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Home > Nappy Liners
Out of Stock, Preorders Accepted.
(Details shown apply to the default selection)
Brand: Little Lamb
Little Lamb paper liners do not feel like paper at all. They are very soft and do not catch on your hands like some of the other liners can. They come on a roll of 100 and fit the majority of all nappies not just Little Lambs.
They are:100% Biodegradable, non Chlorine Bleached, Recycled from preconsumer scrap waste.
Customers have commented on how well they keep baby feeling dry even though the nappy is wet.
For the quality of these liners they are very reasonably priced and the multibuy of 6 rolls saves you even more.
Good product good service. The liners fold a bit with the cloth nappies I use but that is to be expected.
Was this helpful to you? Yes / No
This review has not been appraised.
Bought these as they were quite a bit cheaper than ultra liners but got me they were quite disappointing - too small to be sure of collecting all solids, and although they wick very nicely (to be dry against baby's skin), the material is so flimsy that it gathers up in the nappy. It also snags on my Velcro fingertips (6 months in and my hands are still as dry as sandpaper!). Have gone back to the ultra liners which are soft and wash well many times over so vfm is pretty good !
These are great - softer than other brands. They also wash well which means we get a few uses out of them when nappies are just wet.
These are brilliant.Very wide and the right length. They also wash brilliantly so can be used many times over (if the nappy was just a wet one!)They don't always catch all of the mess, but that's more to do with the consistency of what comes out than what it lands on!I haven't flushed these, since they are still so sturdy after going through the wash, but an airtight bin does the job!Great value for money if you reuse the wet-not-dirty ones!
These are thick and keep liquid away from skin, also wide so they catch all poo. We like them
They don't bunch up and they're made from good material. My favourite liners by far
These liners are strong - they make it through the wash no trouble so I often reuse them. I don't flush them as I'm sure they don't dissolve even though they are 'paper' liners. They're lovely and soft and seem to do the job.
Softer than other paper liners I've used and will withstand a few washes in the washing machine. Because of this I'm not keen on flushing them down the toilet, but this is fine as they can just go in the bin instead. They seem to do a pretty good job of keeping the wetness away from the baby's bottom too.
1 of 1 people found this review helpful.
They are big enough.
These aren't the cheapest liners on the market, but I wash them with the nappies if she's just done an pee and they dry easily and can be reused many times, which works out much cheaper in the end
Read all 24 customer reviews...
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You can now invite anyone to meet at your favorite Starbucks.
Limited-time feature
47 year old woman | Castle Rock, CO, USA | Seeking men 40-49 within 15 miles
SMILE - life is great!
Looking for Mr Right (in my eyes) I am a confident, independent, outgoing woman....with a somewhat sarcastic side!. I love to make people laugh and feel at ease. I have strong family values, enjoy time with my kids - going to my kids games, outdoor adventures, and spending family time together. But let's face it, they only want to spend so much time with mom :) I'm looking for a simple, no-drama relationship. Someone with similar interests, laid back, doesn't take life too seriously and has a playful adventurous side. I prefer being outdoors, biking, boarding, catching a concert, bbq with friends. I have learned over the years that life is about the simple things. I enjoy traveling and new experiences, but want to find that special guy that together we make everyday life exciting. Best of luck in your search!
Camping , Coffee and conversation , Cooking , Gardening/Landscaping , Movies/Videos , Music and concerts , Exploring new areas , Playing sports , Travel/Sightseeing , Watching sports , Wine tasting
Baseball, Golf, Martial arts, Running, Skiing, Walking / Hiking, Weights / Machines, Yoga
I exercise 3-4 times per week.
I have Dogs
Middle of the Road
A white sand beach or any tropical location. Steamboat in the summer or winter. Watching the sunset from my patio.
Metropolitan State College of Denver, Denver, CO
My kids. Hanging out with friends. Concerts at Red Rocks. Listening to a gentle rain. Watching the sunset.
I enjoy mountain biking, long hikes, catching a few sun rays, and watching the sunset. Hanging out and having margarita's with friends on the patio is a favorite way to spend an evening.
Z{{Cta}} {{#if HasMoreInfo}} ?{{CtaSecondary}} {{/if}}
|What she is looking for
|5'5" (165cms)
|5'8" (172cms) to 6'3" (190cms)
|Body type:
|Athletic and toned
|About average, Athletic and toned
|No preference
|No preference
|No Way
|No Way, Cigar aficionado
|Social Drinker
|Social Drinker
|Executive / Management
|No preference
|$100,001 to $150,000
|No preference
|Widow / Widower, Currently Separated, Divorced
|Have kids:
|Yes, and they sometimes live at home (2)
|No preference
|Wants kids:
|No, but it's OK if my partner has kids
|White / Caucasian
|White / Caucasian
|Spiritual but not religious
|Christian / Catholic, Christian / Protestant, Spiritual but not religious, Christian / Other
|Bachelors degree
|No preference

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Can't decide which of the many moving companies in Casselberry to choose from?
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They were very careful, very considerate of our stuff and they did very well. It rained and they covered the ground.
They were very careful, very considerate of our stuff and they did very well. It rained and they covered the ground.
They were very efficient. The packing, loading and delivery was efficient and they are very honest and thoughtful. They found two of my boxes after they left and they brought them back.
The packers did a great job. My coordinator was friendly & she provided good communications. The driver who del my good was a nice guy. I have no complaints. I'm very satisfied.
The way the crew handled everything with the pick and the delivery. They were very professional & very pleasant to deal with.
The professionalism of how they packed every item. I like how they packed the furniture. It's better than my moving experiences in the past.
Everybody that was involved in the moved. The team that they had for both the loading and delivery was good. Everything was great I was happy with the crew. The coordinator was great as well.
I was pleased with courtesy and the extra miles that Allied went for me. The driver and packers were very professional and helpful.
I had some last min things please with the flexibility the sales person showed me. Overall very happy with care and flexibly shown to me, the guys that moved me in were very good had beds put together
Everyone worked very hard, especially the ppl who unloaded in Vegas. There was one item that was broken. Some of the boxes about six to seven. They were pushed down or had heavy things on them.
It seems like everyone really cared. They were there for me. The driver tried to make things as easy as possible for me.


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The 5th Annual New York City Poetry Festival
- Performing & Visual Arts
- 10 South St, #7, New York, NY, 10004
Senior Performance Showcase
Bronx Council on the Arts
Tuesday, May 14, 2013 from 11:00 AM to 1:00 PM (EDT)
Bronx Council on the Arts
Seniors Art & Performance Showcase
In conjunction with NYC Department for the Aging and
Lincoln Art Exchange
Tuesday | May 14, 2013 | 11:00am
Lincoln Medical Center Auditorium
234 E. 149th St., Bronx, NY 10451
Join us as we celebrate
50 Years!
This event is free and open to the public. For more Information:
Sharon Knight at 718-931-9500 x12 or email@example.com
Juanita Lanzo at 718-518-6728 or firstname.lastname@example.com
visitbronxarts.orgfor details
"A pioneering advocate for cultural equity, the Bronx Council on the Arts nurtures the development of a diverse array of artists and arts organizations, and builds strong cultural connections in and beyond The Bronx".
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YIELD: Makes 12 Servings
Mix mayonnaise, garlic and chipotle chilies in medium bowl. Season with salt and pepper. Transfer to serving bowl.
Char bell peppers over gas flame or in broiler until blackened on all sides. Place in bag; let stand 10 minutes. Peel; seed. Cut into 1-inch-wide strips. (Mayonnaise and peppers can be prepared 1 day ahead. Cover separately; refrigerate.) Arrange peppers on platter with greens and tomatoes.
Preheat oven to 400°F. Lightly oil heavy large baking sheet. Place chicken on baking sheet. Brush chicken with oil. Sprinkle with salt and pepper. Bake until cooked through, about 10 minutes. Transfer chicken to cutting board. Cut crosswise into 1/2-inch-wide slices, keeping slices of each breast together. Return chicken to baking sheet. Top with cheese. Bake until cheese melts, about 2 minutes.
Transfer chicken to platter and serve with bread, mayonnaise, roasted bell peppers, mixed greens and tomatoes.


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Product Antipodes Jubilation Ultra Nourishing Hand & Body Cream 120ml
Brand Antipodes
Size 120ml
Price £26.99
In stock
For deeply nourishing skin, replenishing, hydrating.Anoint your hands and body with this deeply nourishing cream that replenishes your skin with a sublime combination of pure plant oils. Essential omegas 3, 6 and 9 unite in a ratio that your skin recognises and easily absorbs. An excellent dose of Vitamins A, C and E provides the ultimate daily nutritional skin boost. Immerse your spirit in the jubilant aroma inspired by exotic feijoa and wild blackcurrant. Suited to most skin conditions, especially dry.
Smooth in to fresh, clean skin after bathing.
