, colored matter encapsulated in liposomes, and the like.
Metal sols are disclosed in Leuvering, U.S. Pat. No. 4,313,734, issued Feb. 2, 1982 and Moeremans, et al., U.S. Pat. No. 4,775,636, issued Oct. 4, 1988, each of which is hereby incorporated by reference in its entirety, and comprise a metal, a metal compound, such as metal oxides, metal hydroxides and metal salts, or polymer nuclei coated with a metal or metal compound. The metal sols can comprise, for example, metals such as platinum, gold, silver and copper. Alternatively, or additionally, the metal sols can comprise metal compounds, such as, for example, silver iodide, silver bromide, copper hydrous oxide, iron oxide, iron hydroxide or hydrous oxide, aluminum hydroxide or hydrous oxide, chromium hydroxide or hydrous oxide, vanadium oxide, arsenic sulphide, manganese hydroxide, lead sulphide, mercury sulphide, barium sulphate and titanium dioxide.
Nonmetal sols, such as carbon sols and their use are described in Kang, et al., U.S. Pat. No. 5,559,041, issued Sep. 24, 1996, which is hereby incorporated by reference in its entirety. Nonmetal colloidal particles, such as selenium particles, are disclosed in Yost, et al., U.S. Pat. No. 4,954,452, issued Sep. 4, 1990, which is hereby incorporated by reference in its entirety. Other nonmetals that can be used include elements within Group VIB. of the Periodic Table, such as sulfur, and tellurium.
Labels can also be formed from dye polymers, whereby dye molecules, or chromogenic monomers, are polymerized to form a colored polymer particle. Examples of such dyes include Congo red, Trypan blue, and Lissamine blue.
Organic polymer latex particles are disclosed in Tarcha, et al., U.S. Pat. No. 5,252,459, issued Oct. 12, 1993, which is hereby incorporated by reference in its entirety. Such particles can comprise a plurality of non-chromophoric monomers.
Particulate labels comprising a dye or other colored substance enclosed in liposome sacs are described in Campbell, et al., U.S. Pat. No. 4,703,017, issued Oct. 27, 1987; and Rosenstein, U.S. Pat. No. 5,591,645, issued Jan. 7, 1997, each of which is hereby incorporated by reference in its entirety.
The apparatuses described in these embodiments use test strips, dams and/or pads that can comprise a dry porous material. By "porous" it is meant that the matrix is composed of a material into which fluids can flow and can pass through. Representative materials include nylon, plastic, fiber containing paper, such as filter paper, chromatographic paper, and the like, nitrocellulose, glass fibers, polysullfone, polyvinylidene difluoride, polyurethane, and other porous polymers, polysaccharides, (e.g., cellulose materials, such as paper and cellulose acetate), silica, inorganic materials, such as deactivated alumina, diatomaceous earth, MgSO4, or other inorganic finely divided material conveniently substantially uniformly dispersed in a porous polymer matrix, with polymers such as vinyl chloride, vinyl chloride-propylene copolymer, and vinyl chloride-vinyl acetate copolymer; cloth, both naturally occurring e.g., cotton and synthetic (e.g., nylon cloth), porous gels, (e.g., silica gel, agarose, dextran, and gelatin), polymeric films, (e.g., polyacrylamide), and the like. In exemplary embodiments, the test strips comprise POREX CHEMISTRY A and/or POREX CHEMISTRY K membranes commercially available from Porex Corporation, Fairburn, Ga., and/or NOVYLON brand membrane commercially available from Cuno Incorporated, Meriden, Conn.
The exemplary embodiments will be described in connection with the detection of HIV in a fluid specimen. Those skilled in the art will readily appreciate adaptation of these embodiments to detect other analytes indicative of other pathogens, or pathogenic conditions within body, food or environmental fluid samples.