Aqua (Water), Glycerine, Persea Gratissima (Avocado Oil), Limnanthes Alba (Meadowfoam Seed Oil), Ribes Nigrum (Blackcurrant Seed Oil),Wheat Straw Glucosides & Cetearyl Alcohol, Actinidia chinensis (kiwifruit) seed oil, Geogard ultra (glucono delta lactone, (0.0962)sodium benzoate, (0.0325)calcium gluconate(0.0013)), Fragrances of feijoa, blackcurrant and fig, Components of essential oils: citral†, citronellol†, dlimonene†, eugenol†, geraniol†, linalool†. * Component Of Essential Oil.
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In This Section
Journal Forum
Clean Audio for TV broadcast: An Object-Based Approach for Hearing-Impaired Viewers - April 2015
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Audibility of a CD-Standard A/DA/A Loop Inserted into High-Resolution Audio Playback - September 2007
13 comments
Sound Board: Food for Thought, Aesthetics in Orchestra Recording - April 2015
2 comments
AES Journal Forum
Time—Frequency Processing
[Feature] As digital signal processing becomes more powerful, there is increasing scope for handling audio signals in the frequency domain—dividing the signal into narrow frequency bands and performing operations on those bands independently. This is not a new concept, having been used in applications such as low bitrate coding for many years, but the amount of work in the field has become so great that the AES organized a conference recently in Finland, chaired by Ville Pulkki, devoted entirely to the topic. This article attempts to condense some of the contributions from that conference, taking what is essentially a heavily mathematical topic and presenting it in a more digestible form.
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Would You Eat This Tropical Fruit Chutney?
by partysugar
Like us on Facebook
A couple weeks ago, at a buffet dinner, I came across this gross-looking condiment. The only ingredient I recognized was pecans.
As I was about to quickly pass by, I noticed a little sign that said, "Tropical Fruit Chutney with Pecans — Tastes better than it looks!" I couldn't help but laugh; the poor chutney was so ugly it needed a disclaimer!
After snapping a quick picture, I scooped some onto my plate. Could you be as brave?
POPSUGAR, the #1 independent media and technology company for women. Where more than 75 million women go for original, inspirational content that feeds their passions and interests.
Rancher'sGirl 6 years
"Tropical" usually means mango or papaya or kiwi (or all three) is involved, so I would pass on this one. I have tried dishes that look grim but are very tasty, though.
LittleMzFit 6 years
I would prefer it to be more colorful & fresh, but might try it. Maybe a spoonful over ice cream? :?
Allytta 6 years
everyone thinks my chicken liver looks disgusting, but it's delicious :) so yeah, i'd give it a go.
dit-dah-dit 6 years
Sadly I have no option but to not get near it as I am allergic to nuts.
opentypeA 6 years
I wouldn't PAY to try it...but if they had free samples or if a friend bought it I might try a little bit. :-P Besides, I've never had chutney!
ilanac13 6 years
i can't say i would try that - i'm all for foods that are pretty to look at too
goatimpact 6 years
I typically love chutney and make it a lot but I wouldn't touch this.
chiefdishwasher 6 years
How was it?
Spectra 6 years
I'd at least try it. I make a dip out of yogurt and salsa that looks kinda weird, but tastes really yummy, so I'd definitely at least give this one a shot. So WAS it any good? I'm curious!
courtneyd 6 years
I actually don't think this looks that bad. The sign would have had me at "chutney".
doogirl 6 years
I'd try it, why not? Life's too short! But I wanna know if it was any good? Was the sign right?
eshellmoyer 6 years
I don't like chutney, so you couldn't pay me to try a chutney that looked like that.
tlsgirl 6 years
So, Party, was it any good?
le-romantique 6 years
I will pretty much try any food, so naturally, I'd try it!
RoaringSilence 6 years
I have said the same thing about some dishes I really love... For example a greek skillet dish with spinach, tomatoes, feta and chickpeas.. it doesn't look so fresh once you mix it all together, but it's sooo good.


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VIEWS: 11 PAGES: 2 POSTED ON: 7/20/2010 Public Domain
Algae Derived Oils Alga Extract
Algae Derived Oils ST. PAUL, Minn. - The 16 big flasks of bubbling bright Douglas, a spokesman for the Energy Department's green liquids in Roger Ruan's lab at the University of National Renewable Energy Laboratory. "It's folks with Minnesota are part of a new boom in renewable energy experience to move it forward." research. A New Zealand company demonstrated a Range Rover Driven by renewed investment as oil prices push $100 powered by an algae biodiesel blend last year, but experts a barrel, Ruan and scores of scientists around the world say it will be many years before algae is commercially are racing to turn algae into a commercially viable energy viable. Ruan expects some demonstration plants to be source. built within a few years. Some varieties of algae are as much as 50 percent oil, Converting algae oil into biodiesel uses the same and that oil can be converted into biodiesel or jet fuel. process that turns vegetable oils into biodiesel. But the The biggest challenge is slashing the cost of production, cost of producing algae oil is hard to pin down because which by one Defense Department estimate is running nobody's running the process start to finish other than in more than $20 a gallon. a laboratory, Douglas said. One Pentagon estimate puts it at more than $20 per gallon, but other experts say it's "If you can get algae oils down below $2 a gallon, then not clear cut. you'll be where you need to be. And there's a lot of people who think you can," said Jennifer Holmgren, director of the If it can be brought down, algae's advantages include renewable fuels unit of UOP LLC, an energy subsidiary growing much faster and in less space than conventional of Honeywell International Inc. energy crops. An acre of corn can produce about 20 gallons of oil per year, Ruan said, compared with a Researchers are trying to figure out how to grow enough possible 15,000 gallons of oil per acre of algae. of the right strains of algae and how to extract the oil most efficiently. Over the past two years they've enjoyed An algae farm could be located almost anywhere. an upsurge in funding from governments, the Pentagon, It wouldn't require converting cropland from food big oil companies, utilities and venture capital firms. production to energy production. It could use sea water. And algae can gobble up pollutants from sewage and The federal government halted its main algae research power plants. program nearly a decade ago, but technology has advanced and oil prices have climbed since then, and an The Pentagon's research arm, the Defense Advanced Energy Department lab announced in late October that it Research Projects Agency, is funding research into was partnering with Chevron Corp., the second-largest producing jet fuel from plants, including algae. DARPA is U.S. oil company, in the hunt for better strains of algae. already working with Honeywell's UOP, General Electric Inc. and the University of North Dakota. In November, it "It's not backyard inventors at this point at all," said George requested additional research proposals. As the single largest energy consumer in the world, the Defense Department needs new, affordable sources of jet fuel, said Douglas Kirkpatrick, DARPA's biofuels program manager. "Our definition of affordable is less than $5 per gallon, and what we're really looking for is less than $3 per gallon, and we believe that can be done," he said. Des Plaines, Ill.-based UOP , which has developed a "green diesel" process that converts vegetable oils into fuels that are more like conventional petroleum products than standard biodiesel , already has successfully converted soybean oil into jet fuel, Holmgren said. And the company has partnered with Arizona State University 10 to obtain algae oil to test for the DARPA project, she Jim Sears of A2BE Carbon Capture LLC, of Boulder, said. Colo., a startup company that's developing fuel-from- algae technologies that tap carbon dioxide from coal- At the University of Minnesota, Ruan and his colleagues fired power plants, compared the challenges to achieving are developing ways to grow mass quantities of algae, space flight. identifying promising strains and figuring out what they can make from the residue that remains after the oil is "It's complex, it's difficult and it's going to take a lot of removed. players," Sears said. Because sunlight doesn't penetrate more than a few On the Net: inches into water that's thick with algae, it doesn't grow University of Minnesota Center for Biorefining: http:// well in deep tanks or open ponds. So researchers are biorefining.cfans.umn.edu/home.php designing systems called "photobioreactors" to provide the right mix of light and nutrients while keeping out wild National Renewable Energy Laboratory: http://www. algae strains. nrel.gov Ruan's researchers grow their algae in sewage plant Defense Advanced Research Projects Agency: http:// discharge because it contains phosphates and nitrates , www.darpa.mil chemicals that pollute rivers but can be fertilizer for algae farms. So Ruan envisions building algae farms next to Pure Energy Systems wiki: http://peswiki.com/index. treatment plants, where they could consume yet another php/Directory:Biodiesel,from,Algae,Oil pollutant, the carbon dioxide produced when sewage sludge is burned.
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Highbury College Community Sports Centre, Portsmouth
Highbury College Community Sports Centre
- Address:
- Dovercourt Road, Cosham
- Postcode/City:
- PO6 2SA Portsmouth
- County:
- Hampshire
- Phone:
- 0239231337302392313373
- Fax:
- 023 9238 3092
- Website:
- www.highbury.ac.uk/default.html
- E-mail:
- Send message
Updated more than 6 months ago | Claim This Business| Report Incorrect Data
Highbury College Portsmouth's Community Sports Centre is perfect for anyone wanting to keep fit and play sports - call 9232 8690
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It can be hard to find Southern dishes downtown, and it still might be hard unless you know just where to look: Tucked on the lower level of 770 N. Jefferson St. is Chic Cafe, a fast-casual restaurant that opened in December with a menu mostly of Southern dishes.
It's next to Shah Jee's, the perpetually popular curry and dal buffet, in what's something of a mini food court — two restaurants with counter service and shared seating in the atrium. Chic Cafe has menu items that are made to order, like a po' boy of cornmeal-crusted shrimp with fries ($9.95), and those take a bit of time, but it has a quick-service buffet as well.
That buffet of homestyle cooking is where it's at. An entrée, such as baked chicken, two sides and a corn bread muffin cost $8.
It would be easy to make a meal — a very good one — just on side dishes. Red beans and rice could put you in a New Orleans state of mind; it's a great rendition, with ample bits of smoked ham.
The collard greens, cooked with smoked turkey to ramp up the flavor, are a little spicy, very nice. And andouille sauce can be added to the cheese grits to bring some heat.
Andouille also appears with chicken in gumbo that's anchored with a robust roux ($4.95 and $7.95).
It seems like every other restaurant serves macaroni and cheese — almost always a chefy version with pasta folded in cheese sauce, maybe with a brief stint in the oven to crisp up a bread crumb topping. I'd forgotten just how satisfying the long-baked version was until I had Chic Cafe's. Talk about comfort food; that's it.
That shrimp po' boy is one of several sandwiches. With delicately flavored shrimp in a crisp crust, it's a good sandwich but for a faux butter flavor, apparently from toasting the roll. It distracts and detracts from the sandwich; better to use pure butter or a neutral oil here and in other dishes.
Daily specials might be something like a sandwich stuffed with great chunks of pulled pork ($8) in a light barbecue sauce, served with salt-and-pepper fries, or fried catfish with fries and coleslaw ($8 on Fridays, $9.59 on the regular daily menu).
The restaurant opens early for breakfast, with two eggs any way ($3.75) and omelets, generous with cheese, meat and vegetable fillings and served with toast (starting at $6.95). Breakfast can be ordered anytime, and that goes for plates like crisp fried chicken atop a big Belgian waffle (starting at $8.75), too. There are some quick grab-and-go items like fruit cups and muffins (one I ordered was dry), and diners can get Stone Creek coffee and espresso drinks.
Owners Craig and Rita Willis will add weekend brunch at the cafe, starting in mid-March; when more civilized weather returns, along with nearby events like Jazz in the Park and Bastille Days, Chic Cafe will start staying open in the evenings.
Contact Carol Deptolla at (414) 224-2841, firstname.lastname@example.com or on Twitter @mkediner.
770 N. Jefferson St., lower level
(414) 882-7708
Fare: Mainly Southern and soul food
Hours: 7 a.m.-3 p.m. Monday-Friday; brunch starting March 15, 8 a.m.-4 p.m. Saturday-Sunday
Prices: Entrées, $7-$12
Parking: On street; paid parking in the connected structure with entrance on E. Mason St.
Wheelchair access: Elevator to lower level; restrooms accessible
Payment: MasterCard, Visa, Discover
Of note: Delivery within a 2-mile radius; catering; grand opening to benefit Boys & Girls Clubs 6-9 p.m. Feb. 28, $15 admission


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The second EP from Violet Vector and the Lovely Lovelies is a fuzzy and infectious listen that, as underproduced as it may be, still puts this North Carolina six-piece in a league of its own when it comes to psych-pop. The band gushes harmonies, not the least of which is featured on the brazen-pipe-bomb-of-track "What's Going on in Your World?" Clearly, this band oozes a good time. Although the its psychedelic influences would lead many to believe that its sound is a meandering one, tracks like "Sunshine in Space" disavow that notion with swift punches. The band's songs pack a mighty punch that lend to more of a booze-fueled club than to a spaced-out festival.
Colette Carr "Static" (video) (Premiere) // Music
House of Blondes "First of July" (audio) (premiere) // Music
Digisaurus 'No More Room For Love' (EP stream) // Music
Fave Five: Alpine
// Sound Affects
"Australian sextet Alpine's newest album is a fantastic expansion of their joyous pop sound, but two members give us five records apiece that helped define their unique musical identities.READ the article


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Great food! Consistent quality! I especially love their crab rangoon, chicken with garlic sauce and their shrimp fried rice!
I must say that for the price, I didn't expect such great food! And ALOT of it. Very pleased with my experience from this restaurant.
To say the least, the portions are generous. There are several Chinese food places in the immediate area and this is by far the best. There are several "family combo" meals to choose from. They can feed a family of 5 with leftovers (3 are teenagers) and not break the bank. Although it is not a place you want to...
Best coupons & the usual delivery guy is the best.
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I stayed at the Maritim Hotel to attend a conferenced in Nuremberg. It is in a great location, between two train stops, both of which are only a 1-2 minute walk away, and directly across the street from the old city. The hotel lobby is beautiful and elegant, and the rooms are very clean and quite comfortable(although they could be a bit plain for some). An amazing buffet breakfast is included with the room rate. The staff were extremely helpful and friendly, and took care of all of my questions and requests promptly and cheerfully. If I return to Nuremberg, I wil definitely stay here again.
- Reservation Options:
- TripAdvisor is proud to partner with Expedia, Hotels.com, Booking.com, Travelocity, Odigeo, Priceline, Cheap Tickets, Agoda and HotelTravel.com so you can book your Maritim Hotel Nurnberg reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
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Evolution News and Views (ENV) provides original reporting and analysis about the debate over intelligent design and evolution, including breaking news about scientific research, academic freedom cases, and educational policy issues. ENV also covers how the rest of the newsmedia report on the debate, offering analysis and corrections to major news stories, as well as a behind-the-scenes look at how journalists and news outlets operate when they report on this issue. Movable Type 5.12
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The pro-Darwin media love to print triumphalist articles, declaring on the thinnest of evidence that "creationists" are deathly scared of the latest science. Casey Luskin http://www.discovery.org/p/188
Bobby Jindal and Louisiana's "Creationist" Law
If I were Jindal and a reporter questioned me about my state's "anti-science" education policy, here's what I would say. David Klinghoffer http://www.discovery.org/p/209
The Missing Factor in Paul Ehrlich's Calculation of a "Sixth Great Mass Extinction"
Fossil extinction rates are smoothed over tens of millennia, whereas today's extinction rates are spiky. Rob Sheldon
In Explaining Dylann Roof's Inspiration, the Media Ignore Ties to Evolutionary Racism
It's worth noting how certain ideas tend to hang together. David Klinghoffer http://www.discovery.org/p/209
Associated Press Orders Media to Stop Using "Committed Suicide"
I believe that we are in the midst of a broad push, across different sectors of society, to make suicide more palatable and normalized. Wesley J. Smith http://www.nationalreview.com/human-exceptionalism
Moths Defy the Possible
Following a moving target in near darkness: just one example of natural visual feats performed by the smallest animal brains. Evolution News & Views
Seeking to Vilify Doubters, New York Times Now Opts for "Denier" Over "Skeptic "
It is disturbing to see so highly regarded a newspaper embrace intimidation, calling it "accuracy." David Klinghoffer http://www.discovery.org/p/209
Listen: "Follow the Evidence Wherever It Leads." Really?
Unlike materialists, who MUST find a naturalistic explanation for everything in nature, intelligent design is without bias. Evolution News & Views
A "Sixth Mass Extinction"? Here's Why No One Trusts Science Reporting Anymore
You may have noted that one of the sources of the claim is Paul Ehrlich. Wesley J. Smith http://www.nationalreview.com/human-exceptionalism
Laudato Si' and Science Apocalypse
I am both pleased and disturbed by the Pope's encyclical. Michael Egnor
Let's Get "Science-Saavy"!
Stephanie Keep, editor of Reports of the National Center for Science Education, is all atwitter about what she calls "science denialism." Donald McLaughlin http://www.discovery.org/p/611
Recommended Viewing: A Great Talk by Michael Lynch
The Indiana University evolutionary biologist is an often-scathing critic of the abuse of natural selection in biological explanation. Paul Nelson http://www.discovery.org/p/45
The Church of Transhumanism: Let Us Upload
I follow transhuman comings and going, often with great amusement. Wesley J. Smith http://www.nationalreview.com/human-exceptionalism
Information from Nothing? The Flatworm's Tale
A computer model mimics Darwinian evolution and offers a solution to how flatworms regenerate missing parts. Is it innovation by blind processes? Evolution News & Views
Say What You Want About Intelligent Design
There's a strange ethical tenet in the media that holds that when it comes to ID, you can assert anything that seems expedient. David Klinghoffer http://www.discovery.org/p/209
RSS Syndication
Antievolutionists Say the Darndest Things
Antievolutionists often express outrage over alleged incivility from those who oppose their efforts to evade the establishment clause of the First Amendment. But they have no difficulty in dishing out the abuse themselves. Here is a sample from the Invidious Comparisons thread that documents egregious behavior on the part of the religious antievolution advocates.
IDC advocate Phillip E. Johnson:
Darwinian evolution with its blind watchmaker thesis makes me think of a great battleship on the ocean of reality. Its sides are heavily armored with philosophical barriers to criticism, and its decks are stacked with big rhetorical guns ready to intimidate any would-be attackers. In appearance, it is as impregnable as the Soviet Union seemed to be only a few years ago.