Referring now to the drawing, there is shown in
The tank 9 has a top opening hermetically sealed by a membrane 10, and a dispensing port 11 in a lower region leading to a first chamber 12 in a first analytical part of the apparatus. The first chamber is located immediately below the sampling well and receives the fluid component and is subjectable to the buffering solution. The dispensing of the buffer solution 8 out of the tank 9 is triggered by puncturing the membrane 10. The puncturing is accomplished by a prong 21 which extends from the underside of the cap 3 and passes through an aperture 22 in the roof of the enclosure. The prong is normally held into a retracted position during storage and shipment of the apparatus, but can be moved to an extended position by manipulating a knob 23 on the outside of the cap. The prong is positioned, shaped and dimensioned to extend sufficiently through the aperture 22 into rupturing contact with the membrane 10. The buffer solution 8 combines with the fluid components of the specimen that come down from the sampling well to form a mixture which flows into the first chamber 12.
The first chamber 12 holds a conjugate pad 13 made of porous inorganic material such as fibreglass or 3M paper, and the like which has been coated with a soluble, lyophized amount of conjugate which includes at least one mobilizable binding member, specific to the analyte or analytes in question, conjugated to a visibly detectable label such as colloidal gold. In HIV testing, for example, the mobilizable binding member can include immuno-determinant epitopes of the HIV virus such as p18, p24, p32, gp36, gp41, p51, p55, p65, gp120, gp160 and subtype o. In this way the pad provides a source of labeled conjugate specific to the analyte or analytes in question. While the fluid mixture is exposed to the conjugate, an immuno-chemical reaction occurs wherein analytes in question from the specimen begin binding to the mobilizable binding members in the conjugate to form the first affinity binding labeled analyte complexes. It should be noted that alternately, the mix buffer solution can carry the an amount of conjugate in suspension. However, this can decrease the shelf life of the apparatus.
An outlet 14 at the bottom of the first chamber 12 leads to a pit 15 which forms a flow interrupting, incubation reservoir where the fluid 30 accumulates behind a porous dam 27 made of diffusive material whose function will be described in greater detail below. In general, the dam further mixes the fluid passing through it so that the fluid has greater chemical uniformity and is provided a temporary, but longer incubation time for the first affinity binding to reach a maximum.
Having passed through the porous, diffusive dam 27, the fluid accumulates in the downstream portion 33 of the pit until it flows over an escape port 16 leading to a second chamber 17 in a second analytical part of the apparatus which holds at least one chromatographic testing strip 18 oriented in an oblique, downward flow orientation, and which can be referred to as a "down-flow" strip. An upper edge 19 of the strip 18 extends into the downstream region 33 of the pit allowing the fluid to flow into and through the strip under the combined forces of gravity, siphoning and capillarity. The flow is enhanced by an absorbing pad 20 positioned in the bottom of the enclosure and in contact with a lower portion of the strip 18. The size of the absorbing pad is selected to accommodate the combined volume of the fluids within the apparatus. It should be understood that the diffusive, interrupting dam 27 is located between the conjugate source and the reaction membrane. In this way, there is no uninterrupted fluid flow contact between the conjugate source and the reaction membrane, but rather the fluid must pass through the diffusive dam before reaching any reaction membrane.
Each down-flow strip 18 can be positioned in an inclined position at a pitch angle A of at least 15 degrees from the horizontal. The down-flow strip differs from those common chromatographic strips typically used in lateral flow tests. The primary difference is that each down-flow strip does not provide a conjugate pad and is without a source of mobilizable labeled binding members, but does provide a reaction membrane having a number of test lines or zones 25 each coated with at least one immobilized capture binding member having an affinity for binding to the analyte or analytes in question. Immobilization techniques include reel to reel dispenser of binding members such as binding molecules. The down-flow test strips are then blocked to facilitate the test. Such a blocking procedure includes, for example, treating the strips with a buffer comprising Triton X-100: 1%; Polyvinyl Alcohol (PVA) (30,000-70,000 mw) or Polyvinyl Pyrrolidone (PVP) (10,000 mw): 1-1.5%; and Sugar: 0.2% and the like. It is important to note that by providing the conjugate and the reaction membrane in its constant, dried form, the apparatus can have a shelf life in excess of 2 years.
As the fluid passes through the membrane, a second immuno-chemical reaction occurs wherein the labeled analyte complex binds to the capture binding member to form the second affinity binding immuno-sandwich complex. The accumulation of the secondly bound immuno-sandwich complex beyond a threshold amount in the zone creates a colored test line. In this way the zones act as a test result signal generator. A transparent window 24 sealed to the enclosure provides a direct viewing of the test line zones 25 on a number of down-flow strips 26.