Pro-Science Sites
Donate | NCSE | PT | TD | TOA | Public BB Archive | PvM's Blog


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Here's a great idea: Let's put the hospitals out of business!
The world's turned upside down. The socially unhealthy practices and behaviors we once discouraged, stigmatized, or outlawed are now being legalized, accepted, and embraced. The age-old wisdom of traditions and taboos has been discarded. When healthy practices were still in the ascendant, we were told that we must have choices and that unhealthy choices were equivalent to healthy ones, if not superior. Now that unhealthy choices have become widely accepted, choice is no longer trumpeted. Instead, we're told that the healthy choices are not really necessary anymore and that we'd be better off without them. Remember when private enterprise, limited government, freedom of religion, patriotism, and family values were celebrated? For years, we've been conditioned to believe that there's something wrong with these foundational principles, and the pride that many Americans once invested in each has devolved into disdain. The medical profession is now going through this inversion process as doctors and hospitals once lauded for their devotion to their patients and to the public good are progressively demonized. Our private health care system worked quite well in the recent past. The extraordinary contributions that hospitals made to society were recognized by government and encouraged with property tax exemptions and other considerations. But our increasingly autocratic state and federal governments seem determined to put our hospitals out of business with excessive regulation and increased taxation. Rep. Dwight Kay (R-Glen Carbon) worries that an Illinois Supreme Court decision depriving a central Illinois hospital of its property tax exemption could eventually be extended to all of the state's hospitals. Kay notes that Illinois hospitals serving the poor are already struggling with low -- and slow -- Medicaid reimbursement rates. "Some of them have to borrow money to keep operating," he laments. "With the loss of tax exemption, they would have to consider even whether to stay in business." If you're planning to seek medical attention anytime soon, you'd better do it now while we still have hospitals.


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Arizona State Sun Devils
Demian Bichir delves into immigration debate
NEW YORK (AP) - Forgive Mexican actor Demian Bichir for pointing out the obvious metaphor in the title of his new TV series "The Bridge," but someone had to do it.
"We need bridges more than walls, you know what I mean?" said Bichir about the immigration and border security debate that is currently occupying the U.S. Congress.
Bichir stars as Detective Marco Ruiz in the FX drama, opposite Diane Kruger, who plays his counterpart in the U.S.
The pair is forced to work together after a body is found on the bridge connecting Juarez, Mexico, and El Paso, Texas. By the end of the pilot, they suspect a serial killer. Their partnership, and subplots involving other characters, allows the show's writers to also address immigration and political issues on the border.
The U.S. Congress is debating a proposal that would strengthen security along its southern border, while providing a path to citizenship for the estimated 11 million workers living in the U.S. without legal permission.
"They're talking about this possible amnesty, but also they're talking about spending millions of dollars building taller, bigger, stronger walls," said Bichir during an interview in New York earlier this month. "We need to find a way of doing it right because that will not stop anybody from coming over here if they see the possibility of having a better life."
Bichir, nominated for an Oscar in 2012 for playing a gardner living in the U.S. without legal permission in "A Better Life," dislikes the political rhetoric that often accompanies the immigration debate.
"Oh, this tremendous enemy called the immigrants. They're taking our jobs and this and that," he said. "They close many factories and fields in Alabama and not even one single American citizen went over there and claimed those jobs and these immigrants, these undocumented workers, just left and it became almost like a ghost town and there was not a single American claiming those jobs, you know what I mean? So it's all a circle of lies that people need to be careful and aware of."
"The Bridge" premieres July 10 at 10 p.m. Eastern on FX.
(Copyright 2013 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.)
Most Popular
Sun Devils Audio
- Rick Neuheisel, CBS AnalystNeuheisel talks recruiting with Diddy and ASU's chances in the PAC-12
- Arizona State Head Basketball Coach Bobby Hurley Bobby Hurley talks about coming to Arizona State and what it's like recruiting in Arizona.
- Corona Del Sol Star Basketball Player Marvin Bagley III Marvin Bagley talks about winning the state title, recruiting, and shows off his musical talent.
- Ray Anderson, ASU athletic directorRay Anderson discusses the importance of scheduling major football opponents.
- Glenn Parker, Pac-12 Football AnalystGlenn Parker discusses the upcoming Pac-12 football season.


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Whether you like romantic comedies or black comedies, have a laugh by Stumbling through funny films.
About StumbleDNA StumbleDNA
Nonan's Interests
Where would movies or video games be without computer graphics? Learn about animation, modeling and more.
No more stick figures! Uncover your inner artist and the world of sketching, charcoals and pastels.
Is Firefox your browser of choice? Learn about the best downloads, updates, extensions and other tips.
Funny jokes, pictures or quotes...whatever your sense of humor, we have something to make you laugh.
Networks, servers, downloads...the Web is complicated. Thank goodness for internet tools.
Music makes the world go round. Discover new bands, songs, lyrics, music videos and more.
See amazing photos and get photography tips and ideas, from Polaroids to digital cameras.
Love snow days? From the mountains of Colorado to Vermont, explore downhill and cross country skiing.
Hawaii or Europe? By air or cruise? Whatever your travel style, you can always use vacation ideas.
Glued to your Xbox, PS3 or Wii? Whatever you prefer, Stumble through video games for your gaming fix.


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Trusted Senior Home Care in Harrisburg and Hershey, Pennsylvania
Whether a family member needs a little extra help around the house, assistance recovering from a hospital stay or someone to check in on them throughout the week, Right at Home's in-home care could be the answer. Our home care services are built around your specific needs.
Our Caregivers are specially trained to provide just the services your loved one needs. We modify our custom care plan for your family member as their needs change, allowing them to live at home as long as possible.
Don't Compromise When it Comes to Care for a Loved One
We know you are busy raising your family, caring for an aging mother or father and balancing your career. Caregiving for a loved one can take its toll and change family dynamics. We know providing care for a loved one can become highly stressful – whether your loved one lives down the street or thousands of miles away.
The Right Care from Right at Home Harrisburg and Hershey, Pennsylvania
We understand your concerns when it comes to making decisions regarding your family. For many people, our in-home senior care is the best solution for maintaining a healthy lifestyle and loving relationships. Whether a family member needs a little extra help around the house, assistance recovering from a hospital stay or someone to check in on them throughout the week, Right at Home can be the perfect solution. We customize our care services, so your loved one always gets the special care they need based on their individual needs. Discover how our many services can help improve your family's quality of life.
|Explore In-Home Care Options
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Care Assessment
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There are a few universal challenges of aging that many families experience. To see what kinds of services may benefit you and your family's situation, see what helps similar families in our Care Scenarios.
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Use our easy online tool to create a printable schedule of daily activities for your loved one.Get Started »
I am very thankful for the services that Right at Home provides for me and my family. As a medically disabled Veteran, the monitoring by the VA and the assistance from the staff at Right at Home enables me to live at HOME. Thank God for your office staff and Home Health staff. They go above and beyond helping me to remain Home. I can't say enough good things about them. Our caregiver is the greatest aide.
Contact Us
If you can't find what you're looking for or have a specific request, simply complete the form below. We're always here to help.
From the Blog
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Five Things to Know When Considering Home Care; Keeping Seniors Safe During Heat WavesJun 25, 2015 Read Full Entry »


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Seriously good sunsets, serene countryside and a relaxed, friendly vibe - Talywerydd Touring and Camping Park is perfect if you're looking to escape the mayhem of modern life with a return to simple pleasures.
With glorious views over the undulating Ceredigion coastline, the site offers good essential amenities and is only 600 yards from a renowned farm shop selling scrummy picnics, home-cooked ready meals and hampers of regional goodies.
There are no large or single-sex groups here, and guests will find the pace is delightfully slow, although there are plenty of options to liven things up in the surrounding area. Fidos are welcomed too (up to two per pitch, no dangerous breeds); there's a dedicated doggie exercise area, but elsewhere on site they'll need to stay on the leash.
Site type
Languages spoken
✓ English
✓ Welsh
Please note
Strictly a family and adult couples only site. Young or single sex groups of 3 or more are not accepted. Group bookings must comprise a recognised organisation or association.
Showers are 50p coin metered. We do this for a few reasons:
- It allows us to keep our pitch prices lower...there's no such thing as a 'free shower': the cost is merely incorporated into a more expensive pitch price. Our way you only pay for what you use.
- It keeps queues to a minimum. People are less inclined to pay for 30 minute showers!
-When the site is busy, it allows the boiler to keep up with the demand for hot water.
Where possible, family groups will be assigned pitches adjacent to one another, if not as near as available.
No availability for your search criteria…
Arrive:Wed 19 Jun 2013
Depart:Thu 20 Jun 2013
(1 night)
Party:2 adults
You can now make a booking for up to 30 adults and 30 children on Pitchup.com.