The reaction membrane region of the down-flow strip can be made from a single layer of substantially uniformly dispersed porous matrix material such as porous polyethylene commercially available from Porex Corporation of Fairburn, Ga. The substantially uniform dispersion of pores in the material reduces the negative effect of lot-to-lot variation present in prior membranes. This greater predictability in how a given strip will perform further enhances the sensitivity and accuracy of the test.
It should be noted that the buffer solution and fluid components of the specimen provide the volume of fluid necessary to fill the incubation reservoir and thus, regulate the transfer of the specimen through the apparatus. By adjusting the volume of buffer solution to what is necessary to create a minor and/or relatively slow overflow of the reservoir, excessive flooding and rapid flow through the strip is avoided. Further, it should be noted that the escape port 16 acts as a means for restricting the flow therethrough. It is further understood that the location, shape and capacity parameters of the pit 15 and the shape and dimension parameters of the dam 27 can be adjusted to provide a temporary, but longer incubation time, or better mixing of the mixture depending on its anticipated volume and viscosity.
Within about 0.5-2 minutes, the relatively slow speed of the flow of the mixture through the dam 27 and over the escape port 16 caused by the combination of siphoning, gravity and capillarity action forces, promotes a maximum degree of the second affinity binding on the down-flow strips. The two maximized affinity binding steps in turn maximize the diagnostic sensitivity of the RCIT apparatus technology.
Further, such sensitivity allows for the creation of a quantitative assay strip having a number of lines where each line is selected to appear at a different concentration threshold. In this way, the apparatus carrying one or more quantitative assay strips can provide the digital display of a quantitative result. Further, the apparatus can be adapted to include an electronic sensor for automatically detecting the result and an electronic display, such as a liquid crystal display (LCD) for displaying the results. Each of a plurality of strips can be coated with a number of corresponding antigenic epitopes (or polymers, proteins, polypeptides, etc.) which are immuno-determinant analytes for the pathogen in question, such as the HIV or the condition in question such as cancer. In HIV confirmatory detection, the appearance of at least two epitope lines on a down-flow strip will not only confirm the presence of HIV, but will also give a qualitative, analytical indication of the type of antibodies present in the specimen which can change during different periods of HIV infection and/or Acquired Immune Deficiency Syndrom (AIDS). Additionally, each strip can include a control line, working as an internal system control indicator. Therefore, any positive result of HIV detection shown by this RCIT method can include at least three (3) lines appearing in the test reaction window.
Referring now to
The diffusive nature of the dam 27 causes the flow to separate at the fluid front into a plurality of branches or furcations 40 which, when these furcations converge and join together again, do so from different directions. The convergence from different directions 41 causes a mixing across the fluid front and hence the entire specimen as it flows through. This mixing can cause the break-up of clumps of non-analyte molecules which may carry mobilizable labeled binding members, and/or clumps of the analyte itself and/or clumps of labeled analyte complexes which could carry additional mobilizable labeled binding members. The breaking up of these clumps help the to reduce the possibility of a false positive result. The mixing also reduces the differences in the concentrations of non-analyte molecules and labeled analyte complexes so that they are spread more evenly. Once the fluid passes through the dam, the concentrations have superior uniformity which leads directly to giving the labeled analyte complexes a greater opportunity to form the second affinity binding and thereby helping to reduce the possibility of a false negative result.
In addition, the diffusive action of the porous dam 27 automatically further delays or interrupts the flow from the first chamber 12 to the reaction membrane of the down-flow strip 18 providing more incubation time for the first affinity binding to reach a maximum, thereby increasing the overall sensitivity and specificity of the test.
Referring now to
The portion of the diffusive dam can be pretreated with a surfactant by immersing the dam material during manufacturing into an amount of liquid surfactant so that it penetrates substantially all of the pores of the dam material. The dam material is then dried. This leaves a residue of the surfactant on the intersecting surface structures. As shown in
An exemplary surfactant is a detergent such as polyethylene glycol sorbitan monolaurate commercially available under the brand name TWEEN 20 from Sigma-Aldrich Corporation of St. Louis, Mo. Other detergents are acceptable such as TRITON X-100 brand, TRITON X-114 brand, TWEEN 80 brand, and sodium dodecyl sulfate ("SDS") detergents also available from Sigma-Aldrich Corporation. Depending on the test being conducted, other anionic, cationic, non-ionic and Zwitterionic detergents may also be acceptable.
Referring now to
Referring now to
Pretreatment of the dam can also be in the form of pH conditioning chemicals, and non-specific adhesive blocking molecules which will selectively filter or "block-out" unwanted non-analyte adhesion molecules, typically proteins, which can non-specifically interfere and/or compete with the analyte in question in either or both of the first and second affinity binding stages of the test.
Referring now to
In the medial region of the apparatus, and immediately under a ceiling hole 95 is a sampling well 96 having a funnel-shaped internal wall 97 and a filter screen 99 to help separate particles and adhesive matters from the fluid component of a specimen 98 such as whole blood or saliva. The sampling well 96 leads downwardly to a first, premix chamber 100 which receives the fluid component of the specimen in a first analytical part of the apparatus. The specimen drops upon a conjugate pad 102 located on the floor 103 of the premix chamber thereby exposing the specimen to a source of conjugate. The viscosity of blood or saliva for example generally prevents it from flowing on its own through to the rest of the apparatus. The shape and dimensions of the first chamber can be adapted for other different viscosity fluid specimens.
The analytical testing reaction is initiated by opening a first tank 105 containing a measured amount of mix buffer solution 106. The tank is formed by a generally inverted cup-like button structure 86 made from a durable, rigid, fluid impermeable material such as hard plastic. The cup structure rim 108 is breakably thermo-sealed by a foil-plastic membrane 109. In its pretest position the mix buffer tank rests above a pair of puncturing pedestals 110 each having a plurality of prongs 111 extending upwardly from the pedestal upper surface 112. The prongs are located near the periphery of each pedestal to help cause fracturing of a pliable foil-plastic membrane. The tank is opened by downward pushing manipulation 113 of the first button 86 which causes the tank to be lowered onto the pedestals, fracturing the foil-plastic membrane. Downward motion is stopped by a peripheral lip 115 straddling the outer lateral edges 116,117 of the pedestals. The pedestals are laterally spaced apart to form a fluid channel 120 therebetween allowing the solution to flow out of the tank and down 121 toward the premix chamber 100.
The mix buffer solution 106 is dispensed into the premix chamber 100 to contact the conjugate pad 102 and mix with the specimen to form a fluid mixture and initiate the first affinity binding reactions. In this way the premix chamber is subjectable to the mix buffer solution which can be characterized as a reactive solution. The button and openable tank forms a built-in manipulable member for triggering the dispensing of the mix buffer solution onto the specimen. The amount or volume of mix buffer solution 106 is selected to adequately react with the amount of specimen. In this embodiment the volume of mix buffer is between about 200 and 300 microliters, and can be about 250 microliters.
Similarly to the previous embodiment, the mixture collects in a pit 123 formed into the floor 103 of the premix chamber 100. The pit is shaped and dimensioned to have a given capacity to form a temporary incubation reservoir behind a porous dam 125. The mixture flows slowly and diffusively under the combined effect of gravity, capillarity, and siphoning forces through the dam and into one or more down-flow testing strips 91 held in a second chamber 126 in the test station 90 and eventual on to a flow absorbing pad 127 contacting the lower edge of the strips. The upper edge 128 of the strips extend into the pit 123 and contact the downstream side of the dam 125. A transparent window 129 sealed to the enclosure provides for direct viewing of the strips 91. A block of desiccant 130 is held in a third chamber 131 in the enclosure and is in communication with the absorbing pad through holes 132 to help extend shelf life. Additionally, another embodiment provides that the entire apparatus is kept in a sealed hermetic aluminum plastic foil pouch bag until use.