Many sites set a maximum occupancy of 6/8 people per pitch, so try breaking your booking down into smaller groups to generate more results. For example, if you're a group of 10, enter 5 people in your initial search and then book 2 pitches.
Use the 'Special requests' box on the booking page to ask to be sited together when booking multiple pitches: the campsite or park will try to grant your request.
Large groups: check the listing page for any group restrictions set out in the terms and section titled 'Please note'.
Large tents/caravans: check the restrictions on unit dimensions to ensure your unit is suitable for the space you will be provided with.
Max. persons: 6x
Dimensions: Max 9.0m x 9.0m (29.5ft x 29.5ft)
Ground type: Grass
Gazebos not allowed.
Max. persons: 6x
Dimensions: Max 8.5m x 9.0m (27.9ft x 29.5ft)
Ground type: Grass
Gazebos not allowed.
Max. persons: 6x
Dimensions: Max 8.5m x 9.0m (27.9ft x 29.5ft)
Ground type: Grass
Gazebos not allowed.


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A method for the diagnosis of Alzheimer's disease (AD) in a patient, comprising the steps of:
(1) providing a sample of an appropriate body fluid from said patient, and
(2) detecting the presence of BuChE with an altered glycosylation pattern in said sample.
1. A method for the diagnosis of Alzheimer's disease in a patient, comprising the steps of:
(1) providing a sample of an appropriate body fluid from said patient, and
(2) detecting the presence of butyrylcholinesterase with an altered glycosylation pattern in said sample.
2. The method of
3. The method of
4. The method of
5. The method of
6. The method of
(1) measuring the proportion of acetylcholinesterase binding to Concanavalin A,
(2) measuring the proportion of acetylcholinesterase binding to wheat germ agglutinin,
(3) determining the ratio of acetylcholinesterase unbound to Concanavalin A to acetylcholinesterase unbound to wheat germ agglutinin, and
(4) comparing the ratio with the relative proportion of butyrylcholinesterase unbound to Concanavalin A.
7. The method of
8. The method of
9. The method of
10. The method of
11. The method of
12. The method of
13. The method of
14. The method of
15. An abnormal isoform of butyrylcholinesterase with an altered glycosylation pattern and a lesser affinity for Concanavalin A and a greater affinity for wheat germ agglutinin than butyrylcholinesterase with an unaltered glycosylation pattern.
16. An abnormal isoform of butyrylcholinesterase with an altered glycosylation pattern and a lesser affinity for Concanavalin A and a greater affinity for wheat germ agglutinin than butyrylcholinesterase with an altered glycosylation pattern.
17. The method of
18. The method of
[0001] The present application is based upon and claims the priority of U.S. Provisional Patent Application Ser. No. 60/195,231 filed Apr. 7, 2000 which is incorporated herein by reference.
[0002] The present invention is concerned with a diagnostic test for Alzheimer's disease.
[0003] Alzheimer's disease (AD) is a common progressive dementia involving loss of memory and higher cognitive function. The disease is characterized by the presence of amyloid deposits in the brains of sufferers. These deposits are found both extracellularly (amyloid plaques) and intracellularly (neurofibrillary tangles). The principal constituent of amyloid plaques is the amyloid protein (Aβ) which is produced by proteolytic cleavage for the amyloid protein precursor (APP) (Evin et al., 1994). The principal constituent of neurofibrillary tangles is the cytoskeletal protein tau (Kosik, 1992).
[0004] One of the characteristic neurochemical changes observed in AD is the loss of acetylcholinesterase (AChE) and choline acetyltransferase activity in regions of the brain such as the cortex, hippocampus, amygdala and nucleus basalis (Whitehouse et al., 1981, 1982; Struble et al., 1982; Mesulam and Geula, 1988). The loss of cholinergic structure and markers correlates with the number of plaque and tangle lesions present, as well as with the clinical severity of the disease (Perry et al., 1978; Wilcock et al., 1982; Neary et al., 1986; Perry, 1986). This loss of AChE is accompanied by an increase in butyrylcholinesterase (BuChE) (Atack et al., 1986).
[0005] Accurate diagnosis of AD during life is essential. However, clinical evaluation is at best only about 80% accurate. Therefore, there is a need to identify specific biochemical markers of AD. So far, analysis of blood or cerebrospinal fluid (CSF) has not yielded a biochemical marker of sufficient diagnostic value (Blass et al., 1998), although detectable differences are reported in the levels of certain proteins (Motter et al., 1995).
[0006] The assay of levels of AChE and BuChE activity in the blood and the cerebrospinal fluid (CSF) have been proposed as an ante mortem diagnostic test for AD. However, no consensus has been reached as to whether the levels of AChE and BuChE are consistently affected in these tissues. The level of serum or plasma AChE has been reported to be increased (Perry et al., 1982; Atack et al., 1985), decreased (Nakano et al., 1986; Yamamoto et al., 1990) or unchanged (St. Clair et al., 1986; Sirvio et al., 1989) in AD patients. The level of erythrocyte AChE has been reported as either unaffected (Atack et al., 1985; Perry et al., 1982) or decreased Chipperfield et al., 1981). The level of AChE activity in the CSF of AD patients has been reported to be decreased (most recently by Appleyard and McDonald, 1992; Shen et al., 1993) or unchanged (most recently by Appleyard et al., 1987; Ruberg et al., 1987).
[0007] AChE and BuChE have been shown to exist as up to six different molecular isoforms, three of which are the monomeric (G1), dimeric (G2) and tetrameric (G4) isoforms (Massouli� et al., 1993). The relative proportion of the different isoforms of AChE and BuChE are markedly affected in AD, with a decrease in the G4 isoform of AChE in the parietal cortex (Atack et al., 1983), and an increase in the G1 isoform of AChE (Arendt et al., 1992). Similar changes have been identified in other AD brain regions including Brodman areas 9, 10, 11, 21 and 40, as well as the amygdala (Fishman et al., 1986). Asymmetric collagen-tailed isoforms (A12) are increased by up to 400% in Brodman area 21, although they represent only a trace amount of the total AChE in the human brain (Younkin et al., 1986).
[0008] However, to date changes in AChE and BuChE expression and isoform distribution have not been found to be of sufficient sensitivity or specificity to be useful diagnostic markers of AD.
[0009] There remains a need for a diagnostic test for AD based on a biochemical analysis of body fluids such as blood or CSF. The present invention provides such a test on the basis that the butyrylcholinesterase (BuChE) of AD patients shows a different glycosylation pattern to the BuChE of non-AD groups.
[0010] According to a first aspect of the present invention there is provided a method for the diagnosis of Alzheimer's disease (AD) in a patient, comprising the steps of:
[0011] (1) providing a sample of an appropriate body fluid from said patient, and
[0012] (2) detecting the presence of BuChE with an altered glycosylation pattern in said sample.
[0013] In one embodiment of the invention the relative proportion of BuChE with a specific glycosylation pattern to the total BuChE is measured.
[0014] Measurement of the relative proportion of the isoforms of BuChE with a specific glycosylation pattern to the total BuChE may be carried out in any convenient manner, for example, by using biochemical analysis techniques such as HPLC and mass spectrometry, or immunological techniques such as ELISA or, assays. However, a particularly preferred means of measuring the relative proportions of the isoforms of BuChE involves a lectin-binding analysis.
[0015] It has been established that on average approximately 93.6% of the BuChE in the CSF of AD patients binds to Concanavalin (Con A). Accordingly, in a particularly preferred embodiment of the invention, in order to detect the presence of BuChE with a to specific glycosylation pattern in the sample, the binding of BuChE to Con A is determined. The percentage of BuChE bound to Con A is characteristic of the proportion of BuChE with the specific glycosylation pattern.
[0016] Also, it is particularly useful to measure the activity of unbound BuChE in each experiment, by determining the amount of BuChE unbound to Con A relative to the total BuChE in the sample.
[0017] In another embodiment of the present invention, it is particularly advantageous to compare the ratio of AChE that binds to Con A with the AChE that binds to wheat germ agglutinin (WGA), hereinafter referred to as the C/W ratio, versus the percentage of BuChE unbound to Con A. The ratio is characteristic of the different glycosylation patterns of AChE. By plotting the C/W ratio versus the percentage BuChE unbound to Con A, the separation of patients diagnosed with AD as compared with non-AD becomes evident when viewing such a plot.
[0018] Approximately 75-95% of the AChE in the CSF of AD patients bind to Concanavalin (Con A) or wheat germ agglutinin (WGA) but with different specificity to each. For patients with AD, the C/W ratio is typically above 0.95 and the percentage of BuChE unbound to Con A relative to the total BuChE is at least about eight percent (8%).
[0019] In an alternative embodiment of the invention there is provided a monoclonal antibody specific for BuChE with an altered glycosylation pattern used to detect its presence.
[0020] The body fluid analysed can be cerebrospinal fluid (CSF), blood or blood plasma. Advantageously, when said body fluid is blood, blood plasma is prepared from the blood for analysis.