The apparatus also provides for a supply of a stop wash buffer solution 135 to the down-flow strips in order to stop the reaction in the strips and to carry away lingering chemicals and residue which could serve to obscure the lines formed in the zones 92 on the strips 91 and also to remove any other non-specific materials from the reaction area. For example, one such stop wash buffer comprises: Tween 20: 1%; Glycerol: 0.5%; Glycine: 5-20 mM; and NaN3: 0.02% and the like.
The stop wash buffer solution 135 is contained in a second tank 136 located upstream from the premix chamber 100 and which is openable in a manner similar to the mix buffer tank 105 thereby providing a built-in, manipulable member for releasing the wash solution onto the down-flow strips.
The wash buffer can be applied after a certain programmed-waiting period which allows for the mixture to be drawn through the strips to an adequate degree. The waiting time can of course be dependent on the type of test being performed. For HIV detection the waiting period can be between about 0.5 and 2 minutes. The amount of wash buffer solution is selected to adequately wash the down-flow strips without unduly increasing the bulk of the apparatus, and in this embodiment is between about 2 and 3 milliliters, and can be about 2.5 milliliters. In this embodiment the volume of wash buffer is about ten times that of the mix buffer. The flow of the stop wash buffer occurs relatively more quickly than the first flow of the mixture. The wash buffer, having about ten times the volume of the mixture, rapidly penetrates the already moistened dam and flushes out the non-specific binding caused by non-specific materials in the reaction area. This action helps to maximize the specificity of the present apparatus to provide RCIT.
It is understood that both of the tanks 105,136 are in fluid flow communication with the channel 120 which is in fluid flow contact with the premix chamber 100 which is in fluid flow contact with the dam 125 which is in fluid flow contact with the strips 91, meaning there is a fluid path from the tanks, through the premix chamber 100, to the test station 90.
Referring now to
This embodiment is further characterized by two, diffusive porous dam structures 142, 143 spaced a distance apart from one another. In this way, the upstream diffusive dam 142 can have a different pretreatment condition than the downstream diffusive dam 143. For example, the upstream dam can be pretreated to have a pH conditioner; and the downstream dam be pretreated to have a non-specific adhesive blocking molecule and a surfactant.
By splitting the pretreatment chemicals between two or more dams, the test apparatus designer is not only given increased accuracy, but also more control and predictability over the reactions occurring at various stages of the testing process. Also, the designer is given the flexibility in assembly to inexpensively use the same housing design for a number of different tests depending on the type of dams, their pretreatment, the type of strips, the type of conjugate pad and buffer solutions which can easily be swapped. Also, using two or more pretreated dams potentially avoids manufacturing inconsistencies such as the second pretreatment chemical dislodging some of the first pretreatment chemical on a single dam.
It should be noted that in the multi-diffusive dam embodiments, no pretreatment can be a pretreatment condition. For example, the upstream dam 142 may simply be a fiberglass filter without any surfactant, pH conditioner or non-specific adhesive blocking molecule. In this case its pretreatment condition would be "unpretreated". This pretreatment condition would be different from the pretreatment condition of the downstream dam 143 which could have a dried surfactant pretreatment condition.
This embodiment shows that the down-flow strips 144 can be further adapted to have a pad 145 made from diffusive material to further mix the fluid as it flows down the strip. The diffusive pad is located upstream from the signal generating zones 146 carrying the immobilized binding members. Further, the pad may be pretreated similarly to the dams described above.
Again it should be noted that the increased accuracy provides the ability to make multi-line strips for detecting different analytes in a single specimen such as for detecting multiple major epitopes, i.e., antigenic determinants of an endogenious disorder such as AMI, or a single exogenous pathogen, or pathogenic organism such as bacteria, viruses such as HIV, parasites, rickettsia, and the like.
Referring now to
As shown in
The interrupted, diffused, down-flow test can rapidly provide an analytical panel or profile of antigen or antibody detection, and confirm the biochemical or pathogenic condition such as HIV infection, or early stage cancer prior to metastasis, or acute cardiac disorder by way of a simple, inexpensive and disposable apparatus that can be manipulated safely by a relatively low skilled person. The quality of the clinical performance of this novel platform technology surpasses previous rapid testing technologies, such as Latex particle agglutination, Flow-Through test, and the currently wide-spread Lateral Flow apparatuses. It is a technology of Rapid Confirmatory Immunological Testing (RCIT).
While the exemplary embodiments have been described, modifications can be made and other embodiments may be devised without departing from the spirit of the invention and the scope of the appended claims.
|Cited Patent
|Filing date
|Publication date
|Feb 8, 1999
|Jun 19, 2001
|Frederic L. Nason
|Self contained diagnostic test unit
|Nov 30, 1998
|Oct 9, 2001
|Provalis Diagnostics Ltd
|Device and apparatus for conducting an assay
|Mar 5, 1999
|Dec 16, 2003
|Strategic Diagnostics Inc.
|Integrated assay device and methods of production and use
|Oct 22, 2002
|May 10, 2005
|Acon Laboratories, Inc.
|In line test device and methods of use
|Oct 18, 2001
|Jul 4, 2002
|Biosite Incorporated
|Diagnostic devices and apparatus for the controlled movement of reagents without membranes
|Aug 23, 2001
|Jan 23, 2003
|Aclara Biosciences, Inc.
|Multiple-site sample-handling apparatus and method
|Apr 18, 2002
|Apr 24, 2003
|Ciphergen Biosystems, Inc.
|Biomolecule characterization using mass spectrometry and affinity tags
|Mar 28, 2002
|Oct 2, 2003
|Stroup David Karl
|Fluid-transfer collection assembly and method of using the same
|Sep 17, 2002
|Mar 18, 2004
|Selena Chan
|Microfluidic devices with porous membranes for molecular sieving, metering, and separations
|Nov 5, 2004
|May 26, 2005
|Greg Liang
|Flow assay device comprising dry reagent cake
|Dec 12, 2002
|Jul 28, 2005
|Proteome Systems Intellectual Property Pty Ltd.
|Diagnostic testing process
|Mar 21, 2005
|Jul 28, 2005
|Patrick Carroll
|Diagnostic sanitary test strip
|Citing Patent
|Filing date
|Publication date
|Apr 20, 2007
|Feb 2, 2010
|Dnt Scientific Research, Llc
|Delayed and diffused flow rapid confirmatory immunological testing apparatus and method
|Jul 27, 2007
|Sep 20, 2011
|Dnt Scientific Research, Llc
|Interrupted, gravity-promoted, diffused flow chromatography strip testing device and method
|Jul 16, 2008
|Sep 20, 2011
|Boston Microfluidics
|Portable, point-of-care, user-initiated fluidic assay methods and systems
|Aug 15, 2011
|Sep 30, 2014
|Boston Microfluidics
|Methods of preparing and operating portable, point-of-care, user-initiated fluidic assay systems
|Jan 5, 2012
|Apr 14, 2015
|American Bio Medica Corporation
|Device and method for testing biological samples
|Feb 17, 2015
|Aug 22, 2017
|David Gordon Bermudes
|Compositions and methods for determining successful immunization by one or more vaccines
|Apr 20, 2007
|Aug 9, 2007
|Naishu Wang
|Delayed and diffused flow rapid confirmatory immunological testing apparatus and method
|Jul 27, 2007
|Nov 22, 2007
|Naishu Wang
|Interrupted, gravity-promoted, diffused flow chromatography strip testing device and method
|Dec 2, 2010
|May 19, 2011
|Johnson Brandon T
|Methods and systems to collect and prepare samples, to implement, initiate and perform assays, and to control and manage fluid flow
|Mar 5, 2013
|Sep 12, 2013
|Calpro As
|Competitive immunoassay for calprotectin
|Mar 5, 2013
|Sep 12, 2013
|Calpro As
|Improved elisa immunoassay for calprotectin
|U.S. Classification
|422/417, 435/287.6, 435/4, 435/287.3, 435/7.1, 435/286.7, 435/286.5, 435/287.2, 435/287.1, 435/288.7, 435/288.5, 435/286.4, 435/287.7, 422/68.1, 422/430
|International Classification
|Cooperative Classification
|European Classification
|Apr 4, 2007
Owner name: DNT SCIENTIFIC RESEARCH, LLC, CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WANG, NAISHU;ZHOU, DAVID F;REEL/FRAME:019115/0438
Effective date: 20070327
|Dec 2, 2010
|Fee payment
Year of fee payment: 4
|Jan 8, 2015
|Surcharge for late payment
Year of fee payment: 7
|Jan 8, 2015
|Fee payment
Year of fee payment: 8


text:
Window colors 6partsItem #: 21256
£8.72incl. VAT, plus shipping
Delivery until 26.09. possible**
Window colors 6parts
Decorate and paint the window to any occasionStains windows are perfect for kids room window, kindergartens, nurseries and nursery windows.Since the children can let off steam when painting.