[0021] According to a further aspect of the present invention there is provided an abnormal isoform of BuChE with an altered pattern of glycosylation and characterised in that it has a relatively lesser affinity for Concanavalin (Con A) than BuChE with an unaltered glycosylation pattern.
[0022] According to another aspect of the present invention there is provided an abnormal isoform of BuChE with an altered glycosylation pattern and characterised in that it has a relatively lesser affinity for Con A than BuChE with an altered glycosylation pattern.
[0023]FIG. 1 shows the correlation between the level of AChE and BChE in cerebrospinal fluid. (Black squares=controls. Open circles=AD.) This figure shows that there is a positive correlation in the levels of AChE and BChE suggesting that similar biochemical mechanisms may underly the decrease in activity of both enzymes in AD CSF.
[0024]FIG. 2 is a plot of the AChE C/W ratio vs. the percentage (%) BChE unbound to Con. A. This figure shows that there is no clear correlation between these analytes. This figure also shows that by combining both measures, almost complete separation can be achieved between the AD and control groups.
[0025]FIG. 3 is a plot of the percentage (%) BChE unbound to Con A vs. age (yr) for both AD and controls. This figures shows that there is no relationship between BChE glycosylation and age. Thus disease status is the only correlate.
[0026]FIG. 4 is a three dimensional plot of the total BChE, C/W ratio and the percentage (%) BChE unbound to Con A showing complete separation of the AD and control groups.
[0027] AChE, acetylcholinesterase; butyrylcholinesterase (BuChE) ChE, cholinesterase; Aβ, amylid β protein; AD, Alzheimer's disease; DP, diffuse plaques; ND, other neurological diseases; PMI, post mortem interval; PBS, phosphate-saline buffer; TB, Tris buffer; TSB, Tris-saline buffer; SS, salt-soluble supernatant; TS, Triton X-100-soluble supernatant; AF, amphiphilic fraction; HF, hydrophilic fraction; Ga, globular amphiphilic isoform; Gna, globular non-amphiphilic isoform; and agglutinins from Canavalia ensiformis (Concanavalin A), Con A; Triticum vulgaris (wheat germ), WGA; Ricinus communis, RCA120 ; Lens culinaris, LCA; Dolichus biflorus, DBA; Ulex europaeus, UEAl ; Glycine max, SBA; and Arachis hypogaea, PNA.
[0028] Immobilised lectins (Con A- and LCA-Sepharose, WGA-, RCA120-, DBA-, UEAl; SBA and PNA-agarose), phenylagarose, bovine liver catalase, E. coli alkaline phosphatase, polyoxyethylene-10-oleyl ether (Brij 97), Triton X-100, tetraisopropyl pyrophosphoramide (iso-OMPA), 1,5-bis(4-allydimethyl-ammoniumphenyl)-pentan-3-1 dibromide (BW284c51), acetylthiocholine iodide and 5,5′-dithio-bis-2-nitrobenzoic acid (DTNB) were all obtained from Sigma-Aldrich Pty. Ltd. (Seven Hills, NSW, Australia). Sepharose CL-4B was purchased from Pharmacia Biotech AB (Uppsala, Sweden).
[0029] The following Examples relate to experiments conducted with acetylcholinesterase (AchE). One skilled in the art would readily be able extrapolate from the following Examples to make a diagnostic test for Alzheimer's Disease comprising the detection of butyrylcholinesterase (BchE) with an altered glycosylation pattern
[0030] Lumbar or ventricular CSF was obtained post mortem; 18 controls with no clinical or pathological dementia and no clinical or pathological dementia and no evidence of brain pathology, 27 cases of AD, 7 cases of dementia non-AD type (DNAT, 5 frontal lobe dementia, 1 Lewy body dementia/Parkinson's disease and 1 multi-infarct dementia/congophilic amyloid angiolpathy), and 6 cases of other neurological disorders (ND, 4 Huntington's disease, 1 schizophrenia and 1 corticobasal degeneration). The average age in the control group was 68�4 years, there were 10 females and 8 males and the PMI was 40�6. In the AD group the age was 81�2 years, there were 13 female and 14 males and the PMI was 35�6. In the ND group the age was 65�6, there were 3 females and 3 males and the PMI was 45�12. In the DNAT group the age was 76�3, there were 4 female and 3 males and the PMI was 34�11. Samples of CSF were stored at −70� C. and centrifuged at 1,000� g for 15 min prior to analysis. AChE activity was assayed at 22� C. by a modified microassay of the Ellman method (Ellman et al. 1961). Aliquots (0.3 ml) were mixed with 0.1 ml of Sepharose 4B in PBS (control), Concanavalin A (Con A) or wheat germ agglutinin (WGA, Triticum vulgaris) immobilised on Sepharose. The enzyme-lectin mixture was incubated overnight at 4� C., and then centrifuged (1,000� g, 15 min). AChE activity was assayed in the supernatant fractions. Data were analysed using a Student's t-test.
[0031] The total AChE values in ventricular CSF samples of subjects=>60 yrs old were significantly lower in the AD group (6.98�0.82 nmol/min/ml) than in controls (17.24�4.28 nmol/min/ml; P<0.001). However, as reported previously, (Appleyard et al., 1983), the large overlap (40%) between the data prevents the use of total AChE as a significant diagnostic marker.
[0032] However, lectin-binding analysis revealed a significant difference between the AD group and controls. Approximately 75-95% of the AChE in the CSFs bound to Con A or WGA. A ratio (C/W ratio) was defined as AChE unbound to Con A divided by AChE unbound to WGA. The mean C/W ratio for the AD group was significantly different from controls (FIG. 1). Of the 27 CSFs from confirmed AD, 21 samples had a C/W ratio>0.95. All 18 control samples had C/W<0.95, without significant differences between younger (n=5, C/W=0.37�0.10) and older subjects (n=6, 0.38�0.08) samples. No correlation in C/W ratio was noted with post mortem interval (PMI). The data are represented graphically in FIG. 1.
[0033] The data indicate that lectin-binding analysis of CSF AChE could provide a diagnostic test for AD which is 80% sensitive and 97% specific. Thus it was proposed that differences observed in the glycosylation pattern of AChE in CSF may be useful as an ante mortem diagnostic marker for AD, particularly when used in combination with measurement of other biochemical markers.
[0034] Ventricular and lumbar CSF, frontal cortical and cerebellar samples were obtained post mortem and stored at −80� C. Three non-AD groups of samples were defined, 1) controls with no clinical or pathological features of dementia (n=18), 2) individuals who showed no clinical signs of dementia but who were found to have a moderate number of non-neuritic Ab-immunoreactive diffuse plaques (DP), but no evidence of neocortical neurofibrillary changes (n=6), and 3) individuals with various neurological diseases (ND) containing 7 cases of non-AD type dementia (5 frontal lobe dementia, 1 Lewy body dementia and 1 vascular dementia) and 7 cases of other neurological disorders (4 Huntington's disease, 1 Parkinson's disease, 1 schizophrenia and 1 corticobasal degeneration). Cases of AD were selected on the basis of their clinical history of dementia and neuropathological CERAD diagnosis (Mirra et al., 1994). All the CSF samples included in the AD and ND groups were ventricular and only 5 control and 1 DP CSF samples (from a total of 18 and 6 subjects, respectively) were taken by lumbar puncture. Immunohistochemical examination of the cerebellar samples showed that, unlike the frontal cortex, none of the AD tissue possessed compact neuritic amyloid plaque deposition (data not shown), consistent with previous studies (Mann etal., 1996).
[0035] It has been shown (Grass) et al., 1982; Fishman et al., 1986; S�ez-Valero etal., 1993) that for a post mortem interval (PMI) greater than 72 hr, storage at −20� C. or repeated cycles of freeze-thawing caused degradation of AChE, which confounded glycosylation analysis. Therefore, only samples with a PMI of less than 72 hr (PMI=36�4 hr) were used. There was no significant difference in PMI between each group of samples.
[0036] Preparation of Samples and Extraction of AChE
[0037] Samples of CSF were thawed slowly at 4� C. and then centrifuged at 1,000� g for 15 min prior to use. Small pieces (0.5 g) of frontal cortex and cerebellum were thawed slowly at 4� C., weighed and homogenised (10% w/v) in ice-cold Tris-saline buffer (TSB; 50 mM Tris-HCl, 1 M NaCl, and 50 mM MgCl2, pH 7.4) containing a cocktail of proteinase inhibitors (Silman et al., 1978). Tissues were homogenised with a glass/Teflon homogeniser and then sonicated with 10-15 bursts at 50% intermittency at setting 4 using a Branson sonifier. The suspension was centrifuged at 100,000� g at 4� C. in a Beckman L8-80M ultracentrifuge using a 70.1 Ti rotor for 1 hr to recover a salt-soluble ChE fraction (SS). The pellet was re-extracted with an equal volume of TSB containing 1% (w/v) Triton X-100, and the suspension centrifuged at 100,000� g at 4� C. for 1 hr to obtain a Triton X-100-soluble ChE fraction (TS). This double-extraction method recovered 80-90% of the total ChE activity (SaezValero et al., 1993; Moral-Naranjo et al., 1996).