Our colorful window stains come in 6 colors: black, green, yellow, red, white and blue.The window colors decor is great for many devices.You can also easily with water and a cloth from the disc.To give the windows an eye-catcher, check in our online shop more window images such as our Oktoberfest Window Sticker and also the Car Glass Grabber Decal Zombie ,
- 1 x Window Colors 6parts
- Colors: black, green, yellow, red, white, blue


text:
WordCollapse Gameplay 1 iOS / Android
By: Raketspel
Genre: Puzzle
Video Tips
Let's play WordCollapse! This is part 1 of my walkthrough guide for the iOS game, WordCollapse by Raketspel.
I will update this post with more tips and tricks, so please bookmark this page and keep on checking in!
If you have any questions, feel free to ask for extra help in the comments section.
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Gameplay Questions
Questions related to gameplay of WordCollapse iPhone game.


text:
Tomcat in Love
O'Brien, Tim
Place Published: New York
Publisher: Broadway Books
Date Published: 1998
Edition: First edition
Binding: Hardcover
Book Id: 17324
SIGNED. 347pp. Large octavo [24 cm] 1/4 black cloth with black paper covered boards and a gilt stamped title on the spine. Fine / Fine.
O'Brien has signed the title page. "A wildly funny, brilliantly inventive novel about a man torn between two obsessions: the desperate need to win back his former wife and a craving to test his erotic charms on every woman he meets" (Jacket).
By This Author: O'Brien, Tim
By This Publisher: Broadway Books


text:
[Page 550]
With woe, heartache and longing,
Father and Grandfather, Mendel Reznick
Mother and Grandmother, Rashka Reznick
Brother and Father, Avraham Reznick and family
Sister-in-law and Mama, Brayna Reznick
Sister and Mama, Rachel-Leah Schidlavitsh and family
Brother-in-law, Hershel Reznick
With grief and travail:
Bayla Reznick and family
Pearl Sladavnik and family
David Reznick and Family
JewishGen, Inc. makes no representations regarding the accuracy of
the translation. The reader may wish to refer to the original material
for verification.
JewishGen is not responsible for inaccuracies or omissions in the original work and cannot rewrite or edit the text to correct inaccuracies and/or omissions.
Our mission is to produce a translation of the original work and we cannot verify the accuracy of statements or alter facts cited.
Drohiczyn, Poland Yizkor Book Project JewishGen Home Page
Copyright © 1999-2017 by JewishGen, Inc.
Updated 12 Mar 2005 by LA


text:
Liz Smith
Published Monday November 12, 2012 at 6:00 am
'Mister President, this is your moment. We're ready to be led," said the Republican Speaker of the House John Boehner.
Here's Gail Collins in The New York Times after the Democrats won the election. "By the end, it sounded as if the only cliff-avoidance John Boehner was really interested in was one that raised new revenue through fewer loopholes and lower rates for all."
She continued: "We have already seen that plan. It was proposed by a man who, on Tuesday, lost the state in which he was born, the state in which he was governor, and the three states in which he owns houses. ... The only candidate for president who lost his home state by a larger margin than Mitt Romney was John Fremont in 1856. And Fremont was coming out of a campaign in which the opposition accused him of being a cannibal."
I guess the GOP, although it lost everything and should be much chastened, doesn't really believe it has lost yet. Maybe they'll put Mitt Romney back up in 2016. Maybe they'll recruit a lot of older white guys from all over the world to fill up their dwindling ranks.
When Eddie Murphy stops in at L.A.'s Coffee Bean on Beverly Drive, he is often accompanied by his gorgeous girlfriend, model Paige Butcher. But Eddie doesn't just sip coffee and gaze meaningfully into Paige's eyes. He often engages and encourages the other customers into discussions on politics and world affairs. He leans toward the right, but is knowledgeable, polite and humorous. He's a deep thinker!
On the professional side, Eddie is excited about a fourth "Beverly Hills Cop" movie. This has been in "deep planning" at Paramount. (As opposed to shallow planning?) The first "BHC" movies were released in 1984, '87 and '94.
Daniel Craig is known to be a sometimes intimidating interview subject. However, Erik Hedegaard caught the star of "Skyfall" in a more jocular, relaxed mood for Rolling Stone. When Hedegaard asks if Daniel ever Googles himself, he says: "I don't, I mean, I really try not to. I really truly try. But then I can't help myself and I disappear up my own a-- and that starts a whole cycle where I gotta look. I mean, I could probably put a lock on the computer, but, yeah, anyway, it's a sickness. But that's it. Except for maybe I'll look up some porn, occasionally. Hey, I'm only human."
Indeed! Not so human, however, that he'd reveal his favorite porn site. Gotta retain some mystery.


text:
Nick Gordon Found Responsible for Bobbi Kristina Brown's DeathIt's been just over a year since the passing of Bobbi Kristina Brown, and now, someone has been found responsible for her death.
Bobby Brown Tell All Book 'Every Little Step' Pulls No PunchesBrown details his own bad boy behaviors, as well as Houston's.
WATCH: Bobby Brown Admits To Having Sex With A GhostIs Bobby For Real?! ~ @RatAndPuffShow
Bobbi Kristina Brown Cause of Death RevealedEight months after Bobbi Kristina's passing, the medical examiner has released the autopsy results.
Bobby Brown's Attorney Blames Bobbi Kristina's Boyfriend for Her DeathBobby Brown's attorney slammed Bobbi Kristina Brown's ex-boyfriend Nick Gordon.
Bobby Brown Opens Up for the First Time Since Daughter's Death"When God calls you, He calls you," Brown said.
Bobby Brown Releases Statement about Bobbi Kristina Brown's Death"Krissy was and is an angel."
Bobby Brown Makes First Comment About Daughter Bobbi Kristina's PassingBobby Brown has released his first official statement about the death of his daughter Bobbi Kristina Brown.
Bobbi Kristina Brown Passes Away At 22Sad news coming from the Houston/Brown family this weekend.
Bobbi Kristina Moved To Hospice Care As Her Condition WorsensOur thoughts are with Bobbi Kristina's family during this difficult time.
Bobby Brown Says Daughter Bobbi Kristina Is 'Awake'Several months after being found unresponsive in a bath tub, reports are saying that Bobbi Kristina Brown has come out of her medically-induced coma.
Bobbi Kristina's Neighbors Called Police Week Before She Was Found Unconscious in Bathtub: ReportOn the third anniversary of Whitney Houston's death, more news related to the days before Bobbi Kristina was found unconscious in her bathtub are being revealed.


text:
A Lee County man is facing a human trafficking charge after an investigation by Collier deputies.
Shawn Anthony Lewis, 35, is incarcerated on a prior conviction for his involvement in a statewide prostitution ring he ran through his escort service 'Perfect 10 Companions.' Those charges came after an investigation by the Lee County Sheriff's Office.
The investigation by the Collier County Sheriff's Office began in July 2013 when a victim told deputies Lewis had threatened her and forced her into sexual activity in four counties. The victim said Lewis blackmailed her by threatening to send sexual videos of her to her family and the Florida Department of Children and Families who might then take her 2-year-old child from her.
'Florida is a zero-tolerance state for human trafficking and my Office of Statewide Prosecution will aggressively prosecute anyone responsible for this abhorrent crime,' Attorney General Pam Bondi said in a press release.
The Attorney General's Office of Statewide Prosecution will prosecute the case. Human Trafficking is a first-degree felony punishable by up to 30 years in prison.
'This investigation demonstrates that human trafficking will not be tolerated in Collier County,' Sheriff Kevin Rambosk said in a press release. 'This is a crime that exploits human beings for forced sex or labor, and it's critical that those responsible be brought to justice.'


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