[0038] AChE Assay and Protein Determination
[0039] AChE activity was determined by a modified microassay method of Ellman (S�ez-Valero et al., 1993). One unit of AChE activity was defined as the number of nmoles of acetylthiocholine hydrolysed per min at 22� C. Protein concentrations were determined using the bicinchoninic acid method with bovine serum albumin as standard (Smith et al., 1985).
[0040] Hydrophobic Interaction Chromatography on Phenyl-agarose
[0041] Amphiphilic AChE forms were separated from hydrophilic forms by hydrophobic interaction chromatography on phenyl-agarose as previously described (S�ez-Valero et al., 1993). CSF (10 ml-pooled from four samples obtained from four different subjects) was applied to a column (10�1 cm) of phenyl-agarose. A hydrophilic fraction (HF) containing hydrophilic isoforms of AChE was eluted with 30 ml of TSB, and then an amphiphilic fraction (AF) containing bound amphiphilic isoforms was eluted with 50 mM Tris-HCl (TB, pH 7.4) containing 2% (w/v) Triton X-100. Peak fractions with high AChE activity were pooled and concentrated using Ultrafree-4 Centrifugal Filter Device Biomax 10 kDa concentrators (Millipore Corporation, Bedford, Mass., USA).
[0042] Sedimentation Analysis
[0043] Molecular isoforms of AChE were analysed by ultracentrifugation at 150,000� g in a continuous sucrose gradient (5-20% w/v) for 18 hr at 4� C. in a Beckman SW40 rotor. The gradients contained 10 ml of 50 mM Tris-HCl (pH 7.4) containing 0.5 M NaCl, 50 mM MgCl2 and 0.5% (w/v) Brij 97. Approximately 40 fractions were collected from the bottom of each tube. Enzymes of known sedimentation coefficient, bovine liver catalase (11.4S, S20,w Svedberg Units) and E. coli alkaline phosphatase (6.1S) were used in the gradients to determine the approximate sedimentation coefficients of AChE isoforms. A ratio of AChE species G4/(G2+G1), that reflected the proportion of G4 molecules (G4 na+G4 a) versus both light globular AChE isoforms, G2 a and G1 a was defined. Estimation of the relative proportions of each molecular form of AChE was performed by adding the activities under each peak (G4 or G2+G1) and calculating the relative percentages (recovery>95%).
[0044] Lectin-binding Analysis of AChE
[0045] Samples (0.3 ml) were added to 0.1 ml (hydrated volume) of Sepharose 4B (control), Con A, WGA, RCA120, LCA, DBA, UEAl, SBA or PNA immobilised in agarose or Sepharose. The enzyme-lectin mixture was incubated overnight at 4� C. with gentle mixing. Bound and free AChE were separated by centrifugation at 1000� g for 15 min at 4� C. in a Beckman J2-21 M/E centrifuge using a JA-20 rotor, and the unbound AChE was assayed in the supernatant fraction. Percentage of unbound AChE in the lectin incubation was calculated as (AChE unbound to lectin/AChE unbound to Sepharose)�100. The C/W ratio was calculated according to the formula, AChE activity unbound in the Con A incubation divided by the AChE activity unbound in the WGA incubation. It was observed that this ratio detects a specific alteration in AChE glycosylation that occurs in AD CSF.
[0046] Lectin Binding of CSF AChE
[0047] To examine the glycosylation of AChE, CSF samples from 18 controls and 30 cases of AD were incubated with different immobilised lectins, which recognise different sugars. AChE bound strongly to Con A, WGA and LCA but weakly to RCA120, PNA, DBA, UEA, and SBA (Table 1), suggesting that most of the enzyme was devoid of terminal galactose, terminal N-acetyl-galactosamine or fucose.
[0048] There was a small but significant difference in the binding of AChE to Con A and WGA between the AD group and controls (Table 1). As the percentage of AChE unbound in the AD CSF was increased for Con A and decreased for WGA, a ratio (C/W=[% AChE that does not bind to Con A]/[% AChE that does not bind to WGA]) was defined, which provided greater discrimination between the two groups (Table 1). Using this method, it was found that the mean C/W ratio for the AD group was significantly greater than for the other control groups, including cases with diffuse plaques (non-demented, DP), and patients with other neurological and neuropsychiatric diseases (ND) (FIG. 2), consistent with the results shown in Example 1. Of the 30 CSF samples from confirmed AD cases, 24 samples were above a cut-off value of C/W=0.95 (FIG. 2). Only one sample from 18 controls, one out of 6 samples from cases with diffuse plaques, and one out of 14 samples from the other neurological diseases group, a frontal lobe dementia case, were above this value. The 6 AD samples with C/W ratios lower than 0.95 had C/W ratios>0.60, a value higher than the C/W mean of the non-AD groups (control=0.53�0.1; DP=0.46�0.2; ND=0.53�0.1).
[0049] No correlation could be found between the C/W ratio and the PMI that could suggest that different C/W ratio in the AD group was due to differences in PMI. Furthermore, there was no significant difference in the PMI between the AD (33�6 hr) and non-AD samples (40�6 hr).
[0050] CSF samples were additionally analysed for total AChE activity (FIG. 2). As previously reported (Appleyard et al., 1983; Atack et al., 1988), the CSF from patients with AD had significantly lower AChE activity (6.5�0.8 U/ml) than controls (15.8�2.9 U/ml) or patients with other diseases (12.4�2.4 U/ml). However, the C/W ratio was a more reliable index of clinical status than the total level of AChE activity in the CSF (FIG. 2).
[0051] AChE Isoforms in CSF
[0052] To determine whether the alteration in glycosylation was due to changes in a specific isoform of AChE, CSF samples were analysed by hydrophobic interaction chromatography to separate amphiphilic (Ga) and hydrophilic species (Gna) (FIG. 3), and by sucrose density gradient centrifugation in 0.5% (w/v) Brij 97 to separate individual molecular weight isoforms (G4,G2 and G1) (FIG. 3). A decrease in the proportion of G4, AChE in AD CSF compared to controls (FIG. 4, top panels) was observed. The ratio of (G4,/(G2+G1) was significantly (P<0.01) higher in controls (1.80�0.12; n=4) than in AD cases (1.16�0.12; n=4). To separate hydrophilic isoforms from amphiphilic isoforms, CSF was fractionated by hydrophobic interaction chromatography on phenyl-agarose (FIG. 3). A smaller percentage of AChE in the normal CSF bound to phenyl agarose (12�3%, n=4) than in the AD CSF (38�4%, n=4; P<0.001). Sedimentation analysis of the unbound hydrophilic fraction (HF) showed a main peak of 10.8S, consistent with a hydrophilic tetrameric (G4 na) isoform (Atack et al., 1987), as well as a small amount of lighter AChE isoforms, 5.1S dimers and 4.3S monomers (FIG. 4). The bound amphiphilic fraction from the phenyl-agarose column contained a minor peak of 9.0-9.5S (probably an amphiphilic tetramer, G4 a and a major peak of amphiphilic globular dimer (G2 a, 4.2S) and monomer (G1 a, 3.1S). The level of the amphiphilic light isoforms was greater in the AD CSF than in controls (FIG. 4).
[0053] Glycosylation of Individual AChE Isoforms in CSF
[0054] Incubation of the HF and AF with immobilised Con A and WGA showed that there was an increase in the C/W ratio in AD CSF, and that the high CIW ratio was associated with an amphiphilic fraction containing dimers and monomers (FIG. 4). The data indicate that the contribution of G2 and G1 AChE in AD CSF was mainly responsible for the increased C/W ratio of total AChE in the AD CSF.
[0055] Levels of AChE in Frontal Cortex and Cerebellum
[0056] To determine whether the changes in AChE glycosylation reflect a change in the expression or glycosylation of brain AChE isoforms, the levels of AChE activity in samples of frontal cortex and cerebellum were examined. Samples were homogenised with salt and Triton X-100 to extract soluble and membrane-bound AChE isoforms, and then the AChE activity determined in both fractions (Table 2). The frontal cortex samples from AD patients had significantly less AChE activity in the Triton X-100-soluble (TS) fraction (˜40%), with no difference in levels in the salt-soluble (SS) fraction compared with controls (Table 3). The results are consistent with previous studies that indicate that the major G4 isoform is decreased only in the TS fraction (Younkin et al., 1986; Seik et al., 1990). A small but significant decrease (˜15%) in the protein content of the TS fraction of both AD and ND groups was also observed. The level of AChE in the frontal cortex samples of the ND group was significantly different from controls in both the SS and TS fraction (Table 2). However, as the ND group was heterogeneous (2 frontal lobe dementia, 1 Huntington's disease and 1 Parkinson's disease), the significance of changes in AChE levels is unclear. Levels of AChE in cerebellum were also significantly decreased in the TS fraction from the AD group (Table 2).
[0057] Glycosylation of AChE in Frontal Cortex and Cerebellar
[0058] To determine whether different glycosylation pattern of AChE in AD CSF is also present in the AD brain, the glycosylation of brain AChE was examined by lectin binding. Homogenates from frontal cortex and cerebellum were incubated with immobilised Con A or WGA and the amount of activity unbound was calculated. In the AD frontal cortex, the % AChE activity that did not bind to Con A or WGA was significantly different from controls (Table 3). Similar to the CSF AChE, the C/W ratio of frontal cortex AChE was greater in AD than in non-AD samples (Table 3). This increase was due to a large increase in the amount of AChE that did not bind to Con A, and was in spite of an increase in the amount of AChE that did not bind to WGA (Table 3). There was no increase in the C/W ratio in the DP and ND group (Table 3). No difference in lectin binding was observed between AD and non-AD groups in the cerebellar fractions (Table 3.)
[0059] AChE Isoforms in Frontal Cortex and Cerebellum
[0060] To determine the cause of the altered glycosylation in AD brain, the pattern of AChE isoforms in the frontal cortex and cerebellum was examined. Equal volumes of SS and ST supernatants (total AChE activity) were pooled and then analysed by sucrose density gradient sedimentation with 0.5% (w/v) Brij 97 to separate the major AChE isoforms (FIG. 5). Based on their sedimentation coefficients (Atack et al., 1986; Massouli� et al., 1982) it was possible to identify hydrophilic (G4 na, 10.7�0.1S) and amphiphilic tetramers (G4 a, 8.6�0.1S) amphiphilic dimers (G2 a, 4.7�0.1S) and monomers (G1 a, 3.0�0.1S) of AChE (FIG. 6). There were no differences in the sedimentation coefficient (S) of individual isoforms from each group. Due to the overlap in the sedimentation coefficients between AChE G4 na and G4 a, it was not possible to separate these isoforms completely (FIG. 5). However, the contribution of G4 a was greater than G4 na. Asymmetric (A12) AChE isoforms were identified in trace amounts (2-5%) in some of the fractions.
[0061] A significant decrease in G4, (40% of the mean control value, P<0.001) and in G2+G1 AChE (60% of the mean control value, P=0.002) was detected in the fractions from AD frontal cortex. This change in the relative proportion of AChE isoforms was reflected in the G4/(G2+G1) ratio, which was significantly lower in the AD samples (Table 3). Interestingly, a similar and statistically significant decrease was found in the G4/(G2+G1) ratio for the DP subjects. This change in ratio was due to a 25% increase in the level of G2+G1 and a small decrease (10%) in G4 AChE, although neither change on its own was statistically significant. No variation in AChE G4/(G2+G1) was found in the AD cerebellum (Table 3), despite a statistically significant decrease (40%) in AChE in the TS fraction (Table 2) and in the total level of G4 AChE (G4 in controls=380�40 U/ml, G4 in ADs=195�70 U/ml; P=0.008).
[0062] Glycosylation of Individual AChE Isoforms in Frontal Cortex and Cerebellum
[0063] Since it was found that the ratio of AChE was altered in the frontal cortex of AD patients, steps were taken to ascertain whether the increase in the C/W ratio of brain AChE was due to a change in glycosylation or in the expression of a specific isoform of AChE. Individual AChE isoforms were separated by sucrose gradient centrifugation and then fractions from the G4 or G2+G1 peaks were pooled, dialysed against TSB-Triton X-100 buffer and concentrated by ultrafiltration. AChE isoforms were then assayed by lectin binding and a C/W ratio calculated for each isoform (FIG. 5).
[0064] No differences were observed in the C/W ratio of G4, AChE between the AD and non-AD groups (FIG. 5). However, in all frontal cortex samples the G2+G1 fraction possessed C/W ratios>1.00, demonstrating that G2 or G1 AChE is glycosylated differently from the G4 isoform. Moreover, the C/W ratio for G2+G1 AChE was higher in the AD group than controls or DP. Similarly, the C/W ratio of the amphiphilic fraction from CSF (containing predominantly G2+G1 AChE) was higher in the AD group than in controls (FIG. 3). There was no correlation between the G4/(G2+G1) ratio and the C/W ratio in the DP group in frontal cortex. In the cerebellum, no differences were observed in the C/W ratios of G4 AChE or G2+G1 AChE between AD and non-AD groups (FIG. 4). The G2+G1 fractions, from both AD and non-AD cerebellar groups, had a C/W<0.50, in contrast to the same fraction from frontal cortex (C/W>1.00) indicating differences in the pattern of glycosylation of G2+G1 AChE between both brain areas.
[0065] This example shows that AChE is glycosylated differently in the frontal cortex and CSF of AD patients compared with AChE from non-AD groups including patients with non AD-type dementias. This difference in glycosylation is due to an increase in the proportion of differentially glycosylated amphiphilic dimeric and monomeric AChE in the AD samples. The results suggest that the abnormally glycosylated AChE in AD CSF may be derived from the brain as a similar difference in glycosylation was also found in the frontal cortex of AD patients.
[0066] All the CSFs were taken post mortem and the diagnosis confirmed by pathological examination. CSF from normal subjects (Control group: n=18; 67�4 years at death; 11 Females/7 Males) and AD patients (AD group: n=30; 79�2 y; 15F/15M) were incubated either with an equal volume of the different immobilized lectins, and then centrifuged. AChE was assayed in the supernatant fractions. The data represent the means�SEM.
[0067] Tissue from frontal cortex or cerebellum was homogenized and salt-soluble (SS) and Triton X-100-soluble (TS) extracts obtained. The extracts were then assayed for AChE and protein. DP=non-demented subjects with diffuse plaques; ND=individuals with other neurological diseases and dementias of non-AD type; AD=individuals with Alzheimer's disease. F=female; M=male; y=age in years. Values are means�SEM.
[0068] SS and TS fractions from frontal cortex and cerebellum were pooled in equal volumes and then analyzed by lectin binding using immobilized Con A and WGA. The C/W ratio was calculated as defined in Table 2. Aliquots of the supernatants (SS+TS) were also analyzed by sucrose density gradient sedimentation to identify AChE isoforms. Values are means�SEM.
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[0123] Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., and Klenk D. C. (1985) Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76-85.
[0124] Smith A. D., Jobst K. A., Navaratnam D. S., Shen Z. X., Priddle J. D., McDonald B., King E., and Esiri M. M. (1991) Anomalous acetylcholinesterase in lumbar CSF in Alzheimer's disease. Lancet 338, 1538.
[0125] Soreq H., Ben-Aziz R., Prody C. A., Seidman S., Gnatt A., Neville L., Lieman-Hurwitz J., Lev-Lehman E., Ginzberg D., Lapidot-Lifson Y., and Zakut H. (1990) Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G+C-rich attenuating structure. Proc. Natl. Acad. Sci. USA 87, 9688-9692.
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[0127] Ulrich J., Meier-Ruge W., Probst A., Meier E., and Ipsen S. (1990) Senile plaques, staining for acetylcholinesterase and A4 protein, a comparative study in the hippocampus and entorhinal cortex. Acta Neuropathol 80, 624-628. Vidal C. J. (1996) Glycosylation of cholinesterases and its alteration in some pathological states. Recent Res. Devell, Neurochem, 1, 37-54.
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Dr. Eric Schertel helps develop the MedVet experience at new locations
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EY founded the EY Entrepreneur Of The Year® Program to recognize these dynamic leaders and to build an influential community of innovative entrepreneurs. This article recognizes the 2015 Northern Ohio honorees.Read Full Article
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Ceases Working Intermittently Rated 2 out of 5 stars
This repeatedly ceases to work (just like v2.8.1 and v 2.7.9 did). The only workaround I've found is to empty the cache and then reinstall v2.7.9 (or if you're using v2.7.9 reinstall v2.8.2). Just be sure you have a high enough "MaxVersion" in the install.rdf file for v.2.7.9.This review is for a previous version of the add-on (2.82.1-signed). This user has other reviews of this add-on.
Have you an error message ? If so which one?
did you try to install in a new clean profile ?


text: After teens noticed a change in the tap water in Oakland due to the California drought, 17-year-old Amber Lee took a tap vs. bottled water taste test in Youth Radio's studios. Jenny Bolario/Youth Radio hide caption itoggle caption Jenny Bolario/Youth Radio Teens Say California Drought Makes Tap Water Taste Funky May 5, 2015 A firsthand look at how the historic drought is affecting local teens' quest to quench their thirst. Listen Loading… 3:36 Playlist Download Embed Embed Close embed modal <iframe src="http://www.npr.org/player/embed/402584148/404352601" width="100%" height="290" frameborder="0" scrolling="no">


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Son Of A Pimp
Released: Jan 2005
Label: Faeva Afta
Rising Bay Area emcee Mistah F.A.B. conjures up Mac Dre's surname (Andre Hicks) early and often on this EP. F.A.B. doesn't have Dre's charisma -- though, to be fair, not many do -- but on "Nation of Thizzlam," "Supa Sic Wit It" and "Brush Em Off" the East Bay emcee projects the same unselfconscious euphoria and chemically-induced goofiness that made Dre the reigning icon of the Bay's hyphy movement.